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• applications(array)
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    • Application(array)
      • id744
      • user_id611
      • trial_status_id6
      • abstract_of_study<p>\n This is an epidemiology study that intends to evaluate the safety, effectiveness and impact of the RTS,S/AS01E vaccine in young children in sub-Saharan Africa. GlaxoSmithKline (GSK) Biologicals has developed a pre-erythrocytic Plasmodium (P.) falciparum malaria vaccine, RTS,S/AS01E, for routine immunisation of children living in malaria-endemic countries of sub-Saharan Africa (SSA). The World Health Organization (WHO)’s Strategic Advisory Group of Experts (SAGE) on Immunization and the Malaria Policy Advisory Committee (MPAC) recommended pilot implementations of RTS,S/AS01E in children of 5–17 months of age, in parts of 3-5 distinct epidemiological settings in sub-Saharan Africa , administering 3 doses of the vaccine to children 5-9 months of age in areas of moderate to-high transmission of malaria with a fourth dose administered 15-18 months following the third dose. In April 2017, the WHO Regional Office for Africa announced that the RTS,S/AS01E vaccine will be first introduced in 3 countries (Ghana, Kenya and Malawi) in 2018 through a WHO-coordinated pilot implementation programme, referred to as the Malaria Vaccine Implementation Programme (MVIP). In order to align with the MVIP, the study sites for the GSK Phase IV studies have been, selected from the 3 countries where the RTS,S/AS01E vaccine will be implemented. Sites from Kenya and Ghana (Malawi sites did not participate in EPI-MAL-002) that were part of study EPI-MAL-002 and also Malawi sites will become study sites in EPI-MAL-003 (EPI-MALARIA-003 VS AME (115056)) which will be exposed clusters. EPI-MAL-003 is a post-implementation study that will further evaluate the safety, effectiveness and impact of the vaccine during initial implementation.</p>\n
      • study_title<p>\n A prospective study to evaluate the safety, effectiveness and impact of the RTS,S/AS01E vaccine in young children in sub-Saharan Africa.</p>\n
      • laymans_summary<p>\n GlaxoSmithKline (GSK) Biologicals has developed a malaria vaccine, RTS,S/AS01E, for routine immunisation of children living in malaria-endemic countries of sub-Saharan Africa (SSA). RTS,S/AS01E is the first vaccine to be implemented for the prevention of malaria in the paediatric population. The World Health Organization (WHO)’s Strategic Advisory Group of Experts (SAGE) on Immunization and the Malaria Policy Advisory Committee (MPAC) recommended pilot implementations of RTS,S/AS01E in children of 5–17 months of age, in parts of 3-5 SSA countries, administering 3 doses of the vaccine to children 5-9 months of age in areas of moderate to- high transmission of malaria with a fourth dose administered 15-18 months following the third dose. In April 2017, the WHO Regional Office for Africa announced that the RTS,S/AS01E vaccine will be first introduced in 3 countries (Ghana, Kenya and Malawi) through a WHO-coordinated pilot implementation programme, referred to as the Malaria Vaccine Implementation Programme (MVIP). In order to align with the MVIP, the study sites for the GSK Phase IV studies have been, selected from the 3 countries where the RTS,S/AS01E vaccine will be implemented. Sites from Ghana and Kenya that were part of study EPI-MAL-002 should become study sites in EPIMAL- 003 which will be exposed clusters. The safety and efficacy of RTS,S/AS01E have been evaluated during pre-authorisation clinical trials conducted mainly in SSA. Study EPI-MALARIA-003 VS AME (115056) will further evaluate the safety, effectiveness and impact of the vaccine during initial implementation. A pre-implementation (i.e. before vaccine implementation) surveillance study, EPI-MALARIA-002 VS AME (115055) will measure the baseline incidence of protocol-defined adverse events of special interest (AESI), other adverse events (AE) leading to hospitalisation or death, meningitis, malaria morbidity and mortality. The mortality rate, overall and by gender, are also being estimated. EPI-MAL-003 is intended primarily as a post-implementation safety study, together with vaccine effectiveness and impact estimations. In parallel with both EPI-MAL-002 and EPI-MAL-003, a third study (EPI-MALARIA-005 BOD AME [116682] is conducted to measure malaria transmission intensity and other malaria control interventions as confounding factors in the study site areas. The three studies will be conducted in similar if not identical settings. A strong capacity development component is included in the baseline study EPIMAL-002. The study staff (e.g. health care/field worker) will visit the study participant at home or at the local health care facility up to 11 times during the study. Each of these planned study visits should take about 1 hour. If the child takes part in the study and if he/she is found to be unwell at any of the study visits (visits 1 to 9), he/she will be referred to a health care facility and treated under existing Kenya Ministry of Health services/programs. If the medical problem cannot be treated at home or at the nearest health care facility, he/she will be referred to a hospital. If this were to happen, transport will be arranged for this visit to see the doctor. The participant will benefit from regular check-up and advice during the planned visits.</p>\n
      • short_titleEPI 003
      • protocol_noECCT/18/11/02
      • version_no1
      • date_of_protocol11-10-2017
      • study_drugMOSQUIRIX
      • disease_conditionMALARIA
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines1
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressdotigondi3@gmail.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum1
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      • applicant_complete_form(null)
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      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
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      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantDr Bernhards Ogutu
      • declaration_date119-11-2018
      • declaration_principal_investigatorDr Berhnards Ogutu
      • declaration_date219-11-2018
      • placebo_presentNo
      • study_objectives<p>\n Primary objectives • To estimate the incidence of protocol-defined potential adverse events of special interest (AESI), and of other adverse events (AE) leading to hospitalisation or death, in children vaccinated with of RTS,S/AS01E. • To estimate the incidence of aetiology-confirmed meningitis in children vaccinated with RTS,S/AS01E. Secondary objectives Safety In children enrolled in EPI-MAL-003 study (vaccinated with RTS,S/AS01E or not vaccinated with RTS,S/AS01E): • To estimate the incidence of aetiology-confirmed and/or probable meningitis (final classification). • To estimate the incidence of probable meningitis (final classification). • To estimate the incidence of aetiology-confirmed, probable and/or clinically suspected meningitis (final classification). • To estimate the incidence of cerebral malaria (malaria diagnosed by rapid diagnostic test [RDT] and/or microscopy). • To estimate the mortality rate (all-cause mortality and deaths attributed to malaria [including P. falciparum]), overall and by gender. • To describe risk factors for AESI, other AE leading to hospitalisation or death, meningitis, and malaria. • To describe the causes of hospitalisation (including AESI, other AE, meningitis and malaria). • To describe the causes of death, overall and by gender. • To assess the risk of febrile convulsions during the 7-day period and 1-month period following each dose of RTS,S/AS01E. In children enrolled in EPI-MAL-002 or EPI-MAL-003 studies (vaccinated with RTS,S/AS01E or not vaccinated with RTS,S/AS01E): • To monitor trends over time of meningitis cases identified at site level (first line laboratory). • To assess the potential association between vaccination and meningitis by comparing the incidence of aetiology-confirmed meningitis in children vaccinated with RTS,S/AS01E with the incidence of these events in children not vaccinated with RTS,S/AS01E. • To assess the potential association between vaccination and meningitis by comparing the incidence of aetiology-confirmed and/or probable meningitis in children vaccinated with RTS,S/AS01E with the incidence of these events in children not vaccinated with RTS,S/AS01E. • To assess the potential association between vaccination and meningitis by comparing the incidence of aetiology-confirmed, probable and/or clinically suspected meningitis in children vaccinated with RTS,S/AS01E with the incidence of these events in children not vaccinated with RTS,S/AS01E. • To assess the potential association between vaccination and AESI, and other AE leading to hospitalisation or death by comparing the incidence of these events in children vaccinated with RTS,S/AS01E with the incidence of these events in children not vaccinated with RTS,S/AS01E. • To assess the potential association between vaccination and cerebral malaria by comparing the incidence of these events in children vaccinated with RTS,S/AS01E with the incidence of these events in children not vaccinated with RTS,S/AS01E. • To assess the potential association, overall and by gender, between vaccination and death by comparing the incidence of these events in children vaccinated with RTS,S/AS01E with the incidence of these events in children not vaccinated with RTS,S/AS01E. Effectiveness and impact • To estimate the vaccine effectiveness (direct effect) and the impact (indirect, total and overall effects) of vaccination with RTS,S/AS01E on the incidence of any malaria (including P. falciparum malaria), severe malaria (including P. falciparum malaria) and cerebral malaria diagnosed by RDT and/or microscopy. • To estimate the vaccine effectiveness (direct effect) and impact (indirect, total and overall effects) of vaccination with RTS,S/AS01E on: o The prevalence of anaemia among hospitalised children. o The incidence of all-cause hospitalizations and hospitalizations attributed to malaria (including P. falciparum). o The mortality rate (all-cause mortality and deaths attributed to malaria [including P. falciparum]) overall and by gender.</p>\n
      • principal_inclusion_criteria<p>\n Study participants’ parent(s)/LAR(s) who, in the opinion of the investigator can comply with the requirements of the protocol • Written Informed Consent provided from either the parent(s) or LAR of the study participant • Study participant living in the HDSS or equivalent surveillance system area For enrolment in the active surveillance – DTP group: children must be aged < 18 months, identified at any administration of DTP/HepB/Hib (or at hospitalisation before 3rd dose of DTP/HepB/Hib in case of hospitalisation and vaccinated with at least one dose of DTP/HepB/Hib). (This group will include children from exposed and unexposed clusters.) OR For enrolment in the active surveillance – Catch-up group: children must be aged < 18 months, received at least one dose of DTP/HepB/Hib vaccine, whose age corresponds to the age after the 3rd dose of DTP/HepB/Hib vaccine and identified at administration of first dose of RTS,S/AS01E vaccine. (This group will include children from exposed clusters only.) OR For enrolment in the enhanced hospitalisation surveillance: children must be aged < 5 years and hospitalised at any time during the study. (This group will include children from exposed and unexposed clusters.)</p>\n
      • principal_exclusion_criteria<p>\n Child in care</p>\n
      • primary_end_points<p>\n • Occurrence of AESI. • Occurrence of other AE leading to hospitalisation or death • Occurrence of aetiology-confirmed meningitis</p>\n
      • scope_diagnosis1
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use1
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<p>\n Principal Investigator- 1 Dr Bernhards Ogutu Sub Investigators-------3 Dr Allan Otieno Dr Fredrick Olewe Dr John Michael Ongecha Clinical Officers--------2 James Otieno Oloo Solomon Ali Juma Study Coordinator-----1 Nelly Koskei Lab Technologists-----2 Grace Owino Kennedy Ogweno Nurses------------------4 Mrs Agnes Onyango Maureen Mbija Wyclife Misiayi Jael Aran Lab Technician--------1 Festus Okute Pharmacist ------------1 Dr Ruth Wasuna Pharmacy Technician-1 Mathew Onyango Data Clerks-------------2 Erick Otiu Dishon Yoweri Odidi Community Health Worker-1 Florence Adhola Community Health Volunteers—10 Site Facilities------ 24 Facilities ( Level 3 and level 4 facilities) out of which 3 can hospitalize. Ahero Sub County Hospital is the referral point for all the facilities Nyando Sub County. The patients are referred to Jaramogi Oginga Odinga Teaching and Referral Hospital from Ahero County Hospital in case of an emergency.</p>\n
      • other_details_explanation<p>\n N/A</p>\n
      • other_details_regulatory_notapproved<p>\n N/A</p>\n
      • other_details_regulatory_approved<p>\n Ghana FDA only acknowledged on 14Sep2018, approval was not sought. Malawi submission to Regulatory Authorities is not applicable</p>\n
      • other_details_regulatory_rejected<p>\n NONE</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration62MONTHS
      • design_controlled_randomised
      • design_controlled_open
      • design_controlled_single_blind
      • design_controlled_double_blind
      • design_controlled_parallel_group
      • design_controlled_cross_over
      • design_controlled_other
      • design_controlled_specify
      • design_controlled_comparator
      • design_controlled_other_medicinal
      • design_controlled_placebo
      • design_controlled_medicinal_other
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states3
      • number_of_sites3
      • multi_country_listGhana, Malawi, Kenya
      • data_monitoring_committeeYes
      • total_enrolment_per_site• Ahero Clinical Trials Unit (Dr Bernhards Ogutu) – 3000 patients\n• KEMRI Walter Reed Army Institute of Research (Dr Walter Otieno) – 3000 patients\n• KEMRI CDC Siaya (Dr Simon Kariuki) – 6000 patients\n
      • total_participants_worldwide45,000
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornYes
      • population_newbornYes
      • population_infant_and_toddlerYes
      • population_childrenNo
      • population_adolescentNo
      • population_above_18No
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifyCHILDREN LESS THAN 5 YEARS OLD
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameBERNHARDS
      • investigator1_middle_name
      • investigator1_family_nameOGUTU
      • investigator1_qualificationMBChB, MMed (Peds), PhD
      • investigator1_professional_addressP.O.BOX 54, AHERO CLINICAL TRIALS CENTRE
      • investigator1_telephone+254 733812613
      • investigator1_emailogutu6@gmail.com
      • organisations_transferred_Yes
      • number_participants12,000
      • notification<p>\n This submission has been done on behalf of the 3 Kenyan sites. The other 2 sites will only now submit their site specific documents for approval once the ethics approval has been obtained.</p>\n
      • approval_date25-03-2019
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted04-03-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-02-10 11:41:44
      • created2018-11-19 17:44:19
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id463
        • application_id744
        • given_nameBERNHARDS
        • middle_name
        • family_nameOGUTU
        • qualificationMBChB, MMed (Peds), PhD
        • professional_addressP.O.BOX 54, AHERO CLINICAL TRIALS CENTRE
        • telephone+254 733812613
        • emailogutu6@gmail.com
        • created2018-11-19 17:46:29
        • modified2020-03-04 14:45:38
    • SiteDetail(array)
      • 0(array)
        • id584
        • application_id744
        • county_id42
        • site_name• Ahero Clinical Trials Unit
        • physical_addressAhero
        • contact_detailsClinical Trials Unit, P.O Box 54, Kisumu, Kenya
        • contact_personDr Bernhards Ogutu
        • site_capacity(null)
        • misc(null)
        • created2018-11-19 17:46:29
        • modified2020-03-04 14:45:38
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 1(array)
        • id585
        • application_id744
        • county_id42
        • site_nameKEMRI Walter Reed Army Institute of Research
        • physical_address Off Kisumu Bondo Road, Kombewa, Kenya
        • contact_detailsP,O Box 54, Kisumu
        • contact_personDr Walter Otieno
        • site_capacity(null)
        • misc(null)
        • created2018-11-19 19:39:14
        • modified2020-03-04 14:45:38
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 2(array)
        • id586
        • application_id744
        • county_id41
        • site_nameKEMRI CDC SIAYA
        • physical_addressSIAYA
        • contact_detailsP.O Box 54840-00200, Kisumu, Nairobi
        • contact_personDr Simon Kariuki
        • site_capacity(null)
        • misc(null)
        • created2018-11-19 19:39:14
        • modified2020-03-04 14:45:38
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
    • Sponsor(array)
      • 0(array)
        • id361
        • application_id744
        • sponsorGlaxoSmithKline Biologicals
        • sponsor_typeIndustry
        • contact_personGodfrey Rikhotso
        • addressFlushing Meadows Building, 57 Sloane Street, The Campus, Bryanston, 2021, Gauteng, South Africa
        • telephone_number+27 11 745 6102
        • fax_number+27 11 388 6213
        • cell_number+27 79 223 2180
        • email_addressgodfrey.n.rikhotso@gsk.com
        • created2018-11-19 17:46:29
        • modified2020-03-04 14:45:38
  • 1(array)
    • Application(array)
      • id171
      • user_id47
      • trial_status_id5
      • abstract_of_study<div>\n <p>\n <strong>Controlled Comparison of Two Moxifloxacin Containing Treatment Shortening Regimens in Pulmonary Tuberculosis (REMoxTB)</strong></p>\n</div>\n<p>\n  </p>\n<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\">\n <tbody>\n <tr>\n <td nowrap=\"nowrap\">\n <p>\n <strong>Official Title:</strong></p>\n </td>\n <td>\n <p>\n A Randomised Placebo - Controlled Double Blind Trial Comparing 1) a Two Month Intensive Phase of Ethambutol, Moxifloxacin, Rifampicin, Pyrazinamide Versus the Standard Regimen (Ethambutol, Isoniazid, Rifampicin, Pyrazinamide) and 2) a Treatment Shortening Regimen Comparing Two Months Moxifloxacin, Isoniazid, Rifampicin, Pyrazinamide Followed by Two Months Moxifloxacin, Isoniazid, Rifampicin Versus the Standard Regimen (Two Months Ethambutol, Isoniazid, Rifampicin, Pyrazinamide Followed by Four Months Isoniazid and Rifampicin) for the Treatment of Adults With Pulmonary Tuberculosis</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n<p>\n <strong>Sponsor:</strong></p>\n<p>\n Global Alliance for TB Drug Development</p>\n<p>\n <strong>Collaborators:</strong></p>\n<p>\n European and Developing Countries Clinical Trials Partnership (EDCTP)</p>\n<p>\n University College, London</p>\n<p>\n Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma</p>\n<p>\n Sanofi</p>\n<p>\n  </p>\n<p>\n <strong>Site:</strong>  Centre for Respiratory Diseases Research, Kenya Medical Research Institute</p>\n<p>\n Current standard TB therapy is based on four medicines discovered forty or more years ago that must be administered for six to eight months, often under the direct observation of a healthcare professional (DOTS). A shorter TB treatment regimen should increase patient compliance, reduce failure rates and lower TB-related healthcare expenditures in endemic countries. REMoxTB is a study for the "Rapid Evaluation of Moxifloxacin in the treatment of sputum smear positive tuberculosis". REMoxTB aims to find and evaluate new drugs and regimens that shorten the duration of tuberculosis therapy. Preclinical studies showed that moxifloxacin could reduce treatment time by two months when substituted for isoniazid or ethambutol, two cornerstones of current TB treatment. The results of clinical phase II studies support the treatment reduction potential of moxifloxacin. Moxifloxacin is currently approved in 123 countries for the treatment of acute bacterial infections. However, Moxifloxacin is not currently approved for the treatment of TB, including multi-drug resistant TB (MDR-TB).</p>\n<p>\n The purpose of REMoxTB is to evaluate the efficacy, safety and acceptability of two moxifloxacin-containing treatment combinations to determine whether substituting ethambutol with moxifloxacin in one combination, and/or substituting isoniazid with moxifloxacin in another combination, makes it possible to reduce the duration of treatment for TB.</p>\n<p>\n The study type is interventional and the study design is a randomized double blinded whose intervention model is parallel assignment and the primary purpose is to evaluate the treatment. The primary end points are efficacy and safety.</p>\n<p>\n The study participants are patients with newly diagnosed previously untreated sputum smear positive pulmonary tuberculosis who fit the inclusion and exclusion criteria.</p>\n<p>\n The study is ongoing but no recruitment of participants.</p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n
      • study_title<p>\n A randomised placebo – controlled double blind trial comparing two treatment shortening regimens with the standard regimen (two months ethambutol,<br />\n isoniazid, rifampicin and pyrazinamide followed by four months isoniazid and rifampicin) namely 1) two months moxifloxacin, isoniazid, rifampicin and<br />\n pyrazinamide followed by two months moxifloxacin, isoniazid and rifampicin and 2) two months ethambutol, moxifloxacin, rifampicin and pyrazinamide followed by<br />\n two months moxifloxacin and rifampicin for the treatment of adults with pulmonary tuberculosis</p>\n
      • laymans_summary(null)
      • short_titleREMoxTB
      • protocol_noECCT/09/03/01
      • version_no6.1
      • date_of_protocol18-08-2011
      • study_drugMoxifloxacin
      • disease_conditionPulmonary tuberculosis
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameMoxifloxacin
      • product_type_medical_device_name
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressbmiheso@kemri.org
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum0
      • applicant_fees1
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      • applicant_hard_copies(null)
      • applicant_signed_checklist(null)
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantBarbara Miheso
      • declaration_date125-07-2013
      • declaration_principal_investigatorDr. Evans I. Amukoye
      • declaration_date225-07-2013
      • placebo_presentYes
      • study_objectives(null)
      • principal_inclusion_criteria<div>\n A. Signed written consent or witnessed oral consent in the case of illiteracy, before undertaking any trial related activity.</div>\n<div>\n B. Two sputum specimens positive for tubercle bacilli on smear microscopy at least one of which must be processed and positive at the study laboratory.</div>\n<div>\n C. Aged 18 years or over.</div>\n<div>\n <div>\n D. No previous anti-tuberculosis chemotherapy.</div>\n <div>\n E. A firm home address that is readily accessible for visiting and willingness to inform the study team of any change of address during the treatment and</div>\n <div>\n follow-up period.</div>\n <div>\n F. Agreement to participate in the study and to give a sample of blood for HIV testing (see appendices 1 & 2).</div>\n <div>\n G. Pre-menopausal women must be using a barrier form of contraception or be surgically sterilised or have an IUCD in place.</div>\n <div>\n H. Laboratory parameters performed up to 14 days before enrolment.</div>\n <div>\n ï‚· Serum aspartate transaminase (AST) and alanine transaminase (ALT) activity less than 3 times the upper limit of normal</div>\n <div>\n ï‚· Serum total bilirubin level less than 2.5 times upper limit of normal</div>\n <div>\n ï‚· Creatinine clearance (CrCl) level greater than 30 mls/min</div>\n <div>\n ï‚· Haemoglobin level of at least 7.0 g/dL</div>\n <div>\n ï‚· Platelet count of at least 50x109cells/L</div>\n <div>\n ï‚· Serum potassium greater than 3.5 mmol/L</div>\n <div>\n I. Negative pregnancy test (women of childbearing potential).</div>\n</div>\n<p>\n  </p>\n
      • principal_exclusion_criteria<div>\n A. Unable to take oral medication.</div>\n<div>\n B. Previously enrolled in this study.</div>\n<div>\n C. Received any investigational drug in the past 3 months.</div>\n<div>\n D. Received an antibiotic active against M. tuberculosis in the last 14 days (fluoroquinolones, macrolides, standard anti-tuberculosis drugs).</div>\n<div>\n E. Any condition that may prove fatal during the first two months of the study period.</div>\n<div>\n F. TB meningitis or other forms of severe tuberculosis with high risk of a poor outcome</div>\n<div>\n G. Pre-existing non-tuberculosis disease e.g. diabetes, liver or kidney disease, blood disorders, peripheral neuritis, chronic diarrhoeal disease in which the</div>\n<div>\n <div>\n current clinical condition of the patient is likely to prejudice the response to, or assessment of treatment.</div>\n <div>\n H. Pregnant or breast feeding.</div>\n <div>\n I. Suffering from a condition likely to lead to uncooperative behaviour e.g. psychiatric illness or alcoholism.</div>\n <div>\n J. Contraindications to any medications in the study regimens.</div>\n <div>\n K. Known to have congenital or sporadic syndromes of QTc prolongation or</div>\n <div>\n receiving concomitant medication reported to increase the QTc interval (e.g.</div>\n <div>\n amiodarone, sotalol, disopyramide, quinidine, procainamide, terfenadine).</div>\n <div>\n L. Known allergy to any fluoroquinolone antibiotic or history of tendinopathy associated with quinolones.</div>\n <div>\n M. Patients already receiving anti-retroviral therapy.</div>\n <div>\n N. Patients whose initial isolate is shown to be multiple drug resistant (i.e. resistant to rifampicin and isoniazid) or monoresistant to rifampicin, or</div>\n <div>\n resistant to any fluoroquinolone). </div>\n <div>\n O. Weight less than 35kg</div>\n <div>\n P. HIV infection with CD4 count less than 250 cells/μL.</div>\n <div>\n Q. End stage liver failure (class Child-Pugh C).</div>\n</div>\n<p>\n  </p>\n
      • primary_end_points<div>\n 1. Efficacy:</div>\n<div>\n Combined failure of bacteriological cure and relapse within one year of completion of therapy as defined by culture using solid media.</div>\n<div>\n  </div>\n<div>\n 2. Safety:</div>\n<div>\n Both comparisons: Proportion of patients with grade 3 or 4 adverse events.</div>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" style=\"width:1017px;\" width=\"1016\">\n <colgroup>\n <col />\n <col />\n <col />\n <col />\n <col span=\"2\" />\n <col />\n </colgroup>\n <tbody>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Nairobi - 0106</td>\n <td colspan=\"6\" style=\"width:845px;\">\n  </td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Staff Member</td>\n <td style=\"width:128px;\">\n Role</td>\n <td style=\"width:101px;\">\n INSTITUTION</td>\n <td colspan=\"4\" style=\"width:616px;\">\n Qualification</td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Dr. Evans Amukoye</td>\n <td style=\"width:128px;\">\n Principal Investigator</td>\n <td style=\"width:101px;\">\n KEMRI</td>\n <td colspan=\"4\" style=\"width:616px;\">\n MB.ChB( MD), M.Med(Pead), Clinical Fellow Pulmunology</td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Dr. Jane Ong'ang'o</td>\n <td style=\"width:128px;\">\n Co-Investigator</td>\n <td style=\"width:101px;\">\n KEMRI</td>\n <td colspan=\"4\" style=\"width:616px;\">\n MBChB, MSc in Pulblic health, Post draduate Dip. STI/HIV, PhD Epidemiology (Ongoing)</td>\n </tr>\n <tr height=\"34\">\n <td height=\"34\" style=\"height:34px;width:172px;\">\n Dr. Samoel Khamadi</td>\n <td style=\"width:128px;\">\n Co-Investigator/Lab Coodinator</td>\n <td style=\"width:101px;\">\n WRP</td>\n <td colspan=\"4\" style=\"width:616px;\">\n PhD Molecular Medicine, Post Graduate Fellow, Dip. Project Management</td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Barbara B. Miheso</td>\n <td style=\"width:128px;\">\n Study Coordinator </td>\n <td style=\"width:101px;\">\n KEMRI</td>\n <td colspan=\"4\" style=\"width:616px;\">\n Bsc Biochemistry, MSc Molecuar Medicine (ongoing), Dip. Project Management</td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Mr Paul Mwangi</td>\n <td style=\"width:128px;\">\n Clinical Officer</td>\n <td style=\"width:101px;\">\n KEMRI</td>\n <td colspan=\"4\" style=\"width:616px;\">\n MSc. Community Health Development, Higher Dip. Lung and skin, Diploma in Clinical Med.and Surgery </td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Susan Mutua</td>\n <td style=\"width:128px;\">\n Clinical Officer</td>\n <td style=\"width:101px;\">\n KEMRI</td>\n <td colspan=\"4\" style=\"width:616px;\">\n Dip. Clinical Med. And Surgery  </td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Margaret N. Karugu</td>\n <td style=\"width:128px;\">\n Nurse</td>\n <td style=\"width:101px;\">\n KEMRI</td>\n <td colspan=\"4\" style=\"width:616px;\">\n Higher Dip. Medical health and Psychological Counseling, KRN</td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Gertrude Nzoka</td>\n <td style=\"width:128px;\">\n Nurse</td>\n <td style=\"width:101px;\">\n MOH</td>\n <td colspan=\"4\" style=\"width:616px;\">\n KRN</td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Dr. Angela Amayo</td>\n <td style=\"width:128px;\">\n Biochemistry Lab </td>\n <td style=\"width:101px;\">\n UON</td>\n <td colspan=\"4\" style=\"width:616px;\">\n MBChB, Msc Med (Human Pathology), Dip. Total Quality Management</td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Dr. Julius Kuria</td>\n <td style=\"width:128px;\">\n Biochemistry Lab</td>\n <td style=\"width:101px;\">\n UON</td>\n <td colspan=\"4\" style=\"width:616px;\">\n MBChB, MSc. Human Pathology</td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Dr. Jessie Githanga</td>\n <td style=\"width:128px;\">\n Hematology</td>\n <td style=\"width:101px;\">\n UON</td>\n <td colspan=\"4\" style=\"width:616px;\">\n MBChB, MSc. Human Pathology, Pst Doc. Cytogenetics and haematology</td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Dr. Peter Maturi Mwamba</td>\n <td style=\"width:128px;\">\n Hematology</td>\n <td style=\"width:101px;\">\n UON</td>\n <td colspan=\"4\" style=\"width:616px;\">\n MBChB, HDip.Computer Science</td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Charles Namutembi</td>\n <td style=\"width:128px;\">\n Lab technologist</td>\n <td style=\"width:101px;\">\n UON</td>\n <td colspan=\"4\" style=\"width:616px;\">\n Hdip. Haematology and Blood transfusion, Dip. Medical Laboratory Technology</td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Mr. Ireri M. Jackson</td>\n <td style=\"width:128px;\">\n Lab technologist</td>\n <td style=\"width:101px;\">\n UON</td>\n <td colspan=\"4\" style=\"width:616px;\">\n MSc. Infectious Diseases Diagnosis, Hdip. Medical Laboratory Science, Dip. Medical Laboratory Science</td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Debora Mogi</td>\n <td style=\"width:128px;\">\n Lab technologist</td>\n <td style=\"width:101px;\">\n UON</td>\n <td colspan=\"4\" style=\"width:616px;\">\n HDip. Clinical Chemistry, Dip. Medical Laboratory Technology</td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Francis Wanyama</td>\n <td style=\"width:128px;\">\n Lab technologist</td>\n <td style=\"width:101px;\">\n UON</td>\n <td colspan=\"4\" style=\"width:616px;\">\n HDip. Medical Laboratory Technology, Dip. Medical Laoratory Technology</td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Joyce Maganga</td>\n <td style=\"width:128px;\">\n Lab technologist</td>\n <td style=\"width:101px;\">\n UON</td>\n <td colspan=\"4\" style=\"width:616px;\">\n HDip. Medical Laboratory Technology, Dip. Medical Laoratory Technology</td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Tabitha Mungai</td>\n <td style=\"width:128px;\">\n Lab technologist</td>\n <td style=\"width:101px;\">\n UON</td>\n <td colspan=\"4\" style=\"width:616px;\">\n HDip. Medical Laboratory Technology, Dip. Medical Laoratory Technology</td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Esther O. Adoyo</td>\n <td style=\"width:128px;\">\n Lab technologist</td>\n <td style=\"width:101px;\">\n MOH</td>\n <td colspan=\"4\" style=\"width:616px;\">\n Dip. Medical Lab. Sciences, BSc. Medical Lab Sciences( On going)</td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Jacline O. Nyaboke</td>\n <td style=\"width:128px;\">\n Lab technologist</td>\n <td style=\"width:101px;\">\n MOH</td>\n <td colspan=\"4\" style=\"width:616px;\">\n Dip. Medical Lab. Sciences </td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Geoffrey Okallo</td>\n <td style=\"width:128px;\">\n Data Manager </td>\n <td style=\"width:101px;\">\n KEMRI</td>\n <td colspan=\"4\" style=\"width:616px;\">\n Microsoft Certiffied Professional Certification, Dip. Statistics, Computer Programming</td>\n </tr>\n <tr height=\"34\">\n <td height=\"34\" style=\"height:34px;width:172px;\">\n Ednah Wanjiku</td>\n <td style=\"width:128px;\">\n Data Manager Back up </td>\n <td style=\"width:101px;\">\n KEMRI</td>\n <td colspan=\"4\" style=\"width:616px;\">\n BSc. Computing, Dip. IT, MBA. Management Information Systems </td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n M’Iti Linda Karimi</td>\n <td style=\"width:128px;\">\n Data Clerk</td>\n <td style=\"width:101px;\">\n KEMRI</td>\n <td colspan=\"4\" style=\"width:616px;\">\n BSc. IT </td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Esther Mogaka</td>\n <td style=\"width:128px;\">\n Data Clerk</td>\n <td style=\"width:101px;\">\n KEMRI</td>\n <td colspan=\"4\" style=\"width:616px;\">\n Cert. Pharmaceutical technology</td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Stella Kamande</td>\n <td style=\"width:128px;\">\n Data Clerk</td>\n <td style=\"width:101px;\">\n KEMRI</td>\n <td colspan=\"4\" style=\"width:616px;\">\n Cert. Library Studies</td>\n </tr>\n <tr height=\"34\">\n <td height=\"34\" style=\"height:34px;width:172px;\">\n Anthony Sore</td>\n <td style=\"width:128px;\">\n Community mobilizer</td>\n <td style=\"width:101px;\">\n MOH</td>\n <td colspan=\"4\" style=\"width:616px;\">\n Cert. HIV/AIDS and counselor</td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Sarah Mulera</td>\n <td style=\"width:128px;\">\n Community mobilizer</td>\n <td style=\"width:101px;\">\n MOH</td>\n <td colspan=\"4\" style=\"width:616px;\">\n Dip. Psychological Counselling, Cert. HIV Counselling and Testing</td>\n </tr>\n <tr height=\"34\">\n <td height=\"34\" style=\"height:34px;width:172px;\">\n Francis Litu Mutange</td>\n <td style=\"width:128px;\">\n Community mobilizer</td>\n <td style=\"width:101px;\">\n MOH</td>\n <td colspan=\"4\" style=\"width:616px;\">\n Cert.HIV Counselling and Testing</td>\n </tr>\n <tr height=\"34\">\n <td height=\"34\" style=\"height:34px;width:172px;\">\n Jackline Achieng' Odhiambo</td>\n <td style=\"width:128px;\">\n Pharmacist</td>\n <td style=\"width:101px;\">\n KEMRI</td>\n <td colspan=\"4\" style=\"width:616px;\">\n B. Pharm, Post grad Dip. Biomedical Research Methodology</td>\n </tr>\n <tr height=\"34\">\n <td height=\"34\" style=\"height:34px;width:172px;\">\n Ezekiel Muinde</td>\n <td style=\"width:128px;\">\n Pharmaceutical Technologist</td>\n <td style=\"width:101px;\">\n KEMRI</td>\n <td colspan=\"4\" style=\"width:616px;\">\n Dip. Pharmacy</td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Simon Maina</td>\n <td style=\"width:128px;\">\n Pharmacist</td>\n <td style=\"width:101px;\">\n KEMRI</td>\n <td colspan=\"4\" style=\"width:616px;\">\n Higher Dip. Psychological Counselling, Cert. Pharmauceutical technology</td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Stephen Chege</td>\n <td style=\"width:128px;\">\n Procurement Officer</td>\n <td style=\"width:101px;\">\n KEMRI</td>\n <td colspan=\"4\" style=\"width:616px;\">\n Dip. Purchasing and Supplies,  Accounts Clerk</td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Fred Orina</td>\n <td style=\"width:128px;\">\n Lab QC</td>\n <td style=\"width:101px;\">\n KEMRI</td>\n <td colspan=\"4\" style=\"width:616px;\">\n Msc. Mycobacteriology, BSc. Medical Microbiology</td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Martha Wambui Njoroge</td>\n <td style=\"width:128px;\">\n Lab Manager</td>\n <td style=\"width:101px;\">\n KEMRI</td>\n <td colspan=\"4\" style=\"width:616px;\">\n HDip. Medical Laboratory Technology, Dip. Medical Laoratory Technology</td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Glennah Kerubo</td>\n <td style=\"width:128px;\">\n TB Lab Staff</td>\n <td style=\"width:101px;\">\n KEMRI</td>\n <td colspan=\"4\" style=\"width:616px;\">\n MSc. Medical Microbiology, BSc Medical Microbiology</td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Dorcus Marionya</td>\n <td style=\"width:128px;\">\n TB Lab Staff</td>\n <td style=\"width:101px;\">\n KEMRI</td>\n <td colspan=\"4\" style=\"width:616px;\">\n MSc. Medical Mycobacteriology, BSc..Biomedical Lab Sciences and Tech., Dip. Community Health Devt.</td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Dorcas  Wachira</td>\n <td style=\"width:128px;\">\n CD4 Lab</td>\n <td style=\"width:101px;\">\n KEMRI</td>\n <td colspan=\"4\" style=\"width:616px;\">\n MSc. Immunology, BSc. Zoology</td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Kenneth Korir</td>\n <td style=\"width:128px;\">\n Driver</td>\n <td style=\"width:101px;\">\n KEMRI</td>\n <td colspan=\"4\" style=\"width:616px;\">\n Driver Grade III</td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Wambui Salome</td>\n <td style=\"width:128px;\">\n Driver</td>\n <td style=\"width:101px;\">\n KEMRI</td>\n <td colspan=\"4\" style=\"width:616px;\">\n Driver Grade III</td>\n </tr>\n <tr height=\"34\">\n <td height=\"34\" style=\"height:34px;width:172px;\">\n Elizabeth Kendi</td>\n <td style=\"width:128px;\">\n Administative support</td>\n <td style=\"width:101px;\">\n KEMRI</td>\n <td colspan=\"4\" style=\"width:616px;\">\n Secretarial</td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Josephine Okwirry</td>\n <td style=\"width:128px;\">\n Accountant</td>\n <td style=\"width:101px;\">\n KEMRI</td>\n <td colspan=\"4\" style=\"width:616px;\">\n CPA I,II,III,IV</td>\n </tr>\n <tr height=\"20\">\n <td height=\"20\" style=\"height:20px;width:172px;\">\n Ephantus Kinyua</td>\n <td style=\"width:128px;\">\n Accountant</td>\n <td style=\"width:101px;\">\n KEMRI</td>\n <td colspan=\"4\" style=\"width:616px;\">\n Bcom. Accounts</td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_explanation<p>\n The sponsor, Global Alliance for TB Drug Development, has its head quaters in <span style=\"font-family: Helvetica, Arial, Tahoma, sans-serif; line-height: 12px;\">New York and has offices in Brussels, Belgium and Pretoria, South Africa, though their work is performed globally through their extensive network of partners .   South Africa was one of the participating sites and is one of the representatives of the sponsor. </span></p>\n
      • other_details_regulatory_notapproved<p>\n Not applicable</p>\n
      • other_details_regulatory_approved<p>\n Not applicable</p>\n
      • other_details_regulatory_rejected
      • other_details_regulatory_halted
      • estimated_duration5 yrs
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorthe standard TB treatment
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKibera D.O Health Centre
      • single_site_physical_addressD.O Office Kibera
      • single_site_contact_personMatron Incharge Mrs. Omune Joyce
      • single_site_telephone+254 721 575427
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states9
      • number_of_sites
      • multi_country_listKenya, South Africa, Zambia, Tanzania, India, China, Thailand, Malaysia, Mexico
      • data_monitoring_committeeYes
      • total_enrolment_per_site136
      • total_participants_worldwide1931
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameStephen
      • investigator1_middle_nameHenry
      • investigator1_family_nameGillespie
      • investigator1_qualificationMD DSc FRCP FRCPath
      • investigator1_professional_addressCentre for Clinical Microbiology, University College Medical School, London, UK.
      • investigator1_telephone+44(0)2077940500 ext 33539
      • investigator1_emails.gillespie@medsch.ucl.ac.uk
      • organisations_transferred_Yes
      • number_participants150
      • notification<p>\n I kindly request for annual approval for the REMoxTB project. I have re submitted the neccesary documents for your review. Looking forwards to a favourable feedback.</p>\n<p>\n Kind Regards</p>\n<p>\n Miheso B, Barbara</p>\n<p>\n Study Coodinator REMoxTB Clinical Trial</p>\n<p>\n  </p>\n
      • approval_date01-07-2013
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted26-07-2013
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<div class=\"views-field views-field-title\" style=\"color: rgb(120, 112, 125); font-family: Roboto, sans-serif; font-size: 16px; line-height: 24px;\">\n <h2 class=\"field-content trial\" style=\"font-size: 1.2em; margin: 0px 0px 0.75em; font-family: Montserrat, sans-serif; font-weight: 400; line-height: 1.3em;\">\n <span style=\"color:#000000;\">REMoxTB</span></h2>\n</div>\n<div class=\"views-field views-field-field-partners classification\" style=\"color: rgb(120, 112, 125); font-family: Roboto, sans-serif; font-size: 16px; line-height: 24px;\">\n <span style=\"color:#000000;\"><span class=\"views-label views-label-field-partners\">Partners: </span><span class=\"field-content\">Medical Research Council at University College London, University College London</span></span></div>\n<div class=\"views-field views-field-field-blurb\" style=\"color: rgb(120, 112, 125); font-family: Roboto, sans-serif; font-size: 16px; line-height: 24px;\">\n <p class=\"field-content blurb-trial\" style=\"margin: 0px 0px 1.5em; line-height: 1.7em;\">\n <span style=\"color:#000000;\">REMoxTB was a global Phase 3 clinical trial conducted at nearly 50 sites. The trial tested whether substituting moxifloxacin for a single drug in the standard TB therapy could reduce treatment of drug-sensitive disease from six months to four.</span></p>\n</div>\n<div class=\"views-field views-field-field-background\" style=\"color: rgb(120, 112, 125); font-family: Roboto, sans-serif; font-size: 16px; line-height: 24px;\">\n <span style=\"color:#000000;\"><span class=\"views-label views-label-field-background block-label\">Background:</span></span>\n <div class=\"field-content\">\n <p style=\"margin: 0px 0px 1.5em; line-height: 1.7em;\">\n <span style=\"color:#000000;\"><span style=\"font-weight: 700;\">Overview</span></span></p>\n <p style=\"margin: 0px 0px 1.5em; line-height: 1.7em;\">\n <span style=\"color:#000000;\">REMoxTB was a global Phase 3 clinical trial conducted at 50 sites across 9 countries. The trial’s aim was to determine whether a </span><a href=\"http://www.tballiance.org/portfolio/compound/moxifloxacin#\" style=\"text-decoration: none; color: rgb(52, 175, 231);\"><span style=\"color:#000000;\">moxifloxacin</span></a><span style=\"color:#000000;\">-containing TB treatment regimen could reduce the time needed to treat drug-sensitive TB patients from 6 months or longer to 4 months. REMox TB was completed in 2013, after enrolling and monitoring 1931 patients across 50 trial sites around the world. </span></p>\n <p style=\"margin: 0px 0px 1.5em; line-height: 1.7em;\">\n <span style=\"color:#000000;\"><span style=\"font-weight: 700;\">About the New Treatments</span></span></p>\n <p style=\"margin: 0px 0px 1.5em; line-height: 1.7em;\">\n <span style=\"color:#000000;\">The REMoxTB trial tested 2 new treatment regimens for drug-sensitive TB. Both of these regimens substitute moxifloxacin, an already approved antibiotic for other indications, for an individual drug in the current first-line TB treatment regimen (</span><a href=\"http://www.tballiance.org/portfolio/compound/isoniazid\" style=\"text-decoration: none; color: rgb(52, 175, 231);\"><span style=\"color:#000000;\">isoniazid</span></a><span style=\"color:#000000;\"> + </span><a href=\"http://www.tballiance.org/portfolio/compound/rifampin\" style=\"text-decoration: none; color: rgb(52, 175, 231);\"><span style=\"color:#000000;\">rifampin</span></a><span style=\"color:#000000;\"> + </span><a href=\"http://www.tballiance.org/portfolio/compound/pyrazinamide\" style=\"text-decoration: none; color: rgb(52, 175, 231);\"><span style=\"color:#000000;\">pyrazinamide</span></a><span style=\"color:#000000;\"> +</span><a href=\"http://www.tballiance.org/portfolio/compound/ethambutol\" style=\"text-decoration: none; color: rgb(52, 175, 231);\"><span style=\"color:#000000;\"> ethambutol</span></a><span style=\"color:#000000;\"> [HRZE]). In separate arms of the trial, REMoxTB evaluated moxifloxacin in place of isoniazid and ethambutol. </span></p>\n <p style=\"margin: 0px 0px 1.5em; line-height: 1.7em;\">\n <span style=\"color:#000000;\"><span style=\"font-weight: 700;\">About the REMox TB trial</span></span></p>\n <p style=\"margin: 0px 0px 1.5em; line-height: 1.7em;\">\n <span style=\"color:#000000;\">REMoxTB was conducted at 50 sites around the world by TB Alliance, Bayer Healthcare AG, University College London, and the Medical Research Council. It was the first Phase 3 TB drug trial conducted and completed in accordance with the most stringent modern regulatory standards, and it helped pave the way for subsequent clinical research and influence regulatory standards in the field. The trial was also conducted with significant involvement from local communities through </span><a href=\"http://www.tballiance.org/access/engaging-communities.php\" style=\"text-decoration: none; color: rgb(52, 175, 231);\"><span style=\"color:#000000;\">community advisory structures</span></a><span style=\"color:#000000;\"> promoted by TB Alliance to give communities a voice in the research process.</span></p>\n <p style=\"margin: 0px 0px 1.5em; line-height: 1.7em;\">\n <span style=\"color:#000000;\"><span style=\"font-weight: 700;\">Results</span></span></p>\n <p style=\"margin: 0px 0px 1.5em; line-height: 1.7em;\">\n <span style=\"color:#000000;\">As reported in the </span><a href=\"http://www.nejm.org/doi/full/10.1056/NEJMoa1407426?query=featured_home#t=articleTop\" style=\"text-decoration: none; color: rgb(52, 175, 231);\"><span style=\"color:#000000;\"><em>New England Journal of Medicine</em></span></a><span style=\"color:#000000;\">, the REMoxTB Phase 3 trial showed that the two regimens tested in the trial were found to be safe, but did not shorten the time it takes to treat drug-sensitive TB from six to four months. The study showed that the experimental regimens, which substituted moxifloxacin for either isoniazid or ethambutol in the first-line treatment for drug-sensitive TB, were more bacteridical in the earlier stages of treatment and converted patients to negative culture sooner than the standard of care, however patients in the experimental arms were more likely to relapse in the year following therapy. Thus, there was insufficient effect to permit regimen shortening by two months.</span></p>\n <p style=\"margin: 0px 0px 1.5em; line-height: 1.7em;\">\n <span style=\"color:#000000;\">The trial also yielded other valuable findings. Importantly, REMoxTB was the first regulatory study to confirm the safety of daily moxifloxacin over four months of therapy. Its safety, combined with its activity against TB, supports the continued clinical testing of moxifloxacin as a component of other, novel regimens, such as </span><a href=\"http://www.tballiance.org/portfolio/regimen/pamz\" style=\"text-decoration: none; color: rgb(52, 175, 231);\"><span style=\"color:#000000;\">PaMZ</span></a><span style=\"color:#000000;\">.</span></p>\n <p style=\"margin: 0px 0px 1.5em; line-height: 1.7em;\">\n <span style=\"color:#000000;\">Also of interest, it had previously been thought that there were regional differences in patients' response to treatment across the world. The trial demonstrated no evidence that populations respond differently to treatment.</span></p>\n </div>\n</div>\n<p>\n  </p>\n
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2018-10-15 16:16:03
      • created2013-07-17 09:12:01
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id111
        • application_id171
        • given_nameEvans
        • middle_nameInyangala
        • family_nameAmukoye
        • qualificationMbChb (MD), M.Med , Clinical fellow Pulmunolgy
        • professional_addressCentre for Respiratory Diseases Research, Kenya Medical Research Institute , Kenyatta Hospital Compound, Next to Government Chemist, Off Ngong Road , P.O. Box 47855 – 00100, Nairobi, Kenya
        • telephone(254) (020) 2724264/5
        • emailamukoye@gmail.com
        • created2013-07-18 15:34:51
        • modified2013-07-26 04:05:30
    • SiteDetail(array)
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        • id140
        • application_id171
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
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        • site_capacity(null)
        • misc(null)
        • created2013-07-18 15:34:51
        • modified2013-07-26 04:05:30
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id87
        • application_id171
        • sponsorGlobal Alliance for TB Drug Development, New York, USA
        • sponsor_type(null)
        • contact_personAlmarie Uys
        • addressJohannesburg
        • telephone_number+27128440953
        • fax_number+27128440959
        • cell_number+27836016136
        • email_addressalmarie.uys@tballiance.org
        • created2013-07-18 15:34:51
        • modified2013-07-26 04:05:30
  • 2(array)
    • Application(array)
      • id704
      • user_id263
      • trial_status_id4
      • abstract_of_study<p>\n Sickle cell disease (SCD) is a genetic, autosomal, recessive blood disorder resulting an altered haemoglobin β-chain (HbS). When the altered haemoglobin is deoxygenated it aggregates into large polymers, distorting the shape of the red cells to sickle-shaped. A vaso-occlusive crisis (VOC) is a severe, acute painful episode that occurs when sickle-shaped red blood cells obstruct the microcirculation and restrict blood flow to an organ or tissue, resulting in ischaemia, necrosis and organ damage. There is a high unmet need for treatment options in SCD and there is a scientific rationale, supported by clinical data, that platelet inhibition has the potential to reduce the risk for acute vaso-occlusions.</p>\n<p>\n This is an international, multicentre, double-blind, randomised, parallel-group, placebo controlled Phase III study to evaluate the effect of ticagrelor versus placebo in reducing the rate of Vaso-Occlusive Crises (VOCs) in paediatric patients with Sickle Cell Disease (SCD). During the treatment period, patients will be monitored for occurrence of VOCs and other acute SCD complications. Study participants should receive standard of care for SCD, adjusted to the individual patient at the discretion of the investigator, including routine health care screening examinations and immunisations according to local guidelines and health care programmes. Study drug will be given on the background of standard treatments for SCD. However, restrictions apply to some medications and interventions that may be necessary for the patient's health and well-being during the study. Temporary hold of study drug dosing could therefore be needed in case of short-term treatment with a medication not to be combined with study drug or in case of surgical interventions. Patients are to be followed until a common study end date (CSED) is reached defined as 12 months after the last patient is randomised. The target population are children aged ≥2 to <18 years of age and body weight of ≥12 kg diagnosed with homozygous sickle cell anaemia (HbSS) or sickle beta-zero-thalassaemia (HbS/β0 ). At least 50 evaluable patients should be recruited in each of the age groups, ≥2 years to <12 years and ≥12 years to <18 years. Dosages: Ticagrelor tablets of 15 mg and its matching placebo (approximately 6 mm in diameter) will be packed in high density polyethylene bottles containing 100 tablets. Subsequent intervals between dispensing visits must not be more than 100 days. Randomization: Randomisation to twice daily double-blind treatment with ticagrelor or placebo will occur at Visit 2 via the IXRS. Eligible patients will be randomly assigned to 1 of 2 treatment regimens, based on body weight at Visit 2:≥12 to ≤24 kg body weight: 15 mg - 1 tablet of ticagrelor 15mg or 1 tablet of placebo to match ticagrelor 15 mg twice daily • >24 to ≤48 kg body weight: 30 mg - 2 tablets of ticagrelor 15mg or 2 tablets of placebo to match ticagrelor 15mg twice daily • >48 kg body weight: 45 mg - 3 tablets of ticagrelor 15mg or 3 tablets of placebo to match ticagrelor 15mg twice daily At Visit 2, the first dose of IP will be administered at the clinic by site staff as soon as possible after randomisation and after all baseline assessments have been completed. Subsequent doses should be taken morning and evening, at approximately 12 hour intervals. Missed doses of ticagrelor or placebo blinded IP should not be compensated (ie, if a dose is missed the next regularly scheduled dose should be taken and should not be doubled). The study drug will be administered orally either swallowed whole or dispersed in water, other suitable liquids or vehicles based on age and/or ability to swallow study drugs. Refer to handling instructions for further details Methods for assigning treatment groups: The randomisation codes will be computer generated by AstraZeneca R&D and loaded into the IXRS database. Randomisation codes will be generated in blocks to ensure approximate balance (1:1) between the 2 treatment arms (ticagrelor or placebo bd). Stratification for baseline hydroxyurea use by country will be applied. For each patient randomised the IXRS will provide the Investigator with a unique kit ID number matching the treatment arm assigned to the patient. Following randomisation, the first dose of study drug will be administered to the patient as soon as possible. At randomisation and subsequent dispensing visits the patient should always be provided medication with the kit ID(s) allocated by the IXRS. If a patient receives the incorrect randomised treatment at any time during the study, this must be corrected as soon as discovered after discussing with the study physician. Methods for ensuring blinding: This is a double-blind study. Ticagrelor and matching ticagrelor placebo tablets will be identical in appearance and packaging. The bottles with IPs will be labelled with unique ID numbers allocated from the IXRS, but it will not indicate treatment allocation. No member of the study team at AstraZeneca or representative, personnel at study centres or any contract research organisation (CRO) handling data will have access to the randomisation scheme during the conduct of the study, with the exception of the AstraZeneca personnel generating the randomisation scheme and the bioanalysis personnel analysing the pharmacokinetic (PK) samples as well as AstraZeneca Supply Chain, the Patient safety data entry site and the CRO companies providing the IXRS and carrying out the packaging and labelling of IPs. This documentation will be kept in a secure location until the end of the study. There will be an independent, unblinded statistical team that will support the DMC with data during the study. Personnel involved in the clinical study at AstraZeneca or representative will remain blinded to these analyses and will have no knowledge of the results presented to the DMC. Dose increase during study For any patient having a weight gain during the study period clearly exceeding the upper weight limit of the band (≥27 kg and ≥54 kg, respectively), the dose will need to be increased according to the next weight band. In case of a dose increase: IXRS will generate correct dose based on body weight range entered Stop date for the old dose and start date for the new dose should be recorded in the eCRF. The patient should return all unused IP and empty bottles and new IP bottles should be dispensed PK and PD samples should be taken at the following visit after the adjusted dose has been dispensed, see Sections 5.4 and 5.5 of Protocol. Justification of Phase Assessment of the safety and efficacy of ticagrelor for the treatment of paediatric and young adult patients with sickle cell disease is ongoing in the HESTIA clinical development. The HESTIA 1 and HESTIA 2 Phase II studies have not indicated increased bleeding risk or raised other safety concerns. This phase III study will evaluate the efficacy, safety and tolerability of ticagrelor versus placebo in children with SCD during treatment for at least 12 months and up to approximately 24 months. Justification for Choice of design: Patients diagnosed with homozygous sickle cell (HbSS) or sickle beta zero thalassemia (HbS/β0) will be eligible. Patients with clinically milder variants (eg, sickle cell haemoglobin C [HbSC]) will not be eligible, since they usually have a lower frequency of painful. The different pattern of SCD manifestations in patients with HbSC could introduce heterogeneity into the study population. In addition, there are data to suggest that platelet activation in HbSS is elevated compared with HbSC, thus, patients with HbSC may be less likely to benefit from P2Y12 inhibition. To be eligible for the study, patients must have experienced at least 2 VOCs (defined as painful crisis and/or ACS) events in the past 12 months prior to Visit 1, indicating that the severity of the patient’s disease justifies preventive chronic long-term treatment. The intent is to enrol only children aged 2 years or above, since VOCs become more frequent with age. Above 2 years of age, children may have experienced more than 1 VOC, and established a pattern of frequency such that an intervention to reduce the rate of VOCs can be justified and meaningfully evaluated. Thus, the unmet need to prevent VOCs is most evident in children from 2 years of age and above. Due to ticagrelor mechanism of action and the potential to reduce symptoms caused by ischemia during a vaso-occlusion, a composite endpoint with painful crises and/or ACS has been selected for the primary endpoint. Painful crisis is the most common reason for emergency department visits for patients with SCD with a significant impact on young patients’ lives, affecting them physically and emotionally. ACS is a potentially life threatening condition involving vaso-occlusion, eg, when caused by pulmonary infarction or indirectly because of fat embolism secondary to bone marrow infarction, and/or a pulmonary infection. Both painful crises and/or ACS are identified by patients/parents as the acute SCD-related complications having the most impact on their lives, and these endpoints are commonly used for evaluation of clinical outcome in trials in SCD. Secondary endpoints are included to broaden the understanding of effects in patients with SCD and to also assess potential benefits on symptomatic disease burden and health-related quality of life (HRQL). Justification for Use of placebo There are no other drugs approved for reduction of VOCs in children with SCD with a similar mechanism of action as ticagrelor. Hydroxyurea is approved for use in children with SCD in some markets and more recently, L-glutamine was approved by the US FDA. Evaluation of ticagrelor when given in addition to standard of care including these medications, where available and when considered medically appropriate, is considered acceptable for studying the efficacy and safety of ticagrelor in this patient group as compared with placebo. Justification of Dosages The ticagrelor PK/PD modelling and simulation work based on the results from HESTIA1 and HESTIA2 studies identifies 15, 30 and 45 mg bd, depending on body weight, as relevant doses in the HESTIA3 study. These doses are predicted to result in a platelet activity measured as P2Y12 reaction units ([PRU] as measured by VerifyNow®) of less than 180, corresponding to >35% platelet inhibition in terms of reduction in PRU assuming a baseline PRU of 280 (which was the baseline PRU observed in HESTIA1, and similar to prasugrel Phase III DOVE study [Heeney et al 2016]). The predicted platelet inhibition in HESTIA3 is similar to what was observed in the 45 mg bd dose group in the HESTIA2 study in young adults, where after 1 week of treatment the mean percentage decrease from baseline PRU was 48% before morning dose and 81% at 2 hrs after dose. The 45 mg bd dose group was well tolerated and events of bleeding were of the same number and similar compared to the placebo and the 10 mg bd dose groups. Given the reversible mechanism of action for ticagrelor, the level of P2Y12 inhibition during ticagrelor treatment is expected to vary within a dosing interval and peak around 2 hours after dosing. When developing the dosing strategy for this study, the target for platelet inhibition was guided by the results from the recent prasugrel Phase III study in paediatric patients with SCD aged 2 to 17 years, showing insufficient efficacy with a mean PRU of 207 (ie, approximately 20% reduction from baseline) (Jakubowski et al 2017). The lack of therapeutic benefit with prasugrel may have been related to a too low platelet inhibition (Heeney et al 2016), and consequently, doses for HESTIA3 were selected to achieve a greater level of platelet inhibition. Moreover, a study with ticlopidine in adolescents and adult patients with SCD showing significant reductions in VOC (Cabannes et al 1984) used doses that generally provide <60% inhibition of platelet aggregation, which provides further support for the platelet inhibition target and the selected doses for the HESTIA3 study. Justification for Randomisation Randomization will be used to minimize bias in the assignment of subjects to treatment arms, to increase the likelihood that known and unknown subject attributes (eg, demographic and baseline characteristics) are evenly balanced across treatment arms, and to enhance the validity of statistical comparisons across treatment arms. Justification for Blinding Blinding will be used to reduce potential bias during data collection and evaluation of clinical endpoints.</p>\n
      • study_title<p>\n A Randomised, Double-Blind, Parallel-Group, Multicentre, Phase III Study to Evaluate the Effect of Ticagrelor versus Placebo in Reducing the Rate of Vaso-Occlusive Crises in Paediatric Patients with Sickle Cell Disease</p>\n
      • laymans_summary<p>\n There is a high-unmet need for treatment options in children with sickle cell disease (SCD) and there is a scientific rationale, supported by clinical data, that preventing platelet clamping has the potential to reduce the risk for acute clogging of small blood vessels. A programme is currently ongoing to assess the potential treatment benefits of ticagrelor in reduction of the occurrence of blood vessel blockage in children with SCD. Before the first study in children, laboratory study to investigate the potency of ticagrelor, showed similar ticagrelor potency in blood from children aged 0 to 2 years old, as compared to older children and adults.</p>\n<div>\n This international, multicenter study will assess the effect of ticagrelor compared to no treatment in reducing the rate of blood vessel blockage crises, which is the composite of painful crisis and/or acute chest syndrome (ACS), in children patients with disease (SCD). During the treatment period, patients will be monitored for occurrence of painful crises and other acute SCD complications. Patients are to be followed until a common study end date is reached defined as 12 months after the last patient is enrolled in the study. In addition to the study drug, standard of care such as background treatment with hydroxyurea will be allowed. The study will be conducted in approximately 20 countries worldwide. Approximately 75 centres will be initiated to enroll approximately 182 patients aged ≥2 years to <18 years. At least 50 evaluable patients should be recruited in each of the age groups, ≥2 years to <12 years and ≥12 years to <18 years.</div>\n<div>\n The target population is children aged ≥2 to <18 years of age and body weight of ≥12 kg</div>\n<div>\n diagnosed with SCD disease variants (sickle cell anaemia (HbSS) or sickle beta-zero-thalassaemia (HbS/β0)). Patients that experienced at least 2 blood vessel blockage crisis events in the past 12 months prior to Visit 1 and fulfil eligibility requiremnts will be enrolled in this study. Eligible patients will receive treatment of the study drug or no no active treatment referred to as (double-blind ticagrelor or placebo) twice a day (bd) until a common study end date is reached defined as 12 months after the last patient is enrolled. The expected average follow-up is 18 months, assuming a uniformly distributed enrolment period of 12 months.</div>\n<div>\n The HESTIA3 study is part of a child development programme with ticagrelor in SCD. The primary outcome of this study is determine the effect of ticagrelor in the reduction of painful crises in children in comparison to no active treatment referred to as placebo.</div>\n
      • short_titleHestia 3
      • protocol_noECCT/18/07/06
      • version_noV 1.0
      • date_of_protocol23-01-2018
      • study_drugTicagrelor
      • disease_conditionSickle Cell Disease
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameTicagrelor
      • product_type_medical_device_name
      • comparatorNo
      • comparator_nameNo comparator, only placebo
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addresscarmen.richelmann@quintiles.com
      • applicant_covering_letter1
      • applicant_protocol1
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      • applicant_investigators_cv1
      • applicant_signed_declaration1
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      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
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      • applicant_impd1
      • applicant_prev_data0
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      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi0
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
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      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantCarmen Richelmann
      • declaration_date131-07-2018
      • declaration_principal_investigatorProf Jessie N Githanga
      • declaration_date231-07-2018
      • placebo_presentYes
      • study_objectives<ul>\n <li>\n <strong>Primary Objectives</strong></li>\n</ul>\n<p style=\"margin-left:36.0pt;\">\n To compare the effect of ticagrelor vs placebo for the reduction of VOCs, which is the composite of painful crisis and/or ACS, in paediatric patients with SCD</p>\n<p style=\"margin-left:36.0pt;\">\n  </p>\n<ul>\n <li>\n <strong>Secondary Objectives</strong>\n <ul>\n <li>\n To compare the effect of ticagrelor vs placebo for the reduction of painful crises</li>\n <li>\n To compare the effect on ticagrelor vs placebo for the reduction of ACS</li>\n <li>\n To compare the effect of ticagrelor vs placebo for the reduction of duration of painful crises</li>\n <li>\n To compare the effect of ticagrelor vs placebo on the number of VOCs requiring hospitalisation or emergency department visits</li>\n <li>\n To compare the effect of ticagrelor vs placebo on reduction of days hospitalised for VOC</li>\n <li>\n To compare the effect of ticagrelor vs placebo on the number of acute SCD complications</li>\n <li>\n To compare the effect of ticagrelor vs placebo on reduction of days hospitalised for acute SCD complications</li>\n <li>\n To compare the effect of ticagrelor vs placebo on the number of sickle cell-related red blood cell (RBC) transfusions</li>\n <li>\n To describe the health-related quality of life (HRQL) and fatigue</li>\n <li>\n To describe absence from school or work due to SCD</li>\n <li>\n To describe intensity of pain during VOC</li>\n <li>\n To describe analgesics use during VOC</li>\n <li>\n To describe patient acceptability of the formulation (palatability and swallowability)</li>\n </ul>\n </li>\n</ul>\n<p>\n  </p>\n<ul>\n <li>\n <strong>Safety Objectives</strong></li>\n <li>\n To assess long-term safety and tolerability of therapy with ticagrelor vs placebo</li>\n</ul>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<ul>\n <li>\n <strong>Exploratory objectives</strong>\n <ul>\n <li>\n To compare the effect of ticagrelor vs placebo for the reduction of duration of ACS</li>\n <li>\n To assess the pharmacokinetics (PK) of ticagrelor and AR-C124910XX in paediatric patients with SCD using a population PK model</li>\n <li>\n To assess the effect of ticagrelor on platelet aggregation</li>\n </ul>\n </li>\n</ul>\n<p>\n  </p>\n
      • principal_inclusion_criteria<p>\n For inclusion in the study, patients must fulfil the following criteria: 1. Provision of signed and dated informed consent prior to any study specific procedures not part of standard medical care (local regulations and international guidelines are to be followed in determining the assent/consent requirements for children). Justification: Signed Inform consent form in order to adhere to GCP and with applicable regulatory requirements 2. Male or female paediatric patients aged ≥2 to <18 years and body weight of ≥12 kg (at Visit 1), diagnosed with HbSS or HbS/β0 as confirmed by high-performance liquid chromatography or haemoglobin electrophoresis. Note: Diagnosis of SCD (if not confirmed prior to screening and records available on the medical file) should be confirmed for HbSS or HbS/β0 by high-performance liquid chromatography or haemoglobin electrophoresis, performed at the site’s local lab, in order to confirm the type of mutation Justification: Only HbSS or HbS/β0 will be eligible as patients with clinically mild variants (HbSC) usually have a lower frequency of painful crises. 3. Have experienced at least 2 VOCs (painful crisis and/or ACS) as judged by the Investigator in the past 12 months prior to Visit 1. These VOCs need to be documented in the patient’s medical records or in other documents that can be reconciled. Justification: Included to assure VOC frequency is sufficiently high to see meaningful changes. Mild patients who have no VOCs for several years at a time would not be useful subjects for this type of study 4. If ≤16 years old, must have had transcranial Doppler (TCD) within the past year prior to Visit 1. If this is not the case, a TCD examination must be done before proceeding in the study. Justification: Screening for cerebrovascular disease as stroke is an important complication of SCD. This criterion ensures that the patients on study are following standard clinical care guidelines as well. This is particularly important as patients with neurovascular disease in sickle cell disease could be at a higher risk to have CNS bleeding with an antiplatelet agent. Screening is mandated to allow at risk patients to be excluded from the study. 5. If ≥10 years old, must have had an ophthalmological examination within the past year prior to Visit 1. If this is not the case, the patient must be examined by an ophthalmologist before proceeding in the study. If local guidelines dictate ophthalmological examination at younger ages, those local guidelines should be followed. Justification: Ophthalmological complications, as retinopathy, due to vascular occlusion can occur in SCD patients. Examination for diagnosis and follow up is required. (Refer to Exclusion criterion #1.) this ensures that the study follows standard clinical management guidelines. 6. If treated with hydroxyurea, the weight-adjusted dose must be stable for 3 months before screening. Justification: Hydroxyureas is allowed as concomitant medication as it is part of standard of care, but recent variations in dose ar</p>\n
      • principal_exclusion_criteria<p>\n Patients should not enter the study if any of the following exclusion criteria are fulfilled: 1. History of transient ischaemic attack (TIA) or cerebrovascular accident (ischaemic or haemorrhagic), severe head trauma, intracranial haemorrhage, intracranial neoplasm, arteriovenous malformation, aneurysm, or proliferative retinopathy. Justification: To exclude subject with known SCD complications that could be a safety risk with an antiplatelet agent 2. Findings on TCD: Current or previous values for time averaged mean of the maximum velocity (TAMMV) that are Conditional or Abnormal. Patients with Conditional TAMMV values or higher (≥153 cm/sec using TCD imaging technique [TCDi] which is corresponding to ≥170 cm/sec by the non-imaging technique). Both the middle cerebral artery and the internal carotid artery should be considered. Any other criteria that would locally be considered as TCD indications for chronic transfusion would also exclude the patient. Justification: To exclude subject with identify risks of stroke or chronic transfusion requirement 3. Active pathological bleeding or increased risk of bleeding complications according to Investigator Justification: Criterion included as the study drug is a platelet inhibitor 4. Haemoglobin <6 g/dL from test performed at Screening (Visit 1) Justification: To exclude subjects with potential risk of complications and blood transfusion 5. Platelets <100 x 109/L from test performed at Screening (Visit 1) Justification: To exclude subjects with higher risk of bleeding 6. Undergoing treatment with chronic red blood cell transfusion therapy Justification: To exclude subjects with chronic use of transfusions that may affect pain episodes and ACS 7. Chronic use of NSAIDs defined as continuous intake >3 days per week that cannot be discontinued Justification: To exclude subjects with frequent/high doses of NSAIDs as these are platelet active drugs and could increase the risk of bleeding in study patients. 8. Receiving chronic treatment with anticoagulants or antiplatelet drugs that cannot be discontinued Justification: To exclude subjects with higher risk of bleeding events 9. Moderate or severe hepatic impairment defined as laboratory values of alanine aminotransferase (ALT) >2 × upper limits of normal (ULN), total bilirubin >2 × ULN (unless judged by the Investigator to be caused by haemolysis), albumin <35 g/L (3.5 g/dL) and International normalised ratio (INR) >1.4, or symptoms of liver disease (eg, ascites) from test performed at Screening (Visit 1). Justification: to exclude subjects with hepatic impairment 10. Renal failure requiring dialysis Justification: To exclude subject with severe renail impairment which may have higher exposure to active metabolite 11. Patient considered to be at risk of bradycardic events (eg, known sick sinus syndrome or second or third degree atrioventricular block) unless already treated with a permanent pacemaker. Justification: Due to observations of mostly asymptomatic ventricular pauses in an earlier clinical study, patients with an increased risk of bradycardic events (eg, patients without a pacemaker who have sick sinus syndrome, 2nd or 3rd degree atrioventricular (AV) block, or bradycardic-related syncope) are excluded 12. Concomitant oral or intravenous therapy with strong or moderate cytochrome P450 3A4 (CYP3A4) inhibitors, CYP3A4 substrates with narrow therapeutic indices, or strong CYP3A4 inducers (see full list in Appendix G), which cannot be stopped at least 5 half-lives before randomisation. Justification: To exclude these medications as CYP3A is major enzyme responsible for ticagrelor metabolism and formation of active metabolite. 13. Active</p>\n
      • primary_end_points<p>\n Primary Objective: To compare the effect of ticagrelor vs placebo for the reduction of VOCs, which is the composite of painful crisis and/or ACS, in paediatric patients with SCD Outcome of measures: Number of VOCs Justification: The most common complications of sickle cell disease are vaso-occlusive events including painful crises and acute chest syndromes and therefore it is common to have the reduction of these events as a primary outcome measure in past SCD studies. It is a clinically meaningful outcome as vaso-occlusive events are a major cause of morbidity in this disease. It is a standard outcome that has been successfully measured in previous studies.</p>\n<p>\n  </p>\n<p>\n Secondary Objectives and outcome measures: 1. To compare the effect of ticagrelor vs placebo for the reduction of painful crises Outcome measure: Number of painful crises Justification: See primary objective justification. This is a further breakdown of the effect on pain crises versus ACS. 2. To compare the effect on ticagrelor vs placebo for the reduction of ACS Outcome measure: Number of ACSs Justification: See primary objective justification. This is a further breakdown of the effect on pain crises versus ACS. 3. To compare the effect of ticagrelor vs placebo for the reduction of duration of painful crises Outcome measure: Duration of painful crises Justification: While decreasing the total number of vaso-occlusive events is a meaningful objective, it is also possible that this type of agent could reduce the duration of a vaso-occlusive crisis if it occurs. This would also be a clinically meaningful outcome and has been a primary endpoint on some previous SCD studies. 4. To compare the effect of ticagrelor vs placebo on the number of VOCs requiring hospitalisation or emergency department visits. Outcome measure: Number of VOCs requiring hospitalisation or emergency department visits Justification: It is possible that ticagrelor could reduce the severity of vaso-occlusion resulting in crises that are less severe to the point that patients do not require hospitalization when they occur. This is important information to understand not only the effect of this drug on the number of vaso-occlusive events but also on the severity of Justification It is possible that ticagrelor could reduce the severity of vaso-occlusion resulting in crises that are less severe to the point that patients do not require hospitalization when they occur. This is important information to understand not only the effect of this drug on the number of vaso-occlusive events but also on the severity of those events. 5. To compare the effect of ticagrelor vs placebo on reduction of days hospitalised for VOC Outcome measure: Number of days hospitalised for VOC Justification: Days in the hospital is a tangible measure of disease severity and another standard endpoint for SCD studies. The recent approval of L-glutamine in the US used reduction of days hospitalized with VOC as one of their secondary measures 6. To compare the effect of ticagrelor vs placebo on the number of acute SCD complications. Outcome measure: Number of acute SCD complications Justification: The aim is to establish if ticagrelor reduces other SCD complications (TIA/ischemic stroke, hepatic sequestration and splenic sequestration, priapism and dactylitis). While VOC painful crises and ACS are most common, it is important to explore the impact of this agent on other complications as well. 7. To compare the effect of ticagrelor vs placebo on reduction of days hospitalised for acute SCD complications. Outcome measure: Number of acute SCD complications Justification: see justification above 8. To compare the effect of ticagrelor vs placebo on the number of sickle cell-related red blood cell (RBC) transfusions Outcome measure: Number of sickle cell-related RBC transfusions Justification: Red blood cell transfusions is an important part of the management of acute and chronic complications in SCD, in general transfusion number is related to sickle cell severity. Many studies use total number of transfusions as a rough measure of disease severity so this study will examine the total number of transfusion in ticagrelor vs placebo. 9. To describe the health-related quality of life (HRQL) and fatigue Outcome measure: HRQL total score and by dimension using Paediatric Quality of Life Inventory (PedsQL) SCD Module and Fatigue total score and by dimension using the PedsQL Multidimensional Fatigue Scale as presented in Appendix I (age appropriate versions) Justification Discussions with patient groups over past years by the FDA and others have shown that SCD patients experience multiple disease related-complications such as fatigue that are not easily measured by simply looking at pain or hospitalizations The aim of this objective is to examine the relationship to helath related quality of life by using HRQL total score and by dimension using Paediatric Quality of Life Inventory (PedsQL) SCD Module and Fatigue total score and by dimension using the PedsQL Multidimensional Fatigue Scale 10. To describe absence from school or work due to SCD Outcome measure: Proportion of days of absence from school or work (only if going to school or work at randomisation) Justification: School and work absences is a surrogate for disease severity at home that might not be easily captured by looking at healthcare utilization or other measures relying on interactions with healthcare providers. It is and important outcome to understand the effect of this agent on all aspects of a patient’s life. 11. To describe intensity of pain during VOC Outcome measure: Intensity of worst pain daily during VOC -For patients ≤4 years of age, observer reported using the Face, Legs, Activity, Cry, Consolability Scale (FLACC) -For patient ages 5 to 18 years of age, self reported using the Faces Pain Scale Revised (FPS-R) Justification: Understanding intensity of pain (using appropriate scales) is one of the essential elements for the therapeutic planning of these patients. Again this outcome is another way to explore whether or not this agent may impact severity of vaso-occlusive events. 12. To describe analgesics use during VOC Outcome measure: Type of analgesics (opioid and non-opioid) use Justification the type amount of pain medication needed by a patient is another way to quantify the amount of pain a patient is having with any particular painful crisis and is a standard measure in many studies. It compliments many of the other measures to understand the impact of this agent on pain inSCD patients 13. To describe patient acceptability of the formulation (palatability and swallowability) Outcome measure: - For patients ≤4 years of age taking the tablet dispersed or whole, an observer assessment of palatability and swallowability will be undertaken - For patients ≥5 years of age taking the tablet dispersed or whole, palatability will be assessed and categorized using the Facial Hedonic Scale Justification: Palatability is always a consideration in giving medications to children. This study would not be complete without examining this feature of the drug. Exploratory Efficacy Endpoints 1. To compare the effect of ticagrelor vs placebo for the reduction of duration of ACS Outcome measures: Duration of ACS Justification: AS with pain, this agent could potentially have an impact on the severity of ACS events which could be measured to some degree by the duration of the episode. Steroids for example have been shown to reduce the duration of ACS. 2. To assess the pharmacokinetics (PK) of ticagrelor and AR-C124910XX in paediatric patients with SCD using a population PK model Outcome measures: Population PK parameters such as oral clearance (CL/F) and ticagrelor exposure (AUC) & Observed plasma concentrations of ticagrelor and the active metabolite AR-C124910XX Justification: To analyse oral clearance and ticagrelor exposure. To determine drug concentration in plasma. 3. To assess the effect of ticagrelor on platelet aggregation Outcome measures: PRI measured by vasodilator stimulated phosphoprotein (VASP) assay Justification: Ticagrelor is an oral, direct-acting, selective, reversibly-binding P2Y12 receptor antagonist that prevents ADP-mediated platelet activation and aggregation. Inhibition of platelet activation has been proposed as a potential therapeutic option in the treatment of SCD. Safety Objective To assess long-term safety and tolerability of therapy with ticagrelor vs placebo Outcome Measures: AEs/SAEs, including bleeding Vital signs and laboratory safety variables Justification: AEs/SAEs, including bleeding Vital signs and laboratory safety variables are to be analyzed in order to grant subject´s safety</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic1
      • scope_bioequivalence0
      • scope_dose_response1
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n Site 8501: Prof J Githanga- Gertrude’s Children’s Hospital</p>\n<p>\n Gertrude’s Children’s Hospital (GCH) is the largest hospital in East and Central Africa dedicated exclusively to the care of children. For over 60 years, the hospital has provided high standards of pediatric care for children from birth to 21 years of age and recently achieved Joint Commission International Accreditation (JCIA). GCH is a non-profit organization, chartered with the responsibility of provision of health services, fostering good health, carrying out research and teaching healthcare professionals. Based in Muthaiga, Nairobi, and spread out to various outpatient clinics all over Nairobi and in several other Counties, the hospital attends to over 300,000 children as outpatients and admits over 6,000 patients on average per year. The 100-bed hospital offers comprehensive paediatric medical services and there are 21 specialist clinics that cover almost every aspect of paediatric healthcare from haematology, chest conditions, cardiology, dermatology, otorhinolaryngology, endocrinology, oncology and HIV/AIDS. Primary care services are also offered including a Well Baby and Immunization clinic. The laboratory is equipped with modern equipment and offers diagnostic laboratory testing in all areas of pathology and is headed by a pathologist supported by a laboratory manager, qualified medical laboratory technologists and a group of sub-specialist pathologists. Qualified pharmacists manage the hospital pharmacy. GCH has an up-to-date paediatric imaging facility that is managed by a team of radiologists and qualified radiographers. Most of the processes at the hospital are fully computerized and supported by a well-integrate Information Technology (IT) Department. The main hospital in Muthaiga is open 24/7 and offers 24 hour laboratory and pharmacy coverage. All the study staff are trained in Good Clinical Practice (GCP). The Hospital runs an Institute of Child Health and Research based at the Muthaiga site which is approved by the Nursing Council of Kenya. The school offers courses in paediatric endocrinology, paediatric phlebotomy, emergency paediatric medicine and several specialised paediatric nursing courses. The Hospital has an Ethics Review Committee (ERC) that acts independently from the appointing authority, hosting institution, researchers, sponsors and any other stakeholders in its review and decision-making processes. The ERC is accredited by the National Commission for Science and Technology and Innovation (NACOSTI), an institution mandated to advise the Government on policies and matters relating to the scientific and technological activities and research required for the proper development of the country. The population served by the hospital is cosmopolitan and English and Kiswahili are the predominantly spoken languages.</p>\n<p>\n Site 8502 and 8503: Dr V Nduba: Sites activities will be located in Nairobi and Siaya Counties, Siaya site is located at the Siaya County Referral Hospital, KEMRI clinical research annex and Chandaria health Centre is in Dagoretti Sub-County, Nairobi. The two sites have been identified for this study because of the geographical distribution of Sickle Cell Disease; Sickle cell disease occurs more often among people from parts of the world where malaria is common. Nairobi is a cosmopolitan city with a population of over 3 million. Due to massive in migration since independence to date and intermarriages, there has been transmission of the sickle cell gene mutation to areas non endemic for malaria. Nairobi has thousands of people living with the disease and the study site will mobilize them to report newly SCD diagnosed patients within the required age bracket to be included into the study. The sites are also well equipped with the facilities required to conduct a sickle cell study. In addition, the sites have staff who are qualified by experience and training in conducting sickle cell trials. The investigational product (IP) will be stored at both sites and IP dispensation will also be done in both sites. Each site will be responsible for recruiting and following up their study participants. KEMRI CGHR has a modern research annex at the Siaya County Referral Hospital with capacity to conduct Phase I to Phase III studies, in addition study activities will also occur at the Chandaria health center which has adequate facilities and staff to conduct clinical trials Site</p>\n<p>\n 8503: Dr V Nduba - Kisumu/Siaya KEMRI</p>\n<p>\n Administrative offices of the PI and co Investigators, procurement and Human Resource functions are housed at the KEMRI Kisian Campus. Recruitment, follow up of study participants will occur in Siaya. KEMRI CDC has a modern research annexe at the district hospital with capacity to conduct phase I to Phase III studies. After community mobilization, screening and enrolment, IP dispensation will occur at the Siaya Clinical Research Annexe. Dr Videlis Nduba: Principal Investigator Roles: Has overall trial oversight, budgetary negotiations, sponsor communication, safety, ethical and regulatory communication. Oversight over clinical care provision Dr Grace Kaguthi: Co-Investigator Roles: day to day management of trial aspects including recruitment, follow up, safety monitoring, data, staff supervision, clinical care provision, IP management. Supports PI and has roles that may be delegated such as ethical and sponsor communication</p>\n<p>\n Site 8502: Dr V Nduba - Nairobi County – Chandaria Health Center</p>\n<p>\n The study clinic is located close to Dagoretti Market at the Chandaria Health Centre. The facility is run by the Nairobi County. The site has clinic rooms, data entry space, temperature controlled pharmacy, laboratory and a -20 freezer for storage samples as needed. Potential participants will be screened and if eligible will be reviewed and followed up at the clinic. KEMRI-CRDR located within Kenyatta National Hospital Grounds is the administrative hub for the study. It may also serve as a site for trial procedures such as screening and follow up visits. Dr Videlis Nduba: Principal Investigator Roles: Has overall trial oversight, budgetary negotiations, sponsor communication, safety, ethical and regulatory communication. Oversight over clinical care provision Dr Grace Kaguthi: Co-Investigator Roles: day to day management of trial aspects including recruitment, follow up, safety monitoring, data, staff supervision, clinical care provision, IP management. Supports PI and has roles that may be delegated such as ethical and sponsor communication</p>\n<p>\n Site 8504: Dr B Ogutu – Strathmore University Medical Centre</p>\n<p>\n The Sickle Cell study will be conducted at SUMC, recruitment will occur at the clinic. SUMC is located at Strathmore University in Madaraka Estate of Nairobi west, Nairobi County. The SUMC is designed for clinical trials and has a full clinical laboratory with bioanalytical capability. The Centre is managed by Strathmore University and the CREATES consortium. The Centre also has a dental unit. The facility supports healthcare to University students and staff and also general public. The centre currently runs a SCD clinic every Tuesday. SUMC is an outpatient facility with a 2bed holding unit. The centre serves as a clinical trials facility for both paediatric and adult studies as proposed in this study. The participants who will require inpatient care will be admitted to Meter Hospital in South B as SUMC already has an existing working arrangement. SUMC will be staffed by qualified research personnel from KEMRI and SUMC. The site has a pharmacy, treatment area, clinical assessment area, data entry area, internal quality control and registration area and space where monitoring can be done. SUMC currently runs a SCD clinic with > 100 patients on follow up comprising of both adults and children. Principal Investigators (PI): Dr. Bernhards Ogutu, Principal Investigator SUMC site (Strathmore University): will be responsible for the overall conduct of the trial at these study site administrative actions between Institutional Review Boards, and the sponsor, oversight of field activities and patient care. He contributed to the protocol development and will contribute to the statistical analysis and writing of the scientific report. CO-PI: Dr. Anastacia Omding will be responsible for the clinical conduct of the trial, the care provided to patients, oversight of field activities. He will contribute to the statistical analysis and writing of scientific report(s). As for the Sickle cell disease, there is a database in place that has about over 100 patients and we hope to base our recruitment on this list. The SUMC is also linked other private, governmental, non-governmental and county health facilities, in Nairobi County that take care patients with SCD. PRINCIPAL INVESTIGATORS (PI): Dr. Bernhards Ogutu, Principal Investigator SUMC site (Strathmore University): will be responsible for the overall conduct of the trial at these study site administrative actions between Institutional Review Boards, and the sponsor, oversight of field activities and patient care. He contributed to the protocol development and will contribute to the statistical analysis and writing of the scientific report. CO-PI: Dr. Anastacia Omding will be responsible for the clinical conduct of the trial, the care provided to patients, oversight of field activities. He will contribute to the statistical analysis and writing of scientific report(s). Study Coordinator Amina Salim, will be responsible for the regulatory activities of the study.</p>\n<p>\n Site 8505: Dr B Ogutu - KEMRI Kondele Children’s Hospital</p>\n<p>\n The Kondele Children’s Hospital is designed for large clinical trials and has a full clinical laboratory including microbiology capability. The hospital is a KEMRI facility managed in collaboration with Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH). The Sickle Cell study will be conducted at KEMRI Kisumu site, recruitment will occur at the Kondele Children’s Hospital within (JOOTRH). The study will be carried out at the KEMRI Kondele Children’s Hospital in Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH). The Kondele Children’s Hospital study site at JOOTRH will be staffed by KEMRI qualified research personnel. The site has a pharmacy, vaccination area, clinical assessment area, data entry area, internal quality control and registration area and space where monitoring can be done. The unit has just completed a study on prasugral (antiplatelet agent) in children < 18 years. The Kondele Children Hospital is a 71 bed unit hospital run by the Ministry of Health. However, KEMRI doctors’ and other clinical staff currently supplement the clinical care services at this children’s hospital. The Kondele Children’s Hospital offers both outpatient and inpatient services. The outpatient is served by clinical officers (physician assistants) who are the primary (first) contacts with the patients. Those who require inpatient care are admitted to the hospital for further clinical evaluation, treatment and care by the medical team (Paediatricians, Medical Officers, Nurses, and Nutritionists). The unit serves and clinical trials facility for both paediatric and adult studies as proposed in this study. Principle Investigators (PI): Dr. Bernhards Ogutu, Principal Investigator Kondele Children’s Hospital Site (Kisumu East): will be responsible for the overall conduct of the trial at these study site administrative actions between Institutional Review Boards, and the sponsor, oversight of field activities and patient care. He contributed to the protocol development and will contribute to the statistical analysis and writing of the scientific report. CO Investigators: Dr. Godfrey Allan Otieno will be responsible for the clinical conduct of the trial, the care provided to patients, oversight of field activities. He will contribute to the statistical analysis and writing of scientific report(s). Study Coordinator Mr. Ishmail Sports, will be responsible for the regulatory activities of the study</p>\n<p>\n Site 8506: Dr Oyieko: Kombewa Clinical Research Center (KCRC), Kisumu</p>\n<p>\n The KEMRI/WRP Kombewa Clinical Research Center (KCRC) is designed for large clinical trials and has a full clinical laboratory including microbiology capability. The KCRC has been recognized as one of the premier sites in Africa to conduct malaria study drug/placebo trials. KCRC is part of The Walter Reed Project (WRP), which is a 40-year collaboration between the Kenya Medical Research Institute, (KEMRI) and the Walter Reed Army Institute of Research (WRAIR). The US Army Medical Research Unit in Kenya (USAMRU-K) is a WRAIR attachment stationed in Kenya with headquarters in Nairobi and field stations in Kericho and Kisumu. WRP-Kisumu conducts a wide spectrum of field and laboratory work including numerous clinical research trials. The study will be conducted at the KCRC and recruitment will occur at the Kisumu West District hospital as well as in the surrounding health facilities. The KEMRI/WRP Clinical Research Centre in Kombewa is staffed by KEMRI/WRP qualified research personnel some of whom will be involved with recruitment of study subjects and conduct of the study. The KCRC is located opposite the Kombewa County Hospital in Kisumu West District of Nyanza Province in Western Kenya. It is located about 40 kilometres west of Kisumu town and has previously been used as a site for many clinical trials and epidemiological studies involving both adults and children on malaria, trypanosomiasis, leishmaniasis, entomology, HIV/AIDS and arboviruses. The Kisumu-West and East districts both border Lake Victoria. Kisumu West is divided into two divisions (Kombewa and Maseno). Power supply in the study area is unstable, but elaborate backup power systems have been established at the KCRC. Two mobile phone service providers offer communication services. Dr. Janet Oyieko, Principal Investigator Kombewa Clinical Research Centre: will be responsible for the overall conduct of the trial at this study site, administrative actions between WRP, Institutional Review Boards, and the sponsor, oversight of field activities and patient care. She contributed to the site protocol development and will contribute to the statistical analysis and writing of the scientific report. Dr. Walter Otieno, Associate Investigator: will be responsible for the clinical conduct of the trial, the care provided to patients, oversight of field activities. He contributed to the protocol development and will contribute to the statistical analysis and writing of scientific report(s). Dr. Lucas Otieno, Associate Investigator : will be responsible for the clinical conduct of the trial, the care provided to patients, oversight of field activities. He contributed to the protocol development and will contribute to the statistical analysis and writing of scientific report(s). Dr. Valentine Sing’oei, Associate Investigator: will be responsible for the clinical conduct of the trial, the care provided to patients, oversight of field activities. He will contribute to the statistical analysis and writing of scientific report(s). Dr. John Owuoth, Associate Investigator: will be responsible for the clinical conduct of the trial, the care provided to patients, oversight of field activities. He will contribute to the statistical analysis and writing of scientific report(s). Stacey M. Okalo Gondi- Regulatory Affairs oversight, will be responsible for communication with IRBs and ECs. Millicent Achola, Clinical Research Coordinator; responsible for overall study coordination while working in a team environment under the direction of the investigators. Coordinating the recruiting, screening, and enrolling of study volunteers; arranging follow-up visits; completing and ensuring the accuracy of CRFs and regulatory documents; and ensuring the adherence to GCP guidelines.</p>\n<p>\n  </p>\n
      • other_details_explanation<p>\n The study is conducted in many parts of the world. Sickle Cell Disease is not very prevalent in Western Europe and thus did not include many countries from that region. The sponsor included Kenya based on the expected higher patient population.</p>\n
      • other_details_regulatory_notapproved<p>\n Please attached List of CA’s and Decisions dated 19 Jun 2018, section 22 of the application</p>\n
      • other_details_regulatory_approved<p>\n • South Africa, MCC approval 11 Jun 2018 • Spain RA approval, 14 Mar 2018 • Canada, RA Approval 20 Apr 2018 • UK MHRA approval, 04 Apr 2018 • Belgium (famhp)RA approval, 14 May 2018 • US FDA cover letter dated 09 Feb 2018 • CDER notification</p>\n
      • other_details_regulatory_rejected<p>\n No Rejections have been received</p>\n
      • other_details_regulatory_halted<p>\n Not applicable</p>\n
      • estimated_durationTreatment duration is at least 12 months for study participants, and patients will continue on treatment until 12 months after last randomized patient. The expected average follow-up is 18 mths, assuming a uniformly distributed enrolment period of 12 mths
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPlacebo
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states76
      • number_of_sites6
      • multi_country_listUSA, UK, Turkey, Spain, Italy, Belgium, South Africa, Tanzania, Kenya, Ghana, Uganda, Egypt, Lebanon, Saudi Arabia, Brazil
      • data_monitoring_committeeYes
      • total_enrolment_per_siteThere are 6 sites in Kenya, 120 projected screened patients, 28 projected patients to be randomised between the 6 sites.There is competitive enrolment.\nThere is no minimum or maximum number per site.\nIt is anticipated that each site randomises 4-5 participants\n
      • total_participants_worldwideThe study randomize approximately 182 participants globally.
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenYes
      • population_adolescentYes
      • population_above_18No
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifyparticipants aged ≥2 years to <18 years
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameProf Jessie
      • investigator1_middle_nameNyokabi
      • investigator1_family_nameGithanga
      • investigator1_qualificationMBChB, Mmed (Path)(UON), FCPath ECSA
      • investigator1_professional_addressDepartment of Human Pathology, School of Medicine, College of Health Sciences, University
      • investigator1_telephone00254 020 7206000
      • investigator1_emailJgithanga3@gmail.com
      • organisations_transferred_Yes
      • number_participants6
      • notification
      • approval_date06-10-2018
      • submitted1
      • deleted0
      • deleted_date2019-08-21 14:06:21
      • deactivated0
      • date_submitted20-03-2020
      • is_child0
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      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report
      • implication_results
      • quantity_imported1689
      • quantity_dispensed675
      • quantity_destroyed
      • quantity_exported
      • balance_site1014
      • final_date0000-00-00
      • modified2021-08-24 12:57:17
      • created2018-07-20 12:50:34
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id441
        • application_id704
        • given_nameProf Jessie
        • middle_nameNyokabi
        • family_nameGithanga
        • qualificationMBChB, MMed (Path)(UON), FCPath ECSA
        • professional_addressAssociate Professor, Department of Human Pathology, School of Medicine, College of Health Sciences, University
        • telephone+254 721245721
        • emailgithanga3@gmail.com
        • created2018-07-20 13:03:27
        • modified2020-03-20 08:01:54
      • 1(array)
        • id442
        • application_id704
        • given_nameVidelis
        • middle_name
        • family_nameNduba
        • qualificationBachelor of Medicine and Surgery; Master of Public Health, PHD in Epidemiology
        • professional_addressKenya Medical Reserach Institure (KEMRI), Reserachy Collaboration Campus, Off Busia Road, Kisian, Kenya
        • telephone+254 724 522 474
        • emailVNduba@kemricdc.org
        • created2018-07-20 13:08:34
        • modified2020-03-20 08:01:54
      • 2(array)
        • id443
        • application_id704
        • given_nameJanet
        • middle_nameN
        • family_nameOyieko
        • qualificationMD, MMed (Paediatrics and Child Health)
        • professional_addressKEMRI Kombewa, Kombewa Clinical Research Centre, Walter Reed Project Off Kisumu Bondo Road Opposite Kombewa
        • telephone+254733333530
        • emailjanet.oyieko@usamru-k.org
        • created2018-07-20 13:08:34
        • modified2020-03-20 08:01:54
      • 3(array)
        • id444
        • application_id704
        • given_nameBernards
        • middle_nameRagama
        • family_nameOgutu
        • qualificationMBChB, MMed (Paediatrics), PhD (Clinical Pharmacology)
        • professional_addressKEMRI - Centre for Clinical Research, Kondele Children\'s Hospital (within Jaramogi Oginga Odinga Hospital), Kisumu-
        • telephone+254733966065
        • emailbernhards.ogutu@usamru-k.org
        • created2018-07-20 13:08:34
        • modified2020-03-20 08:01:54
    • SiteDetail(array)
      • 0(array)
        • id556
        • application_id704
        • county_id47
        • site_nameGertrude’s Children’s Hospital
        • physical_addressMuthaiga, Nairobi, 42325, Kenya
        • contact_detailsProf Jessie Githanga, +254-721245721, jgithanga3@gmail.com
        • contact_personProf Jessie Githanga
        • site_capacity(null)
        • misc(null)
        • created2018-07-20 13:03:28
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          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 1(array)
        • id557
        • application_id704
        • county_id47
        • site_nameChandaria Health Center Clinical Research Clinic
        • physical_addressKEMRI/CRDR Thogoto Mutarakwa Road, Kikuyu, Kenya, 00100
        • contact_detailsVidelis Nduba, +254724522474, vnduba@gmail.com
        • contact_personDr Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2018-07-20 13:22:39
        • modified2020-03-20 08:01:54
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 2(array)
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        • site_nameKenya Medical Research Institute (KEMRI) Kisumu
        • physical_addressCentres for Disease Control and Prevention Research Collaboration Campus Off Busia Road Kisian
        • contact_detailsVidelis Nduba, +254724522474, vnduba@gmail.com
        • contact_personDr Videlis Nduba
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          • created2012-06-15 10:27:02
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      • 3(array)
        • id559
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        • county_id47
        • site_nameKEMRI Kombewa Clinical Research Centre
        • physical_addressWalter Reed Project Off Kisumu Bondo Road Opposite Kombewa Sub-County Hospital, Kombewa, Kenya
        • contact_detailsJanet Oyieko, +254 721996988, janet.oyieko@usamru-k.org
        • contact_personDr Janet Oyieko
        • site_capacity(null)
        • misc(null)
        • created2018-07-20 13:22:39
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          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 4(array)
        • id560
        • application_id704
        • county_id42
        • site_nameKondele Children\'s Hospital
        • physical_addressKEMRI - Centre for Clinical Research Kondele Children\'s Hospital (within Jaramogi Oginga Odinga Hospital)
        • contact_detailsDr Bernards Ogutu, +254733966065, bernhards.ogutu@usamru-k.org
        • contact_personDr Bernards Ogutu
        • site_capacity(null)
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          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 5(array)
        • id561
        • application_id704
        • county_id47
        • site_nameStrathmore University Medical Centre
        • physical_addressMadaraka Estate Ole Sangale Road, off Langata Road, Nairobi, Kenya, 00200
        • contact_detailsDr Bernards Ogutu, +254733966065, bernhards.ogutu@usamru-k.org
        • contact_personDr Bernhards Ogutu
        • site_capacity(null)
        • misc(null)
        • created2018-07-20 13:22:39
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          • created2012-06-15 10:27:40
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    • Sponsor(array)
      • 0(array)
        • id349
        • application_id704
        • sponsorAstraZeneca AB
        • sponsor_typeIndustry
        • contact_personGalina Meier-Abdi
        • addressS-151 85 Södertälje,
        • telephone_number+46 8 553 260 00
        • fax_number+46 8 553 290 00
        • cell_number+49 162 1399223
        • email_addressgalina.meier-abdi@astrazeneca.com
        • created2018-07-20 13:03:27
        • modified2020-03-20 08:01:54
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      • id518
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      • trial_status_id6
      • abstract_of_study<div>\n <p style=\"margin-left:5.85pt;\">\n <strong>1</strong><strong>.</strong><strong>0      THE NEED FOR A TRIAL</strong></p>\n <p style=\"margin-left:5.85pt;\">\n <strong>1</strong><strong>.</strong><strong>1      What is the problem to be addressed? </strong>Cardiovascular disease is a leading cause of death globally estimated to be responsible for ~ 17 million deaths annually. Heart  disease and stroke account for nearly one third of all deaths and are a major cause of hospitalization. Patients with</p>\n <p style=\"margin-left:5.85pt;\">\n congestive heart failure (CHF) are at particularly high risk. Clinical trials demonstrate that nearly one</p>\n <p style=\"margin-left:5.85pt;\">\n third of patients with CHF will experience a myocardial infarction (MI), stroke, or hospitalization for CHF. Observational studies have established an association between influenza infection and major adverse vascular events. Mechanisms that have been postulated to explain this increased risk include the precipitation  of plaque  rupture,  endothelial dysfunction,  reactivation  of  other latent infections leading to plaque rupture, fever-associated tachycardia, and metabolic derangements related to infection, including elevation of triglycerides and serum glucose levels. It follows that vaccinating such a high risk group as patients with CHF against influenza may prevent adverse vascular events. Studies examining influenza vaccination and vascular events however have shown conflicting results. As we describe below, we recently conducted an observational study using databases from two large clinical trials, indicating that influenza vaccination may be associated with a reduction of major adverse vascular  events;  however,  because  of  the  strong  possibility  of  bias,  these  results  need  to be rigorously confirmed in a prospective, randomized trial. Therefore, while national guidelines endorse influenza vaccination for patients with chronic cardiac disease, actual vaccination rates remain low, and importantly, these guidelines are largely based on observational  data and expert opinion, with data lacking from adequately powered, prospective, randomized trials. Clinical equipoise exists as to whether influenza vaccine in fact prevents cardiovascular events in patients with CHF. Consequently, a randomized controlled trial is needed to address the question. Adverse vascular events are a global threat to health and have an enormous impact in low to middle income countries.</p>\n <p style=\"margin-left:5.85pt;\">\n <strong>1</strong><strong>.</strong><strong>2      Why is a trial needed now?</strong></p>\n <p style=\"margin-left:5.85pt;\">\n <strong>1</strong><strong>.</strong><strong>2</strong><strong>.</strong><strong>1   Preliminary data</strong>. Using a large clinical database consisting of prospectively collected data from the ONTARGET and TRANSCEND randomized controlled trials (these include most INTER-</p>\n <p style=\"margin-left:5.85pt;\">\n CHF sites),  we  performed  an  analysis  to determine the association between influenza vaccination</p>\n <p style=\"margin-left:5.85pt;\">\n and major adverse vascular events. Annual immunization status with trivalent influenza vaccine was determined using a self-reported questionnaire at the study enrolment visit, 2-year follow-up visit and end of study visit. There was an associated reduced risk of the primary outcome in the influenza vaccinated group when the influenza virus matched the vaccine antigen well (2004-2005 (OR 0.62,</p>\n <p style=\"margin-left:5.85pt;\">\n 95% CI 0.50 – 0.77), 2005-2006 (OR 0.69, 95% CI 0.53 – 0.91) and 2006-2007 (OR 0.52 95% CI</p>\n <p style=\"margin-left:5.85pt;\">\n 0.42 – 0.65)), but there was no association in 2003- 2004 when there was an incomplete vaccine antigen match with the circulating influenza virus (odds ratio 0.96 95% CI 0.73-1.27). The summary OR for the 4 adjusted OR from the influenza seasons was 0.65 (95% CI 0.58 – 0.74, p<0.001), and there was statistically significant heterogeneity (p=0.003). Although our findings suggest an association, residual confounding cannot be excluded and it remains uncertain as to whether influenza vaccination can reduce major adverse vascular events.</p>\n <p style=\"margin-left:5.85pt;\">\n <strong>1</strong><strong>.</strong><strong>2</strong><strong>.</strong><strong>2   Systematic  reviews:  </strong>There  have  been  3  systematic  reviews  of  the  effect  of  influenza</p>\n <p>\n vaccination on major adverse vascular events. A Cochrane review summarized the results of 2 small randomized controlled trials. One of these trials, the FLUVAC study, although reported as one study, consisted of two randomized controlled trials, one of which randomized 200 patients with acute MI to influenza vaccine or placebo (FLUVAC MI) and the second randomized 102 patients planned to have PCI (FLUVAC PCI). The FLUCAD study was a randomized double blinded placebo controlled single centre trial where 658 patients with coronary disease were randomized to influenza vaccine or placebo. The pooled RR for cardiovascular death in these studies was 0.39 (95%CI 0.20 to 0.77) and meta- analysis led to a pooled RR of 0.85 (95% CI 0.44 to 1.62) for MI. A recent trial randomized patients with a history of ACS to either influenza vaccination or no treatment. Twenty-one of 221 patients in the vaccine group compared to 42 of 218 in the comparison group had major adverse vascular events (unadjusted HR 0.70; 95% CI, 0.57 to 0.86). Although these findings suggest an effect, the fact that the trial was open label may have introduced bias, and an accompanying editorial to this study stressed the need for a large simple randomized controlled trial of influenza vaccination. Two trials of participants that were not enrolled on the basis of cardiovascular illness and reported a risk ratio of 0.64 (0.48 to</p>\n</div>\n<div>\n <p style=\"margin-left:5.85pt;\">\n 0.86) for adverse cardiovascular events and a risk ratio of 0.81 (95% CI 0.36 to 1.83) for cardiovascular death. The conclusion of the authors in the latest systematic review was that “A large, adequately powered, multicenter trial is warranted to address these findings and assess individual cardiovascular</p>\n <p style=\"margin-left:5.85pt;\">\n end points”.</p>\n <p style=\"margin-left:5.85pt;\">\n <strong>1</strong><strong>.</strong><strong>2</strong><strong>.</strong><strong>3   Pilot work. </strong>We have piloted logistics of conducting this trial using internal funding. We have</p>\n <p style=\"margin-left:5.85pt;\">\n conducted a survey of participants in INTER-CHF sites (all low to middle income countries) for influenza vaccination and observed that vaccine update was 11% on average and < 25% in all sites.. We have established recruitment through INTER-CHF where 5,813 participants have been successfully enrolled. We have previously demonstrated our ability to randomize and measure outcomes in landmark cardiovascular trials (ONTARGET, ORIGIN) conducted in these same sites using the same data collection methods that we propose in this study. We obtained ethics approval from McMaster University in October 2013. Ethics submissions have been submitted and approved for three Southern Hemisphere sites in Philippines, Uganda and Mozambique. We have demonstrated feasibility of shipping vaccine, as we have successfully sent mock vaccine shipments to Nigeria, Uganda, Mozambique and Philippines and trial vaccine to Mozambique and Philippines. We have completed enrolment at two Southern Hemisphere sites in Spring 2015. We are in the process of submitting for ethics approval and finalizing contracts with all Northern Hemisphere sites.</p>\n <p style=\"margin-left:5.85pt;\">\n <strong>1</strong><strong>.</strong><strong>3      How will the results of the trial be used? </strong>This proposed randomized trial has important implications for the management of patients at high risk for major adverse vascular events. Although the influenza vaccine is recommended annually for groups with diabetes and cardiovascular disease in many counties, uptake of these recommendations is relatively low. Cardiologists in most jurisdictions do not routinely recommend annual influenza vaccine for their patients as a strategy to reduce future adverse vascular events such as acute coronary syndrome or stroke. Uptake of influenza vaccine in patients with heart disease varies by country but in INTER-CHF sites is 11% on average and < 25% in all sites. Rigorous demonstration of influenza vaccine leading to a reduction in major adverse vascular events would represent a landmark study. We anticipate that such a trial would influence management decisions by physicians for patients at high risk for major vascular events. The effect size we propose testing is comparable to secondary prevention strategies available and given the fact that a vaccine is given once annually it is simple and inexpensive. Given the large burden of disease, the possibility to reduce cardiovascular and stroke related death is a compelling argument for this trial.  If influenza vaccine is shown to reduce adverse vascular events, it will represent an important change in how prevention of adverse vascular events is thought about. The fact that our primary outcome is a composite, including various forms of vascular disease will increase generalizability.</p>\n <p style=\"margin-left:5.85pt;\">\n <strong>1</strong><strong>.</strong><strong>4      Describe any risks to the safety of participants involved in the trial.</strong></p>\n <p style=\"margin-left:5.85pt;\">\n The major risk of influenza vaccine, although rare (1 per 200,000 doses), is an anaphylactic reaction, characterized by hives, swelling of mouth and throat, difficulty breathing, and low blood pressure. Such a rare event occurs immediately after injection. Less than one third of individuals receiving study vaccine may experience some soreness or redness at the site for 1-2 days. Fever, malaise, nausea, loss of appetite, muscle aches occur infrequently and may last 1-2 days. It is unclear whether Guillain- Barré syndrome is associated with influenza vaccination, however it has been estimated that if there was such an association, it would be at a rate of 1 or 2 incremental episodes of Guillain-Barré syndrome per million doses of influenza vaccine given. There is no evidence that receiving two influenza vaccines (i.e. for participants who are randomized to influenza vaccine and also receive a vaccine outside of the trial) within a given season leads to any additional adverse events other than those described above. In fact, children under the age of 9 years are routinely immunized with two doses of influenza vaccine four weeks apart to increase protection against influenza. By contrast the risks of death and other major cardiovascular disease events exceeds 30%.</p>\n <p style=\"margin-left:5.85pt;\">\n <strong>1</strong><strong>.</strong><strong>5      Ethical considerations. </strong>There is uncertainty in the medical community about the benefit</p>\n <p style=\"margin-left:5.85pt;\">\n of influenza vaccination to prevent adverse vascular events as outlined below in sections 3.2 and 3.3. Observational studies cannot definitely address the question because of confounding.  There is also uncertainty about the non-cardiovascular benefits of the vaccine. A recent Cochrane review of influenza vaccine in persons > 65 years, pooled 3 RCTs (2217 participants, including those from a nursing home and a psychiatric hospital) found a RR of 0. 42 (0.27, 0.66) for preventing influenza but complications were not assessed. However, in observational studies, vaccines were ineffective in the prevention of influenza, RR 0.19 (0.02, 2.01), influenza-like illness, RR 0.75 (0.42, 1.33), pneumonia, RR 0.88 (0.64, 1.20), or hospital admissions or deaths from any respiratory disease, RR0.88 (0.54,1.43).  Selection bias because of differential vaccine uptake has been extensively cited as the most likely explanation for these counter-intuitive results (i.e. lack of effect on influenza, influenza-like illness,  pneumonia,  respiratory hospital  admissions  but  prevention  of influenza  and  pneumonia hospitalizations  and  death). In  fact,  the  reduction  in  death  from  all causes far exceeds the estimated impact of influenza vaccine on winter season mortality of 5% in an average season.  A report of reduced influenza/pneumonia hospitalization (RR 0.72; 0.59, 0.89) and reduced all  cause death  (RR  0.39;    0.33,  0.47)  when  seniors  were  vaccinated  and  outcomes  assessed prior to influenza season offers evidence of selection bias due to preferential vaccination of healthy seniors. Seniors with greater frailty (i.e. at increased risk for hospitalization and death) were shown to be less likely to receive influenza vaccination.  The authors of the Cochrane review conclude that “to resolve the uncertainty of the role of vaccines, an adequately powered, publicly-funded, high quality placebo- controlled trial run over several seasons should be undertaken”. Given broad consensus among experts in the field that clinical equipoise exists on the effect of influenza vaccine in CHF patients, a large, prospective randomized trial is delivery.</p>\n</div>\n<p>\n  </p>\n
      • study_title<p>\n A Randomized Trial of Inflienza Vaccine to Reduce Adverse Vascular Events</p>\n
      • laymans_summary(null)
      • short_titleA Randomized Trial of Inflienza Vaccine to Reduce Adverse Vascular Events
      • protocol_noECCT/16/07/02
      • version_noVersion 1.0
      • date_of_protocol08-07-2015
      • study_drug inactivated trivalent influenza vaccine (VAXIGRIP vaccine)
      • disease_conditionadverse Vascular events over influenza season among heart failure Patients
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines1
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressmaureen.njeru@aku.edu
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries1
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd(null)
      • applicant_prev_data(null)
      • applicant_stability_data(null)
      • applicant_analysis_cert(null)
      • applicant_pictorial_sample(null)
      • applicant_gcp_training(null)
      • applicant_dsmb_charter(null)
      • applicant_detailed_budget(null)
      • applicant_indemnity_pi(null)
      • applicant_practice_license(null)
      • applicant_registration_ctr(null)
      • applicant_pan_african(null)
      • applicant_hard_copies(null)
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      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantMaureen Njeru
      • declaration_date108-07-2016
      • declaration_principal_investigatorProf. Gerald Yonga
      • declaration_date208-07-2016
      • placebo_presentYes
      • study_objectives(null)
      • principal_inclusion_criteria<p style=\"margin-left:5.85pt;\">\n Age ≥ 18 years and NYHA functional class II, III and IV. Patients will be randomized to either influenza vaccine or placebo. Given that there is no evidence that two influenza vaccinations can cause harm, they will be allowed to obtain influenza vaccination from their primary care providers.</p>\n
      • principal_exclusion_criteria<p style=\"margin-left:5.85pt;\">\n a) anaphylactic reaction to a previous dose of TIV.</p>\n<p style=\"margin-left:5.85pt;\">\n b) known IgE- mediated hypersensitivity to eggs manifested as hives, swelling of the mouth and throat, difficulty in breathing,  hypotension,  or  shock.</p>\n<p style=\"margin-left:5.85pt;\">\n c) Guillain-Barré syndrome within eight  weeks of  a  previous influenza vaccine.</p>\n<p style=\"margin-left:5.85pt;\">\n d) anaphylactic reaction to neomycin. We will exclude patients who have had influenza vaccine in two of the three previous years. This is because such patients are more likely to receive the influenza vaccine annually and will be more likely to wish to receive it outside of the trial.</p>\n<p style=\"margin-left:5.85pt;\">\n Patients with severe valvular disease that are candidates for surgical or percutaneous valve repair or replacement will be excluded.</p>\n
      • primary_end_points<p style=\"margin-left:5.85pt;\">\n The primary outcome will be a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and hospitalizations for heart failure using standardized criteria.</p>\n<p>\n  </p>\n<p>\n  </p>\n
      • scope_diagnosis0
      • scope_prophylaxis1
      • scope_therapy0
      • scope_safety0
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<div>\n <p>\n <u>staff names, qualifications and experiences</u></p>\n <p>\n   1. Prof. Gerald Yonga- Principal investigator, head, non-communicable Diseases Research to policy unit, clinical  </p>\n <p>\n   trials investigator,Associate professor of medicine and cardiology since July 2007 at Aga Khan University Hospital</p>\n <p>\n  2. Dr. Mzee Ngunga- Co-Investigator, senior instructor and cardiologist at Aga Khan University Hospital for over   </p>\n <p>\n       10 years.</p>\n <p>\n 3. Jaimini Gohil- Chief pharmacist and clinical trial pharmacist, at the Aga Khan University Hospital  since 2013</p>\n <p>\n   4.. Maureen Njeru- study coordinator, clinical trial nurse at the Aga Khan University Hospital since 2014</p>\n <p>\n   5.. George Odinya- Regulatory Officer and study coordinator at Aga Khan University Hospital since 2013</p>\n <p>\n  <u>Facility</u></p>\n <p>\n Aga Khan University Hospital, heart clinic with an emergency response system in place, Pharmacy   </p>\n Department will provide storage the vaccines.</div>\n<p>\n  </p>\n
      • other_details_explanation<p style=\"margin-left:5.85pt;\">\n he proposed study will be conducted by the international network of investigators that have participated in other trials run by the Population Health Research Institute (PHRI). Sites that participated in the INTER-CHF R e g i s t r y,  a prospective study of 5,813 patients with CHF in 16 low-middle income countries in  Asia,  Africa,  the  Middle  East  and South America, will be approached first.  The primary objective of INTER-CHF is to assess clinical risk factors, management strategies and outcomes in this cohort. The key study infrastructure of INTER- CHF is the relationship with the site investigators, their ability to identify and recruit  patients with CHF, and their familiarity with case- record forms.   We have adapted the data collection forms for this trial from existing INTER-CHF forms.  Since INTER-CHF will be complete by the time this study is started, there will be no impact on INTER-CHF. Importantly, preliminary data from INTER-CHF show that, despite existence of guidelines recommending influenza vaccine in high risk CV patients, vaccination rates in CHF patients in these countries remain low at an average of 11%.</p>\n<p>\n <br />\n  </p>\n
      • other_details_regulatory_notapproved<p>\n N/A</p>\n
      • other_details_regulatory_approved<ul>\n <li>\n Hamilton Integrated Research Ethics Board (HIREB project ♯ 13-694) 10^th July 2015</li>\n</ul>\n<p style=\"margin-left:5.7pt;\">\n  </p>\n<ul>\n <li>\n Aminu Kano Teaching hospital, Nigeria 19^th Aug 2015, one site.</li>\n</ul>\n<p style=\"margin-left:5.7pt;\">\n  </p>\n<ul>\n <li>\n University of Philippines Manila Research Ethics Board 13^th February 2015</li>\n</ul>\n<p style=\"margin-left:5.7pt;\">\n  </p>\n<ul>\n <li>\n Servico de Cariologia Mozambique 3^rd November 2015, one site.</li>\n</ul>\n<p>\n  </p>\n<ul>\n <li>\n Aga Khan University Hospital Research ethics committee, the study was approved on the 18^th of May 2016, one site</li>\n</ul>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration3 years
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorSterile Saline
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaThe Aga Khan University Hospital
      • single_site_physical_address3rd parklands avenue, p.o box 30270-00100, Nairobi
      • single_site_contact_personGerald Yonga
      • single_site_telephone+2547222206209
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states11
      • number_of_sites
      • multi_country_list1.China\n2.Nigeria\n3.Saudi Arabia\n4.Sudan\n5.Mozambique\n6.Philippines\n7.Uganda\n8.India\n9.Kenya\n10.Cameroon\n11.United Arab Emirates\n
      • data_monitoring_committeeYes
      • total_enrolment_per_site300 for one site in Kenya
      • total_participants_worldwide3500 participants
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyYes
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameGerald
      • investigator1_middle_nameOchieng
      • investigator1_family_nameYonga
      • investigator1_qualificationSenior Consultant Cardiologist
      • investigator1_professional_addressAga Khan University Hospital Nairobi, 30270-00100, 3rd parklands Avenue Nairobi
      • investigator1_telephone+254722206209
      • investigator1_emailgerald.yonga@aku.edu
      • organisations_transferred_No
      • number_participants300 participants
      • notification<p>\n Dear sir/Madam,</p>\n<p>\n This clinical trial involves recruitment of participants during the influenza season in each site, our Kenyan season is July and early August, your expedited approval wil be highly appreciated by this intitution.</p>\n<p>\n  </p>\n<p>\n Kind regards Maureen</p>\n
      • approval_date17-08-2016
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted18-07-2016
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
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      • balance_site(null)
      • final_date(null)
      • modified2018-04-03 07:50:11
      • created2016-07-08 10:06:36
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id339
        • application_id518
        • given_nameMark
        • middle_name
        • family_nameLoeb
        • qualificationDivision Director, Infectious Diseases
        • professional_addressMc Master University, MDCL 3200 1280 Main St. West. Hamilton
        • telephone905-525-9140
        • emailloebm@mcmaster.ca
        • created2016-07-08 10:37:50
        • modified2016-08-01 15:23:23
    • SiteDetail(array)
      • 0(array)
        • id403
        • application_id518
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2016-07-08 10:37:50
        • modified2016-08-01 15:23:23
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id269
        • application_id518
        • sponsorHamilton Health sciences corporation, population health research institute
        • sponsor_type(null)
        • contact_personKimberly Begley
        • address237 Barton Street east, Hamilton ON L8L 2X2
        • telephone_number905-527-4322X40328
        • fax_number905-297-3786
        • cell_number905-527-4322X40328
        • email_addresskimberly.begley@phri.ca
        • created2016-07-08 10:37:50
        • modified2016-08-01 15:23:23
      • 1(array)
        • id270
        • application_id518
        • sponsorMc Master University
        • sponsor_type(null)
        • contact_personMark Loeb
        • address1200 Main Street West MDCL3203 Hamilton, ontario canada L8N3Z5
        • telephone_number905-525-9140X24066
        • fax_number
        • cell_number905-525-9140X24066
        • email_addressloebm@mcmaster.ca
        • created2016-07-08 11:08:32
        • modified2016-08-01 15:23:23
  • 4(array)
    • Application(array)
      • id1028
      • user_id32
      • trial_status_id6
      • abstract_of_study<div>\n Scabies is a skin infestation caused by a mite called Sarcoptes scabiei. Scabies is characterised by a rash and severe itching, which is an allergic reaction to the eggs and feces the females deposit as they tunnel under the skin. Oral ivermectin is a very safe and beneficial drug which has been shown to be highly effective for the treatment of scabies and more than a dozen different neglected tropical diseases (NTDs), many of which are associated with important public health problems. Current label indications for ivermectin prevent use in small children weighing less than 15 kg, due to limited safety data in this group. Many of the NTD treatment options for small children rely on compounds that are less safe and/or efficacious compared to oral ivermectin. Our proposal will establish the safety and pharmacokinetics of escalating doses of ivermectin (200, 400, 800 μg/kg) to treat scabies infected children weighing 5 to less than 15 kg. The safety assessment will provide crucial evidence on the use of ivermectin for numerous diseases in children weighing 5 to less than 15 kg. The information from measuring drug concentrations in the patients will inform the optimal dosing of this drug in small children. Assessment of the efficacy of ivermectin, compared to permethrin cream, for the treatment of scabies in small children can provide an important alternative treatment for this widespread disease.</div>\n<div>\n This trial will evaluate the safety, pharmacokinetics, and efficacy of ivermectin in scabies infected children weighing 5 to less than 15kg. This will allow future efforts to expand the indication of ivermectin treatment to infants weighing 5 to less than 15kg to treat numerous NTDs, allowing this young age group equitable access to the numerous benefits of ivermectin therapy.</div>\n
      • study_title<p>\n A randomized, double-blind, placebo-controlled trial to assess the safety, pharmacokinetics, and efficacy of escalating doses of oral ivermectin in scabies infected children weighing 5 to less than 15 kilograms in Kenya</p>\n
      • laymans_summary<p>\n Scabies is a skin disease that is caused by a mite and manifests as a rash and severe itching. The rash and itching are caused by an allergic reaction to the eggs and faeces of the mites as they burrow under the skin. Ivermectin, taken by mouth is an effective treatment of scabies and more than one dozen tropical diseases referred to as neglected tropical diseases (NTDs) many of which are associated with important public health problems. At the moment, ivermectin is indicated only for persons at or above 15kg body weight because of the scarcity of data in children under this weight. The optional medicines available to treat children who are under 15kgs are less safe and do not work as effectively as ivermectin. We propose to assess the efficacy and safety of increasing doses of ivermectin (200, 400, 800 μg/kg) to treat scabies infected children whose weight is between 5 to less than 15kg. This information will enable us come up with the best dose of ivermectin to use to treat scabies in children of the target age group. A control group of children will be treated with permethrin cream which is currently one of the recommended medicines for treatment of scabies in children of these ages. The results of this study will inform of the best dose to use for treatment of scabies in children of the target age, allowing them to benefit from the numerous benefits of ivermectin treatment.</p>\n
      • short_titleISSC
      • protocol_noECCT/22/10/03
      • version_no4.0
      • date_of_protocol14-07-2022
      • study_drugIvermectin
      • disease_conditionScabies
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameIvermectin
      • product_type_medical_device_name
      • comparatorYes
      • comparator_namePermethrin Cream
      • comparator_registeredYes
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addresstonysangke@gmail.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantRuth Njoroge
      • declaration_date117-10-2022
      • declaration_principal_investigatorDr. Menno Smit
      • declaration_date217-10-2022
      • placebo_presentYes
      • study_objectives<div>\n Primary Objective</div>\n<ul>\n <li>\n To compare safety of oral ivermectin to topical permethrin cream</li>\n</ul>\n<div>\n Secondary Objectives</div>\n<ol>\n <li>\n To characterize the pharmacokinetics of escalating doses of repeated ivermectin (200, 400, 800 μg/kg).</li>\n <li>\n To compare efficacy of oral ivermectin to topical permethrin cream.</li>\n</ol>\n<p>\n Exploratory Objectives</p>\n<ol>\n <li>\n To characterize the effects of pharmacogenomics on ivermectin related study outcomes.</li>\n</ol>\n<div>\n  </div>\n<div>\n  </div>\n
      • principal_inclusion_criteria<ul>\n <li>\n Male or female child weighing 5 to <15 kilograms</li>\n <li>\n ≥2 months old</li>\n <li>\n Scabies infestation</li>\n <li>\n Available to attend all study visits</li>\n <li>\n Parents/guardians/carers able to provide consent.</li>\n</ul>\n
      • principal_exclusion_criteria<div>\n The participant may not enter the trial if ANY of the following apply:</div>\n<ul>\n <li>\n A history of renal or hepatic impairment.</li>\n <li>\n Any other significant disease or disorder (e.g. moderate or severe malnutrition) which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial.</li>\n <li>\n Participants who have participated in another research trial involving an investigational product in the past 12 weeks.</li>\n <li>\n Children with Crusted/Norwegian scabies or severe secondary bacterial infections (e.g. sepsis)</li>\n <li>\n Children who have taken ivermectin or topical permethrin cream within the last month</li>\n <li>\n Children with known allergies to ivermectin or topical permethrin cream or excipients</li>\n <li>\n Loa loa infection risk, assessed based on travel history to endemic areas</li>\n <li>\n Use of prescription (especially CYP3A4 inhibitors or inducers) or non-prescription drugs (except paracetamol at doses of up to 90 milligrams/kg/day), including vitamins (especially vitamin C), herbal and dietary supplements (including St. John�s Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 times the drug half-life (whichever is longer) prior to the first dose of study medication until the completion of the follow-up procedure, unless in the opinion of investigator, the medication will not interfere with the study procedures or compromise patient safety; the investigator will take advice from the manufacturer representative as necessary.</li>\n <li>\n The investigator, health care provider or study staff feel that the patient is not suitable for study participation due to chronic illness, suspected underlying illness, or concerns that the patient will adhere to follow-up schedule.</li>\n <li>\n Previously enrolled into this study</li>\n</ul>\n
      • primary_end_points<p>\n The primary outcome is safety of oral ivermectin compared to permethrin control group. This will be assessed by comparing the occurrence of adverse events between the intervention (ivermectin) and control (perme<text data-test=\"textbox\" direction=\"ltr\" height=\"7.62300109863281\" lengthadjust=\"spacingAndGlyphs\" textlength=\"403.583557128906\" x=\"129.379028320312\" y=\"-214.404022216797\">thrin) groups</text>.<br />\n  </p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic1
      • scope_bioequivalence0
      • scope_dose_response1
      • scope_pharmacogenetic0
      • scope_pharmacogenomic1
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p style=\"margin-left:18.0pt;\">\n <strong><u>KEMRI-LSTM collaboration:</u></strong><br />\n The study will be conducted in Kisumu, through the Kenya Medical Research Institute, in collaboration with the Liverpool School of Tropical Medicine (LSTM). The institute has state of the art laboratories, research-linked hospital in- and out-patient units, and highly trained staff. LSTM will act as the study’s lead institution in Kenya and will provide technical oversight, utilizing an existing collaborative network of LSTM scientists located at the research field station.<br />\n <br />\n <strong><u>Site:</u></strong><br />\n The study will be conducted at the Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH). Dependent on the recruitment rate, enrolment will be expanded to other hospitals in Kisumu and Siaya counties including Kisumu, Vihiga and Siaya County Hospitals among others (see protocol). JOOTRH is a major tertiary care hospital with self-contained paediatric, medical, and obstetric wards, as well as an intensive care unit with mechanical ventilators and telemetry capabilities.<br />\n <br />\n <strong><u>Investigators:</u></strong><br />\n Menno Smit (MD, MPH, PhD), is an Honorary Associate Professor at LSTM and Specialty Trainee in Paediatrics at Amsterdam UMC. He conducted his PhD research in Kisumu on High-dose Ivermectin as a Mosquitocidal Drug. He will act as the Kenyan site co-principal.</p>\n<p style=\"margin-left:18.0pt;\">\n <br />\n Eunice Akinyi Ouma (MD), is a Medical Doctor and Senior Research officer at the Kenya Medical Research Institute. She is the Kenyan site co-principal investigator together with Menno Smit, and will share overall responsibility for the study. She will serve as the lead medical doctor on the study, overseeing clinical aspects.</p>\n<p style=\"margin-left:18.0pt;\">\n Eric Ochomo (PhD), is an entomologist at KEMRI with a PhD from Maseno University. He will serve as the lead entomologist on the study.</p>\n<p style=\"margin-left:18.0pt;\">\n Simon Kariuki (PhD), is the KEMRI CGHR Malaria Branch Chief and will take leadership for technical malaria components, laboratory oversight, liaising with research staff, and KEMRI CGHR management.</p>\n<p style=\"margin-left:18.0pt;\">\n Feiko Ter Kuile (MD, PhD), is a Professor of Tropical Epidemiology from the Liverpool School of Tropical Medicine (LSTM) based at KEMRI in Kisumu. He will support the study based on his extensive experience with safety and efficacy trials.<br />\n <br />\n <strong><u>Staff:</u></strong></p>\n<p style=\"margin-left:18.0pt;\">\n The study staff, to be hired, will consist of:</p>\n<ul>\n <li style=\"margin-left: 18pt;\">\n Study coordinator (1x)</li>\n <li style=\"margin-left: 18pt;\">\n Clinical officers (3x)</li>\n <li style=\"margin-left: 18pt;\">\n Lab technologists (1.5x)</li>\n <li style=\"margin-left: 18pt;\">\n Project administrator (1x)</li>\n <li style=\"margin-left: 18pt;\">\n Data manager (1x)</li>\n <li style=\"margin-left: 18pt;\">\n Driver (1x)</li>\n <li style=\"margin-left: 18pt;\">\n Community health workers (4x)</li>\n</ul>\n
      • other_details_explanation<p>\n n/a</p>\n
      • other_details_regulatory_notapproved<ol>\n <li>\n Bangladesh: Bangladesh Drug Authority (DGDA), pending submission.</li>\n <li>\n Brazil: Brazilian Regulatory Health Agency (ANVISA), pending submission.</li>\n <li>\n The Gambia: Medicines Control Agency(MCA), pending submission.</li>\n</ol>\n<p>\n  </p>\n<div>\n  </div>\n
      • other_details_regulatory_approved<p>\n None, pending submissions (see 12.3).</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n n/a</p>\n
      • estimated_durationOne year
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPermethrin topical cream
      • design_controlled_other_medicinalYes
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaJaramogi Oginga Odinga Teaching and Referral Hospital
      • single_site_physical_addressKisumu-Kakamega Road Kisumu, Kenya
      • single_site_contact_personDr. Eunice Ouma
      • single_site_telephone+254 724 152 943
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states4
      • number_of_sites
      • multi_country_listBangladesh\nBrazil\nKenya\nThe Gambia
      • data_monitoring_committeeYes
      • total_enrolment_per_site100
      • total_participants_worldwide400
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerYes
      • population_childrenYes
      • population_adolescentNo
      • population_above_18No
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifyThe study participants will be young children who weigh between 5 kilograms to less than 15 kilograms. Consent will be given by the parents, guardians or caregivers.
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameMenno
      • investigator1_middle_name
      • investigator1_family_nameSmit
      • investigator1_qualificationMD, MPH, PhD
      • investigator1_professional_addressLiverpool School of Tropical Medicine (LSTM), Pembroke Place, Liverpool L3 5QA, United Kingdom
      • investigator1_telephone+31 6 4436 4327
      • investigator1_emailmenno.smit@lstmed.ac.uk
      • organisations_transferred_Yes
      • number_participants100
      • notification
      • approval_date14-02-2024
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted17-10-2022
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-04-07 11:05:56
      • created2021-06-21 13:23:15
      • total_sites(null)
      • ecitizen_invoice(null)
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      • 0(array)
        • id712
        • application_id1028
        • given_nameEunice
        • middle_nameAkinyi
        • family_nameOuma
        • qualificationMD
        • professional_addressKenya Medical Research Institute (KEMRI), Centre for Global Health Research (CGHR), P.O. Box 1578, Kisumu 40100, Kenya
        • telephone+254 724 152 943
        • emailakinyiepet@gmail.com
        • created2021-08-30 14:39:05
        • modified2022-10-17 08:15:46
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        • application_id1028
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        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2021-08-30 14:39:05
        • modified2022-10-17 08:15:46
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
    • Sponsor(array)
      • 0(array)
        • id534
        • application_id1028
        • sponsorUniversity of Oxford
        • sponsor_typeResearch Institution
        • contact_person
        • addressCentre for Tropical Medicine and Global Health, New Richards Building, Old Road Campus, Roosevelt Drive, Oxford, OX3 7LG, United Kingdom
        • telephone_number+44 (0)1865 612 900
        • fax_number
        • cell_number+44 (0)1865 612 900
        • email_addressLorenz@tropmedres.ac
        • created2021-08-30 14:39:05
        • modified2022-10-17 08:15:46
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  • 1Form
  • 2Session
  • 3Text
  • 4Number
  • 5SimpleGraph
  • 6Paginator
  • 7DebugTimer
  • 8Toolbar
  • 9HtmlToolbar

App Constants

CakePHP Constants

PHP Environment

Included Files

Include Paths

• 0/var/www/html/ctr/app/Plugin/Media/Lib/mm/src
• 1/var/www/html/ctr/lib
• 3/usr/share/php
• 4-> /var/www/html/ctr/lib/Cake/

Included Files

• core(array)
  • Behavior(array)
    • 0CORE/Model/Behavior/TreeBehavior.php
    • 1CORE/Model/Behavior/ContainableBehavior.php
    • 2CORE/Model/Behavior/AclBehavior.php
  • Cache(array)
    • 0CORE/Cache/Cache.php
    • 1CORE/Cache/Engine/FileEngine.php
    • 2CORE/Cache/CacheEngine.php
  • Component(array)
    • 0CORE/Controller/Component/AclComponent.php
    • 1CORE/Controller/Component/Acl/DbAcl.php
    • 2CORE/Controller/Component/Acl/AclInterface.php
    • 3CORE/Controller/Component/AuthComponent.php
    • 4CORE/Controller/Component/RequestHandlerComponent.php
    • 5CORE/Controller/Component/SessionComponent.php
    • 6CORE/Controller/Component/PaginatorComponent.php
  • Config(array)
    • 0CORE/Config/routes.php
    • 1CORE/Config/config.php
  • Controller(array)
    • 0CORE/Controller/Controller.php
    • 1CORE/Controller/ComponentCollection.php
    • 2CORE/Controller/Component.php
  • Datasource(array)
    • 0CORE/Model/Datasource/CakeSession.php
    • 1CORE/Model/Datasource/Database/Mysql.php
    • 2CORE/Model/Datasource/DboSource.php
    • 3CORE/Model/Datasource/DataSource.php
  • Error(array)
    • 0CORE/Error/exceptions.php
    • 1CORE/Error/ErrorHandler.php
  • I18n(array)
    • 0CORE/I18n/I18n.php
    • 1CORE/I18n/L10n.php
  • Log(array)
    • 0CORE/Log/CakeLog.php
    • 1CORE/Log/LogEngineCollection.php
    • 2CORE/Log/Engine/FileLog.php
    • 3CORE/Log/Engine/BaseLog.php
    • 4CORE/Log/CakeLogInterface.php
  • Model(array)
    • 0CORE/Model/ConnectionManager.php
    • 1CORE/Model/Permission.php
    • 2CORE/Model/Model.php
    • 3CORE/Model/BehaviorCollection.php
    • 4CORE/Model/Aro.php
    • 5CORE/Model/AclNode.php
    • 6CORE/Model/Aco.php
    • 7CORE/Model/ModelBehavior.php
  • Network(array)
    • 0CORE/Network/CakeRequest.php
    • 1CORE/Network/CakeResponse.php
  • Other(array)
    • 0CORE/bootstrap.php
    • 1CORE/basics.php
    • 2CORE/Core/App.php
    • 3CORE/Core/Configure.php
    • 4CORE/Core/CakePlugin.php
    • 5CORE/Event/CakeEventListener.php
    • 6CORE/Event/CakeEvent.php
    • 7CORE/Event/CakeEventManager.php
    • 8CORE/Core/Object.php
  • Routing(array)
    • 0CORE/Routing/Dispatcher.php
    • 1CORE/Routing/Filter/AssetDispatcher.php
    • 2CORE/Routing/DispatcherFilter.php
    • 3CORE/Routing/Filter/CacheDispatcher.php
    • 4CORE/Routing/Router.php
    • 5CORE/Routing/Route/CakeRoute.php
    • 6CORE/Routing/Route/PluginShortRoute.php
  • Utility(array)
    • 0CORE/Utility/Hash.php
    • 1CORE/Utility/Inflector.php
    • 2CORE/Utility/ObjectCollection.php
    • 3CORE/Utility/Debugger.php
    • 4CORE/Utility/String.php
    • 5CORE/Utility/ClassRegistry.php
    • 6CORE/Utility/Set.php
    • 7CORE/Utility/Sanitize.php
  • View(array)
    • 0CORE/View/HelperCollection.php
• app(array)
  • Behavior(array)
    • 0APP/Model/Behavior/SoftDeleteBehavior.php
  • Config(array)
    • 0APP/Config/core.php
    • 1APP/Config/bootstrap.php
    • 2APP/Config/routes.php
    • 3APP/Config/database.php
  • Controller(array)
    • 0APP/Controller/ApplicationsController.php
    • 1APP/Controller/AppController.php
  • Model(array)
    • 0APP/Model/AppModel.php
    • 1APP/Model/Application.php
    • 2APP/Model/User.php
    • 3APP/Model/TrialStatus.php
    • 4APP/Model/InvestigatorContact.php
    • 5APP/Model/Sponsor.php
    • 6APP/Model/SiteDetail.php
    • 7APP/Model/County.php
  • Other(array)
    • 0APP/webroot/index.php
• plugins(array)
  • CakePdf(array)
    • Config(array)
      • 0CakePdf/Config/bootstrap.php
      • 1CakePdf/Config/routes.php
  • CakeResque(array)
    • Config(array)
      • 0CakeResque/Config/bootstrap.php
    • Plugin(array)
      • 0CakeResque/Lib/CakeResque.php
      • 1CakeResque/vendor/kamisama/php-resque-ex/lib/Resque.php
      • 2CakeResque/vendor/kamisama/php-resque-ex/lib/Resque/Event.php
      • 3CakeResque/vendor/kamisama/php-resque-ex/lib/Resque/Exception.php
  • DebugKit(array)
    • Component(array)
      • 0DebugKit/Controller/Component/ToolbarComponent.php
    • Plugin(array)
      • 0DebugKit/Lib/DebugMemory.php
      • 1DebugKit/Lib/Panel/HistoryPanel.php
      • 2DebugKit/Lib/DebugPanel.php
      • 3DebugKit/Lib/Panel/SessionPanel.php
      • 4DebugKit/Lib/Panel/RequestPanel.php
      • 5DebugKit/Lib/Panel/SqlLogPanel.php
      • 6DebugKit/Lib/Panel/TimerPanel.php
      • 7DebugKit/Lib/Panel/LogPanel.php
      • 8DebugKit/Lib/Log/Engine/DebugKitLog.php
      • 9DebugKit/Lib/Panel/VariablesPanel.php
      • 10DebugKit/Lib/Panel/EnvironmentPanel.php
      • 11DebugKit/Lib/Panel/IncludePanel.php
      • 12DebugKit/Lib/DebugTimer.php
  • Media(array)
    • Config(array)
      • 0Media/Config/bootstrap.php
    • Plugin(array)
      • 0Media/Lib/mm/src/Mime/Type.php
      • 1Media/Lib/mm/src/Mime/Type/Magic/Adapter/Fileinfo.php
      • 2Media/Lib/mm/src/Mime/Type/Magic/Adapter.php
      • 3Media/Lib/mm/src/Mime/Type/Glob/Adapter/Memory.php
      • 4Media/Lib/mm/src/Mime/Type/Glob/Adapter.php
      • 5Media/Lib/mm/src/Media/Process.php
      • 6Media/Lib/mm/src/Media/Info.php
  • Search(array)
    • Component(array)
      • 0Search/Controller/Component/PrgComponent.php
    • Behavior(array)
      • 0Search/Model/Behavior/SearchableBehavior.php
  • Shim(array)
    • Config(array)
      • 0Shim/Config/bootstrap.php
  • Tools(array)
    • Config(array)
      • 0Tools/Config/bootstrap.php