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• applications(array)
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    • Application(array)
      • id513
      • user_id336
      • trial_status_id4
      • abstract_of_study<p>\n The specific aim of the proposed study is to test the safety and feasibility (Phase 1) and preliminary efficacy (Phase 2) of a new low cost device (Odon Device) to deliver the fetus during prolonged second stage of labor. Although the focus of the proposed study is on the Odon Device as an alternative to available management options for complicated second stage of labour, other potential indications to be studied in the future could include use for assistance during normal delivery and prevention of infections acquired during delivery.</p>\n<p>\n This device may be potentially safer and easier to apply than forceps/vacuum extractor for assisted deliveries, and a safe alternative to some Caesarean sections. It has potential for wide application in resource poor settings even by mid-level providers. If proven safe and effective, the Odon Device will be the first innovation in operative vaginal delivery since the independent development of forceps and the vacuum extractor centuries ago. The Odon device could play a major role in improving intrapartum obstetric care in low resource settings by making possible effective management of intrapartum complications in facilities lacking surgical capacity and/or personnel adequately trained in the use of forceps and the vacuum extractor.</p>\n<p>\n Intrapartum complications are responsible for approximately half of all maternal deaths and two million stillbirth and neonatal deaths per year. Prolonged second stage of labor is associated with potentially fatal maternal complications such as hemorrhage and infection and is a major cause of stillbirth and newborn morbidity and mortality. Evidence indicates that the majority of intrapartum deaths in low-resource settings could be prevented through the introduction of innovative strategies that would increase accessibility of obstetric care (e.g., task shifting). Technological developments such as the Odon device that reduce the skill level and equipment required to provide quality obstetric care are clearly needed.      </p>\n<p>\n Currently, the three main options for managing prolonged second stage of labor are Cesarean section, forceps and vacuum extractor. All three clinical practices require relatively expensive equipment (e.g., a surgical theatre for cesarean section) and highly trained staff that are often not available in low resource settings. Even when these options are available, their use is associated with increased maternal and perinatal complications. Safe use of forceps requires very high-level training that is seldom available in low-resource settings. Use of the vacuum extractor is limited by the need for fairly complex equipment requiring maintenance, and it is contra-indicated in women who are HIV positive or with unknown HIV status.</p>\n<p>\n The Odon device is a low cost, easy to use technological innovation to facilitate operative vaginal delivery and designed to minimize trauma to the mother and baby.  It may also protect the baby from intrapartum infection. These features combined make it a potentially revolutionary development in obstetrics, particularly for improving intrapartum care in low resource settings. </p>\n<p>\n The Odon Device was invented by Mr Jorge Odon who holds an intellectual property patent. Mr Odon does not have a medical or biological research background and will participate in the proposed study only in relation to issues on device development.</p>\n<p>\n This study has been registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) as one of the Primary Registries in the WHO Registry Network. The registration number of this trial is ACTRN12613000141741.</p>\n<p>\n The Department of Reproductive Health and Research (HRP/RHR) at the World Health Organization (WHO) is the sponsor of the trial and performs overall coordination.</p>\n
      • study_title<p>\n Feasibility, safety and preliminary efficacy study of a new device (Odón  Device) for assisted vaginal delivery</p>\n
      • laymans_summary<p>\n The specific aim of the proposed study is to test the safety and feasibility (Phase 1) and preliminary efficacy (Phase 2) of a new low cost device (Odon Device) to deliver the fetus during prolonged second stage of labor. Although the focus of the proposed study is on the Odon Device as an alternative to available management options for complicated second stage of labour, other potential indications to be studied in the future could include use for assistance during normal delivery and prevention of infections acquired during delivery.</p>\n<p>\n This device may be potentially safer and easier to apply than forceps/vacuum extractor for assisted deliveries, and a safe alternative to some Caesarean sections. It has potential for wide application in resource poor settings even by mid-level providers. If proven safe and effective, the Odon Device will be the first innovation in operative vaginal delivery since the independent development of forceps and the vacuum extractor centuries ago. The Odon device could play a major role in improving intrapartum obstetric care in low resource settings by making possible effective management of intrapartum complications in facilities lacking surgical capacity and/or personnel adequately trained in the use of forceps and the vacuum extractor.</p>\n<p>\n Intrapartum complications are responsible for approximately half of all maternal deaths and two million stillbirth and neonatal deaths per year. Prolonged second stage of labor is associated with potentially fatal maternal complications such as hemorrhage and infection and is a major cause of stillbirth and newborn morbidity and mortality. Evidence indicates that the majority of intrapartum deaths in low-resource settings could be prevented through the introduction of innovative strategies that would increase accessibility of obstetric care (e.g., task shifting). Technological developments such as the Odon device that reduce the skill level and equipment required to provide quality obstetric care are clearly needed.      </p>\n<p>\n Currently, the three main options for managing prolonged second stage of labor are Cesarean section, forceps and vacuum extractor. All three clinical practices require relatively expensive equipment (e.g., a surgical theatre for cesarean section) and highly trained staff that are often not available in low resource settings. Even when these options are available, their use is associated with increased maternal and perinatal complications. Safe use of forceps requires very high-level training that is seldom available in low-resource settings. Use of the vacuum extractor is limited by the need for fairly complex equipment requiring maintenance, and it is contra-indicated in women who are HIV positive or with unknown HIV status.</p>\n<p>\n The Odon device is a low cost, easy to use technological innovation to facilitate operative vaginal delivery and designed to minimize trauma to the mother and baby.  It may also protect the baby from intrapartum infection. These features combined make it a potentially revolutionary development in obstetrics, particularly for improving intrapartum care in low resource settings. </p>\n<p>\n The Odon Device was invented by Mr Jorge Odon who holds an intellectual property patent. Mr Odon does not have a medical or biological research background and will participate in the proposed study only in relation to issues on device development.</p>\n<p>\n This study has been registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) as one of the Primary Registries in the WHO Registry Network. The registration number of this trial is ACTRN12613000141741.</p>\n<p>\n The Department of Reproductive Health and Research (HRP/RHR) at the World Health Organization (WHO) is the sponsor of the trial and performs overall coordination.</p>\n
      • short_titleOdón Device for assisted vaginal delivery
      • protocol_noECCT/17/04/01
      • version_noOdon device Protocol Phase I v8 June 2016
      • date_of_protocol01-06-2016
      • study_drugOdon device
      • disease_conditionDelivery process
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device1
      • product_type_chemical_name
      • product_type_medical_device_nameOdon device
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addresszahida@qureshi.co.ke
      • 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_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_applicantZahida Qureshi
      • declaration_date120-02-2017
      • declaration_principal_investigatorZahida Qureshi
      • declaration_date220-02-2017
      • placebo_presentNo
      • study_objectives<div>\n The main objective of the study is to evaluate the safety and feasibility, in terms of ease of application </div>\n<div>\n and successful delivery, of the BD Odonâ„¢ Device in assisting vaginal delivery in singleton term </div>\n<div>\n pregnancies during the second stage of labour.</div>\n<div>\n  </div>\n
      • principal_inclusion_criteria<div>\n Written informed consent obtained preferably during an antenatal care visit, and always before the initiation of labour. In centres where regular attendance of antenatal care visits might be limited or where no on-site visits are proposed, it is planned that women could be ask to consent during early labour (less than 4 cm dilatation) if not too distressed),</div>\n<div>\n 2. Woman attended at least one antenatal visit at 36 weeks of gestation or more,</div>\n<div>\n 3. Woman is able to read and fully understand the consent information,</div>\n<div>\n 4. Age ≥ 18 and less or equal to 35 years of age,</div>\n<div>\n 5. Singleton pregnancy,</div>\n<div>\n 6. Gestational age equal to or more than 37+0 weeks by best estimate according to local protocols,</div>\n<div>\n 7. Live fetus assessed by methods used according to local protocols,</div>\n<div>\n 8. Fully dilated cervix,</div>\n<div>\n 9. Ruptured membranes (spontaneous or artificial),</div>\n<div>\n 10. Any anterior occiput presentation,</div>\n<div>\n 11. Station level equivalent to 2 cm or more below the spines (e.g. station +2 or lower), or equivalent grading used in study sites,</div>\n<div>\n 12. Fetal heart rate pattern recorded by continuous fetal electronic monitoring meeting the following criteria:</div>\n<div>\n a. Stable baseline rate between 110 and 160 beats/min,</div>\n<div>\n b. normal short and long term variability,</div>\n<div>\n c. absence of late decelerations,</div>\n<div>\n 13. Slightly prolonged second stage of labour, defined as women who have been pushing for at least 30 minutes if nulliparous and 15 minutes if multiparous.</div>\n
      • principal_exclusion_criteria<div>\n Suspected or confirmed maternal infection: Suspected infection will be diagnosed if any of the following are present:</div>\n<div>\n i. Fever ≥ 38 ºC,</div>\n<div>\n ii. Foul smelling amniotic fluid.</div>\n<div>\n 2. More than 24 hours rupture of membranes at the time of delivery or timing of rupture of membranes unknown,</div>\n<div>\n 3. Meconium-stained amniotic fluid,</div>\n<div>\n 4. History of coagulation disorder,</div>\n<div>\n 5. Previous uterine surgery,Intrapartum haemorrhage,</div>\n<div>\n 7. Absolute cephalopelvic disproportion,</div>\n<div>\n 8. Known recto-vaginal-urethral Streptoccocus B Haemolyticcus colonization,</div>\n<div>\n 9. Known HIV positive women,</div>\n<div>\n 10. A history of allergy or previous adverse reaction to latex</div>\n<div>\n 11. Any other condition or circumstance that, in investigator’s opinion, would compromise the safety of the mother or the fetus.</div>\n
      • primary_end_points<p>\n Failure rate of device application</p>\n<div>\n delivery with forceps or vacuum extraction</div>\n<div>\n ï‚· Caesarean section</div>\n<div>\n ï‚· Episiotomy</div>\n<div>\n ï‚· Lacerations of the low genital tract (vulvar, vaginal)</div>\n<div>\n ï‚· Perineal lacerations</div>\n<div>\n ï‚· Cervical laceration</div>\n<div>\n ï‚· Uterine rupture</div>\n<div>\n ï‚· Pelvic haematoma</div>\n<div>\n ï‚· Perineal or vaginal haematoma</div>\n<div>\n ï‚· Postpartum haemorrhage as routinely assessed and defined at the study centres</div>\n<div>\n ï‚· Postpartum endometritis or other infection as reported by study centres</div>\n<div>\n ï‚· Blood transfusion</div>\n<div>\n ï‚· Maternal pain during insertion of the device, using a scale</div>\n<div>\n ï‚· Perineal pain after delivery</div>\n<div>\n ï‚· Maternal experience</div>\n<div>\n 3.3.3.2. Infant outcomes</div>\n<div>\n Incidence of:</div>\n<div>\n ï‚· Abnormal respiratory rate at 2 hours after birth</div>\n<div>\n ï‚· Birth trauma or injuries (skull fracture, caput succedaneum, cephalohaematoma, cutaneous facial lesions and facial palsy, extracranial haemorrhages, subgaleal haemorrhage, subaponeurotic haemorrhage, intracranial injuries)</div>\n<div>\n ï‚· Low Apgar Scores (less than 7 at 1st minute and less than 7 at 5th minute)</div>\n<div>\n ï‚· Any other measure of asphyxia at birth, if collected routinely</div>\n<div>\n ï‚· Admission to Neonatal Intensive Care Unit</div>\n<div>\n ï‚· Length of stay (> 7 days) in neonatal intensive care unit</div>\n<div>\n <div>\n ï‚· Retinal haemorrhage</div>\n <div>\n ï‚· Anaemia</div>\n <div>\n ï‚· Jaundice</div>\n <div>\n ï‚· Infection</div>\n <div>\n ï‚· Phototherapy</div>\n <div>\n ï‚· Fetal or neonatal death</div>\n</div>\n<p>\n  </p>\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_pharmacology1
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other1
      • trial_other_specifyPhased trial in humans
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<p>\n Staff</p>\n<p>\n Prof Zahida Qureshi MBChB MMed ObGyn- PI</p>\n<p>\n Dr Alfred Osoti MBChB MMed (ObGyn) MPH-CoPI</p>\n<p>\n Midwives (2) to be identfied</p>\n<p>\n Infraestructure</p>\n<p>\n Comprehensive emergency obstetric and newborn care available on-site</p>\n
      • other_details_explanation<p>\n The study wil be implemented in low-middle-income countries</p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n Kenyatta National Hospital University of Nairobi ERC</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration6 months
      • 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_stateYes
      • location_of_areaKenyatta National Hospital
      • single_site_physical_addressOff Ngong Road
      • single_site_contact_personZahida Qureshi
      • single_site_telephone00254733605140
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states3
      • number_of_sites
      • multi_country_listArgentina, South Africa, kenya
      • data_monitoring_committeeYes
      • total_enrolment_per_site20
      • total_participants_worldwide108
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male0
      • subjects_healthyNo
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenYes
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameZahida
      • investigator1_middle_name
      • investigator1_family_nameQureshi
      • investigator1_qualificationMBChB MMed
      • investigator1_professional_addressDepartment of Obs and Gyn, University of Nairobi,PO Box 19676 Nairobi Kenya
      • investigator1_telephone00254733605140
      • investigator1_emailzahida@qureshi.co.ke
      • organisations_transferred_Yes
      • number_participants20
      • notification
      • approval_date22-06-2017
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted14-08-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<p>\n This was a proposal for implementation of the WHO A65711 study in four hospitals in South AfricaThis was a proposal for implementation of the WHO A65711 study in one hospital at Kenyatta Hospital, in Nairobi. No woman was recruited under this study in Kenya.</p>\n<p>\n A prototype of the BD Odon device^TM  (BD, Franklin Lakes, NJ, USA) was used in one case in South Africa in 2017, before the company decided to stop supplying the devices to the WHO study and this trial was consequently terminated.One woman was recruited and application of the device failed.</p>\n<p>\n  </p>\n
      • implication_results(null)
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      • quantity_destroyed(null)
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      • balance_site(null)
      • final_date(null)
      • modified2020-08-14 11:45:02
      • created2016-07-01 14:46:35
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id337
        • application_id513
        • given_nameZahida
        • middle_name
        • family_nameQureshi
        • qualificationMBCHB MMed
        • professional_addressDepartment of Obs and Gyn, University of Nairobi,PO Box 19676 Nairobi Kenya
        • telephone00254733605140
        • emailzahida@qureshi.co.ke
        • created2016-07-06 06:48:19
        • modified2020-08-14 11:45:02
    • SiteDetail(array)
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        • id399
        • application_id513
        • county_id(null)
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        • misc(null)
        • created2016-07-06 06:48:19
        • modified2020-08-14 11:45:02
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id267
        • application_id513
        • sponsorThe World Health Organization
        • sponsor_typeResearch Institution
        • contact_personMercedes Bonet
        • addressThe World Health Organization Headquarters
        • telephone_number004122 791 3347
        • fax_number
        • cell_number004122 791 3347
        • email_addressbonetm@who.int
        • created2016-07-06 06:48:19
        • modified2020-08-14 11:45:02
  • 1(array)
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      • user_id335
      • trial_status_id5
      • abstract_of_study<p>\n <strong>Introduction</strong></p>\n<p>\n Sickle cell disease is an inherited blood disorder resulting from a genetic mutation of the beta</p>\n<p>\n hemoglobin chain (HbSS), with high prevalence in Sub-Saharan Africa. Due to a complex interplay of adhesive events, these altered erythrocytes can obstruct the vasculature, producing episodes of pain, organ ischemia and infarction and early mortality.  Activated platelets promote the adherence of sickle cells to endothelial cells and thus participate in the vaso-occlusive process.  Inhibition of platelet activation has therefore been proposed as a potential therapeutic option in the treatment of children and adults with SCD.</p>\n<p>\n Ticagrelor is an orally active, reversibly binding cyclopentyl-triazolo-pyrimidine P2Y₁₂ receptor antagonist that produces dose‑related inhibition of adenosine diphosphate (ADP) induced platelet aggregation. Ticagrelor is indicated to reduce the rate of thrombotic cardiovascular events in patients with acute coronary syndrome (ACS). The ticagrelor development program to date has focused on adult patients since there is no paediatric correlate for the adult condition of ACS. This study will therefore seek to characterise the relationship between ticagrelor dose and inhibition of platelet aggregation in paediatric patients with SCD to support a Phase III study.</p>\n<p>\n <strong>Primary Objective:</strong></p>\n<p>\n To characterise the relationship between ticagrelor dose and inhibition of platelet aggregation in paediatric patients with SCD, using PK-PD modelling, to support dose selection for Phase III</p>\n<p>\n <strong>Secondary Objective:</strong></p>\n<p style=\"margin-left:32.2pt;\">\n 1.       To determine the PK properties of ticagrelor and its active metabolite in paediatric patients with SCD and to assess impact of weight, age and other demographic on the ticagrelor pharmacokinetics.</p>\n<p style=\"margin-left:32.2pt;\">\n 2.       Investigation of efficacy of ticagrelor vs. placebo in paediatric patients with SCD in reducing the number and severity of VOCs</p>\n<p style=\"margin-left:32.2pt;\">\n 3.       To assess safety and tolerability of single and multiple doses of ticagrelor in paediatric patients with SCD</p>\n<p style=\"margin-left:32.2pt;\">\n 4.       To determine the percent of patients with haemorrhagic events requiring medical intervention.</p>\n<p style=\"margin-left:32.2pt;\">\n 5.       Investigation of efficacy of ticagrelor vs. placebo in paediatric patients with SCD in reducing frequency and intensity of pain*</p>\n<p>\n * These do not apply to the study arm in Kenya</p>\n<p>\n <strong>Study site(s) and number of subjects planned</strong></p>\n<p>\n This study is currently conducted in 5 countries (United States, United Kingdom, South Africa, Canada and Lebanon) and approximately 8 to 20 sites, with a minimum of 36 patients and a maximum of 50 patients to be randomised in the study, depending on how many patients are required in order to have 36 evaluable patients.</p>\n<p>\n <strong>Study design</strong></p>\n<p>\n This is a multicenter, open-label, dose-ranging study of ticagrelor followed by a double blind, placebo-controlled extension phase in paediatric patients with sickle cell disease (SCD). </p>\n<p>\n <strong>Part A:</strong> Patients will be randomised in a 1:1 ratio to receive one of the two dosing schedules. All patients will receive 0.75 mg/kg as their initial single dose, followed 7 days later by 1.125 mg/kg or 2.25 mg/kg with determination of pharmacokinetic (PK) parameters and pharmacodynamic (PD) platelet inhibition following each single dose. The PK and platelet aggregation data are intended to support modelling-based selection of a weight-based dose for Phase III. Platelet aggregation will be measured using the VerifyNow™ P2Y₁₂ assay and reported as P2Y₁₂ reaction units (PRU).</p>\n<p>\n Following the 2 single doses, all patients will receive open-label one-week treatment with ticagrelor 0.75 mg/kg twice daily to determine tolerability prior to randomisation into Part B.</p>\n<p>\n <strong>Part B</strong>: Part B will be optional for patients. The investigator should present Part B to each patient and the decision to participate in Part B should be made by the patient (or parents/legal guardian). In this part patients will be randomised (2:1 ratio) to ticagrelor 0.75 mg/kg twice daily or placebo for a 4-week treatment phase. In some countries (Lebanon, Ghana, and Kenya), Part B will not be performed.</p>\n<p>\n <strong>Kenya centres: In Kenya patients will not be randomised to Part B. The patients will finish study treatment after 1 week open-label treatment and will visit site 30 days after treatment is stopped for follow-up. </strong></p>\n<p>\n During the study, patients will be followed for the occurrence of vaso-occlusive crisis (VOC) and for other disease manifestations such as daily pain, analgesic use and complications of SCD.</p>\n<p>\n For safety reasons the dosing schedule will be modified for individual patients as follows: If PRU at 2 hr following dosing of 0.75 mg/kg is <95, the subsequent maximum dose for this patient will be 0.563 mg/kg throughout the study. If PRU <95 following dosing of 0.563 mg/kg, the patient will be discontinued from further study drug.</p>\n<p>\n Since Part A of the study is open‑label, the PK and PD results will be monitored as the study proceeds and the doses may be further adjusted in both Part A and B based on emerging PK and PD results. Doses may be adjusted following assessment by AstraZeneca and the Steering Committee of open-label Part A results in the first 6 to 12 patients randomised under this amendment. Dose adjustment decisions will be based upon a review of PK, PD and adverse events.</p>\n<p>\n <strong> Target subject population</strong></p>\n<p>\n Patients eligible for this study include all children aged ≥2 to <18 years of age (age from birth to Visit 1) who are diagnosed with SCD (homozygous sickle cell [HbSS] or sickle beta‑zero‑thalassemia [HbS/β⁰]). </p>\n<p>\n <strong>Duration of treatment</strong></p>\n<p>\n In Part A the treatment period consists of 2 single doses (separated by at least 7 days) followed by 7 days open-label ticagrelor treatment twice daily. In Part B patients will be randomised to 4 weeks twice-daily treatment. There is no washout period between Part A and Part B. The total expected study duration for an individual patient participating in both Part A and Part B is approximately 3 months (including 30 days follow-up after last dose) and approximately 2 months for an individual patients participating in only Part A (including 30 days follow-up after last dose). For Kenya centres, Part B will not be conducted).</p>\n<p>\n <strong>Investigational product, dosage and mode of administration</strong></p>\n<p>\n <strong>Part A:</strong></p>\n<p>\n Ticagrelor 0.563 mg/kg, 0.75 mg/kg, 1.125 mg/kg or 2.25 mg/kg given as oral single doses.</p>\n<p>\n Ticagrelor 0.563 mg/kg or 0.75 mg/kg twice daily given orally.</p>\n<p>\n These doses may be adjusted based upon evaluation of PK/PD data as described in Appendix E of full protocol attached.</p>\n<p>\n <strong>Part B:</strong></p>\n<p>\n Ticagrelor 0.563 mg/kg or 0.75 mg/kg twice daily given orally and matching placebo.</p>\n<p>\n These doses may be adjusted based upon evaluation of PK/PD data as described in Appendix E.</p>\n<div>\n <p>\n The investigational product (active or placebo) will be granules for oral suspension supplied in glass bottles. Before each dosing occasion the granules will be constituted with 10 mL of purified water in the glass bottle to form a suspension suitable for oral dosing.</p>\n <p>\n <strong>Statistical methods</strong></p>\n <p>\n The relationship between ticagrelor dose, plasma concentration and PRU will be characterized using a population PK/PD approach (i.e non-linear mixed effect modelling). This analysis will be based on all available PK and PRU data from which complete dosing and sampling history is collected.</p>\n <p>\n No statistical comparisons are planned for the primary objective. PK, PD and safety measures will be summarised descriptively.</p>\n <p>\n A statistical analysis will be done comparing ticagrelor and placebo for each of the following variables:</p>\n <p>\n ·                              Percentage of days with pain (ages ≥4 years only)</p>\n <p>\n ·                              Percentage of days of opioid analgesic use</p>\n <p>\n ·                              Percentage of days of analgesic use (ages ≥4 years only)</p>\n <p>\n ·                              Percentage of days hospitalized for VOC or other complications of SCD</p>\n <p>\n ·                              Percentage days of absence from school or work (ages ≥6 years only)</p>\n <p>\n A t-test will be performed for each of these variables at 5% significance level, provided that the efficacy analysis set contains at least 30 patients, otherwise only descriptive statistics will be used. The p-value and a 95% confidence interval for the difference between ticagrelor and placebo will be reported. There will be no adjustment for multiple comparisons. If it is inappropriate to assume a normal distribution, a Wilcoxon rank sum test may be performed. Number of VOC requiring hospitalization and intensity of pain will be summarised descriptively.</p>\n <p>\n For Kenya centres, no comparison of ticagrelor vs placebo will be done; all efficacy variables and exploratory variables will be summarised descriptively.</p>\n</div>\n<p>\n  </p>\n
      • study_title<p>\n Multicentre, open-label, randomised, pharmacokinetic (PK) and pharmacodynamic (PD) dose-ranging Phase II study of ticagrelor followed by a double-blind, randomised, parallel-group, placebo-controlled 4 weeks extension phase in paediatric patients with sickle cell disease</p>\n
      • laymans_summary(null)
      • short_titleHESTIA 1
      • protocol_noECCT/16/07/05
      • version_no1
      • date_of_protocol03-02-2016
      • study_drugTiicagrelor
      • 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
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressjgithanga3@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_countries1
      • applicant_addendum1
      • 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)
      • applicant_signed_checklist(null)
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantProf Jessie N Githanga
      • declaration_date120-07-2016
      • declaration_principal_investigatorProf Jessie N. Githanga - Coordinating investigator
      • declaration_date220-07-2016
      • placebo_presentYes
      • study_objectives(null)
      • principal_inclusion_criteria<p>\n 1.   Children aged ≥2 to <18 years* of age and body weight >16 kg to <70 kg diagnosed with homozygous sickle cell (HbSS) or sickle beta-zero-thalassaemia (HbS/β⁰).</p>\n<p>\n 2.   If ≤16 years, 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.</p>\n<p>\n 3.    If ≥6 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.</p>\n<p>\n 4.   If treated with an anti-sickling agent such as hydroxyurea, the weight-adjusted dose must be stable for 1 month before enrolment.</p>\n<p>\n 5. Suitable venous access for the study-related blood sampling.</p>\n<p>\n 6.  Provision of signed and dated written informed consent prior to any study specific procedures that are not part of standard medical care, (local regulations and international guidelines are to be followed in determining the assent/consent requirements for children).</p>\n<p style=\"margin-left:14.2pt;\">\n *    Age from birth to Visit 1. </p>\n
      • principal_exclusion_criteria<p style=\"margin-left:36.0pt;\">\n 1.      Previous history of transient ischemic attack (TIA) or clinically overt cerebrovascular accident (CVA) (ischemic or haemorrhagic), severe head trauma, intracranial haemorrhage, intracranial neoplasm, arteriovenous malformation, aneurysm, or proliferative retinopathy.</p>\n<p style=\"margin-left:36.0pt;\">\n 2.      Findings on TCD: Current or previous values for time averaged mean of the maximum velocity (TAMMV) that are Conditional or Abnormal*.</p>\n<p style=\"margin-left:72.0pt;\">\n Conditional TAMMV values are ≥153 cm/sec using imaging TCD (TCDi) technique (corresponding to ≥170 cm/sec by the non-imaging technique). Both the middle cerebral artery and the internal carotid artery should be considered. Abnormal TAMMV values are ≥180 cm/sec using TCDi (corresponding to ≥200 cm/sec by the non-imaging technique) and are an indication for chronic transfusions because of a high stroke risk. Any other criteria that would locally be considered as TCD indications for chronic transfusion would also exclude the patient.</p>\n<p style=\"margin-left:36.0pt;\">\n 3.      Undergoing treatment with chronic RBC transfusion therapy.</p>\n<p style=\"margin-left:36.0pt;\">\n 4.      Use of non-steroidal anti-inflammatory drugs (NSAIDs) >3 days per week.</p>\n<p style=\"margin-left:36.0pt;\">\n 5.      Receiving chronic treatment with anticoagulants or antiplatelet drugs that cannot be discontinued.</p>\n<p style=\"margin-left:36.0pt;\">\n 6.      Moderate or severe hepatic impairment, defined as Child-Pugh Class B or C (see Appendix H) or renal failure requiring dialysis.</p>\n<p style=\"margin-left:36.0pt;\">\n 7.      Active pathological bleeding or increased risk of bleeding complications according to Investigator.</p>\n<p style=\"margin-left:36.0pt;\">\n 8.      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.</p>\n<p style=\"margin-left:36.0pt;\">\n 9.      Concomitant oral or intravenous therapy (see Restrictions) with strong CYP3A4 inhibitors**, CYP3A4 substrates with narrow therapeutic indices, or strong CYP3A4 inducers**, which cannot be stopped at least five half-lives, but not shorter than 10 days, before enrolment.</p>\n<p style=\"margin-left:36.0pt;\">\n 10.  Surgical procedure planned to occur during the study.</p>\n<p style=\"margin-left:36.0pt;\">\n 11.  Patients who are currently pregnant or breastfeeding, or planning to become pregnant during the study.</p>\n<p style=\"margin-left:36.0pt;\">\n 12.  Females (if after menarche) who are not willing to use a highly effective method of contraception which results in a low failure rate (i.e. less than 1% per year).</p>\n<p style=\"margin-left:36.0pt;\">\n 13.  Known hypersensitivity or contraindication to ticagrelor.</p>\n<p style=\"margin-left:36.0pt;\">\n 14.  Concern for the inability of the patient or parents to comply with study procedures and/or follow-up.</p>\n<p style=\"margin-left:36.0pt;\">\n 15.  Any condition which, in the opinion of the Investigator, would make it unsafe or unsuitable for the patient to participate in this study.</p>\n<p style=\"margin-left:36.0pt;\">\n 16.  Previous randomisation in the present study***.</p>\n<p style=\"margin-left:36.0pt;\">\n 17.  Participation in another clinical study with an investigational product or device during the last 30 days preceding enrolment.</p>\n<p style=\"margin-left:36.0pt;\">\n 18.  Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).</p>\n<p>\n  </p>\n
      • primary_end_points<p>\n The primary study endpoint is the evaluation of the pharmacokinetic and pharmacodynamic properties of ticagrelor and its active metabolite in children after administration as single doses and after attainment of steady-state following twice-daily administration of ticagrelor.</p>\n<p>\n  </p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • 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_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n Site No 8501 Gertudes Children's Hospital Sub-investigators: Dr. Jaspreet Singh, consultant paediatrician; Dr Nyambura Kariuki – consultant paediatric haemato-oncologist. Pharmacist: Dr Monica Mirigo Gichuhi   Nurse/coordinator – Grace Njuguna</p>\n<p>\n Gertrude’s Children’s Hospital (GCH) is a dedicated children’s specialist hospital founded as a non-profit organization.  Based in Muthaiga, Nairobi, and spread out to various outpatient clinics including in Mombasa, 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 including haematology, chest conditions, cardiology, dermatology, otorhinolaryngology, endocrinology, oncology and HIV/AIDS. The Hospital has a laboratory equipped with modern equipment offering 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.  The pharmacy is manned by qualified pharmacists and a specified pharmacist will be managing the study subject medications.  GCH has an up-to-date paediatric imaging facility that is managed by a qualified radiologist and radiographers.  Most of the processes at the hospital are computerized and supported by a well-integrated Information Technology Department.  The Hospital is Muthaiga is open 24hours every day of the week and offers 24 hour laboratory and pharmacy coverage. Emergencies are attended to in the outpatient facility.  The population served by the hospital is cosmopolitan and English and Kiswahili are the predominantly spoken languages.     The site  completed a similar study on prasugral (antiplatelet agent) in children < 18 years.</p>\n<p>\n  Site 8502 – PI Videlis Nduba -  Dr. Grace Kiringa: Co-Investigator Chandaria Health Centre Dagoretti, Dagoretti sub-county, Nairobi; The Centre has adequate facilities and staff to conduct clinical trials . The laboratory tests will be referred to Lancet Laboratories in Nairobi and the TCD tests will be performed in Nairobi. </p>\n<p>\n Site 8503 – PI Videlis Nduba - Siaya County Referral Hospital, Siaya County.  Dr. Grace Kiringa: Co-Investigator.  Kenya Medical Research Institute (KEMRI) has a Clinical Research Annex at the Siaya County Referral Hospital.  This modern research at has the capacity to conduct Phase I to Phase III studies.  There are adequate facilities and qualified staff, including nurses and pharmacist to conduct clinical trials. The IP will be stored in the Clinical Research Annex and laboratory tests will be referred to the Lancet Laboratory Branch in Kisumu.  Transcranial Doppler studies will be performed in Kisumu.  Patients needing inpatient medical treatment will be admitted at the Siaya County referral Hospital. </p>\n<p>\n Site 8504 - 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/WRP sites, recruitment will occur at the Kondele Children’s Hospital within (JOOTRH). The study will be carried out at the KEMRI/WRP Kondele Children’s Hospital in Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH). The Kondele Children’s Hospital at the Jaramogi Oginga Odinga Teaching and Referral Hospital is located adjacent to the KEMRI/WRP Kisumu headquarters in Kondele within Kisumu East district.</p>\n<p>\n 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 completed a study on prasugral (antiplatelet agent) in children < 18 years.</p>\n
      • other_details_explanation<p>\n Sickle cell disease is primarily found in Africa where it is endemic in certain countrie, Kenya included.   Patients with SCD suffer chronic pain and reduced quality of life due to recurrent hospitalizations, grave complications  from the disease including organ damage, stroke and long term disabilities.  Although hydroxyurea has been found to have ameliorating effects on the disease, response in some patients is suboptimal and in some cases there are serious adverse effects.  Blood transfusions are also associated with various hazards.  New treatment modalities are therefore urgently needed and these options should also be validated in this region.</p>\n
      • other_details_regulatory_notapproved<ol>\n <li>\n Submission to CSR Centre for Respiratory Diseases Research, KEMRI, Ethics Review Committee has been made for the KEMRI CGHR site at the Siaya Country Referral Hospital and  Chandaria Health Centre in Dagoretti.  Application submitted on 24 March 2016.</li>\n <li>\n Submission to Kenya Medical Research Institute (KEMRI) SERU Ethics Review Committee has been made for the Kondele Children’s Hospital, KEMRI – Centre for Clinical Research.  Response to initial application received on 26 May 2016.  The PI for the site is re-submitting response to the corrections/clarifications sought.</li>\n</ol>\n
      • other_details_regulatory_approved<p>\n List of Competent Authorities which the application has been submitted and details of decisions:</p>\n<ol>\n <li>\n Canada: Competent Authority-  Health Canada Holland Cross, Tower B, 5th floor 1600 Scott Street 3105A, Ottawa, Ontario K1AOK9. Date of submission: 03-July-2014 . Approved 30-July-2014. One site open for enrollement  </li>\n <li>\n South Africa: The Registrar of Medicines,  Department of Health, Medicines Control Council, Private Bag X828, Pretoria 0001, REPUBLIC OF SOUTH AFRICA. Submission date:  08-July -2014.  Approved 21-Oct-2014. Two sites open for enrollement </li>\n <li>\n United Kingdom: Medicines and Healthcare products Regulatory Agency (MHRA), Information Processing Unit, Area 6, 151 Buckingham Palace Road, Victoria, London, SW1W 9SZ. Submission date: 06-June -2014 . Approved 23-July-2014. Two sites open for enrollement </li>\n <li>\n United States: Food and Drug Administration, Center for Drug Evaluation and Research, Division of Hematology Products, 5901-B Ammendale Road, Beltsville, MD 20705-1266. Approval not required.  Four sites haave EC approval. </li>\n <li>\n Kenya:  EC approval from Gertrude's Children's Hospital - Ethics Review Board. Submission on 11 March 2016. Approved 15 June 2016</li>\n</ol>\n<p>\n  </p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_durationPart A - 5 weeks; Part B will not be performed in Kenya
      • 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_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_states10 (ten)
      • number_of_sitesFour (4)
      • multi_country_listCanada, UK, USA, Lebanon, Egypt, South Africa, Kenya, Ghana, Italy, Turkey
      • data_monitoring_committeeYes
      • total_enrolment_per_siteCompetitive enrollment\nMinimum per site = 1 (one); Maximum per site = 9 (nine)
      • total_participants_worldwideMinimum=36 (thirty-six); Maximum =50 (fifty)
      • 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_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifyThe subjects are individuals with sickle cell disease (SCD) and these are expected to be patients at various times during their lives. The majority are on follow-up for their disease. Females (if after menarche) must be willing to use a highly effective method of contraception which results in a low failure rate (i.e. less than 1% per year). Children less than 18 years will be recruited and their parents/guardians will be asked to provide consent. Those over 12 years will be asked to provide assent in addition.
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameJessie
      • investigator1_middle_nameNyokabi
      • investigator1_family_nameGithanga
      • investigator1_qualificationMBChB, MMed (Pathology)
      • investigator1_professional_addressCollege of health Sciences (KNH), University of Nairobi, P. O. Box 19676 - 00202 Nairobi, Kenya
      • investigator1_telephone+254-721-245721
      • investigator1_emailjgithanga3@gmail.com
      • organisations_transferred_Yes
      • number_participants12 (twelve)
      • notification<p>\n Kind request for an expidited review.  Payment of a toyal of USD 2,000 has been made to facilitate this.</p>\n
      • approval_date19-09-2016
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted20-07-2016
      • 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)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2017-05-26 16:44:26
      • created2016-06-29 12:40:52
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id334
        • application_id511
        • given_nameJessie
        • middle_nameNyokabi
        • family_nameGithanga
        • qualificationMBChB, MMed (Pathology)
        • professional_addressCollege of health Sciences (KNH), University of Nairobi, P. O. Box 19676 - 00202 Nairobi, Kenya
        • telephone+254-721-245721
        • emailjgithanga3@gmail.com
        • created2016-06-29 12:51:47
        • modified2016-07-20 12:55:52
      • 1(array)
        • id335
        • application_id511
        • given_nameVidelis
        • middle_name
        • family_nameNduba
        • qualificationMBChB, MPH, PhD
        • professional_addressP.O Box 1578, Kisumu, Kenya, Post code 40100
        • telephone+254 -724 –522474
        • emailvnduba@kemricdc.org
        • created2016-06-29 13:24:17
        • modified2016-07-20 12:55:52
      • 2(array)
        • id336
        • application_id511
        • given_nameBernhards
        • middle_nameRagama
        • family_nameOgutu
        • qualificationMBChB, Med (Paediatrics), PhD (clinical Pharmacology)
        • professional_addressP.O. Box 54840, 00200, Nairobi, 00200, Kenya
        • telephone+254-733-812613
        • emailogutu6@gmail.com
        • created2016-06-29 13:24:17
        • modified2016-07-20 12:55:52
    • SiteDetail(array)
      • 0(array)
        • id398
        • application_id511
        • county_id47
        • site_nameGertrude’s Children’s Hospital
        • physical_addressMuthaiga Road, Off Thika Superhighway, Muthaiga, NAIROBI
        • contact_detailsTel: 020 720600 Nairobi. P. O. Box 42325 – 00100, NAIROBI, Kenya.
        • contact_personProf Jessie Githanga
        • site_capacity(null)
        • misc(null)
        • created2016-06-29 12:51:47
        • modified2016-07-20 12:55:52
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 1(array)
        • id408
        • application_id511
        • county_id47
        • site_nameKemri CRDR research center at Chandaria Health Centre Dagoretti
        • physical_addressKikuyu/Dagoretti Road, Dagoretti, Nairobi
        • contact_detailsP.O. Box: 43678, 00100 Nairobi GPO, Nairobi, Kenya. Tel 0790484654
        • contact_personDr Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2016-07-13 20:17:13
        • modified2016-07-20 12:55:52
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 2(array)
        • id409
        • application_id511
        • county_id41
        • site_nameClinical Research Annex at the Siaya County Referral Hospital
        • physical_addressHospital Road, Mulaha, (Within Siaya town) Township location, Karemo division, Siaya County. Siaya
        • contact_detailsP.O Box 144, Siaya 40600. TEL +254 724 278 886
        • contact_personDr Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2016-07-13 20:30:16
        • modified2016-07-20 12:55:52
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
      • 3(array)
        • id410
        • application_id511
        • county_id42
        • site_nameKondele Children’s Hospital, KEMRI – Centre for Clinical Research
        • physical_addressKondele Children\'s Hospital, Jaramogi Oginga Odinga Teaching and Referral Hospital grounds, Kisumu-Kakamega Road, Kisumu Town
        • contact_detailsTEL: Box 54-40100, Kisumu
        • contact_personDr Bernhards Ogutu
        • site_capacity(null)
        • misc(null)
        • created2016-07-13 20:51:31
        • modified2016-07-20 12:55:52
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
    • Sponsor(array)
      • 0(array)
        • id266
        • application_id511
        • sponsorAstraZeneka
        • sponsor_type(null)
        • contact_personLisa Harlin
        • addressAstraZeneca R&D Mölndal SE-431 83 Mölndal, Sweden
        • telephone_numberTel: +46 31 706 10 91
        • fax_number
        • cell_number+46 70 259 19 53
        • email_addresslisa.harlin@astrazeneca.com
        • created2016-06-29 12:51:47
        • modified2016-07-20 12:55:52
  • 2(array)
    • Application(array)
      • id508
      • user_id56
      • trial_status_id6
      • abstract_of_study<p>\n We will prospectively enroll up to 350 young women who choose to initiate PrEP at two clinical sites in Kenya. We will use wireless adherence monitoring to understand PrEP adherence behavior, as well as patterns of PrEP discontinuation (and re-initiation), in this cohort. We will randomize half of the women to SMS reminders to determine its impact on adherence. We will assess the technical function, acceptability, cost, and validity of the next generation Wisepill device coupled to SMS reminders, thus helping to determining the potential for this technology to assess and support PrEP adherence in future studies and potentially clinical care. Additionally, we will longitudinally assess HIV risk behaviors and perceptions using SMS in all women to determine how well risk for HIV infection is aligned with adherence (a concept called prevention-effective adherence). The study will involve a combination of quantitative and qualitative methods</p>\n
      • study_title<p>\n Next generation real-time monitoring for PrEP adherence in young adult women.</p>\n
      • laymans_summary<p>\n Real-time electronic monitoring is the optimal approach for understanding patterns of adherence, which is critical for determining if adherence to daily oral pre-exposure prophylaxis (PrEP) aligns with an individual’s risk for HIV acquisition. Compared with earlier adherence measurement devices, next generation Wisepill technology offers significant innovations in data storage and transmission reliability, cost, and usability and is ready for implementation in resource-limited settings. Coupling Wisepill monitoring to SMS adherence reminders has great potential to support adherence at the precise time it is needed. Real-time strategies may be particularly important for young women- a population in need of self-controlled HIV prevention strategies, but one that has previously struggled with PrEP adherence. Triangulating weekly SMS measurement of sexual behavior with adherence may explain how PrEP can be used most effectively for HIV prevention (i.e., prevention-effective adherence). This protocol describes a longitudinal study of young Kenyan women at high risk for HIV who will be offered PrEP for up to two years. Adherence will be monitored in all women with the next generation Wisepill; half will be randomized to receive SMS reminders. The technical function, acceptability, cost, and validity of the next generation Wisepill device coupled to SMS reminders will be determined among this cohort of young Kenyan women. Additionally, SMS will be used for longitudinal assessment of risk perception and its alignment with PrEP adherence.</p>\n
      • short_titleMonitoring Pre-Exposure Prophylaxis for Young Adult Women ( (MPYA)
      • protocol_noECCT/16/09/02
      • version_no2.0
      • date_of_protocol19-04-2016
      • study_drugTENOFOVIR/ EMTRICITABINE TABLETS (TRUVADA)
      • disease_conditionPrEP ADHEREENCE
      • 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_nameTRUVADA
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressaachoka@kemri-ucsf.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_letter1
      • applicant_statement1
      • applicant_participating_countries0
      • 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_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantProf. Elizabeth Bukusi. P.O BOX 614-40100 Kisumu
      • declaration_date128-06-2016
      • declaration_principal_investigatorProf. Elizabeth Bukusi. P.O BOX 614-40100 Kisumu
      • declaration_date228-06-2016
      • placebo_presentNo
      • study_objectives<p>\n Aim 1. Use the next generation Wisepill device in a cohort of young HIV-uninfected Kenyan women initiating PrEP to a) measure real-time adherence and b) determine the impact of SMS reminders on adherence. We will monitor adherence among all women with Wisepill. We will randomize half to receive daily SMS reminders with the option of switching to SMS reminders only as triggered by missed doses; the other half will receive no SMS reminders. There will be two primary outcomes for this aim. First, we will determine enacted adherence (i.e., pill taking) and persistence (i.e., continuation of PrEP over time) as determined by Wisepill from initiation of PrEP use (when adherence patterns are often established) through 24 months of use, comparing those randomized or not to SMS reminders. Second, we will compare dried blood spot (DBS) tenofovir-diphosphate levels between the two groups at multiple time points. With both outcomes, we will be assessing the synergy of SMS reminders coupled to real-time monitoring.</p>\n<p>\n Aim 2. Determine the technical function, acceptability, cost, and validity of the next generation Wisepill device coupled to SMS reminders. We will measure data transmission reliability, battery life, and other technical features through the two-year cohort study. We will assess acceptability and usability of our strategy via quantitative surveys in all women, as well as qualitative interviews in about 50 women. We will additionally assess costs and ease of use with a time and motion study. Using these cost estimates and adapting an existing mathematical model of HIV transmission, we will estimate the cost-effectiveness of Wisepill plus the SMS reminders per HIV case averted. Adherence validity will be determined by comparing the Wisepill data with DBS tenofovir levels as measured in Aim 1. Discrepancies between the two measures will be explored through qualitative interviews at the conclusion of the study.</p>\n<p>\n Aim 3. Triangulate Wisepill adherence data with weekly assessment of HIV risk behaviors and perceptions, to measure prevention-effective adherence. After the first 6 months of PrEP use (i.e., when initial decisions about PrEP may start to change), we will send all women a weekly SMS survey asking about recent sexual behavior, use of alternate HIV prevention tools, subjective HIV risk, and perception of their PrEP adherence. We will explore the overlap of perceptions and behaviors and PrEP adherence, through quantitative surveys in all women and qualitative interviews in about 50 women. Our goal is to measure dynamic changes in HIV risk and perception of risk or other motivators for HIV prevention that may lead to PrEP discontinuation (appropriately or inappropriately). We will use these SMS surveys to quantify prevention-effective adherence in young women at risk for HIV infection (individually and for the cohort overall).</p>\n
      • principal_inclusion_criteria<p>\n • Female • HIV-uninfected (as determined by Kenya national testing algorithms) • Age 18-24 years • Wanting to start PrEP with an initial recommendation of 6 months of use • Clinically safe to receive PrEP, in accordance with CDC guidelines:  Creatinine clearance >60 mL/min  Not infected with hepatitis B  No other medical condition that in the discretion of the site investigator would make participation unsafe or complicate the goals of the study • Sexually active (defined as vaginal or anal sex) within the last 3 months • At high risk for HIV infection based on a score of >5 [46] or being in an HIV serodiscordant relationship • Not pregnant • Owns a personal cell phone (not shared) compatible with the technology used in the study and the ability to charge it • Intending to stay in the area for at least the next year</p>\n
      • principal_exclusion_criteria<p>\n Exclusion • Unable to provide consent • Breast-feeding (Truvada is not currently approved for use during breast-feeding) • Concurrent participation in another research study that may influence adherence to PrEP and/or interfere with the procedures of this study.</p>\n
      • primary_end_points<p>\n We will assess the technical function, acceptability, cost, and validity of the next generation Wisepill device coupled to SMS reminders, thus helping to determining the potential for this technology to assess and support PrEP adherence in future studies and potentially clinical care. Additionally, we will longitudinally assess HIV risk behaviors and perceptions using SMS in all women to determine how well risk for HIV infection is aligned with adherence (a concept called prevention-effective adherence</p>\n
      • scope_diagnosis0
      • scope_prophylaxis1
      • scope_therapy0
      • scope_safety0
      • scope_efficacy0
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others1
      • scope_others_specifyAdherence monitoring
      • 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</p>\n<p>\n Co-Principal Investigators-1</p>\n<p>\n Study coordinator-1</p>\n<p>\n Research Assistants-2</p>\n<p>\n Laboratory technologist-1</p>\n<p>\n Pharmaceutical Technologist-1</p>\n<p>\n Receptionist-1</p>\n<p>\n Data manager-1</p>\n<p>\n  </p>\n
      • other_details_explanation<p>\n The trial will be conducted in two sites in Kenya</p>\n
      • other_details_regulatory_notapproved<p>\n NONE</p>\n
      • other_details_regulatory_approved<p>\n 1. PARTNERS HUMAN RESERACH COMMITTEE IRB</p>\n<p>\n 2. uNIVERSITY OF WASHINGTON IRB</p>\n
      • other_details_regulatory_rejected<p>\n NONE</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration24 Months
      • 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_countriesNo
      • multiple_member_states
      • number_of_sites2
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_site175
      • total_participants_worldwide350
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male0
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsNo
      • 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_nameJessica Haberer
      • investigator1_middle_name
      • investigator1_family_nameHaberer
      • investigator1_qualificationMD, MS
      • investigator1_professional_addressPartners Human Research Committer
      • investigator1_telephone116 Huntington Avenue,Suite 1002
      • investigator1_emailjhaberer@partners.org
      • organisations_transferred_No
      • number_participants350
      • notification
      • approval_date27-09-2016
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted18-05-2020
      • 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)
      • modified2020-08-19 18:59:29
      • created2016-06-28 13:19:16
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id332
        • application_id508
        • given_nameProf. Elizabeth Anne Bukusi
        • middle_name
        • family_nameBukusi
        • qualificationBachelor of Medicine and Bachelor of surgery/Masters of Medicine in Obstetrics and Gynecology
        • professional_addressP.O BOX 614 -40100 KISUMU
        • telephone(254) (020) 2722541 (Nairobi) 254 57 2021036
        • emailebukusi@kemri.org
        • created2016-06-28 13:57:51
        • modified2020-05-18 18:53:29
      • 1(array)
        • id333
        • application_id508
        • given_nameDr. Stella Njuguna
        • middle_name
        • family_nameNjuguna
        • qualificationB.Pharm/ MPH
        • professional_addressP.O BOX 614 -40100 KISUMU
        • telephone+254 722422977
        • emailnjugunastella@gmail.com
        • created2016-06-28 14:04:29
        • modified2020-05-18 18:53:29
    • SiteDetail(array)
      • 0(array)
        • id396
        • application_id508
        • county_id42
        • site_nameKISUMU SITE
        • physical_addressAGOI STREET
        • contact_detailsP.O Box 614-40100 KISUMU
        • contact_personDr. Stella Njuguna
        • site_capacity(null)
        • misc(null)
        • created2016-06-28 13:57:51
        • modified2020-05-18 18:53:29
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
    • Sponsor(array)
      • 0(array)
        • id264
        • application_id508
        • sponsorUniversity of Washington
        • sponsor_typeOthers
        • contact_personJared Beaten
        • addressP.O BOX 359470
        • telephone_number206-543-0098
        • fax_number206-543-9218
        • cell_number206-520-3831
        • email_addressCWSCOV@UW.edu
        • created2016-06-28 13:57:51
        • modified2020-05-18 18:53:29
  • 3(array)
    • Application(array)
      • id505
      • user_id613
      • trial_status_id1
      • abstract_of_study<p style=\"margin-left:.5in;\">\n The ability of the HIV virus to establish latency in the infected individual is a major obstacle to curing the infection. HIV latency in long lived cells, particularly resting memory CD4+ T cells, promotes viral quiescence, which renders latently infected CD4+ memory cells non-susceptible to antiretroviral drugs or HIV-specific immunity. A case of prolonged HIV remission was reported in a child who was treated with three drug ART by 31 hours of life for high-risk HIV-exposure from untreated maternal infection. Longitudinal follow-up revealed eventual return of viremia at 46 months of age after being off ART for nearly 2.3 years. The re-emergence of viremia in this child provides further support that viral remission is achievable in perinatal infection through time-limited very early ART, although the exact timing of ART initiation and duration of ART required to achieve cure is unknown and will be studied in P1115. This study (P1115) will address the hypothesis that very early therapy in HIV-infected neonates substantially limits the establishment of HIV reservoirs to permit long-term control of HIV replication off ART, leading to HIV remission. This protocol is designed to focus on the effect of starting ART within the first 48 hours of life on likelihood of achieving HIV remission in <em>in utero </em>infection. The primary objective is to assess HIV remission among HIV-infected neonates who initiate ART within 48 hours of birth. Infants and their mothers will be enrolled in two cohorts; Cohort 1 being infants≤ 48 hours of age at high risk for HIV infection (i.e. born to a mother with confirmed or presumed HIV infection and mother did not receive ARVs during the current pregnancy or mother first identified as HIV-infected in labor or postpartum). Cohort 2 will be infants ≤ 10 days of age who are HIV-infected and ART-started within the first 48 hours of life. The study consists of four steps: Step 1 (evaluation and initial treatment of high-risk infants), Step 2 (management of subjects with confirmed HIV infection), HIV-infected infants who meet defined eligibility criteria will undergo ART cessation at or after Step 2 Week 96 <strong>will enter Step 3 and undergo ART cessation, as per protocol defined criteria, </strong>and remain off ART unless there is a confirmed HIV RNA rebound to ≥ LOD.  After step 3, participants who develop viral rebound <strong>or meet other Step 4 inclusion criteria </strong>will enter  Step 4 (ART re-initiation for those with confirmed viral rebound at step 3).</p>\n<p>\n  </p>\n
      • study_title<p>\n Very Early Intensive Treatment of HIV-Infected Infants to Achieve HIV Remission: A Phase I/II Proof of Concept Study</p>\n
      • laymans_summary<p>\n The main purpose of this study is to find out if starting anti-HIV medicines (ARVs) within 48 hours of birth can make it possible for babies who are infected with HIV to control HIV so well that HIV cannot be detected in their blood. As of now, when children with HIV start taking ARVs, they usually need to keep taking them for life. For newborn babies who start ARVs very soon after birth, it might be possible to later stop taking ARVs for a prolonged period of time and still stay healthy.  This has only been seen in one baby so far. That child started ARVs soon after birth, then stopped ARVs, and was able to stay healthy, with no HIV detected in the blood, for more than two years.  About 27 months after stopping ARVs, HIV was detected in this child’s blood and the child restarted ARVs.  The amount of HIV in the child’s blood quickly dropped and the child has remained healthy.  This study is being done to find out if this can be seen in other babies who start ARVs very soon after birth.  This study is also looking at the levels of ARVs that are safe and work well for babies this young.</p>\n<p>\n Kericho site plan to enroll upto 60 mothers and their infants into this study.</p>\n<p>\n  </p>\n
      • short_titleP1115
      • protocol_noECCT/16/06/01
      • version_noVersion 1.0
      • date_of_protocol12-03-2014
      • study_drugNevirapine, Lopinavir/r, Abacavir, Zidovudine
      • disease_conditionHIV
      • 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_nameAnti Retrovirals
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressjosphat.kosgei@usamru-k.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_letter1
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum1
      • 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_african0
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantDr Josphat Kosgei
      • declaration_date123-06-2016
      • declaration_principal_investigatorDr Fredrick Sawe
      • declaration_date223-06-2016
      • placebo_presentNo
      • study_objectives<div>\n Primary Objective</div>\n<div>\n 2.1.1 To assess HIV remission among neonates with in utero HIV infection who initiate early intensive therapy within 48 hours of birth. HIV remission is defined as having no confirmed plasma HIV-1 RNA ≥ LOD through 48 weeks of ART cessation.</div>\n<div>\n 2.2 Secondary Objectives</div>\n<div>\n 2.2.1 To assess the safety and tolerability of early intensive therapy regimens in neonates and young infants.</div>\n<div>\n 2.2.2 To assess, by regimen (Regimen 1L separately from Regimens 2R+2RV combined), the proportion of infants receiving early intensive therapy who achieve viral suppression (plasma HIV-1 RNA <lod) at=\"\" div=\"\" week=\"\">\n <div>\n 2.2.3 To assess, by regimen (Regimen 1L separately from Regimens 2R+2RV combined), the proportion of infants receiving early intensive therapy who meet virologic and immunologic criteria for treatment cessation.</div>\n <div>\n 2.2.4 To assess, by regimen (Regimen 1L separately from Regimens 2R+2RV combined), the relationship between time to achieve confirmed viral suppression (plasma HIV-1 RNA < LOD) and meeting the virologic and immunologic criteria for treatment cessation.</div>\n <div>\n 2.2.5 To assess the extent of HIV persistence in infants who achieve HIV remission.</div>\n <div>\n 2.2.6 To evaluate immune activation and host and viral determinants, including maternal factors and HIV-specific immune responses, associated with HIV remission.</div>\n <div>\n 2.2.7 To assess biomarkers of HIV reservoir size among infants receiving early intensive therapy (including but not limited to proviral HIV DNA load and HIV serostatus).</div>\n <div>\n 2.2.8 To assess resistance to ARVs included in the study regimens and to VRC01.</div>\n <div>\n 2.2.9 To describe RAL and VRC01 exposures in neonates and young infants.</div>\n </lod)></div>\n
      • principal_inclusion_criteria<p>\n Stipulated on pages 27-31 of the main protocol.</p>\n
      • principal_exclusion_criteria<p>\n Stipulated on page 31 of the main protocol.</p>\n
      • primary_end_points<p>\n Section 8.226 of the Main Protocol attached, page 56.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy0
      • scope_pharmacokinetic1
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology1
      • trial_administration_humans0
      • trial_bioequivalence_study1
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<p>\n The site capacity is detailed in the attached SSA page 19-20.</p>\n
      • other_details_explanation<p>\n Not Applicable.</p>\n
      • other_details_regulatory_notapproved<p>\n None.</p>\n
      • other_details_regulatory_approved<p>\n KEMRI SERU. Date: 03 Aug 2015.</p>\n
      • other_details_regulatory_rejected<p>\n None.</p>\n
      • other_details_regulatory_halted<p>\n None.</p>\n
      • estimated_duration9 years
      • 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_stateYes
      • location_of_areaKEMRI WALTER REED PROJECT KERICHO
      • single_site_physical_addressOFF HOSPITAL ROAD
      • single_site_contact_personDR JOSPHAT KOSGEI
      • single_site_telephone0729 110 122
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states13
      • number_of_sites
      • multi_country_listKenya, USA, Malawi, Uganda, Thailand, India, Argentina, Brazil, South Africa, Zambia, Zimbabwe, Tanzania, Mozambique.
      • data_monitoring_committeeYes
      • total_enrolment_per_site60
      • total_participants_worldwide472
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornYes
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18No
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsNo
      • 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_nameDavid
      • investigator1_middle_name
      • investigator1_family_nameWekulo
      • investigator1_qualificationBSc Nursing
      • investigator1_professional_addressKEMRI Walter Reed Project Kericho
      • investigator1_telephone0729 110 146
      • investigator1_emaildavid.wekulo@usamru-k.org
      • organisations_transferred_No
      • number_participants60
      • notification
      • approval_date25-07-2016
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted27-05-2020
      • 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)
      • modified2025-03-27 11:57:33
      • created2016-06-20 09:06:19
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id331
        • application_id505
        • given_nameFredrick
        • middle_name
        • family_nameSawe
        • qualificationMBChB, MMED
        • professional_addressKEMRI Walter Reed Project Kericho
        • telephone0703 247 902
        • emailfredrick.sawe@usamru-k.org
        • created2016-06-20 09:12:58
        • modified2020-05-27 12:22:44
    • SiteDetail(array)
      • 0(array)
        • id395
        • application_id505
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2016-06-20 09:12:58
        • modified2020-05-27 12:22:44
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id263
        • application_id505
        • sponsorThe US National Institute of Allergy and Infectious Diseases (NIAID)
        • sponsor_typeResearch Institution
        • contact_personYvonne Bryson, M.D.
        • address10833 Le Conte Ave. MDCC 22-442 Los Angeles, CA 90095-1752
        • telephone_numberPhone: 310-825-5235
        • fax_number
        • cell_numberPhone: 310-825-5235
        • email_addressybryson@mednet.ucla.edu
        • created2016-06-20 09:12:58
        • modified2020-05-27 12:22:44
  • 4(array)
    • Application(array)
      • id504
      • user_id63
      • trial_status_id3
      • abstract_of_study<p style=\"margin-left: 0.25in;\">\n The study titled “A Randomized Comparison of <strong>two</strong> Regimens of Chemotherapy with Compatible Antiretroviral Therapy for Treatment of Advanced AIDS-KS in Resource-Limited Settings” is a phase III, open-label, prospective, <strong>2-arm</strong> randomized study stratified by CD4+ lymphocyte cell count and by country. This study will estimate the difference in event (KS progression, death, entry into an additional step, or loss to follow-up, prior to week 48) rates between two “experimental” regimens (ART initiation + BV   which are considered standard of care therapies in resource limited settings) and an active control (ART initiation + Paclitaxel - PTX: a standard treatment in the United States that is sometimes used as salvage therapy for relapsed/refractory KS in resource-limited settings) for the treatment of HIV-infected, ART-naive participants presenting with advanced KS.</p>\n<p style=\"margin-left: 0.25in;\">\n The target population includes males and females ³ 18 years of age with the following characteristics: documentation of HIV-1 infection, biopsy diagnostic of KS, current advanced  KS ( T1 stage KS), systemic chemotherapy for KS and radiation treatment naïve, and currently not receiving ART. A total of 706 participants, ≥18 years of age will be enrolled across all sites. Randomization will be stratified by screening peripheral blood CD4+ lymphocyte cell count (< 100 or  ³ 100 cells/mm³) and ART history (naïve or experienced). At study entry participants will be randomized in 1:1 fashion to one of the following <strong>2</strong> <strong>arms</strong> in Step 1: , arm 1B, co-formulated EFV/FTC/TDF with blemomycin/Vincristine(BV) and Arm 1C, Co-formulated EFV/FTC/TDF with PTX . In Step 2, at the discretion of the site investigator, after confirmation of disease progression by the IERC (Independent Endpoint Review Committee), participants who experience KS progression will receive second course of chemotherapy utilized in Step 1 (up to 6 cycles)  co-formulated EFV/FTC/TDF. In step 3, participants will receive randomly assigned chemotherapy co-formulated with EFV/FTC/TDF. In Step 4, following Clinical Management Committee (CMC) and IERC-confirmed KS progression on Step 3, or if there is dose-limiting toxicity after receiving less than 4 cycles of chemotherapy in Step 3, in the absence of a complete response (CR) or partial response (PR), participants will be assigned to the remaining study-provided chemotherapy not given in Step 1, Step 2, or Step 3. All participants will be followed for 5 years after randomization or assignment to the last step they enter.</p>\n<p style=\"margin-left: 0.25in;\">\n The primary endpoint incorporates lack of KS progression, death, entry into an additional step, or loss to follow-up<strong>, prior to week 48</strong>. The main interest of the study is the outcome at 48 weeks after the treatment initiation. The primary analyses will consist of the construction in the proportion of 48-week event rates between each experimental regimen and the active control (ART initiation with <strong>PTX</strong>).  </p>\n
      • study_title<p style=\"margin-left:.25in;\">\n <strong> A Randomized Comparison of Three Regimens of Chemotherapy with Compatible Antiretroviral Therapy for Treatment of Advanced AIDS-KS in Resource-Limited Settings</strong></p>\n
      • laymans_summary(null)
      • short_titleA5263: A Randomized Comparison of Three Regimens of Chemotherapy with Compatible Antiretroviral Therapy for Treatment of Advanced AIDS-KS in Resource-Limited Settings
      • protocol_noECCT/16/06/02
      • version_no2.0
      • date_of_protocol07-08-2012
      • study_drugPaclitaxel, Bleomycin,Vincristine and Etoposide
      • disease_conditionAdvanced AIDS-KS
      • 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_namePaclitaxel, Bleomycin,Vincristine and Etoposide
      • product_type_medical_device_name
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressEokeyo@kemricdc.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
      • 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)
      • applicant_signed_checklist(null)
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantDr.Vincent Oliver otieno
      • declaration_date121-06-2016
      • declaration_principal_investigatorDr.Vincent Oliver otieno
      • declaration_date221-06-2016
      • placebo_presentNo
      • study_objectives(null)
      • principal_inclusion_criteria<p>\n  Inclusion Criteria Step 1</p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n a.         HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load.</p>\n<p>\n  </p>\n<p style=\"margin-left:1.45in;\">\n  </p>\n<p style=\"margin-left:1.0in;\">\n b.         Biopsy diagnostic of KS at any time prior to study entry.</p>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<p style=\"margin-left:.5in;\">\n c.         Current KS stage T1 using ACTG criteria [29].</p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n KS stage T1 is KS with any of the following:</p>\n<p style=\"margin-left:1.75in;\">\n ·         symptomatic tumor-associated edema</p>\n<p style=\"margin-left:1.75in;\">\n ·         tumor ulceration</p>\n<p style=\"margin-left:1.75in;\">\n ·         extensive oral KS (other than flat KS confined to the hard palate)</p>\n<p style=\"margin-left:1.75in;\">\n ·         gastrointestinal KS</p>\n<p style=\"margin-left:1.75in;\">\n ·         KS in any other non-nodal visceral organ (e.g., lung)</p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:1.25in;\">\n d.          A minimum of five indicator KS cutaneous marker lesions plus an additional two lesions greater or equal to 4x4 mm that are accessible for punch biopsy.</p>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n e.         CD4+ lymphocyte cell count obtained within 28 days prior to study entry at a DAIDS-approved laboratory.</p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n f.          The following laboratory values obtained within 14 days prior to study entry:</p>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<p style=\"margin-left:1.75in;\">\n ·         Absolute neutrophil count (ANC) ³1000 cells/mm³</p>\n<p style=\"margin-left:1.75in;\">\n ·         Hemoglobin ³9 g/dL</p>\n<p style=\"margin-left:1.75in;\">\n ·         Platelet count ³100,000/mm³</p>\n<p style=\"margin-left:1.75in;\">\n ·         Estimated creatinine clearance of ≥60 mL/min using the formula:</p>\n<p>\n CrCl  = {[140 - age(yr)]x [weight(kg)]}÷ [72 x serum Cr(mg/dL)] (multiply the result x 0.85 for female participants)</p>\n<p>\n NOTE:  The Cockroft-Gault calculation program can be found on DMC website (<a href=\"http://www.fstrf.org/ACTG/index.html\">http://www.fstrf.org/ACTG/index.html</a>  </p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.75in;\">\n ·         AST (SGOT), ALT (SGPT), and alkaline phosphatase <5 ´ ULN</p>\n<p style=\"margin-left:1.75in;\">\n ·         Total bilirubin of <1.5 X ULN</p>\n<p>\n  </p>\n<p style=\"margin-left:1.5in;\">\n g.          Female study volunteers of reproductive potential (defined as girls who have reached menarche, women who have not been post-menopausal for at least 24 consecutive months, i.e., who have had menses within the preceding 24 months, or women who have not undergone surgical sterilization, specifically hysterectomy and/or bilateral oophorectomy) must have a negative serum or urine pregnancy <strong>test with a sensitivity of 15-25 mIU/mL </strong>performed within 48 hours before initiating the protocol-specified medications.  </p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n h.         All participants must agree <u>not</u> to participate in a conception process (active attempt to become pregnant or to impregnate, donate sperm, in vitro fertilization).</p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n i.          If participating in sexual activity that could lead to pregnancy, the study volunteer must agree that two reliable forms of contraceptives will be used simultaneously while receiving protocol-specified medications, and for <strong>12</strong> weeks after stopping the medications.</p>\n<p style=\"margin-left:1.45in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n Study volunteers who are not of reproductive potential (women who have been post-menopausal for at least 24 consecutive months or have undergone hysterectomy and/or bilateral oophorectomy or men who have documented azoospermia) are eligible without the use of contraceptives. (Main protocol page 113).</p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n j.          Men and women age ³18 years.</p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n k.         Ability to swallow oral medications and adequate venous access.</p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n l.          Karnofsky performance status ≥60 within 28 days prior to entry.</p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n m.        Ability and willingness of participant or legal guardian/representative to provide informed consent.</p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p>\n      <strong>Inclusion Criteria Step 2 </strong></p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n a.         Complete or partial response to the chemotherapy regimen used in <strong>S</strong>tep 1.</p>\n<p style=\"margin-left:1.5in;\">\n b.         KS progression at a time point greater than 12 weeks after the last dose of Step 1 chemotherapy.</p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n c.         Less than 72 weeks after Step 1 entry.</p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n d.         The following laboratory values obtained within 14 days prior to Step 2 entry:</p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:1.75in;\">\n ·         ANC ≥1,000 cells/mm³</p>\n<p style=\"margin-left:1.75in;\">\n ·         Hemoglobin ≥9.0 g/dL</p>\n<p style=\"margin-left:1.75in;\">\n ·         Platelet count ≥100,000/mm³</p>\n<p style=\"margin-left:1.75in;\">\n ·         Estimated creatinine clearance of ≥60 mL/min using the formula: </p>\n<p style=\"margin-left:95.0pt;\">\n  CrCl  = {[140 - age(yr)]x [weight(kg)]}÷ [72 x serum Cr(mg/dL)] (multiply the result x 0.85 for female participants)</p>\n<p style=\"margin-left:95.0pt;\">\n NOTE:  The Cockroft-Gault calculation program can be found on DMC website (<a href=\"http://www.fstrf.org/ACTG/index.html\">http://www.fstrf.org/ACTG/index.html</a></p>\n<p>\n  </p>\n<p style=\"margin-left:1.75in;\">\n ·         AST (SGOT), ALT (SGPT), and alkaline phosphatase <5 ULN</p>\n<p style=\"margin-left:1.75in;\">\n ·         Total bilirubin of <u><</u>1.5 X ULN</p>\n<p>\n  </p>\n<p style=\"margin-left:1.5in;\">\n e.         For females of reproductive potential, negative serum or urine pregnancy test within 7 days prior to Step 2 entry. <strong>The urine test must have a sensitivity of 15-25 mIU/mL.</strong></p>\n<p>\n  </p>\n<p style=\"margin-left:1.5in;\">\n f.          Karnofsky performance status ≥ 50 within 28 days prior to Step 2.</p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n g.         All participants must agree not to participate in a conception process (active attempt to become pregnant or to impregnate, donate sperm, in vitro fertilization).</p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p>\n    Inclusion Criteria Step 3</p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n a.         Inability to continue on Step 1 or Step 2 due to KS progression OR lack of a CR or PR after receiving less than 4 cycles of chemotherapy in Step 1 or Step 2 because of the development of dose-limiting toxicity.</p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n b.         Less than 72 weeks after Step 1 entry.</p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n c.         The following laboratory values obtained within 14 days prior to Step 3 entry:</p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:1.75in;\">\n ·         ANC ≥1,000 cells/mm³</p>\n<p style=\"margin-left:1.75in;\">\n ·         Hemoglobin ≥9.0 g/dL</p>\n<p style=\"margin-left:1.75in;\">\n ·         Platelet count ≥100,000/mm³</p>\n<p style=\"margin-left:1.75in;\">\n ·         Estimated creatinine clearance of ≥ 60 mL/min using the formula:  </p>\n<p style=\"margin-left:1.25in;\">\n CrCl  = {[140 - age(yr)]x [weight(kg)]}÷ [72 x serum Cr(mg/dL)]</p>\n<p style=\"margin-left:1.25in;\">\n  (multiply the result x 0.85 for female participants)</p>\n<p>\n                       NOTE:  The Cockroft-Gault calculation program can be found on DMC website (<a href=\"http://www.fstrf.org/ACTG/index.html\">http://www.fstrf.org/ACTG/index.html</a></p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:1.75in;\">\n ·         AST (SGOT), ALT (SGPT), and alkaline phosphatase <5 ULN</p>\n<p style=\"margin-left:1.75in;\">\n ·         Total bilirubin of <u><</u>1.5 X ULN</p>\n<p>\n  </p>\n<p style=\"margin-left:1.5in;\">\n d.         For females of reproductive potential, negative serum or urine pregnancy test within 7 days prior to Step 3 entry. <strong>The urine test must have a sensitivity of 15-25 mIU/mL.</strong></p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:.5in;\">\n e.         Karnofsky performance status ≥ 50 within 28 days prior to Step 3 entry.</p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n f.          All participants must agree not to participate in a conception process (active attempt to become pregnant or to impregnate, donate sperm, in vitro fertilization).</p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p>\n  Inclusion Criteria Step 4</p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n a.         Inability to continue on Step 3 due to KS progression OR lack of a CR or PR after receiving fewer than 4 cycles of chemotherapy in Step 3 because of the development of dose-limiting toxicity.</p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n b.         Less than 72 weeks after Step 1 entry.</p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n c.         The following laboratory values obtained within 14 days prior to Step 4 entry:</p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:1.75in;\">\n ·         ANC ≥1,000 cells/mm³.</p>\n<p style=\"margin-left:1.75in;\">\n ·         Hemoglobin ≥9.0 g/dL.</p>\n<p style=\"margin-left:1.75in;\">\n ·         Platelet count ≥100,000/mm³.</p>\n<p style=\"margin-left:1.75in;\">\n ·         Estimated creatinine clearance of ≥ 60 mL/min using the formula:</p>\n<p style=\"margin-left:95.0pt;\">\n  CrCl  = {[140 - age(yr)]x [weight(kg)]}÷ [72 x serum Cr(mg/dL)] (multiply the result x 0.85 for female participants)</p>\n<p style=\"margin-left:95.0pt;\">\n NOTE:  The Cockroft-Gault calculation program can be found on DMC website (<a href=\"http://www.fstrf.org/ACTG/index.html\">http://www.fstrf.org/ACTG/index.html</a></p>\n<p>\n  </p>\n<p style=\"margin-left:1.75in;\">\n ·         AST (SGOT), ALT (SGPT), and alkaline phosphatase <5 ULN.</p>\n<p style=\"margin-left:1.75in;\">\n ·         Total bilirubin of <u><</u>1.5 X ULN.</p>\n<p>\n  </p>\n<p style=\"margin-left:1.5in;\">\n d.         For females of reproductive potential, negative serum or urine pregnancy test within 7 days prior to Step 4 entry. <strong>The urine test must have a sensitivity of 15-25 mIU/mL.</strong></p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:.5in;\">\n e.         Karnofsky performance status ≥ 50 within 28 days prior to Step 4 entry.</p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n f.          All participants must agree not to participate in a conception process (active attempt to become pregnant or to impregnate, donate sperm, in vitro fertilization).</p>\n
      • principal_exclusion_criteria<p>\n  </p>\n<p>\n       Exclusion Criteria step 1</p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n a.         Current chronic, acute, or recurrent infections that are serious, in the opinion of the site investigator, for which the participant has not completed at least 14 days of therapy prior to study entry and/or is not clinically stable.  </p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n b.         Serious illness requiring systemic treatment and/or hospitalization within 14 days prior to entry.</p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n c.         Current or history of known pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), emphysema, bronchiectasis, or diffuse or significant local radiographic interstitial infiltrates on chest x-ray (CXR) or computed axial tomography (CAT), that in the opinion of the investigator would exclude bleomycin use.</p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:.5in;\">\n             d.       Oxygen saturation less than 90% and/or exercise desaturation greater than 4% within 14 days prior to study enrollment. </p>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n NOTE:  Exercise is defined as any activity that will increase a participant’s resting heart rate by at least 20 beats/minute.</p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:.5in;\">\n e.         Grade ≥3 peripheral neuropathy (PN) at entry.</p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n NOTE:  Severity of PN will be determined by the symptom severity scores from the Brief Peripheral Neuropathy Screen (BPNS), discussed in section 6.3.2<strong>0</strong>. </p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:.5in;\">\n f.          Breastfeeding.</p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n g.         Receipt of ART for more than 28 days immediately prior to entry. ART is allowed within the 28-day window prior to study entry.</p>\n<p style=\"margin-left:.75in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n NOTE:  The use of single-dose nevirapine (NVP) or zidovudine (ZDV) for any period of time during pregnancy to prevent mother to child transmission (MTCT) of HIV is allowed.</p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n NOTE:  Successful post-exposure prophylaxis is allowed. Unsuccessful post-exposure prophylaxis is not allowed.</p>\n<p style=\"margin-left:.75in;\">\n  </p>\n<p style=\"margin-left:.75in;\">\n h.         Prior or current systemic or locally administered chemotherapy.</p>\n<p style=\"margin-left:.75in;\">\n  </p>\n<p style=\"margin-left:.75in;\">\n i.          Prior or current radiation therapy.</p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n j.          Prior or current immunotherapy, e.g., interferon alfa.</p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n k.         Corticosteroid use at doses above those given as replacement therapy for adrenal insufficiency within the last 30 days prior to study entry. A tapering course of corticosteroids as acute therapy for <em>Pneumocystis carinii</em> pneumonia (PCP) or other conditions is an exception and is allowed.</p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n l.          Any immunomodulator, HIV vaccine, live attenuated vaccines, or other investigational therapy or investigational vaccine within 30 days prior to study entry.</p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n m         Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation.</p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n n          Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.</p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n o.         Current or anticipated receipt of any of the prohibited medications listed in section 5.5.2.of the main protocol</p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n p.         In the opinion of the investigator, any psychological or social condition, or addictive disorder that would preclude compliance with the protocol.</p>\n<p>\n Exclusion Criteria Step 2</p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n a.         Current chronic, acute, or recurrent infections that are serious, in the opinion of the site investigator, for which the participant has not completed at least 14 days of therapy prior to Step 2 entry and/or is not clinically stable. </p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n b.         Severe toxicity to the chemotherapy regimen used in Step 1 requiring discontinuation of study chemotherapy.</p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n c.         Serious illness, other than progressive KS, requiring systemic treatment and/or hospitalization within 14 days prior to Step 2 entry.</p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n d.         For patients who have not received bleomycin in Step 1:</p>\n<p style=\"margin-left:110.25pt;\">\n  </p>\n<p style=\"margin-left:1.75in;\">\n ·         Development of pulmonary fibrosis, COPD, emphysema, bronchiectasis, and diffuse or significant local radiographic interstitial infiltrates on CXR or CT scan that in the opinion of the site investigator would exclude bleomycin use.</p>\n<p style=\"margin-left:1.75in;\">\n ·         Patients with an abnormal CXR or CT scan (which may indicate pulmonary KS) should undergo screening evaluations to rule out an infectious cause, per standard of care. If available, other diagnostic procedures such as bronchoscopy should be considered to confirm the presence or absence of pulmonary KS and/or an infectious agent. These procedures should be completed outside the study. These participants should be excluded if, in the opinion of the investigator, use of bleomycin in Step 2 would be detrimental.</p>\n<p style=\"margin-left:1.75in;\">\n ·         Oxygen saturation less than 90% or exercise desaturation greater than 4% within the last 30 days prior to Step 2 entry. </p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.25in;\">\n d.    For patients who received vincristine or <strong>PTX</strong> in Step 1, Grade ≥3 PN at Step 2 entry. </p>\n<p style=\"margin-left:1.25in;\">\n NOTE: Severity of PN will be determined by the symptom severity scores from the BPNS, discussed in section 6.3.20 of the main protocol</p>\n<p style=\"margin-left:1.25in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:.5in;\">\n f.          Breastfeeding.</p>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n g.         Other concurrent chemotherapy, immunotherapy, or radiotherapy.</p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n h.         Systemic corticosteroid use at doses above those given as replacement therapy for adrenal insufficiency within 30 days of Step 2 entry.</p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n NOTE:  A tapering course of corticosteroids as acute therapy for PCP or if required for management of IRIS is an exception.</p>\n<p>\n Exclusion Criteria Step 3</p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n a.         Current chronic, acute, or recurrent infections that are serious, in the opinion of the site investigator, for which the participant has not completed at least 14 days of therapy prior to Step 3 entry and/or is not clinically stable. </p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n b.         Serious illness, other than progressive KS, requiring systemic treatment and/or hospitalization within 14 days prior to Step 3 entry.</p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n c.         For patients who did NOT receive bleomycin in Step 1 or Step 2:</p>\n<p style=\"margin-left:110.25pt;\">\n  </p>\n<p style=\"margin-left:1.75in;\">\n ·         Development of pulmonary fibrosis, COPD, emphysema, bronchiectasis, and diffuse or significant local radiographic interstitial infiltrates on CXR or CT scan that in the opinion of the site investigator would exclude bleomycin use.</p>\n<p style=\"margin-left:1.75in;\">\n ·         Patients with an abnormal CXR or CT scan (which may indicate pulmonary KS) should undergo screening evaluations to rule out an infectious cause, per standard of care. If available, other diagnostic procedures such as bronchoscopy should be considered to confirm the presence or absence of pulmonary KS and/or an infectious agent. These procedures should be completed outside the study. These participants should be excluded if, in the opinion of the investigator, use of bleomycin in Step 3 would be detrimental.</p>\n<p style=\"margin-left:1.75in;\">\n ·         Oxygen saturation less than 90% or exercise desaturation greater than 4% within the last 30 days prior to Step 3 entry. </p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.25in;\">\n e.    For participants who did NOT receive vincristine or <strong>PTX</strong> in Step 1 or Step 2, Grade ≥3 PN at Step 3 entry. </p>\n<p style=\"margin-left:58.0pt;\">\n NOTE: Severity of PN will be determined by the symptom severity scores from the BPNS, discussed in section 6.3.20 of the main protocol</p>\n<p>\n  </p>\n<p>\n  </p>\n<p style=\"margin-left:1.25in;\">\n f.     Breastfeeding.</p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:1.25in;\">\n g.    Other concurrent chemotherapy, immunotherapy, or radiotherapy.</p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:1.25in;\">\n h.    Systemic corticosteroid use at doses above those given as replacement therapy for adrenal insufficiency within 30 days of Step 3 entry.</p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n NOTE:  A tapering course of corticosteroids as acute therapy for PCP or if required for management of IRIS is an exception.</p>\n<p>\n Exclusion Criteria Step 4</p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n a.         Current chronic, acute, or recurrent infections that are serious, in the opinion of the site investigator, for which the participant has not completed at least 14 days of therapy prior to Step 4 entry and/or is not clinically stable. </p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n b.         Serious illness, other than progressive KS, requiring systemic treatment and/or hospitalization within 14 days prior to Step 4 entry.</p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n c.         For patients who did NOT receive bleomycin in Step 1, Step 2, or Step 3:</p>\n<p style=\"margin-left:110.25pt;\">\n  </p>\n<p style=\"margin-left:1.75in;\">\n ·         Development of pulmonary fibrosis, COPD, emphysema, bronchiectasis, and diffuse or significant local radiographic interstitial infiltrates on CXR or CT scan that in the opinion of the site investigator would exclude bleomycin use.</p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.75in;\">\n ·         Patients with an abnormal CXR or CT scan (which may indicate pulmonary KS) should undergo screening evaluations to rule out an infectious cause, per standard of care. If available, other diagnostic procedures such as bronchoscopy should be considered to confirm the presence or absence of pulmonary KS and/or an infectious agent. These procedures should be completed outside the study. These participants should be excluded if, in the opinion of the investigator, use of bleomycin in Step 4 would be detrimental.</p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:1.75in;\">\n ·         Oxygen saturation less than 90% or exercise desaturation greater than 4% within the last 30 days prior to Step 4 entry. </p>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<p style=\"margin-left:1.75in;\">\n NOTE: Exercise is defined as any activity that will increase a participant’s resting heart rate by20 beats/minute.</p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n d.         For participants who did NOT receive vincristine or <strong>PTX</strong> in Step 1, Step 2, or Step 3:</p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.75in;\">\n ·         Grade ≥3 PN at Step 4 entry. </p>\n<p style=\"margin-left:1.25in;\">\n NOTE: Severity of PN will be determined by the symptom severity scores from the BPNS, discussed in section 6.3.20 of the main protocol</p>\n<p>\n  </p>\n<p>\n  </p>\n<p style=\"margin-left:.5in;\">\n e.         Breastfeeding.</p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n f.          Other concurrent chemotherapy, immunotherapy, or radiotherapy.</p>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n g.         Systemic corticosteroid use at doses above those given as replacement therapy for adrenal insufficiency within 30 days of Step 4 entry.</p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p>\n NOTE:  A tapering course of corticosteroids as acute therapy for PCP or if required for management of IRIS is an exception</p>\n
      • primary_end_points<div>\n PFS defined as a lack of KS progression, death, entry into an additional step, or</div>\n<div>\n loss to follow-up, prior to week 48.</div>\n
      • scope_diagnosis1
      • scope_prophylaxis0
      • scope_therapy1
      • 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_controlledNo
      • site_capacity(null)
      • staff_numbers<p>\n 1. Dr. Kevin Cain MD </p>\n<p>\n 2. Dr. Vincent Oliver Otieno MBcHB, MPH</p>\n<p>\n 3. Dr. Joan Cain MD, Oncology</p>\n<p>\n 3. Dr. Elisha Okeyo MBcHB</p>\n<p>\n 4. John Okanda BSc, Nutrition</p>\n<p>\n  </p>\n<p>\n  </p>\n
      • other_details_explanation<p>\n The study is designed for resource limited settings, a criteria that does not fit the host/sponsors country.</p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n KEMRI Scientific and Ethics Review Unit, 26 May 2016.</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_durationFive years
      • 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_states6
      • number_of_sites3
      • multi_country_listKenya, Uganda, South Africa, Malawi, Peru and Zimbabwe
      • data_monitoring_committeeYes
      • total_enrolment_per_siteNone
      • total_participants_worldwide706
      • 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_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenYes
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
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      • subjects_others_specify
      • investigator1_given_nameVincent
      • investigator1_middle_nameOliver
      • investigator1_family_nameOtieno
      • investigator1_qualificationMD
      • investigator1_professional_addressP.O BOX 1578-40100 Kisumu
      • investigator1_telephone+254720798294
      • investigator1_emailvoliver@kemricdc.org
      • organisations_transferred_Yes
      • number_participants50
      • notification
      • approval_date28-07-2016
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted27-06-2016
      • is_child0
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      • initial_date_submitted(null)
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      • admin_stopped_reason(null)
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      • modified2018-05-08 15:58:07
      • created2016-06-17 13:22:29
      • total_sites(null)
      • ecitizen_invoice(null)
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        • application_id504
        • given_nameVincent
        • middle_nameOliver
        • family_nameOtieno
        • qualificationMD
        • professional_addressP.O BOX 1578-40100 Kisumu
        • telephone+254 720798294
        • emailvoliver@kemricdc.org
        • created2016-06-17 13:28:26
        • modified2016-06-23 12:56:29
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        • contact_detailsP.O BOX 1578-40100
        • contact_personDr. Vincent Oliver Otieno
        • site_capacity(null)
        • misc(null)
        • created2016-06-17 13:28:26
        • modified2016-06-23 12:56:29
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
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        • id262
        • application_id504
        • sponsorThe National Institute of Allergy and Infectious Diseases (NIAID) The National Cancer Institute (NCI) National Institute of Dental Craniofacial Research (NIDCR)
        • sponsor_type(null)
        • contact_personDr. Kevin Cain
        • addressP.O BOX 1578-40100 Kisumu
        • telephone_number+254710602786
        • fax_number
        • cell_number+254710602786
        • email_addressbvz1@cdc.gov
        • created2016-06-17 13:28:26
        • modified2016-06-23 12:56:29
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