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  • 1Recruiting
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    • Application(array)
      • id623
      • user_id81
      • trial_status_id5
      • abstract_of_study<p>\n Resistance to artemisinins and their partner drugs resulting in high treatment failure with artemisinin-based combination therapies (ACTs) severely threatens treatment of falciparum malaria. A spread of artemisinin and partner drug resistance to Sub-Saharan-Africa would have devastating consequences. Currently, there is no good alternative to ACTs for the treatment of uncomplicated falciparum malaria. This study aims to evaluate two alternative treatments with existing antimalarials for the treatment of uncomplicated Plasmodium falciparum infections in children in Kenya. The synthetic trioxolane arterolane maleate (OZ277), marketed in combination with piperaquine (PPQ) under the brand name Synriam®, is a promising new antimalarial drug combination to treat artemisinin resistant falciparum malaria. It is produced in India by the company Ranbaxy and is likely to be affordable in Lower Middle Income Countries. The use of multiple drugs with independent mechanisms of action aims to reduce emergence of drug resistance and is common practice in a range of human diseases, including HIV and tuberculosis. The triple combination dihydroartemisinin-piperaquine (available in Sub-Saharan Africa as Artekin) with mefloquine (now off-patent) has been shown to be as tolerable and safe as the more usual double combination dihydroartemisinin- piperaquine). The combination arterolane-piperaquine with mefloquine (where the DHA is replaced by arterolane) might be a very valuable addition to the potential future arsenal of combination drugs. TACT (i.e. triple artemisinin combination therapy), rather than double therapies with ACTs, might become the new standard treatment to prevent spread of resistance. We propose a randomised controlled clinical trial comparing the safety, tolerability, therapeutic efficacy and pharmacokinetics and pharmacodynamics of arterolane-piperaquine, arterolane-piperaquine plus mefloquine versus artemether-lumefantrine.in children with uncomplicated falciparum malaria in Kilifi, Kenya. This study will also provide an up to date insight on the current presence of antimalarial resistance in this site. In addition, all children will be treated with a single low dose of primaquine according to WHO guidelines, in order to prevent onward transmission of parasites to mosquitoes. We will recruit 219 patients aged 2 years to 12 years with acute uncomplicated falciparum malaria in Kilifi County Hospital. The primary endpoint will be day 42, PCR corrected assessments of adequate clinical and parasitological response (ACPR). In addition, we will collect data on parasite clearance during treatment, on adverse events, and on drug levels.</p>\n
      • study_title<p>\n An open-label randomised trial to assess the therapeutic efficacy and tolerability of arterolane-piperaquine plus single low dose primaquine versus arterolane-piperaquine plus mefloquine and single low dose primaquine versus artemether-lumefantrine plus single low dose primaquine in the treatment of uncomplicated falciparum malaria in children in Kenya.</p>\n
      • laymans_summary<p>\n <strong>What is the problem/background?</strong></p>\n<p>\n The first-line drugs world-wide to treat malaria are artemisinin-based combination therapies (ACTs).  Resistance to artemisinins and their partner drugs has now been noted, and the resulting treatment failure now severely threatens treatment of falciparum malaria in the South-East Asia.  A spread of artemisinin and partner drug resistance to Sub-Saharan-Africa would have devastating consequences.  We urgently need new combinations of drugs which will reduce the threat of resistance. The drug arterolane used in combination with piperaquine under the brand name Synriam®, is a promising new antimalarial drug combination to treat artemisinin resistant falciparum malaria.  It is produced in India and is likely to be an affordable treatment in Sub Saharan Africa.  Furthermore, the use of multiple drugs with different modes of action has the potential to reduce emergence of drug resistance and is common practice in a range of human diseases, including HIV and tuberculosis. We are therefore considering triple drug combinations, and propose a randomized controlled trial to compare the effect and safety of such combinations.</p>\n<p>\n <strong>What questions are we trying to answer?</strong></p>\n<p>\n This study aims to evaluate two alternative combination treatments for malaria in the setting of uncomplicated Plasmodium falciparum infections in children in Kenya.</p>\n<p>\n <strong>Where is the study taking place, how many people does it involve and how are they selected? </strong></p>\n<p>\n The study will be recruiting children from Pingilikani dispensary and Kilifi County Hospital. All children will be admitted in the Kilifi County Hospital for the duration of treatment. We will recruit 219 children in this study after being identified from the outpatient facility or at admission as a child with mild malaria (not ordinarily needing admission).</p>\n<p>\n <strong>What does the study involve for those who are in it?</strong></p>\n<p>\n Children with febrile malaria will be eligible to participate.  Instead of being treated as an outpatient they will be admitted to Kilifi Hospital andwill be randomized either to standard care or to a new treatment regimen. .A number of blood tests will be done during the 3 days they spend in hospital and they will also be followed-up as outpatients for 6 further occasions.</p>\n<p>\n <strong>What are the benefits and risks/costs of the study for those involved?</strong> <strong>       How will the study benefit society?     </strong></p>\n<p>\n Although most children with uncomplicated malaria can be successfully treated without admission, a few will experience complications requiring inpatient treatment. The main benefit to the individual involved in the trial will be closely supervised treatment for malaria.  There are risks of side effects from anti-malarial drugs, which are mitigated by the previous experience with these drugs, where minimal side effects have been seen, and by the close medical supervision.  The costs will include the inconvenience of a hospital stay for research purposes and frequent outpatient visits, and the discomfort associated with additional blood tests.</p>\n<p>\n <strong>When does the study start and finish?</strong></p>\n<p>\n The study will start upon receipt of ethical clearance. Data collection, analysis and write up will take place over 18 months.</p>\n
      • short_titleA trial to compare two new combinations of antimalarial drugs with the standard combination of antimalarial drugs in Kenyan children
      • protocol_noECCT/17/08/09
      • version_no1.1
      • date_of_protocol30-06-2017
      • study_drug1. Primaquine 2. Arterolane-piperaquine 3. Mefloquine 4. Artemether-lumefantrine
      • disease_conditionMalaria
      • 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_name1. 1. Primaquine 2. Arterolane-piperaquine 3. Mefloquine 4. Artemether-lumefantrine
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressctfuser@kemri-wellcome.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
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      • applicant_complete_form(null)
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      • 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_applicantPatricia Njuguna
      • declaration_date115-08-2017
      • declaration_principal_investigatorProf. Philip Bejon
      • declaration_date215-08-2017
      • placebo_presentNo
      • study_objectives<address>\n <strong><>1.1.</strong><strong>Primary objective</strong></address>\n<p>\n To assess the therapeutic efficacy (i.e. cure rate) of arterolane-piperaquine versus arterolane-piperaquine plus mefloquine versus artemether-lumefantrine in the treatment of uncomplicated falciparum malaria in children in Kenya as defined by the 42-day PCR corrected adequate clinical and parasitological response (ACPR).</p>\n<address>\n <>1.1.<!-- -->To assess and compare\n <ul>\n <li>\n P. falciparum asexual parasite clearance rates</li>\n <li>\n Clearance dynamics in mixed infections</li>\n </ul>\n <p style=\"margin-left:.5in;\">\n after treatment with i) arterolane-piperaquine, ii) arterolane-piperaquine plus mefloquine or iii) artemether-lumefantrine.</p>\n <ul>\n <li>\n To assess and compare the safety and tolerability of arterolane-piperaquine and arterolane-piperaquine plus mefloquine and artemether-lumefantrine.</li>\n <li>\n To assess the pharmacokinetic interaction between arterolane-piperaquine and mefloquine.</li>\n <li>\n To assess the pharmacokinetic properties of arterolane, piperaquine and mefloquine and primaquine</li>\n <li>\n To assess haemoglobin dynamics over time as a function of G6PD status, assessed by genotyping and a qualitative G6PD rapid test (phenotype).</li>\n </ul>\n</address>\n
      • principal_inclusion_criteria<p>\n a) Male or female aged 2 years to <13-year-old b) Uncomplicated falciparum malaria as defined as: i. Positive blood smear with asexual forms of P. falciparum (may be mixed with non-falciparum species) ii. Parasitaemia between 5,000-250,000 parasites/µL iii. Fever defined as tympanic temperature >37.5°C or history of fever within last 48 hours c) Ability to take oral medication d) Willingness and ability to comply with study protocol for study duration e) Written informed consent given to participate in the trial</p>\n
      • principal_exclusion_criteria<p>\n a) Signs of severe/complicated malaria* b) Any clinical reason suggesting that the child’s treatment should be given immediately and not delayed during the transfer to Kilifi County Hospital in the opinion of the treating physician. c) Acute illness other than malaria requiring urgent systemic treatment as assessed by the treating physician d) Previous splenectomy e) Treatment with artemisinin or ACT within the previous 7 days f) Treatment with mefloquine in the 2 months prior to presentation g) Known hypersensitivity or contraindication to arterolane-piperaquine, DHA-piperaquine, artemisinin, mefloquine (epilepsy, major psychiatric illness) or primaquine h) QTc interval >450 milliseconds at point of presentation i) Known personal or family history of cardiac conduction problems j) Participation within another clinical trial in the previous 3 months</p>\n
      • primary_end_points<p>\n Day 42, PCR corrected adequate clinical and parasitological response (ACPR)</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • 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_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n Clinical officer - 1</p>\n<p>\n Nurses -2</p>\n<p>\n Fieldworkers - 2</p>\n<p>\n Lab tech - 1</p>\n<p>\n Study Coordinator -1</p>\n<p>\n The inpatient facility is already staffed with 3 clincians, 1 paediatrician and 20 nurses.</p>\n<p>\n All staff are trained in basic life support and resuscitation facilitaties are available</p>\n
      • other_details_explanation<p>\n Not applicable</p>\n
      • other_details_regulatory_notapproved<p>\n We are submitting only to the Kenyan regulator</p>\n
      • other_details_regulatory_approved<p>\n Not applicable</p>\n
      • other_details_regulatory_rejected<p>\n Not applicable</p>\n
      • other_details_regulatory_halted<p>\n Not applicable</p>\n
      • estimated_duration12 months
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorArtemether-lumefantrine
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • 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_countriesNo
      • multiple_member_states
      • number_of_sites2
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_site219
      • total_participants_worldwide219
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerYes
      • population_childrenYes
      • population_adolescentNo
      • population_above_18No
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationYes
      • subjects_incapable_consentYes
      • subjects_specifyChildren hence the parent or legal guardian need to provide consent
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_namePhilip
      • investigator1_middle_name
      • investigator1_family_nameBejon
      • investigator1_qualificationPhD
      • investigator1_professional_addressP.O.Box 230, Kilifi 80108, Kenya
      • investigator1_telephone+254709983549
      • investigator1_emailPBejon@kemri-wellcome.org
      • organisations_transferred_No
      • number_participants219
      • notification
      • approval_date04-01-2018
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted17-05-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<p>\n The study aimed at detremining the safety, tolerability, efficacy and pharmacological aspects of the Triaple combination arterolone- piperaquine plus mefloquine compared to the double arterolone-piperaquine and the ACT artemether-lumefantrine in Kilifi.</p>\n<p>\n The participants were children aged between 2 to < 3 years with acute uncomplixated falciparum malaria with parasite count limit of ,5000 to 250 000/microL. The participants whose parents had consented were screened for eligibilty and to rule out severe malaria. those found eligible were admitted to the Kilifi Hospital for 3 days while the receive AL or arterolane- piperaquine or arterolone-piperaquine +mefloquine as treatment. tehy had a 42 day fellow up period to assess the long term tolerability, safety and efficacy (recrudencence and reinfections).</p>\n
      • implication_results<p>\n if the triple therapy is found to be superior to doube therapy, then this will imform policy makers on the next move incase there is need to change guinelines due to resistance to the current standard treatment.</p>\n
      • quantity_importedarterolane piperaquine-2316, mefloquine-256, artemether lumefantrine 2232, primaquine 7.5mg-300, primaquine, 5mg-600 and primaquine 2.5mg-1050
      • quantity_dispensedarolane piperaquine-1409, mefolquine- 228, artemether-lumefantrin-1010, primaquine 7.5mg-114. primaquine 5mg-265 and primaquine 2.5mg-249
      • quantity_destroyedarterolane piperaquine-905, mefloquine-26, artemether lumefantrine 1222, primaquine 7.5mg-156, primaquine 5mg- 335 and primaquine 2.5mg- 801
      • quantity_exported0
      • balance_site0
      • final_date0000-00-00
      • modified2022-07-01 16:15:10
      • created2017-07-28 10:46:13
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id398
        • application_id623
        • given_namePhilip
        • middle_name
        • family_nameBejon
        • qualificationPhD
        • professional_addressP.O. Box 230, Kilifi 80108, Kenya.
        • telephone+254709983549
        • emailPBejon@kemri-wellcome.org
        • created2017-07-28 10:50:27
        • modified2020-05-17 15:02:25
    • SiteDetail(array)
      • 0(array)
        • id505
        • application_id623
        • county_id3
        • site_nameKilifi County Hospital - Paediatric Out patient and Inpatient department
        • physical_addressKilifi County Hospital
        • contact_detailsP.O. Box 230-80108
        • contact_personProf. Philip Bejon
        • site_capacity(null)
        • misc(null)
        • created2017-07-28 10:50:27
        • modified2020-05-17 15:02:25
        • County(array)
          • id3
          • county_nameKilifi
          • created2012-05-31 16:15:49
          • modified2012-05-31 16:15:49
      • 1(array)
        • id506
        • application_id623
        • county_id3
        • site_namePingilikani Dispensary
        • physical_addressPingilikani Dispensary
        • contact_detailsP.O. Box 230-80108
        • contact_personProf. Philip Bejon
        • site_capacity(null)
        • misc(null)
        • created2017-07-28 11:03:32
        • modified2020-05-17 15:02:25
        • County(array)
          • id3
          • county_nameKilifi
          • created2012-05-31 16:15:49
          • modified2012-05-31 16:15:49
    • Sponsor(array)
      • 0(array)
        • id320
        • application_id623
        • sponsorUniversity of Oxford
        • sponsor_typeResearch Institution
        • contact_personShahista Hussain
        • addressJoint Research Office Block 60 Churchill Hospital Oxford OX3 7LE
        • telephone_number +44 01865 572231
        • fax_numberN/A
        • cell_number +44 01865 572231
        • email_addressshahista.hussain@ouh.nhs.uk
        • created2017-07-28 10:50:27
        • modified2020-05-17 15:02:25
  • 1(array)
    • Application(array)
      • id610
      • user_id81
      • trial_status_id5
      • abstract_of_study<div>\n Our study will assess the impact of an intervention consisting of a consensus acute HIV infection risk score algorithm for acute and prevalent (i.e., seropositive) HIV testing among 1,500 adult patients aged 18-39 years who seek urgent care for symptoms at primary care facilities. We will link all newly diagnosed HIV-infected patients to care, offer immediate treatment, and offer assisted partner notification, evaluation for prevalent or acute HIV infection, and either antiretroviral therapy (if HIV-infected) or pre-exposure prophylaxis (if uninfected with a serodiscordant, HIV-positive partner). We will also model the potential impact of the AHI testing and assisted partner notification interventions on the Kenyan HIV epidemic, estimating incremental costs per HIV infection averted, death averted, and disability-adjusted life-year (DALY) averted using data on outcomes from our innovative program.</div>\n<div>\n  </div>\n<div>\n We will use a modified stepped wedge design to evaluate the yield of the AHI testing intervention at 2-4 public and 2-4 private health facilities in Kenya, before (1,375 patients) and after (1,500 patients) intervention delivery. We expect to diagnose over two-fold more HIV infections through this intervention than are currently diagnosed through provider-initiated testing and counselling. Assisted partner notification should identify at least two-fold more previously undiagnosed individuals for each index case identified than passive referral strategies (the current standard of care), augmenting intervention impact. Through modelling, we will estimate the impact of this combined intervention on HIV transmission and evaluate the potential cost-effectiveness of such an approach under a wide range of estimations. We expect this work to provide invaluable data that will help improve HIV testing and treatment as prevention in sSA.</div>\n
      • study_title<p>\n Impact of a novel HIV-1 RNA testing intervention to detect acute and prevalent HIV infection and reduce HIV transmission – Tambua Mapema Plus</p>\n
      • laymans_summary<div>\n <strong>What is the problem/background?</strong></div>\n<div>\n Patients who seek health care for symptoms are occasionally tested for prevalent HIV (i.e. positive on rapid antibody tests). A small proportion (~1%) of patients who test negative for prevalent HIV may actually have ‘acute HIV’ (i.e. positive on a special test, qualitative X-pert RNA test) as the cause of their symptoms. Patients with acute HIV infection (AHI) are very infectious and would benefit from early diagnosis and early treatment, and their partners would benefit from prompt notification and evaluation.</div>\n<div>\n  </div>\n<div>\n <strong>What questions are we trying to answer?</strong></div>\n<div>\n We will test whether a new AHI testing intervention will identify more HIV infections (both prevalent and acute HIV) compared to standard testing (provider-initiated testing and counselling, PITC for prevalent HIV) among patents aged 18-39 years seeking care for symptoms, and determine whether assisted partner notification and care navigation offered by HIV-1 RNA testing intervention staff will lead to more infections diagnosed among partners, more HIV-infected persons starting treatment, and more viral suppression among treated patients.</div>\n<div>\n  </div>\n<div>\n <strong>Where is the study taking place, how many people does it involve and how are they selected?</strong></div>\n<div>\n The study will take place at six health facilities (2-4 government and 2-4 private) in Kilifi and Mombasa County. A total of 2875 patients seeking care and up to 300 partners of HIV-infected patients will be enrolled. Patients eligible for participation will be invited to participate upon urgent care seeking.</div>\n<div>\n  </div>\n<div>\n <strong>What does the study involve for those who are in it?</strong></div>\n<div>\n Participants will either be observed (PITC, comparison group) or undergo AHI testing intervention (both prevalent and AHI testing, intervention group). All participants will undergo a brief questionnaire about symptoms and sexual risk behavior. Participants who are diagnosed with acute or prevalent HIV infection will be asked about partners, who will be a contacted by research staff for HIV evaluation. All participants and partners diagnosed with HIV infection will be offered immediate treatment, and HIV-negative partners whose partner is HIV-infected will be offered pre-exposure prophylaxis (PrEP) for the duration of 6 months, or until viral suppression is achieved by the HIV-infected partner.</div>\n<div>\n  </div>\n<div>\n <strong>What are the benefits and risks/costs of the study for those involved?</strong></div>\n<div>\n Benefits include learning about research, obtaining accurate HIV status, immediate treatment when infected, and protecting one’s partner. There is some risk of loss of privacy or confidentiality.</div>\n<div>\n  </div>\n<div>\n <strong>How will the study benefit society?</strong></div>\n<div>\n Results of this study will be directly applicable to implementation of HIV-1 RNA testing intervention for acute and prevalent HIV infection among young adults in resource-limited settings. In addition, the diagnosis and immediate treatment of persons with acute and previously undiagnosed prevalent HIV infection will reduce HIV transmission risk.</div>\n<div>\n  </div>\n<div>\n <strong>When does the study start and finish?</strong></div>\n<div>\n The study will start in November 2017 and will continue for 4 years.</div>\n
      • short_titleTambua Mapema Plus
      • protocol_noECCT/17/08/07
      • version_no1.3
      • date_of_protocol06-03-2017
      • study_drugTenofovir disoproxil fumarate 300mg/ emtricitabine 200mg tablets
      • 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_nameTenofovir disoproxil fumarate 300mg/ emtricitabine 200mg tablets
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addresspmugo@kemri-wellcome.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)
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      • applicant_stability_data0
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      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter0
      • applicant_detailed_budget1
      • applicant_indemnity_pi0
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist0
      • statistical_analysis_plan0
      • applicant_contractual_agreement0
      • declaration_applicantEduard Sanders, Co-PI
      • declaration_date123-06-2017
      • declaration_principal_investigatorSusan Graham, Co-PI
      • declaration_date223-06-2017
      • placebo_presentNo
      • study_objectives<div>\n <strong>General Objective</strong>: To conduct a proof-of-concept study to test the efficacy of a health facility-based HIV-1 RNA testing intervention to identify acute (i.e., RNA-positive, seronegative or discordant rapid results) and prevalent (i.e., RNA-positive, seropositive) HIV infection.</div>\n<div>\n  </div>\n<div>\n <strong>Specific Objectives:</strong></div>\n<div>\n 1. To identify and test 1,500 adults identified by our HIV-1 RNA testing intervention for acute and prevalent (i.e., seropositive) HIV, linking all newly diagnosed HIV-infected patients to care and offering immediate treatment.</div>\n<div>\n 2. To offer assisted partner notification services (aPS) to all cases detected in objective 1, testing partners for acute and prevalent HIV infection and identifying local sexual networks.</div>\n<div>\n 3. To model the potential impact of the HIV-1 RNA testing and aPS interventions on the Kenyan HIV epidemic, estimating incremental costs per HIV infection averted, death averted, and disability-adjusted life-year (DALY) averted using data on outcomes from our innovative program.</div>\n<div>\n 4. To conduct qualitative in-depth interviews with up to 60 newly diagnosed prevalent and AHI patients and seronegative partners in discordant relationships to gain insights into intervention uptake, including barriers and facilitators to ART or PrEP uptake and adherence in these groups.</div>\n<div>\n 5. To conduct interviews or focus groups with up to 60 individuals who work in the 6 health facilities where the trial will take place (up to 10 participants per facility), to obtain their views on the detection of acute HIV infection and the research carried out at the facility, including challenges to intervention scale-up.</div>\n
      • principal_inclusion_criteria<p>\n Volunteers will be included in the PrEP component of the study if they meet the following criteria:</p>\n<p>\n 1. Sexual partner to a newly diagnosed index case (prevalent or acute HIV)</p>\n<p>\n 2. Age over 18 years</p>\n<p>\n 3. HIV negative</p>\n
      • principal_exclusion_criteria<p>\n None</p>\n
      • primary_end_points<p>\n Proportion of participants with the following outcomes in the observation and intervention periods:</p>\n<ul>\n <li>\n tested for HIV infection;</li>\n <li>\n newly diagnosed with prevalent HIV; and</li>\n <li>\n newly diagnosed with AHI</li>\n</ul>\n
      • scope_diagnosis1
      • scope_prophylaxis1
      • scope_therapy1
      • scope_safety1
      • scope_efficacy0
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others1
      • scope_others_specifyCost-effectiveness
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other1
      • trial_other_specifyProof of concept of the HIV-1 RNA testing intervention
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n <u>STAFF QUALIFICATIONS (see attached CVs for experience of core staff)</u></p>\n<p>\n <strong>PRINCIPAL INVESTIGATORS</strong></p>\n<p>\n Eduard Sanders, MD MPH PhD (Medical Epidemiologist)</p>\n<p>\n Susan Graham, MD MPH PhD (Consultant Infectious Diseases)</p>\n<p>\n  </p>\n<p>\n <strong>SOCIAL SCIENCE</strong></p>\n<p>\n Elise Van der Elst, MA, PhD (Social Scientist)</p>\n<p>\n Bernadette Kombo, BA, MPH (Social Scientist)</p>\n<p>\n  </p>\n<p>\n <strong>CLINICAL</strong></p>\n<p>\n Clara Agutu, MBChB, MPH (Lead physician & Project Manager)</p>\n<p>\n Peter Mugo, BPharm MSc (Pharmacist)</p>\n<p>\n Salome Chira, DCM (Clinician & Study coordinator)</p>\n<p>\n Fred Ogada, DCM (Clinician)</p>\n<p>\n Joseph Nzioka, Dip (Counselor coordinator)</p>\n<p>\n Elizabeth Njogu, Dip (Counselor)</p>\n<p>\n Aisha Galole, Dip (Counselor)</p>\n<p>\n Nana Mukuria, Dip (Counselor)</p>\n<p>\n  </p>\n<p>\n <strong>LABORATORY</strong></p>\n<p>\n Caroline Ngetsa, Dip (Laboratory Manager)</p>\n<p>\n John Mwambi, Dip (Snr. Lab Technologist)</p>\n<p>\n Clara Karani, Dip (Lab Technologist)</p>\n<p>\n  </p>\n<p>\n <strong>REGULATORY & QUALITY ASSURANCE</strong></p>\n<p>\n Jennifer Kanungi, Dip Nursing (Study Co-ordinator)</p>\n<p>\n Esther Ndiang’ui, Dip IT (Quality Officer)</p>\n<p>\n  </p>\n<p>\n <strong>DATA AND ICT</strong></p>\n<p>\n Elizabeth Wahome, BSc, MSc (Data Manager & Epidemiologist)</p>\n<p>\n Cliff Oduor, BSc (data Manager)</p>\n<p>\n  </p>\n<p>\n <strong>COMMUNITY ENGAGEMENT & RETENTION</strong></p>\n<p>\n Evanson Gichuru, BSc Psych (Community Liaison Officer)</p>\n<p>\n Brenda Nekesa, Dip (community facilitator)</p>\n<p>\n Maureen Sikubali, Dip (Tracer)</p>\n<p>\n Masuu Paiki, Dip (Receptionist)</p>\n<p>\n  </p>\n<p>\n <strong>FINANCE & HUMAN RESOURCE</strong></p>\n<p>\n Lucie Ikumi, Dip (Project Administrator)</p>\n<p>\n Alice Khonde, Dip (Admin Assistant)</p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n
      • other_details_explanation<p>\n The intervention is targeted at Kenya healthcare settings, hence the trial will be conducted in Kenya to enhance generalizability</p>\n
      • other_details_regulatory_notapproved<p>\n Not applicable</p>\n
      • other_details_regulatory_approved<p>\n Not applicable</p>\n
      • other_details_regulatory_rejected<p>\n Not applicable</p>\n
      • other_details_regulatory_halted<p>\n Not applicable</p>\n
      • estimated_duration4 years
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherYes
      • design_controlled_specifystepped wedge
      • design_controlled_comparatorstandard practice
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKEMRI Mtwapa Research Clinic
      • single_site_physical_addressMtwapa, Kilif County, Kenya
      • single_site_contact_personDr. Clara Agutu
      • single_site_telephone+254 720735000
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_site75
      • total_participants_worldwide75
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenYes
      • subjects_nursing_womenYes
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameEduard
      • investigator1_middle_nameJ
      • investigator1_family_nameSanders
      • investigator1_qualificationMD MPH PhD
      • investigator1_professional_addressKEMRI-Wellcome Trust Research Programme, P.O. Box 230, Kilifi, 80108
      • investigator1_telephone+254 723 593762
      • investigator1_emailESanders@kemri-wellcome.org
      • organisations_transferred_Yes
      • number_participants75
      • notification
      • approval_date25-08-2017
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted07-10-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<p>\n In sub-Saharan Africa, adult outpatients with symptoms of acute infectious illness are not routinely tested for prevalent or acute HIV infection (AHI) when seeking healthcare.</p>\n<p>\n  </p>\n<p>\n Adult symptomatic outpatients aged 18-39 years were evaluated by a consensus</p>\n<p>\n AHI risk score. Patients with a risk score ≥2 and no previous HIV diagnosis were enrolled in</p>\n<p>\n a stepped-wedge trial of opt-out delivery of point-of-care (POC) HIV-1 nucleic acid testing</p>\n<p>\n (NAAT), compared to standard provider-initiated HIV testing using rapid tests in the</p>\n<p>\n observation period. The primary outcome was the number of new diagnoses in each study</p>\n<p>\n period. Generalized estimating equations with a log-binomial link and robust variance</p>\n<p>\n estimates were used to account for clustering by health facility. The trial is registered with</p>\n<p>\n ClinicalTrials.gov NCT03508908.</p>\n<p>\n  </p>\n<p>\n Between 2017-2020, 13 (0.9%) of 1374 participants in the observation period and</p>\n<p>\n 37 (2.5%) of 1500 participants in the intervention period were diagnosed with HIV infection.</p>\n<p>\n Of the 37 newly diagnosed cases in the intervention period, 2 (5.4%) had AHI. Participants in</p>\n<p>\n the opt-out intervention had a 2-fold greater odds of being diagnosed with HIV (odds ratio:</p>\n<p>\n 2.2, 95% confidence interval: 1.39–3.51) after adjustment for factors imbalanced across</p>\n<p>\n study periods.</p>\n<p>\n  </p>\n<p>\n Among symptomatic adults aged 18-39 years targeted by our POC NAAT intervention, we identified one chronic HIV infection for every forty patients and one AHI patient for every 750 patients tested. While AHI yield was low in this population, routinely offered opt-out testing could diagnose twice as many patients as an approach relying on provider discretion.</p>\n
      • implication_results<p>\n Detection of acute and prevalent HIV infection using point-of-care nucleic acid amplification testing (POC-NAAT) among outpatients with symptoms compatible with acute HIV is critical to HIV prevention but it is not clear if it is cost-effective compared to existing HIV testing strategies. </p>\n<p>\n  </p>\n<p>\n We developed and parametrized a decision tree to compare the cost-effectiveness of: (1) provider-initiated testing and counseling (PITC) using rapid tests, the standard of care; (2) expanded PITC (E-PITC) in which all patients were tested with rapid tests unless they opted out; and (3) opt-out testing and counseling using POC-NAAT, which detects both acute and prevalent infection. We obtained data from the Tambua Mapema Plus randomized controlled trial of a POC-NAAT intervention in Kenya, supplemented with results from a stochastic, agent-based network model of HIV-1 transmission to evaluate population-level and HIV prevention impact. The analysis was conducted from the perspective of the Kenyan government using a primary outcome of cost per DALY averted over a 10-year time horizon.</p>\n<p>\n  </p>\n<p>\n The average per patient cost of POC-NAAT was $214.9 compared with $173.6 for E-PITC and $47.3 for PITC. The mean DALYs accumulated per patient for POC-NAAT were 0.160 compared with 0.176 for E-PITC and 0.214 for PITC. In the incremental analysis, E-PITC was eliminated due to extended dominance and the ICER comparing POC-NAAT to PITC was $3,098 per DALY averted. The ICER was sensitive to disability weights for HIV/AIDs and the costs of antiretroviral therapy.</p>\n<p>\n  </p>\n<p>\n Expanded POC-NAAT offered to adult outpatients in Kenya who present for care with symptoms compatible with AHI is cost-effective and should be considered for inclusion as the standard of HIV testing in this population.</p>\n<p>\n  </p>\n
      • quantity_imported300
      • quantity_dispensed31
      • quantity_destroyed269
      • quantity_exported0
      • balance_site0
      • final_date0000-00-00
      • modified2023-03-09 10:58:01
      • created2017-06-15 12:29:03
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id388
        • application_id610
        • given_nameEduard
        • middle_nameJ
        • family_nameSanders
        • qualificationMD MPH PhD
        • professional_addressKEMRI-Wellcome Trust Research Programme, P.O. Box 230, Kilifi, 80108
        • telephone+254 723 593762
        • emailESanders@kemri-wellcome.org
        • created2017-06-15 12:51:45
        • modified2020-10-07 11:20:46
      • 1(array)
        • id390
        • application_id610
        • given_nameSusan
        • middle_nameM
        • family_nameGraham
        • qualificationMD MPH PhD
        • professional_addressUniversity of Washington School of Medicine, Box 359909, 325 9th Avenue, Seattle, WA 98104-2499
        • telephone(206) 543 4278
        • emailgrahamsm@u.washington.edu
        • created2017-06-20 12:02:57
        • modified2020-10-07 11:20:46
    • SiteDetail(array)
      • 0(array)
        • id492
        • application_id610
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2017-06-15 12:51:45
        • modified2020-10-07 11:20:46
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id312
        • application_id610
        • sponsorDivision of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), United States (US)
        • sponsor_typeOthers
        • contact_personUsha Sharma
        • addressClinical Prevention Research Branch, PSP, DAIDS, NIAID, NIH, DHHS, 5601 Fishers Lane, Rm 8C29, Bethesda, MD 20892
        • telephone_number+1 240-292-4809
        • fax_number
        • cell_number+1 240-292-4809
        • email_addressusharma@niaid.nih.gov
        • created2017-06-15 12:51:45
        • modified2020-10-07 11:20:46
  • 2(array)
    • Application(array)
      • id613
      • user_id357
      • trial_status_id5
      • abstract_of_study<p>\n <strong>Broad Objectives: </strong>Children with SCA are particularly vulnerable to infectious diseases and in malaria endemic areas, malaria is one of the leading causes of hospitalization and death among children with SCA. The current recommendation is chemoprevention with daily proguanil. However, this regimen suffers from suspected low adherence rates and probable reduced efficacy due to parasite resistance to antifolate drugs. We are conducting a randomized, three-arm, open-label, clinical trial of malaria chemoprevention in children with sickle-cell anemia at a single site in Homa Bay, Kenya in order to identify more effective chemotherapy regimens for malaria in children with SCA.</p>\n<p>\n <strong>Specific Objectives:</strong>Primary: To compare the efficacy of daily proguanil with monthly sulfadoxine/pyrimethanine-amodiaquine (SP-AQ) and with monthly dihydroartemisinin-piperaquine (DP) on the incidence of falciparum malaria in children with SCA.Secondary: To compare the efficacy of these malaria chemoprevention strategies on the incidence of major complications of SCA.</p>\n<p>\n <strong>Study setting: </strong>Homa Bay County Hospital, Homa Bay, Kenya</p>\n<p>\n <strong>Study population: </strong>Children of both genders between 1 and 10 years of age with laboratory-confirmed SCA living in malaria-endemic portions of Homa Bay or Migori Counties, Kenya</p>\n<p>\n <strong>Number of subjects to be contacted: </strong>246 children to be enrolled</p>\n<p>\n <strong>Study procedures (main) done on participants: </strong>This is a randomized, three-arm, open-label, clinical trial of malaria chemoprevention in children with sickle-cell anemia (SCA) at a single site in Homa Bay, Kenya. The study will enroll 246 children under 10 years of age, randomize participants 1:1:1 to one of three malaria chemoprevention regimens, and follow participants monthly for 12 months in order to record clinical episodes of malaria or SCA-related morbidity. Analyses will compare the efficacy of each regimen to prevent malaria and SCA morbidity. Blood samples will be taken every three months (5 time points – baseline, 3, 6, 9, 12months) for laboratory testing and dried bloodspots will also be collected. Participants will also receive a malaria rapid diagnostic test using a finger-prick blood sample when they are ill. </p>\n<p class=\"Default\">\n <o:p></o:p></p>\n<p>\n  </p>\n
      • study_title<p>\n <strong>Enhancing Preventive Therapy of Malaria In children with Sickle cell anemia in East Africa (EPiTOMISE)</strong></p>\n
      • laymans_summary<p>\n It is a malaria prevention study for children between the ages of 1 to 10 years with sickle cell anaemia. They should be living in Homabay county and 2 subcounties of Migori county  i.e Rongo and Awendo.</p>\n<p>\n The study clinic is based in Homabay County Teaching and refferal hospital.</p>\n<p>\n The study is to enrol 246 children confirmed to have sickle cell anaemia HbSS.</p>\n<p>\n In the study there are 3 antimalarial drugs being used which are already in the market. They are randomly given to the participants. The drugs are namely; Proguanil and Dihydroartemisinin(DP) which are given based on weight then Sulphadoxine pyrimethamine Amodiaquine( SPAQ) given based on age.</p>\n<p>\n Follow-up period is 12 months per participant and the clinic visits are monthly.</p>\n<p>\n Reason for doing the study  is to compare whether DP or SPAQ is better at preventing malaria than Proguanil.</p>\n
      • short_titleEnhancing Preventive Therapy of Malaria In children with Sickle cell anemia in East Africa (EPiTOMISE)
      • protocol_noECCT/17/08/06
      • version_no4
      • date_of_protocol27-03-2017
      • study_drugProguanil, Sulfadoxine/Pyrimethamine-Amodiaquine (SPAQ) and Dihydroartemisinin-Piperaquine (DP)
      • disease_conditionMalaria in Children with Sickle Cell Anemia
      • 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_name Sulfadoxine/Pyrimethamine-Amodiaquine (SPAQ) and Dihydroartemisinin-Piperaquine (DP)
      • product_type_medical_device_name
      • comparatorYes
      • comparator_namePROGUANIL
      • comparator_registeredYES
      • comparator_countriesKENYA
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressjosepeddykipkoech@gmail.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd0
      • applicant_prev_data0
      • applicant_stability_data0
      • applicant_analysis_cert1
      • applicant_pictorial_sample0
      • applicant_gcp_training0
      • applicant_dsmb_charter0
      • applicant_detailed_budget0
      • applicant_indemnity_pi0
      • applicant_practice_license0
      • applicant_registration_ctr(null)
      • applicant_pan_african0
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantJoseph kipkoech -0720393547
      • declaration_date112-07-2017
      • declaration_principal_investigatorDr. Festus Njuguna - 0721219761
      • declaration_date212-07-2017
      • placebo_presentNo
      • study_objectives<p>\n The primary objective of the EPiTOMISE trial is to compare the efficacy of daily Proguanil with that of monthly SP-AQ or monthly DP to prevent <em>P. falciparum</em> malaria in children with SCA.</p>\n<p>\n  </p>\n<p>\n The secondary objectives of this trial are to:</p>\n<ol>\n <li>\n compare the efficacy of daily Proguanil, monthly SP-AQ, and monthly DP to prevent painful events in children with sickle cell anemia, and</li>\n <li>\n compare the impact of malaria chemoprevention regimens on molecular markers of parasite drug resistance to Proguanil, SP-AQ, and DP.</li>\n</ol>\n<p>\n  </p>\n
      • principal_inclusion_criteria<p>\n 1)    Age greater than 12 months and less than 10 years at enrollment;</p>\n<p>\n 2)    Current attendance at or willingness to attend the study SCA clinic at HBCH;</p>\n<p>\n 3)    Residence in either Homa Bay County or the Rongo or Awendo sub-counties of Migori County;</p>\n<p>\n 4)    Confirmed hemoglobin genotype of HbSS by electrophoresis, HPLC, or PCR;</p>\n<p>\n 5)    No immediate, apparent, or reported plans to relocate residence from Homa Bay County or the Rongo or Awendo sub-counties of Migori County in the next 2 years;</p>\n<p>\n 6)    Ability to take oral medication and be willing to adhere to the medication regimen or caregiver willingness to give the medical regimen as prescribed;</p>\n<p>\n 7)    Ability and willingness of parent or legally authorized representative (LAR) to give informed consent;</p>\n<p>\n 8)    Assent of child in those > 7 years.</p>\n
      • principal_exclusion_criteria<p>\n 1)    Taking routine antimalarial prophylaxis for another indication (including co-trimoxazole for HIV infection);</p>\n<p>\n 2)    Temperature of <u>≥</u> 37.5C at screening or history of objective or subjective fever in the preceding 24 hours during screening;</p>\n<p>\n 3)    Known allergy or sensitivity to sulfadoxine, pyrimethamine, amodiaquine, proguanil, dihydroartemisinin, piperaquine, artemether, lumefantrine, pencillin (if under 5 years old), or derivatives of these compounds;</p>\n<p>\n 4)    Known chronic medical condition other than SCA (i.e. malignancy, HIV) requiring frequent medical attention;</p>\n<p>\n 5)    Currently participating in another clinical research study, or having participated in one in the prior 30 days;</p>\n<p>\n 6)    Living in the same household as a previously-enrolled study participant;</p>\n<p>\n 7)    Chronic use of medications known to prolong the QT interval in children (see Appendix J);</p>\n<p>\n 8)    Fridericia’s corrected QT interval (QTcF) interval > 450msec.</p>\n
      • primary_end_points<p>\n The primary endpoint is incidence of clinical malaria expressed as episodes per person-year at risk.  Time at risk will begin when study participants are randomized and receive study drug (i.e. begin chemoprevention) and end when participants reach the end of the observation period. Clinical malaria will be detected by passive surveillance and will be defined as:</p>\n<p style=\"margin-left:1.0in;\">\n ·      Presence of <em>P. falciparum</em> parasitemia of any density AND</p>\n<p style=\"margin-left:1.0in;\">\n ·      Temperature of ≥ 37.5C or history of objective or subjective fever in the preceding 24 hours OR</p>\n<p style=\"margin-left:1.0in;\">\n ·      Case meeting the definition of severe malaria according to WHO criteria</p>\n<p style=\"margin-left:1.5in;\">\n o   Hospitalization for Malaria</p>\n<p style=\"margin-left:2.0in;\">\n §  Case meeting criteria for clinical or severe malaria who requires hospitalization (as adjudged by the treating clinician)</p>\n<p style=\"margin-left:1.5in;\">\n o   Fatal Malaria</p>\n<p style=\"margin-left:2.0in;\">\n §  Case meeting criteria as severe malaria which results in death while an inpatient</p>\n<p>\n  </p>\n<p>\n Those screening positive will be tested for malaria parasites by rapid immunochromatographic diagnostic test (RDT). The RDT will be used to guide clinical treatment. Only RDT-positive events will be recorded as primary endpoints.</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_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use1
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n Homa Bay County Hospital is a full-service public hospital located in Homa Bay County. The study site offers a full range of services, including OPD, IPD with pediatric and adult wards, surgical wards, and obstetric wards. The OPD includes MCH clinics. Emergency evaluation and inpatient admission are available on site at HBCH for study participants.</p>\n<p>\n 1.      Dr. Steve Taylor - MD, PI – Duke University, DCRI</p>\n<p>\n 2.      Dr. Festus Njuguna MD, PI Moi University</p>\n<p>\n 3.      Dr. Wendy O'Meara - PhD, Co-Investigator</p>\n<p>\n 4.      Dr. Fredrick Asirwa Chite - MD, Co-Investigator</p>\n<p>\n 5.      Sheila Clapp  - MBA, EITOMISE Project Lead,DCRI</p>\n<p>\n 6.      Dr. Linet Kugo  -Pharmacist, Study Pharmacist</p>\n<p>\n 7.      Joseph Kipkoech  -BA, MSc cont, Kenya Project Manager</p>\n<p>\n 8.      Steve Karuru - BSc, MSc, Data Manager – Programming</p>\n<p>\n 9.      Sara Korwa - Diploma Clinical Medicine, BA,  Site Coordinator and Study Clinician</p>\n
      • other_details_explanation<p>\n The purpose of this trial is to test alternate strategies for chemoprevention of malaria in children with sickle-cell anemia. For this reason, the Duke Clinical Research Institute (the sponsor-investigator) has partnered with colleagues at Moi University with expertise in sickle-cell anemia to enroll patients in Homa Bay. This utilizes the existing relationships between Moi University investigators and the clinical staff of Homa Bay County Hospital, where Moi clinicians routinely hold outreach clinics for children with sickle-cell anemia.</p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n Moi University Institutional Research Ethics Committee (IREC), 8 June 2017</p>\n<p>\n Duke University, 31 May 2017</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n None</p>\n
      • estimated_duration12 months per participant, overall 18-24 months
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorDaily proguanil is the st
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaHoma Bay County Hospital
      • single_site_physical_addressPO Box 52, Homa Bay 40300
      • single_site_contact_personDr. Liru, HBCH CEO
      • single_site_telephoneNone
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_site246
      • total_participants_worldwide246
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerYes
      • population_childrenYes
      • population_adolescentNo
      • population_above_18No
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameFestus
      • investigator1_middle_nameMuigai
      • investigator1_family_nameNjuguna
      • investigator1_qualificationMBChB PhD
      • investigator1_professional_addressPO Box 4606-30100
      • investigator1_telephone+254 721 219 761
      • investigator1_emailmuigaifes2000@yahoo.com
      • organisations_transferred_Yes
      • number_participants246
      • notification
      • approval_date03-10-2017
      • submitted1
      • deleted0
      • deleted_date2020-03-04 13:58:32
      • deactivated0
      • date_submitted09-03-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<p>\n Background: Children with sickle cell anemia in areas of Africa with endemic malaria transmission are commonly prescribed malaria chemoprevention. The comparative efficacy of prevention regimens is largely unknown. Methods: We enrolled Kenyan children aged 1-10 years with HbSS in a randomized, open-label trial. Children were assigned 1:1:1 to daily Proguanil (the standard of care), monthly sulfadoxine/pyrimethamineamodiaquine (SP-AQ), or monthly dihydroartemisinin/piperaquine (DP). The primary outcome was the cumulative incidence of clinical malaria at 12 months and the main secondary outcome was the cumulative incidence of painful events. Negative-binomial models were used to estimate incidence rate ratios (IRRs) per patient-year (PPY) at risk relative to Proguanil. The primary analytic population was the As-Treated Population. Results: 246 children were randomized to daily Proguanil (n=81), monthly SP-AQ (n=83), or monthly DP (n=82). The clinical malaria incidence was 0.04 episodes/PPY; relative to the daily Proguanil group, incidence rates were similar in the monthly SP-AQ (IRR: 3.05, 95% confidence interval [CI]: 0.36–26.14; p=0.39) and DP (IRR: 1.36, 95% CI: 0.21–8.85; p=0.90) groups. Among secondary outcomes, relative to the daily Proguanil group, the incidence of painful events was similar in the monthly SP-AQ and DP groups, while monthly DP reduced the rate of dactylitis (IRR: 0.47; 95% CI: 0.23–0.96; p=0.04) and of P. falciparum infection (IRR 0.21; 95% CI: 0.08—0.56; p<0.01). Serious adverse events were common but distributed between groups. Conclusions: Despite limited malaria transmission, monthly malaria chemoprevention with dihydroartemisininpiperaquine reduced dactylitis and P. falciparum parasitization in Kenyan children with sickle cell anemia.</p>\n
      • implication_results<ol class=\"bulleted\" style=\"box-sizing: border-box; margin: 0px 0px 0.8125rem 1.25rem; padding-right: 0px; padding-left: 0px; font-family: Helvetica, Arial, sans-serif; font-size: 0.8125rem; line-height: 1.125rem; list-style-position: outside; color: rgb(32, 32, 32);\">\n <li style=\"box-sizing: border-box; margin: 0px 0px 9px; padding: 0px 0px 0px 1.25rem; position: relative;\">\n Monthly DP may be an alternative to existing chemoprevention regimens for children with SCA owing to its safety, acceptability, and efficacy on hematologic events.</li>\n <li style=\"box-sizing: border-box; margin: 0px 0px 9px; padding: 0px 0px 0px 1.25rem; position: relative;\">\n SP-AQ-associated mortality among children with SCA was unexpected and though it did not achieve statistical significance merits further evaluation.</li>\n <li style=\"box-sizing: border-box; margin: 0px 0px 9px; padding: 0px 0px 0px 1.25rem; position: relative;\">\n Further studies are needed to compare chemoprevention regimens on parasitologic and hematologic outcomes in areas of high <em style=\"box-sizing: border-box; line-height: inherit;\">P</em>. <em style=\"box-sizing: border-box; line-height: inherit;\">falciparum</em> transmission and delivered through routine SCA providers.</li>\n</ol>\n
      • quantity_imported
      • quantity_dispensed
      • quantity_destroyed
      • quantity_exported
      • balance_site
      • final_date0000-00-00
      • modified2023-03-21 08:41:25
      • created2017-06-23 12:32:06
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id391
        • application_id613
        • given_nameFestus
        • middle_nameMuigai
        • family_nameNjuguna
        • qualificationMBChB PhD
        • professional_addressPO Box 4606-30100
        • telephone+254 721 219 761
        • emailmuigaifes2000@yahoo.com
        • created2017-06-23 12:38:52
        • modified2020-03-09 15:41:18
    • SiteDetail(array)
      • 0(array)
        • id496
        • application_id613
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2017-06-23 12:38:52
        • modified2020-03-09 15:41:18
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id314
        • application_id613
        • sponsorDuke Clinical Research Institute
        • sponsor_typeResearch Institution
        • contact_personDr Steve Taylor
        • addressBox 102359 DUMC, 303 Research Dr, Sands Bldg Rm 301, Durham, NC 27710, USA
        • telephone_number+01-919-684-5815
        • fax_number
        • cell_number+01-919-824-5232
        • email_addresssteve.taylor@duke.edu
        • created2017-06-23 12:38:52
        • modified2020-03-09 15:41:18
  • 3(array)
    • Application(array)
      • id618
      • user_id613
      • trial_status_id5
      • abstract_of_study<p>\n Mother to Child Transmission of HIV is still an important public health concern. Kenya has approximately 1.5 million live births per year, 200,000 thousands of which are HIV exposed. While there is a critical need for ARVs for use as prophylaxis and treatment of neonates, neonatal safety and dosing information are not available for most ARVs. Only zidovudine, lamivudine, emtracitabine, and nevirapine are approved for use in neonates under 14 days old. Lopinavir/ritonavir is only approved in neonates more than 2 weeks of age. The three-drug ARV regimen with the greatest experience in neonates is ZDV/3TC/NVP, and alternative agents for use in this population are urgently needed. Maraviroc is a CCR5 receptor antagonist used in the treatment of HIV-1 infection. The safety and efficacy of maraviroc have been confirmed in Phase II-IV clinical trials. Maraviroc works as an entry inhibitor, blocking entry of HIV into vulnerable host lymphocytes. It was approved to treat CCR5 tropic HIV-1 infected adults in 2007. Current United States (US) guidelines recommend maraviroc for use in HIV-1 infected adults as second line therapy. Postnatal prophylaxis with multiple antiretroviral agents is currently recommended for HIV-exposed neonates at high risk for acquiring HIV infection. Due to the lack of adequate neonatal safety and PK data, the ARV options are limited to several NRTI’s and the NNRTI nevirapine, as indicated above, that can be safely used in neonates. Maraviroc, as an HIV entry inhibitor, has a different mechanism of action from the NRTIs and NNRTIs, making it attractive as a potential component of neonatal prophylaxis regimens. Maraviroc’s novel mechanism of action might be especially valuable for infants born to mothers with HIV strains resistant to the more commonly used ARV classes. This study aims to study the study the pharmacokinetics and safety of maraviroc in HIV-1 exposed infants at risk of acquiring HIV-1 infection. HIV-1 exposed infants who are less than 3 days old and are HIV negative will be enrolled in this study. The infants will be stratified into efavirenz exposure and no efavirenz exposure. A total of 72 mother-infant pairs to achieve a target of 36 evaluable infants receiving the final recommended dose of maraviroc. The Kericho site will enroll 20 mother –infant pairs. The study duration will be approximately 28 months. Accrual is expected to last approximately 24 months and enrolled infants will be followed for 4 months.</p>\n
      • study_title<p>\n Phase I Safety and Pharmacokinetic Study of Maraviroc in HIV-1-Exposed Infants at Risk of Acquiring HIV-1 Infection.</p>\n
      • laymans_summary<p>\n Mother to Child Transmission of HIV is still an important public health concern. Kenya has approximately 1.5 million live births per year, 200,000 thousands of which are HIV exposed. While there is a critical need for HIV drugs for use as prevention and treatment of newborns, newbornl safety and dosing information are not available for most HIV drugs. Only zidovudine, lamivudine, emtracitabine, and nevirapine are approved for use in newborns under 14 days old. Lopinavir/ritonavir is only approved in newborns more than 2 weeks of age.  Maraviroc is a new HIV drug used in the treatment of HIV-1 infection. The safety and efficacy of maraviroc have been confirmed in adults.  This study will look at the safety and dosing of maraviroc in newborns who are HIV exposed</p>\n
      • short_titlePhase I Safety and Pharmacokinetic Study of Maraviroc in HIV-1-Exposed Infants at Risk of Acquiring HIV-1 Infection.
      • protocol_noECCT/17/08/05
      • version_no1.0
      • date_of_protocol13-04-2016
      • study_drugMaraviroc
      • 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_nameSelzentry
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressisaac.tsikhutsu@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_letter0
      • applicant_statement1
      • applicant_participating_countries1
      • 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_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantIsaac Tsikhutsu
      • declaration_date102-08-2017
      • declaration_principal_investigatorIsaac Tsikhutsu
      • declaration_date202-08-2017
      • placebo_presentNo
      • study_objectives<h1>\n . OBJECTIVES</h1>\n<p>\n  </p>\n<h2>\n 9.1Primary Objectives</h2>\n<p>\n  </p>\n<p style=\"margin-left:5.75pt;\">\n 9.1.1 To evaluate the safety and tolerability of maraviroc solution, during the first six weeks of life, when administered with ARV prophylaxis to HIV-1 exposed infants at risk of acquiring HIV-1 infection with and without exposure to maternal EFV.</p>\n<p style=\"margin-left:5.75pt;\">\n 9.1.2 To evaluate the pharmacokinetics of maraviroc solution, during the first six weeks of life, when administered with ARV prophylaxis to HIV-1 exposed infants at risk of acquiring HIV-1 infection with</p>\n<p style=\"margin-left:5.75pt;\">\n and without exposure to maternal EFV.</p>\n<p style=\"margin-left:5.75pt;\">\n 9.1.3 To determine an appropriate dose of maraviroc solution during the first six weeks of life.</p>\n<p>\n  </p>\n<h2>\n 9.2 Secondary Objectives</h2>\n<p>\n  </p>\n<p style=\"margin-left:5.75pt;\">\n 9.2.1 To assess safety through 16 weeks of life following administration of maraviroc solution during the first six weeks of life.</p>\n<p style=\"margin-left:5.75pt;\">\n 9.2.2 To determine age-related changes in maraviroc pharmacokinetic parameters during the first six weeks of life.</p>\n<p style=\"margin-left:5.75pt;\">\n 9.2.3 To explore the impact of maraviroc treatment on viral tropism in the event of perinatal transmission of an X4/dual-mixed tropic strain of HIV.</p>\n
      • principal_inclusion_criteria<p>\n HIV exposed infants, at least 37 weeks estimated gestational age , less than or equal to 3 days old, and  at least 2kg</p>\n
      • principal_exclusion_criteria<p>\n Infant has a positive HIV nucleic acid test at entry and mother received maraviroc during pregnancy</p>\n
      • primary_end_points<p>\n To evaluate the safety and tolerability of maraviroc solution, during the first six weeks of life, when administered with ARV prophylaxis to HIV-1 exposed infants at risk of acquiring HIV-1 infection with and without exposure to maternal EFV. To evaluate the pharmacokinetics of maraviroc solution, during the first six weeks of life, when administered with ARV prophylaxis to HIV-1 exposed infants at risk of acquiring HIV-1 infection with and without exposure to maternal EFV. To determine an appropriate dose of maraviroc solution during the first six weeks of life.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy0
      • scope_pharmacokinetic1
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response1
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology1
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<p>\n The U.S. Army Medical Research Directorate-Kenya (USAMRD-K) is a Special Foreign Activity of the Walter Reed Army Institute of Research (WRAIR), Washington, DC. USAMRD-K is affiliated through a Cooperative Agreement with the Kenya Medical Research Institute (KEMRI). The unit was activated on a temporary basis in 1969 at the invitation of the Government of Kenya to study trypanosomiasis. The success of that initial venture led to the establishment of a permanent activity in 1973. Over the past 46 years, research has been conducted on malaria, trypanosomiasis, leishmaniasis, entomology, HIV/AIDS and arboviruses, with more than 250 manuscripts published. The USAMRD-K HIV Program is a component of the U.S. Military HIV Research Program (USMHRP). In Kenya, the HIV Program field site is located at the Kenya Medical Research Institute/Walter Reed Project Clinical Research Center (KEMRI/WRP CRC) about 260 kilometers northwest of Nairobi along the Nairobi-Kisumu highway in the rural Kenyan town of Kericho. Kericho County’s population is approximately 900,000, although the larger catchment area for both HIV research and treatment is approximately 2.7 million covering the Southern portion of the former Rift Valley Province. Kericho town is located among the Kenyan Highlands in the Rift Valley and well known for the growing of tea that forms the rolling “seas of green” within the tea plantations. Kiswahili is most spoken language within the town. The primary industry in this region is tea farming, with two large international tea companies namely Finlay’s Kenya Ltd. and Unilever Tea Kenya Ltd. being centered in Kericho County. Kericho was ranked as the twentieth richest County in Kenya in the 2005/06 National Integrated Household Budget Survey. Income in Kericho comes mainly from agricultural activities, with about 40-50% of the population living below the poverty line. The annual national gross domestic product per capita in 2005 averaged Kenyan shilling (Ksh) 35,045 (equivalent to 350 United States dollar (USD) at current exchange rates of 1 USD = Ksh 100). In Kenya, the age of majority (i.e. legal age of recognized adulthood or independence) is 18 years. The Kenyan national literacy level according the Kenya Adult Literacy Survey report published in March 2007 by the Kenya National Bureau of Statistics was 64%. In Kericho, the literacy level is 74.3% in men and 68.9% in women. The Kericho CRC, established in 1998, is located 260 km Northwest of Nairobi in Kericho town on the grounds of the Ministry of Health, Kericho County Referral Hospital. USAMRD-K has been in Kenya for 45 years and has partnered with KEMRI since 1980. KEMRI is a Government of Kenya Para-state Corporation responsible for health research. The CRC has three integrated main components: HIV care, HIV and microbiology research. Since 2003 the CRC has been conducting diverse studies including randomized, double-blind, placebo controlled and IND/FDA-regulated studies The CRC has 181 local and one U.S. staff with appropriate trainings to support the clinical trials and HIV care and treatment programs. The staff includes; 10 doctors, 3 pharmacists, 12 clinical officers, 25 nurses, 36 laboratory technologists and six 6 accountants among others. The CRC has a Community Advisory Board, strong community engagement programs, efficient participant recruitment, retention and follow-up processes. The CRC protocols are reviewed by the KEMRI and WRAIR IRBs. The CRC’s, secure physical infrastructure includes: 1) 13,400 square feet (sq. ft.) clinical research building for reception, waiting areas, clinical procedures, consultation, sample collection, pharmacy, quality assurance, IT servers, data entry, participants’ chart archives, and sample storage, 2) 26,115 sq. ft. Laboratory space, 3) two liquid nitrogen plants, 4) four back-up generators 5) 13,500 sq. ft. administration and 6) 6,000 sq. ft. store. Both the CRC pharmacy and laboratory are approved by the National Institute of Allergy and Infectious Diseases/Division of AIDS (NIAID/DAIDS) to participate in DAIDS sponsored vaccine (Site # 1502) and therapeutics (Site #12501) and International Maternal, Pediatric, and Adolescent AIDS Clinical Trials (IMPAACT) Group (Site # 5121) studies, the only research site with such approval in Kenya. The laboratory is also College of American Pathologists (CAP) accredited and consists of three main sections: HIV, Microbiology and Mycobacterium Tuberculosis (TB). The KEMRI/WRP CRC research activities are integrated with a large comprehensive public health HIV care, treatment and prevention program managed by KEMRI/WRP and supported by PEPFAR which covers a population of about 2.7 million people in the SRV which is also the CRC research catchment area. Elements supported by the program includes: Antiretroviral Therapy (ART), non-ART, TB/HIV co-infections, Prevention of Mother To Child Transmission of HIV (PMTCT), HIV Testing and Counseling Services (HTS), primary HIV infection prevention in both low and high-risk populations, Orphans and Vulnerable Children (OVC), and Voluntary Medical Male Circumcision (VMMC). Kenya had an estimated population in 2012 of 43 million people, 22% of whom are urban and with an annual population growth rate of 2.4%. The adult (15-64 years) HIV/AIDS prevalence rate is 5.6% (6.9% in women, and 4.4% in men). HIV prevalence among children aged 18 months to 14 years was 0.9%. Approximately 2000 HIV exposed infants are born each year in the South Rift.</p>\n
      • other_details_explanation<p>\n The trial is being conducted in Kenya and the host country of the sponsor( USA)</p>\n
      • other_details_regulatory_notapproved<p>\n Walter Reed Army Institute of Research (WRAIR) IRB- 17 Jan 2017</p>\n
      • other_details_regulatory_approved<p>\n KEMRI SERU- 19th april 2017</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration28 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_areaKenya Medical Research Institute/Walter Reed Project HIV Program, Kericho
      • single_site_physical_addressHospital Road, Kericho
      • single_site_contact_personDr Isaac Tsikhutsu
      • single_site_telephone0729110124
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states5
      • number_of_sites
      • multi_country_listKenya, USA, South Africa, Uganda, Thailand
      • data_monitoring_committeeYes
      • total_enrolment_per_site20
      • total_participants_worldwide72
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornYes
      • population_infant_and_toddlerYes
      • population_childrenNo
      • population_adolescentNo
      • population_above_18No
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifynew born children less than 3 days old
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameEdner
      • investigator1_middle_name
      • investigator1_family_nameOpenda
      • investigator1_qualificationDip. Clinical Medicine
      • investigator1_professional_addressP.O. Box 1357-20200, Kericho
      • investigator1_telephone0729110129
      • investigator1_emailEdner.Openda@usamru-k.org
      • organisations_transferred_No
      • number_participants20
      • notification
      • approval_date12-10-2017
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted25-09-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"1053\">\n <tbody>\n <tr>\n <td colspan=\"3\" style=\"width:702px;height:21px;\">\n <ol style=\"list-style-type:upper-alpha;\">\n <li>\n <strong>General Information</strong>: All Principal Investigators listed in Protocol must sign the Closure Form.</li>\n </ol>\n </td>\n </tr>\n <tr>\n <td style=\"width:288px;height:17px;\">\n <p align=\"center\">\n  </p>\n <p align=\"center\">\n <strong>Name of Principal Investigator(s):</strong></p>\n </td>\n <td style=\"width:180px;height:17px;\">\n <p>\n  </p>\n <p>\n <strong>Institutional Affiliation</strong></p>\n </td>\n <td style=\"width:234px;height:17px;\">\n <p align=\"center\">\n  </p>\n <p align=\"center\">\n <strong>Sign and Date</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:288px;height:48px;\">\n <p>\n  </p>\n <p>\n Isaac Tsikhutsu MBChB; MMED, FPCCM </p>\n </td>\n <td style=\"width:180px;height:48px;\">\n <p>\n  </p>\n <p>\n KEMRI/Walter Reed Project</p>\n </td>\n <td style=\"width:234px;height:48px;\">\n <p align=\"center\">\n  </p>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"width:702px;height:48px;\">\n <p>\n <strong>Study Title: </strong>Phase I Safety and Pharmacokinetic Study of Maraviroc in HIV-1-Exposed Infants at Risk of Acquiring HIV-1 Infection.</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"width:702px;height:18px;\">\n <p>\n  <strong>B. Study Status at Close-out:</strong></p>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"width:702px;height:85px;\">\n <p>\n [X] Study was completed</p>\n <p>\n [] Study was started but closed prior to completion</p>\n <p>\n [] Study was not started</p>\n <p>\n [] Study is being transferred to another institution</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"width:702px;height:24px;\">\n <p>\n <strong>D. Provide a summary of research objectives:</strong></p>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"width:702px;height:79px;\">\n <p>\n <strong>Primary Objectives </strong></p>\n <ol>\n <li>\n To evaluate the safety and tolerability of maraviroc solution, during the first six weeks of life, when administered with ARV prophylaxis to HIV-1 exposed infants at risk of acquiring HIV-1 infection with and without exposure to maternal EFV.</li>\n <li>\n To evaluate the pharmacokinetics of maraviroc solution, during the first six weeks of life, when administered with ARV prophylaxis to HIV-1 exposed infants at risk of acquiring HIV-1 infection with and without exposure to maternal EFV.</li>\n <li>\n To determine an appropriate dose of maraviroc solution during the first six weeks of life. </li>\n </ol>\n <p>\n  <strong>Secondary Objectives </strong></p>\n <ol>\n <li>\n To assess safety through 16 weeks of life following administration of maraviroc solution during the first six weeks of life.</li>\n <li>\n To determine age-related changes in maraviroc pharmacokinetic parameters during the first six weeks of life.</li>\n <li>\n To explore the impact of maraviroc treatment on viral tropism in the event of perinatal transmission of an X4/dual-mixed tropic strain of HIV.</li>\n </ol>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"width:702px;height:46px;\">\n <p>\n <strong>F. Summary of Study Results: </strong>Please summarize the results of this research project, even if only for the study cohort enrolled locally.</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"width:702px;height:35px;\">\n <p>\n <strong>Objective:</strong> The aim of this study was to evaluate safety and pharmacokinetics of maraviroc administered with standard antiretroviral prophylaxis to HIV-1 exposed infants and to determine the appropriate dose of maraviroc during the first 6 weeks of life.</p>\n <p>\n <strong>Design:</strong> A phase I, multicenter, open-label study enrolling two sequential cohorts.</p>\n <p>\n <strong>Methods:</strong> Participants enrolled by day 3 of life and were stratified by exposure to maternal efavirenz. Cohort 1 participants received two single 8 mg/kg maraviroc doses 1 week apart with pharmacokinetic sampling after each dose. Cohort 2 participants received 8 mg/kg maraviroc twice daily through 6 weeks of life with pharmacokinetic sampling at weeks 1 and 4. Maraviroc exposure target was Cavg at least 75 ng/ml. Laboratory and clinical evaluations assessed safety.</p>\n <p>\n <strong>Results:</strong> Fifteen Cohort 1 and 32 Cohort 2 HIV-exposed neonates were enrolled (median gestational age 39 weeks, 51% male). All 13 evaluable Cohort 1 infants met the pharmacokinetic target. Median exposure for the 25 evaluable Cohort 2 infants met the pharmacokinetic target but variability was high, with 17–33% of infants below</p>\n <p>\n target at Weeks 1 and 4. Pharmacokinetic target achievement was similar between efavirenz exposure strata. No Grade 3þ toxicities, early study or treatment discontinuations due to maraviroc occurred. Conclusion: Median maraviroc exposure met the Cavg target in neonates receiving 8 mg/kg twice daily, although exposures were variable. Maternal efavirenz use did not impact maraviroc exposure and no discontinuations were due to maraviroc toxicity/intolerance. No infants acquired HIV-1 infection during follow-up. Maraviroc 8 mg/kg</p>\n <p>\n twice daily appears well tolerated during the first 6 weeks of life.</p>\n <p>\n  </p>\n <p>\n <strong>The Kericho site was to enroll 20 mother –infant pairs.</strong> The study briefed 8 participants, 4 were screened and 2 were enrolled. The 2 enrolled were 1 female and 1 male neonate. They all successfully completed the study visits after 4 months of follow up.</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"width:702px;height:41px;\">\n <p>\n <strong>G. List Outputs arising from study e.g. Manuscripts, Thesis, Research Reports, Technical Briefs, Policy Briefs, Abstracts, Patents, Book Chapter etc. (attach copies of the outputs(s). </strong></p>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"width:702px;height:25px;\">\n <ul style=\"list-style-type:circle;\">\n <li>\n Manuscript on Pharmacokinetics and Safety of maraviroc in neonates.</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"width:702px;height:14px;\">\n <ol style=\"list-style-type:upper-alpha;\">\n <li value=\"8\">\n <strong>Confirm destruction of each study participant’s identifiers and provide an assurance/evidence that the destruction has occurred (send copies of the blacked-out books). </strong></li>\n </ol>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"width:702px;height:31px;\">\n <p>\n Study documents have been transferred to a safe, secured, long-term archive room that is only accessible to regulatory personnel. All other research staff do not have access to this archive room. Access to study documents is controlled and restricted and the site is responsible for ensuring that any access is accurately recorded and any documents accessed/removed and returned are recorded. Destruction approval will be obtained from the sponsor and the IRBs will be notified when this is done.</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"width:702px;\">\n <p>\n <strong>I. Detail the plan for future use of data from the study (if applicable) </strong></p>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"width:702px;height:33px;\">\n <ul style=\"list-style-type:circle;\">\n <li>\n There are currently no plans for future analysis of individual participant data by study site personnel.</li>\n <li>\n Any plans for future (non-aggregated) analyses will be reviewed and approved by KEMRI SERU prior to the work being completed.</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"width:702px;\">\n <p>\n <strong>J. Confirm destruction of surplus investigational agents and provide an assurance/evidence that the destruction has occurred (if applicable).</strong></p>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"width:702px;height:25px;\">\n <table border=\"1\" cellpadding=\"0\" cellspacing=\"0\">\n <tbody>\n <tr>\n <td style=\"width:646px;height:18px;\">\n <p>\n Please find attached IP  Certificate of Destruction.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:646px;height:4px;\">\n <p>\n  </p>\n </td>\n </tr>\n </tbody>\n </table>\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"width:702px;\">\n <p>\n <strong>K. Detail the plan for the destruction, storage, or future use of biological specimens obtained as part of this study (include number of samples being destroyed or stored) </strong></p>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"width:702px;height:23px;\">\n <p style=\"margin-left:.25pt;\">\n All work for this study is complete and there are no stored samples.  </p>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"width:702px;\">\n <p>\n <strong>L. Were the study results communicated to the local community? If yes provide details where and when- if not kindly explain why not.</strong></p>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"width:702px;height:27px;\">\n <p>\n  </p>\n <p>\n The study results will be communicated to the local community through continuous medical education and meeting with the community Advisory Board.</p>\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"width:702px;\">\n <p>\n <strong>M. Is there a policy implication or best practice that should be forwarded to the MOH or any relevant authority?  </strong></p>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"width:702px;height:81px;\">\n <p>\n Yes, from the Publication:</p>\n <ul style=\"list-style-type:circle;\">\n <li>\n Maraviroc solution appears well tolerated at the dose of approximately 8mg/kg given b.i.d. over the first 6weeks of life in HIV-1-exposed neonates at risk of acquiring infection. There were no safety concerns identified through 16 weeks of follow-up, as none of the participants who received at least one dose of the study drug met any of the safety endpoints.</li>\n <li>\n As with other antiretrovirals in young infants, maraviroc pharmacokinetic parameters showed high intra and inter-participant variability, but approximately two-thirds of the infants in Cohort 2 achieved the pharmacokinetic target of Cavg atleast 75 ng/ml at Weeks 1 and 4. Maternal efavirenz use prenatally or during breastfeeding appeared to have no effect on maraviroc exposure so infant dose adjustment should not be required. Maraviroc is a promising agent in combination with standard antiretrovirals for prophylaxis and presumptive treatment of HIV-1-exposed term neonates.</li>\n </ul>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • implication_results<p>\n Yes, from the Publication:</p>\n<p>\n Ø  Maraviroc solution appears well tolerated at the dose of approximately 8mg/kg given b.i.d. over the first 6weeks of life in HIV-1-exposed neonates at risk of acquiring infection. There were no safety concerns identified through 16 weeks of follow-up, as none of the participants who received at least one dose of the study drug met any of the safety endpoints.</p>\n<p>\n As with other antiretrovirals in young infants, maraviroc pharmacokinetic parameters showed high intra and inter-participant variability, but approximately two-thirds of the infants in Cohort 2 achieved the pharmacokinetic target of Cavg atleast 75 ng/ml at Weeks 1 and 4. Maternal efavirenz use prenatally or during breastfeeding appeared to have no effect on maraviroc exposure so infant dose adjustment should not be required. Maraviroc is a promising agent in combination with standard antiretrovirals for prophylaxis and presumptive treatment of HIV-1-exposed term neonates.</p>\n
      • quantity_importedFind attached product accountability documents
      • quantity_dispensedFind attached product accountability documents
      • quantity_destroyedFind attached product accountability documents
      • quantity_exportedFind attached product accountability documents
      • balance_site0
      • final_date0000-00-00
      • modified2023-12-04 15:56:23
      • created2017-07-17 12:43:32
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id395
        • application_id618
        • given_nameIsaac
        • middle_name
        • family_nameTsikhutsu
        • qualificationMBCHB, MMED, FPCCM
        • professional_addressP.O. Box 1357-20200, Kericho
        • telephone0729110124
        • emailisaac.tsikhutsu@usamru-k.org
        • created2017-07-17 12:50:38
        • modified2020-09-25 11:26:43
    • SiteDetail(array)
      • 0(array)
        • id502
        • application_id618
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2017-07-17 12:50:38
        • modified2020-09-25 11:26:43
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id317
        • application_id618
        • sponsorNational Institute Of Allergy and Infectious Diseases
        • sponsor_typeResearch Institution
        • contact_person
        • address5601 Fishers Lane, MSC 9806, Bethesda, MD 20892-9806, Rockville, MD 20852, USA
        • telephone_number301-402-1663
        • fax_number
        • cell_number301-496-5717
        • email_addressocpostoffice@niaid.nih.gov
        • created2017-07-17 12:50:38
        • modified2020-09-25 11:26:43
  • 4(array)
    • Application(array)
      • id580
      • user_id66
      • trial_status_id4
      • abstract_of_study<p>\n A PHASE IV RANDOMIZED TRIAL TO EVALUATE THE VIROLOGIC RESPONSE AND PHARMACOKINETICS OF TWO DIFFERENT POTENT REGIMENS IN HIV INFECTED WOMEN INITIATING TRIPLE ANTIRETROVIRAL REGIMENS BETWEEN 28 AND 36 WEEKS OF PREGNANCY FOR THE PREVENTION OF MOTHER-TO-CHILD TRANSMISSION: NICHD P1081</p>\n<p>\n  </p>\n<p style=\"margin-left:99.0pt;\">\n <strong><u>DESIGN</u>:</strong>                Multicenter two arm randomized open-label trial comparing the ability to achieve virologic suppression at delivery, tolerability, and safety.</p>\n<p style=\"margin-left:99.0pt;\">\n  </p>\n<p style=\"margin-left:99.0pt;\">\n <strong><u>SAMPLE SIZE</u>:</strong>     334 evaluable mother-infant pairs (approximately 167 per arm), which is projected to require enrolling approximately 394 mother-infant pairs.</p>\n<p style=\"margin-left:99.0pt;\">\n  </p>\n<p style=\"margin-left:99.0pt;\">\n <strong><u>POPULATION</u>:</strong>     Human Immunodeficiency Virus (HIV)-1 infected pregnant women with a gestational age between 28 and 36 weeks who are antiretroviral (ARV) naïve or have received short-course zidovudine (maximum of 8 weeks) only for prevention of mother-to-child transmission (PMTCT) in previous pregnancies, and their infants.</p>\n<p style=\"margin-left:99.0pt;\">\n  </p>\n<p style=\"margin-left:99.0pt;\">\n <strong><u>STRATIFY BY</u>:</strong>    Gestational age at enrollment (28-30 weeks or 31-33 weeks or 34-36 weeks) and whether the women will use lamivudine/zidovudine or an alternative, locally supplied nucleoside reverse transcriptase inhibitor (NRTI) backbone.</p>\n<p style=\"margin-left:99.0pt;\">\n  </p>\n<p style=\"margin-left:99.0pt;\">\n <strong><u>REGIMEN</u>:</strong>            Antepartum – Participants will be randomized 1:1</p>\n<p style=\"margin-left:99.0pt;\">\n  </p>\n<p style=\"margin-left:99.0pt;\">\n                                  Arm A: Lamivudine 150 mg/zidovudine 300 mg* twice daily (BID) + efavirenz 600 mg every night (QHS).</p>\n<p style=\"margin-left:99.0pt;\">\n  </p>\n<p style=\"margin-left:99.0pt;\">\n                                  Arm B: Lamivudine 150 mg/zidovudine 300 mg* BID + raltegravir 400 mg BID.</p>\n<p style=\"margin-left:99.0pt;\">\n                                  ____________________</p>\n<p style=\"margin-left:99.0pt;\">\n                                  *Alternative, locally supplied NRTI backbone may be used in place of lamivudine/zidovudine with permission of protocol team obtained prior to randomization.</p>\n<p style=\"margin-left:99.0pt;\">\n  </p>\n<p style=\"margin-left:99.0pt;\">\n                                  <u>Active labor</u>:</p>\n<p style=\"margin-left:99.0pt;\">\n                                  All participants will continue to receive study drugs during labor. In addition, in place of the oral fixed dose combination of lamivudine 150 mg/zidovudine 300 mg (or alternative NRTI backbone), participants may receive intravenous zidovudine, other dosing regimens of oral zidovudine, oral lamivudine and/or additional drugs during labor, according to local standard of care/guidelines.</p>\n<p style=\"margin-left:99.0pt;\">\n  </p>\n<p style=\"margin-left:99.0pt;\">\n                                  <u>Infants</u>:</p>\n<p style=\"margin-left:99.0pt;\">\n                                  Infants will receive ARV according to specific local guidelines.</p>\n<p style=\"margin-left:99.0pt;\">\n <strong><u>TREATMENT</u></strong></p>\n<p style=\"margin-left:99.0pt;\">\n <strong><u>DURATION</u>:</strong>          All women will receive their randomized study regimen from study entry through delivery. Women who meet local guidelines for receiving antiretroviral therapy (ART) will continue triple ART after delivery according to local guidelines. These women can receive study supplied drugs for up to 8 weeks after delivery to facilitate the transition to local standard of care for treatment for maternal health and/or prevention of breast milk transmission. Women who do not meet local guidelines for receiving triple ART will stop study supplied drugs immediately after delivery. Women randomized to Arm A (efavirenz) may continue lamivudine/ zidovudine for a period of time after stopping efavirenz at the discretion of the local investigator.</p>\n<p style=\"margin-left:99.0pt;\">\n  </p>\n<p style=\"margin-left:99.0pt;\">\n <strong><u>STUDY </u></strong></p>\n<p style=\"margin-left:99.0pt;\">\n <strong><u>DURATION</u>:</strong>          Women will be followed for 6 months after delivery. Infants will be followed until 6 months of age and may participate in an extension phase: developmental assessment of infants, lasting up to 4 years of age.</p>\n<p style=\"margin-left:99.0pt;\">\n  </p>\n<p>\n <strong><u>OBJECTIVES</u>:       </strong><u>Primary Objectives</u>:</p>\n<p style=\"margin-left:1.45in;\">\n  </p>\n<p style=\"margin-left:1.9in;\">\n 1.                To compare the ability of two triple ARV regimens (one containing efavirenz and the other raltegravir) begun during the third trimester of pregnancy to achieve a viral load of < 200 copies/mL at the time of delivery.</p>\n<p style=\"margin-left:1.9in;\">\n 2.                To compare the safety and tolerability of two triple ARV regimens (one containing efavirenz and the other raltegravir) begun during the third trimester of pregnancy.</p>\n<p style=\"margin-left:1.45in;\">\n  </p>\n<p style=\"margin-left:1.45in;\">\n <u>Secondary Objectives</u>:</p>\n<p style=\"margin-left:1.45in;\">\n  </p>\n<p style=\"margin-left:1.95in;\">\n 1.                  To compare the kinetics of viral decay between the treatment regimens:</p>\n<p style=\"margin-left:2.2in;\">\n a.       Compare decay of plasma and vaginal HIV-1 RNA and DNA between the treatment regimens.</p>\n<p style=\"margin-left:2.2in;\">\n b.      Compare decay of plasma HIV-1 infectivity between the treatment regimens.</p>\n<p style=\"margin-left:131.4pt;\">\n 2.            To compare infant outcomes including stillbirth, premature birth, low birth weight, perinatal HIV transmission, neurodevelopmental outcomes and to compare (in HIV-infected infants) drug resistance between the two treatment regimens.</p>\n<p style=\"margin-left:131.4pt;\">\n 3.            To assess the baseline prevalence and selection of HIV-1 drug-resistance to the study drugs, using standard genotyping and ultrasensitive genotyping methods.</p>\n<p>\n  </p>\n<p>\n  </p>\n<p style=\"margin-left:1.45in;\">\n <u>Exploratory Objectives</u>:</p>\n<p style=\"margin-left:1.45in;\">\n  </p>\n<p style=\"margin-left:1.7in;\">\n 1.      To describe the population pharmacokinetic (PK) parameters of efavirenz and raltegravir during the third trimester of pregnancy and postpartum using sparse sampling and to evaluate potential relationships between PK parameters, pharmacogenomics and viral load changes.</p>\n<p style=\"margin-left:1.7in;\">\n  </p>\n<p style=\"margin-left:1.7in;\">\n 2.      To describe the maternal vaginal and infant nasopharyngeal and oropharyngeal microbiome environment and the potential association with adverse outcome in HIV exposed uninfected children.</p>\n<p>\n  </p>\n
      • study_title<p align=\"center\" style=\"margin-left:.1in;\">\n <strong>A PHASE IV RANDOMIZED TRIAL TO EVALUATE THE VIROLOGIC RESPONSE AND PHARMACOKINETICS OF TWO DIFFERENT POTENT REGIMENS IN HIV INFECTED WOMEN INITIATING TRIPLE ANTIRETROVIRAL REGIMENS BETWEEN 28 AND 36 WEEKS OF PREGNANCY FOR THE PREVENTION OF MOTHER-TO-CHILD TRANSMISSION: </strong></p>\n<p align=\"center\" style=\"margin-left:.1in;\">\n <strong>NICHD P1081</strong></p>\n
      • laymans_summary(null)
      • short_titleP1081
      • protocol_noECCT/17/08/04
      • version_no3.0
      • date_of_protocol02-04-2015
      • study_drugRaltegravir, Efavirenz, Lamivudine, Zidovudine
      • disease_conditionHIV/AIDS
      • 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_nameRaltegravir, Efavirenz, Lamivudine, Zidovudine
      • product_type_medical_device_name
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressjoel.chebon@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_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_applicantLucy Koech - +254719193275
      • declaration_date101-08-2017
      • declaration_principal_investigatorDr. Frederick Sawe - +254703247902
      • declaration_date201-08-2017
      • placebo_presentNo
      • study_objectives(null)
      • principal_inclusion_criteria<h2>\n 4.1       Inclusion Criteria</h2>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<p>\n 4.1.1    Naïve to ART or have received ART with short course zidovudine (maximum of 8 weeks) for PMTCT in previous pregnancies.</p>\n<p>\n 4.1.2    Willingness and ability to sign informed consent. Participant must be of an age to provide legal informed consent as defined by the country in which the participant resides. If not, the informed consent must be signed by a legal guardian<strong>/</strong>parent, as per country guidelines.</p>\n<p>\n 4.1.3    Documentation of HIV-1 infection defined as positive results from <u>two</u> samples collected at <u>different</u> time points. The same method may be used at both time points. All samples tested must be whole blood, serum or plasma. Documentation maybe abstracted from medical records to satisfy these criteria for infection.</p>\n<p>\n The first test may be any of the following:</p>\n<p>\n  </p>\n<p>\n ·         HIV-1/2 Antigen and Antibodies test and confirmed HIV-1 from HIV-1/2 antibody differentiation test</p>\n<p>\n ·         Two rapid antibody tests from different manufacturers or based on different principles and epitopes</p>\n<p>\n ·         One rapid antibody test AND one [enzyme immunoassay OR Western blot OR immunofluorescence OR chemiluminescence]</p>\n<p>\n ·         One enzyme immunoassay AND one [Western blot OR immunofluorescence OR chemiluminescence]</p>\n<p>\n ·         One HIV DNA PCR</p>\n<p>\n ·         One quantitative HIV RNA PCR (above limit of detection)</p>\n<p>\n ·         One qualitative HIV RNA PCR</p>\n<p>\n ·         One HIV culture (prior to August 2009)</p>\n<p>\n ·         One total HIV nucleic acid</p>\n<p>\n If the first test(s) is positive, a second sample must be collected and tested using any of the tests listed above (except for qualitative RNA assays) at a laboratory participating in an appropriate external quality assurance program and either College of American Pathologists/CLIA approved (for US laboratories) or DAIDS-approved (for non-US laboratories).</p>\n<p>\n  </p>\n<p>\n It is strongly recommended that all kits/methods of analysis are Food and Drug Administration (FDA) approved.</p>\n<p>\n  </p>\n<p>\n 4.1.4    Viable pregnancy with gestational age of  ≥ 28 to ≤ 36 weeks based upon menstrual history and/or ultrasound.</p>\n<p>\n             <strong>Note: </strong>If menstrual history is unknown or if there is a discrepancy between menstrual history and ultrasound, determination of gestational age should be based upon best available methodology at each site.</p>\n<p>\n 4.1.5    Participant intends to continue pregnancy.</p>\n<p>\n 4.1.6    Willingness and intent to deliver at the participating clinical site and to be followed for the duration of the study at the site or associated outpatient facility.</p>\n<p>\n 4.1.7    Participant willing to comply with study regimen.</p>\n<p>\n 4.1.8    Participant agrees to use two reliable methods of contraception after delivery if randomized to the efavirenz arm and is sexually active. A barrier method of contraception (condoms, diaphragm, or cervical cap) together with another reliable form of contraception must be used for 4 weeks after stopping efavirenz.</p>\n
      • principal_exclusion_criteria<h2>\n 4.2       Exclusion Criteria</h2>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<p>\n 4.2.1    Active labor defined as onset of regular contractions or cervical dilatation greater than 2cm.</p>\n<p>\n 4.2.2    Use of ART during current pregnancy.</p>\n<p>\n 4.2.3    Chemotherapy for active malignancy.</p>\n<p>\n 4.2.4    HIV genotypic resistance, as defined in Appendix IV, to efavirenz or raltegravir or to NRTIs that will be included in the ART regimen. Note: A lack of HIV drug-resistance test results at the time of enrollment is not exclusionary.</p>\n<p>\n 4.2.5    Serious active opportunistic infection and/or serious bacterial infection including active TB or unstable or severe medical condition within 14 days of study entry.</p>\n<p>\n 4.2.6    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>\n 4.2.7    Any clinically significant diseases (other than HIV infection) or clinically significant findings during the screening medical history or physical examination that, in the investigator’s opinion, would compromise the outcome of this study.</p>\n<p>\n 4.2.8    Vomiting or inability to swallow medications due to an active, pre-existing condition that prevents adequate swallowing and absorption of study medication.</p>\n<p>\n 4.2.9    Known allergy/sensitivity to any study drugs or their formulations or sulfonamide allergy.</p>\n<p>\n 4.2.10  The following laboratory values (within 30 days of enrollment):</p>\n<p>\n ·         Hemoglobin ≥ Grade 3</p>\n<p>\n ·         Absolute neutrophil count ≥ Grade 2</p>\n<p>\n ·         Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) ≥ Grade 2</p>\n<p>\n ·         Serum creatinine ≥ Grade 1</p>\n<p>\n ·         Platelet count ≥ Grade 3</p>\n<p>\n 4.2.11  Evidence of pre-eclampsia (such as persistent diastolic blood pressure > 90 mmHg).</p>\n<p>\n 4.2.12  Receipt of disallowed medications described in Section 4.3.</p>\n
      • primary_end_points<p style=\"margin-left:1.0in;\">\n  </p>\n<h2>\n 8.2       Outcome Measures</h2>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<h3>\n 8.2.1    Primary Outcome Measures</h3>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p>\n <u>Efficacy</u>:</p>\n<p>\n  </p>\n<p>\n ·         Plasma HIV-1 viral load <200 copies/mL at the delivery visit (or if there is no viral load measurement at the delivery visit, viral load <200 copies/mL within 3 weeks prior to delivery).</p>\n<p>\n  </p>\n<p>\n Evaluable women will be those who have a viral load measurement at the delivery visit or within 3 weeks prior to delivery. Non-evaluable women (missing viral load measurement due to missed visits, specimen or laboratory error) will be excluded from the primary analysis. Sensitivity analyses will be conducted to assess the potential impact of missing evaluations on the conclusions of the study (see Section 8.6 for details).</p>\n<p>\n  </p>\n<p>\n <u>Tolerability until labor and delivery</u>:</p>\n<p>\n  </p>\n<p>\n ·         Discontinuation of efavirenz or raltegravir (whichever was assigned) prior to labor and delivery for any reason (including loss to follow-up) will be considered a treatment failure in this analysis (note: switching any of the NRTIs with continuation of efavirenz or raltegravir will not be considered a treatment failure).</p>\n<p>\n  </p>\n<p>\n Women who received at least one dose of efavirenz or raltegravir will be evaluable for the tolerability analysis.</p>\n<p>\n <u>Safety through week 24 postpartum</u>:</p>\n<p>\n  </p>\n<p>\n ·         Maternal and infant AEs of Grade ≥3 as defined in the DAIDS toxicity table.</p>\n<p>\n  </p>\n<p>\n Women who received at least one dose of a study drug, and their infants will be evaluable for the safety outcome measures.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
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      • scope_pharmacodynamic0
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      • trial_human_pharmacology0
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      • site_capacity(null)
      • staff_numbers<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">See the SSA section 24 page 49 WHICH STATES THE KEMRI /WRP CRC ROLES OF STUDY PERSONNEL</span></p>\n
      • other_details_explanation<p>\n N/A</p>\n
      • other_details_regulatory_notapproved<p>\n N/A</p>\n
      • other_details_regulatory_approved<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Walter Reed Army Institute of Research IRB approved through letter dated: Nov 09 2016</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n KEMRI SERU approved through letter dated: Nov 15 2016</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_durationEach study participant will be in the study for up to 28 Weeks. The trial is projected to last 2 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
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      • design_controlled_other_medicinal
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      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKenya Medical Research Institute Walter Reed Project Clinical Research Centre.
      • single_site_physical_addressOff Hospital Road
      • single_site_contact_personFredrick K Sawe
      • single_site_telephone+254 703 247 902
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states6 Countries
      • number_of_sites
      • multi_country_listUS = 13 Sites\nBrazil = 8 Sites\nArgentina = 2 Sites\nThailand = 2 Sites\nTanzania = 2 Sites\nKenya = 1 Site
      • data_monitoring_committeeYes
      • total_enrolment_per_siteN/A
      • total_participants_worldwide334
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornYes
      • population_infant_and_toddlerYes
      • population_childrenNo
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male0
      • subjects_healthyNo
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenYes
      • subjects_nursing_womenYes
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameFREDRICK
      • investigator1_middle_nameKIPYEGON
      • investigator1_family_nameSAWE
      • investigator1_qualificationMBChB, MMED
      • investigator1_professional_addressP.O. BOX 1357-20200 KERICHO
      • investigator1_telephone(05220)30388/30686
      • investigator1_emailFredrick.Sawe@usamru-k.org
      • organisations_transferred_Yes
      • number_participants100
      • notification
      • approval_date13-11-2017
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted01-08-2017
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
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      • final_report<p>\n <strong>INTRODUCTION:</strong></p>\n<p>\n  </p>\n<p>\n NICHD P1081 was a multicenter, phase IV, randomized, open-label, trial to evaluate the safety, tolerance, virologic response, pharmacologic and pharmacokinetics of representatives of two different potent ARV classes in HIV infected pregnant women initiating triple ARV regimens for PMTCT. The primary objectives of the study are to compare two triple ARV regimens (one containing efavirenz and the other raltegravir) 1) ability to achieve a viral load of < 200 copies/mL at the time of delivery and 2) safety and tolerability.</p>\n<p>\n  </p>\n<p>\n The participants were 334 (the Kericho site was to enroll 100) evaluable mother-infant pairs (approximately 167 per arm) of HIV infected pregnant women with a gestational age between 20 and 36 weeks who were antiretroviral (ARV) naïve or had received short-course zidovudine (maximum of 8 weeks) only for PMTCT. The participants were to be randomized 1:1 during the antepartum period to:  Arm A that was to use Lamivudine 150 mg/zidovudine 300 mg twice daily (BID) + efavirenz 600 mg every night (QHS) and Arm B that was to use Lamivudine 150 mg/zidovudine 300 mg BID + raltegravir 400 mg BID. The Infants were to receive ARV according to specific local guidelines i.e they were to be started on 12 weeks of infant prophylaxis:- AZT+NVP for 6 weeks, followed by NVP for 6 weeks. Women were to continue receiving triple antiretroviral therapy (ART) after delivery. Women were to be followed for 6 months after delivery. Infants will be followed until 6 months of age .</p>\n<p>\n  </p>\n<p>\n <strong>The study's objectives were as follows:  </strong></p>\n<p>\n <strong>Primary Objective</strong></p>\n<ol>\n <li>\n To compare the ability of two triple ARV regimens (one containing efavirenz and the other raltegravir) begun during the third trimester of pregnancy to achieve a viral load of < 200 copies/mL at the time of delivery.</li>\n <li>\n To compare the safety and tolerability of two triple ARV regimens (one containing efavirenz and the other raltegravir) begun during the third trimester of pregnancy.</li>\n</ol>\n<p style=\"margin-left:.5in;\">\n <strong>Secondary Objectives</strong></p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<ol>\n <li>\n To compare the kinetics of viral decay between the treatment regimens:</li>\n</ol>\n<p style=\"margin-left:.75in;\">\n  a. Compare decay of plasma and vaginal HIV-1 RNA and DNA between the treatment regimens.</p>\n<p style=\"margin-left:.75in;\">\n b. Compare decay of plasma HIV-1 infectivity between the treatment regimens.</p>\n<ol>\n <li value=\"2\">\n To compare infant outcomes including stillbirth, premature birth, low birth weight, perinatal HIV transmission, and to compare (in HIV-infected infants) drug resistance between the two treatment regimens.</li>\n <li value=\"3\">\n To assess the baseline prevalence and selection of HIV-1 drug-resistance to the study drugs, using standard genotyping and ultrasensitive genotyping methods.</li>\n</ol>\n<p style=\"margin-left:.5in;\">\n <strong>Exploratory Objectives</strong></p>\n<p style=\"margin-left:.5in;\">\n To describe the population PK parameters of efavirenz and raltegravir during the third trimester of pregnancy and postpartum using sparse sampling and to evaluate potential relationships between PK parameters, pharmacogenomics and viral load changes.</p>\n<p>\n  </p>\n<p>\n <strong>ENROLLMENT:      </strong>Nil. The study was a multi-center trial and full accrual occurred in other sites.</p>\n<p>\n  </p>\n<p>\n <strong>PRELIMINARY STUDY REPORT:          </strong>None.</p>\n<p>\n  </p>\n<p>\n <strong>LIST OF ABBREVIATIONS AND DEFINITION OF TERMS:   </strong>N/A</p>\n<p>\n  </p>\n<p>\n <strong>ETHICS: </strong>KEMRI SERU approval received. The KEMRI SERU Study Close-Out Approval is attached.</p>\n<p>\n  </p>\n<p>\n <strong>INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE: </strong>The site Principal Investigator was Dr Fredrick Sawe and Study Coordinator was Priscilla Bii.</p>\n<p>\n  </p>\n<p>\n <strong>INVESTIGATIONAL PLAN: N/A</strong></p>\n<p>\n  </p>\n<p>\n <strong>STUDY PATIENTS: None</strong></p>\n<p>\n  </p>\n<p>\n <strong>EFFICACY EVALUATION: N/A</strong></p>\n<p>\n  </p>\n<p>\n <strong>SAFETY EVALUATION: N/A</strong></p>\n<p>\n  </p>\n<p>\n <strong>DISCUSSION AND OVERALL CONCLUSIONS: </strong>The study never accrued any participants at the site.</p>\n<p>\n  </p>\n<p>\n <strong>REFERENCE LIST: </strong>N/A</p>\n<p>\n  </p>\n<p>\n <strong>APPENDICES: </strong>N/A</p>\n<p>\n  </p>\n<p>\n <strong>FUTURE PLANS: </strong>N/A</p>\n<p>\n  </p>\n<p>\n Thank you for your time and review.</p>\n<p>\n  </p>\n
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      • modified2019-07-10 14:07:10
      • created2017-01-23 15:48:05
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        • application_id580
        • given_nameFREDRICK
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        • professional_addressP.O. BOX 1357-20200 KERICHO
        • telephone(05220)30388/30686
        • emailFredrick.Sawe@usamru-k.org
        • created2017-01-23 15:54:00
        • modified2017-08-01 13:12:42
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        • county_id(null)
        • site_name
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        • created2017-01-23 15:54:00
        • modified2017-08-01 13:12:42
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        • application_id580
        • sponsorThe Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and The National Institute of Allergy and Infectious Diseases (NIAID)
        • sponsor_type(null)
        • contact_person
        • addressBoston Medical Center 771 Albany Street Dowling 4N, Room 4111 Boston, MA 02118
        • telephone_number617-414-3754
        • fax_number
        • cell_number617-414-3754
        • email_addressmarkm@bu.edu
        • created2017-01-23 15:54:00
        • modified2017-08-01 13:12:42
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