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      • id1489
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      • abstract_of_study<div>\n <strong>Title:</strong> Delivery strategies for malaria chemoprevention in the post-discharge management of hospitalised children with severe anaemia or severe malaria: cluster and individually randomised controlled implementation trials with nested economic evaluation in Kenya and Benin.</div>\n<div>\n Short Title: PDMC-Saves Lives (PDMC-SL)</div>\n<div>\n <strong>Background and rationale:</strong> In June 2022, the World Health Organization (WHO) recommended PDMC for the post-discharge management of children with severe anaemia in settings with moderate to high perennial malaria transmission to reduce hospital readmissions and deaths after discharge. However, there is no obvious delivery platform for PDMC, unlike for intermittent preventive treatment in infants (IPTi) or pregnant women (IPTp). Furthermore, a potential limitation of PDMC is adherence to the 3-day dosing regimen, which is provided monthly three times after discharge. Therefore, implementation research is urgently needed to support the introduction and scale-up of PDMC. We propose to conduct two implementation trials to evaluate delivery strategies to optimise adherence to PDMC in different contexts: one in East Africa (Kenya) and one in West Africa (Benin). The actual interventions to be evaluated differ between the two trials as they have been co-designed with national stakeholders during an initial formative research stage, conducted under a separate protocol (LSTM Protocol #23-053, KEMRI-SERU #480/4870).</div>\n<div>\n <strong>Aim:</strong> To conduct implementation trials, co-designed with national stakeholders, to evaluate different delivery strategies to optimise health system delivery of PDMC drugs and adherence to PDMC to provide evidence-based data including acceptability, feasibility and cost-effectiveness that are useful to decision-makers.</div>\n<div>\n Study Type: Kenya: A multi-centre, 2-arm, cluster-randomised trial evaluating two health system delivery strategies and a 3-arm nested individually randomised trial evaluating two new intervention strategies to enhance end-user adherence to PDMC compared to the standard of care without adherence strategies. Benin: A multi-centre, 3-arm, individually randomised trial evaluating two intervention strategies to enhance end-user adherence to PDMC compared to a control arm of PDMC without specific adherence support strategies.</div>\n<div>\n <strong>Sites: </strong>Health facilities with blood transfusion services in malaria-endemic areas in Benin and western Kenya.</div>\n<div>\n <div>\n Study Population:</div>\n <div>\n <strong>Clusters (Kenya only) inclusion criteria:</strong> health facilities with blood transfusion services offering in-patient care for children with severe anaemia and severe malaria. Exclusion criteria: primary health facilities without subservient lower-level health facilities. Individuals (Kenya and Benin) inclusion criteria: convalescent children aged <10 years, weighing ≥5 kg admitted with severe anaemia (haemoglobin<5g/dL) or severe malaria; clinically stable, able to take or switch to oral medication; post-transfusion Hb >5g/dL. Exclusion criteria: blood loss due to trauma, malignancy, known bleeding disorders or sickle cell disease, known hypersensitivity to study drug, known heart conditions, non-resident in the study area, previous participation in the study, known need at enrolment for prohibited medication and scheduled surgery during the 4-month course of the study. HIV infection and cotrimoxazole prophylaxis are not exclusion criteria.</div>\n <div>\n <strong>Study Interventions:</strong></div>\n <div>\n Cluster randomised trial (Kenya only): Hospitals will be randomised to one of two delivery platforms for PDMC (A or B). The choice of the two delivery strategies to be evaluated has been informed by formative research conducted under a separate standalone protocol (LSTM Protocol #23-053, KEMRI-SERU #480/4870) and stakeholder engagements. Strategy A comprises delivery of the initial PDMC course at the primary admitting facility two weeks after discharge during a post-discharge follow-up clinic visit. The subsequent 2 courses will be dispensed monthly at the closest health facility. Strategy B comprises delivery of all 3 PDMC courses at the primary admitting facility two weeks after discharge during a post-discharge follow-up clinic visit.</div>\n <div>\n Individually randomised trial (Kenya and Benin): The final choice of the adherence support strategies to be evaluated has been informed by formative research conducted under the same separate standalone protocol. In Kenya, these include: Arm a - SMS reminders to caregivers, Arm b - Community Health Promoter (CHP) support through monthly home visits and Arm c - no reminders (control). In Benin, these include: Arm a- a telephone reminder to the community health worker (CHW)/qualified community health worker (ASCQ); Arm b - regional social mobilisation research and support officer (CRAMS) reminder through monthly visits to CHW/ASCQ; and Arm c - no reminder (control).</div>\n <div>\n All participating children will receive standard in-hospital care for severe anaemia or severe malaria (blood transfusion, often combined parenteral artesunate, followed by a 3-day course of AL whether they initially had malaria or not), which will be started in-hospital as soon as they are able to take oral medication. Many children are likely to receive parenteral antibiotics as well as part of the standard of care.</div>\n <div>\n <strong>Endpoints:</strong> Cluster randomised trial (Kenya only): The primary endpoint will be the proportion of eligible participants who were not prescribed the full 3 courses of dpoints:PDMC. Individually randomised trial (Kenya and Benin): Primary endpoint: proportion of children with incomplete adherence to the 9 doses of PDMC (three courses of 3-day treatments 3x3=9). Secondary endpoints include 1) clinical effectiveness (all-cause and malaria-specific sick-child clinic visits, all-cause and cause-specific readmissions and all-cause mortality by the end of week 14 after discharge, 2) safety (incidence of serious adverse events), 3) cost-effectiveness, and 4) acceptability and feasibility.</div>\n <div>\n <strong>Follow-up procedures:</strong> Children will be followed for 14 weeks (i.e., four weeks after the last PDMC course) through passive surveillance of clinic visits and hospitalisations. Each child will then be seen for an end-of-study visit towards the end of week 14. Children will also be visited at home for unannounced home visits one to three days from the last day of the last dose of each 3-day course of PDMC medication to assess adherence.</div>\n <div>\n Sample size: Cluster randomised trial (Kenya only): Approximately 60 participants per cluster (cluster size will vary between clusters), or approximately 600 overall (300 in each of the two study arms) is estimated to provide over 80% power to detect a risk difference of 20% from 35% in the control arm to 15% in the intervention clusters (RR=0.43), using a two-sided alpha of 0.05, and assuming an intra-cluster correlation coefficient (ICC) of 0.03, a coefficient of variation of 0.39,15% loss to follow-up and small-sample correction to account for the small number of clusters. Individually randomised trial (Kenya and Benin): A sample size of 147 participants in the control arm (c) and 147 in each of the two intervention arms (a and b), totalling 441 participants, would provide 90% power to detect a 50% reduction in the primary endpoint (proportion of children with incomplete adherence to the 9 doses of PDMC) from 36.8% in the control arm to 18.4% (RR=0.50) in any of the two intervention arms using a 1:1:1 allocation after accounting for the multiple comparisons (α = 0.025). A total of 519 participants (173 per arm) will be recruited to allow for a 15% loss to follow-up.</div>\n <div>\n <strong>Data Analysis:</strong> Risk ratios and corresponding 95% confidence intervals will be computed to compare treatment effects using multi-level mixed models (Kenya) or mixed models (Benin) accounting for clustering effects.</div>\n <div>\n <strong>Partners institutions</strong>: IRCB, Benin; KEMRI Kisumu, Kenya; LSTM, UK; Epicentre, France; IRD, France; Centers for Disease Control and Prevention, US; TRUE, Malawi.</div>\n</div>\n<div>\n  </div>\n
      • study_title<p>\n Delivery strategies for malaria chemoprevention in the post-discharge management of hospitalised children with severe anaemia or severe malaria: cluster and individually randomised controlled implementation trials with nested economic evaluation in Kenya and Benin</p>\n
      • laymans_summary<div>\n <strong>Background:</strong> The World Health Organization (WHO) recommended post-discharge malaria chemoprevention (PDMC) in June 2022 for managing children with severe anaemia in areas with moderate to high perennial malaria transmission. The goal is to reduce hospital readmissions and deaths after discharge. However, there is no clear delivery platform for PDMC, and adherence to the 3-day dosing regimen, provided monthly three times after discharge, is a potential limitation. Implementation research is necessary to support the introduction and scale-up of PDMC.</div>\n<div>\n <strong>Aim: </strong>Implementation trials in Kenya and Benin will be co-designed with national stakeholders to evaluate alternative health system delivery strategies for optimizing delivery of PDMC drugs and adherence to PDMC. The trials will provide evidence on the acceptability, feasibility, and cost-effectiveness of each strategy to inform effective implementation and scale-up of PDMC in different country and health system contexts.</div>\n<div>\n <strong>Methods:</strong> The project involves two separate trials, one in each country. Formative research with the Ministries of Health in the two countries and their stakeholders has informed the delivery strategy interventions selected to be evaluated in each trial. In Kenya, a multi-centre, 2-arm cluster randomised trial will compare two “delivery strategies” for the 3 courses of monthly PDMC with dihydroartemisinin-piperaquine (DP). The trial will randomize 10 hospitals (the clusters) to one of two delivery platforms (A and B) in a 1:1 ratio, with the final choice of intervention informed by formative research. The primary endpoint will be the proportion of eligible participants prescribed with incomplete courses of PDMC. A nested 3-arm individually randomised trial involving 600 children ( 200 per arm) will evaluate 3 different “adherence support” strategies, including SMS reminders to caregivers, Community Health Worker (CHW) support through home visits, and a control arm comprising of provision of all 3 PDMC courses by the hospital where the child was admitted i.e. standard of care. The primary endpoint will be the proportion of children with incomplete adherence (i.e. not receiving all 9 doses of PDMC).</div>\n<div>\n Secondary endpoints include clinical effectiveness, cost-effectiveness, acceptability and feasibility, provision of adherence support mechanisms, and linkage to subsequent levels of service provision along the PDMC delivery continuum. All participating children will receive standard in-hospital care for severe anaemia or severe malaria and a 3-day course of artemether-lumefantrine (AL), started in-hospital as soon as they can take oral medication.</div>\n<div>\n In Benin, a 3-arm individually randomised trial involving 519 children (173 per arm) will be conducted to evaluate different “adherence support” strategies only, including: mobile phone reminders to CHW/ASCQ , monthly reminder visits to CHW/ASCQ by the regional social mobilisation research and support officer (CRAMS), and a control arm without any reminder intervention.</div>\n<div>\n LSTM-UK will act as the legal sponsor of the trials in Kenya. The Institut de Recherche Clinique du Bénin (IRCB) will act as the sponsor for the trial in Benin.</div>\n
      • short_titlePDMC-Saves Lives (PDMC-SL)
      • protocol_noECCT/24/12/01
      • version_no1.3
      • date_of_protocol06-09-2024
      • study_drugDihydroartemisinin-piperaquine
      • 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_nameDihydroartemisinin-piperaquine
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressruth.njoroge@ke.lstmed.ac.uk
      • applicant_covering_letter1
      • applicant_protocol1
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      • applicant_investigators_brochure1
      • applicant_investigators_cv1
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      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum0
      • applicant_fees1
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      • declaration_applicantDr. Ruth Njoroge - Pharmacist
      • declaration_date105-12-2024
      • declaration_principal_investigatorDr. Juliet Otieno Awori - Principal Investigator
      • declaration_date205-12-2024
      • placebo_presentNo
      • study_objectives<div>\n <div>\n <strong>Primary Objectives</strong></div>\n</div>\n<div>\n <strong>1. Cluster RCT of health systems delivery mechanism:</strong></div>\n<div>\n - To determine the effectiveness of different delivery strategies to optimise health system delivery of PDMC</div>\n<div>\n <div>\n <strong>2. Individually RCT of end-user adherence support</strong></div>\n <div>\n - To determine the effectiveness of different adherence support strategies to optimise end-user adherence to PDMC</div>\n <div>\n  </div>\n <div>\n <strong>Secondary Objectives</strong></div>\n</div>\n<div>\n <strong>1. Cluster RCT of health systems delivery mechanism:</strong></div>\n<div>\n - To evaluate the adoption of the health system delivery mechanisms and adherence support mechanisms for the 3 courses of PDMC</div>\n<div>\n <div>\n <strong>2. Individually RCT of end-user adherence support:</strong></div>\n <div>\n To determine the clinical effectiveness of the different PDMC delivery strategies (all-cause and malaria-specific readmissions and sick-child clinic visits, all-cause mortality).</div>\n <div>\n 3. To evaluate the effectiveness of the linkage mechanisms between the various health facility levels along the PDMC delivery continuum</div>\n</div>\n<p>\n  </p>\n
      • principal_inclusion_criteria<div>\n 1. Aged <10 years of both sexes</div>\n<div>\n 2. Hospitalised with severe anaemia or severe malaria: Initially hospitalised with haemoglobin <5.0 g/dl or PCV <15%, or requirement for blood transfusion for other clinical reasons on or during admission to the hospital, or severe malaria, defined as a requirement for parenteral artesunate in the opinion of the treating clinician and the presence of microscopy or RDT confirmed Plasmodium infection</div>\n
      • principal_exclusion_criteria<div>\n 1. Recognised specific other causes of severe anaemia (i.e., trauma, haematological malignancy, known bleeding disorders, such as haemophilia)</div>\n<div>\n 2. Sickle cell anaemia/sickle cell disease</div>\n<div>\n 3. Body weight <5 kg</div>\n
      • primary_end_points<div>\n 1. The proportion of participants receiving an incomplete set of PDMC courses</div>\n<div>\n 2. The proportion of participants with incomplete adherence to the 9 doses of PDMC</div>\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<div>\n <strong>INVESTIGATORS AND INSTITUTIONS</strong></div>\n<div>\n <strong>Chief Investigators</strong></div>\n<div>\n Dr Jenny Hill, PhD - Liverpool School of Tropical Medicine (LSTM)</div>\n<div>\n Prof Feiko ter Kuile, MD, PhD - KEMRI/CDC and LSTM</div>\n<div>\n <strong>Country Principal Investigator</strong></div>\n<div>\n Dr Juliet Otieno Awori, MBChB, PhD - Kenya Medical Research Institute (KEMRI), Centre for Global Health Research (CGHR) and CDC Collaboration</div>\n<div>\n <strong>Country Co- Principal Investigator</strong></div>\n<div>\n Dr Simon Kariuki, PhD - Kenya Medical Research Institute (KEMRI), Centre for Global Health Research (CGHR) and CDC Collaboration</div>\n<div>\n <strong>Co-Investigators</strong></div>\n<div>\n Dr Titus Kwambai, MBChB, PhD - Centers for Disease Control and Prevention, Kenya (CDC-Kenya), KEMRI Centre for Global Health Research (CGHR) and CDC Collaboration</div>\n<div>\n Dr. Ruth Njoroge, BPharm, Dr Prisca Oria, PhD - Kenya Medical Research Institute (KEMRI), Centre for Global Health Research (CGHR) and CDC Collaboration</div>\n<div>\n Dr Eve Worrall, PhD, Carole Khairallah, Jenna Hoyt, Dr Tao Chen, MD, MSc, PhD, Amanda McCoy, MSc - Liverpool School of Tropical Medicine (LSTM)</div>\n<div>\n <strong>Collaborators</strong></div>\n<div>\n Dr. Sammy Mahugu, MBChB, MPH,MBA, Ms. Regina Kandie, MSc - Ministry of Health Kenya, National Malaria Control Programe</div>\n<div>\n Dr Valérie Briand, Dr Adrian Luty - Epicentre, Paris, France</div>\n<div>\n Prof Kamija Phiri, MD, PhD; Dr Lucinda Manda-Taylor - Training Research Unit of Excellence, Blantyre, Malawi</div>\n
      • other_details_explanation<p>\n N/A</p>\n
      • other_details_regulatory_notapproved<p>\n N/A</p>\n
      • other_details_regulatory_approved<p>\n N/A</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration17 months
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorDiff. delivery strategies
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaHealth facilities with blood transfusion services in malaria-endemic areas in Western Kenya
      • single_site_physical_addressKEMRI-CGHR P.O. Box 1578-40100, Kisumu, Kenya.
      • single_site_contact_personJuliet Otieno Awori
      • single_site_telephone+254721432548
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states2
      • number_of_sites
      • multi_country_listKenya\nBenin
      • data_monitoring_committeeYes
      • total_enrolment_per_site600
      • total_participants_worldwide1119
      • 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_consentYes
      • subjects_specifyChildren aged under 10 years
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameFeiko
      • investigator1_middle_nameter
      • investigator1_family_nameKuile
      • investigator1_qualificationMD, PhD
      • investigator1_professional_addressKEMRI CGHR 1578-40100 Kisumu, Kenya
      • investigator1_telephone+254708739228
      • investigator1_emailFeiko.terkuile@lstmed.ac.uk
      • organisations_transferred_No
      • number_participants600
      • notification
      • approval_date16-04-2025
      • submitted1
      • deleted0
      • deleted_date(null)
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      • date_submitted05-12-2024
      • is_child0
      • unsubmitted1
      • initial_date_submitted05-12-2024
      • admin_stopped0
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      • approved2
      • approved_reasonReviewer comments have ben addressed
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      • final_date(null)
      • modified2025-08-06 12:20:54
      • created2024-11-18 15:41:01
      • total_sites1
      • ecitizen_invoice330507
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        • id1202
        • application_id1489
        • given_nameJuliet
        • middle_nameOtieno
        • family_nameAwori
        • qualificationMBChB
        • professional_addressKEMRI CGHR 1578-40100 Kisumu, Kenya
        • telephone+254721432548
        • emailJuliet.Otieno@lstmed.ac.uk
        • created2024-12-04 16:37:28
        • modified2025-02-03 10:22:51
      • 1(array)
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        • application_id1489
        • given_nameSimon
        • middle_name
        • family_nameKariuki
        • qualificationPhD
        • professional_addressKEMRI CGHR 1578-40100 Kisumu, Kenya
        • telephone+254725389246
        • emailskariuki1578@gmail.com
        • created2024-12-05 11:57:10
        • modified2025-02-03 10:22:51
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        • created2024-12-04 16:37:28
        • modified2025-02-03 10:22:51
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        • id795
        • application_id1489
        • sponsorLiverpool School of Tropical Medicine (LSTM
        • sponsor_typeResearch Institution
        • contact_personProf Feiko ter Kuile, MD, PhD
        • addressPembroke Place, Liverpool L3 5QA, UK.
        • telephone_number+44 0151 7053794
        • fax_number
        • cell_number+44 0151 7053794
        • email_addresslstmgov@lstmed.ac.uk
        • created2024-12-04 16:37:28
        • modified2025-02-03 10:22:51
  • 1(array)
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      • user_id353
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      • abstract_of_study<p>\n Background: Several subpopulations, including adolescent girls and young women (AGYW, ages 15-24), lag behind the 3rd 90-90-90 UNAIDS goal of viral suppression, particularly in resource-limited settings (RLS).1 AGYW living with HIV (AGYWLHIV) face unique challenges in persistence to anti-retroviral therapy,2 and overcoming barriers such as stigma and poverty that hinder achieving viral suppression among AGYW.5 Long-acting (LA) antiretroviral therapy (ART), such as injectable cabotegravir and rilpivirine, has been receiving global clinical approvals and has the potential to address these barriers and improve patient adherence and persistence to treatment. LA ART regimens can potentially also increase options for patients and providers to individualize treatment plans, provide a powerful treatment option for those experiencing adherence issues related oral treatment options, and may ease the burden of health systems in RLS. Another major threat to AGYW’s health is unintended pregnancies,3 and AGYWLHIV also face unique challenges in uptake and continuation of LA contraceptives. Use of LA ART may foster synergy in usage of LA contraceptives among AGYWLHIV.</p>\n<p>\n Methods: This proposed research study has three main components: 1) a prospective, non-randomized, parallel-group pharmacokinetic (PK) study among a sentinel cohort of five distinct groups of AGYW, and will leverage existing control groups from the PARVI study (Aim 1a); 2) a qualitative study that will conduct individual interviews with four different subgroups of AGYWLHIV from the sentinel cohort from the PK study, as well as focus group discussions with providers, policy makers, and other stakeholders for health systems readiness for wider scale-up (Aim 1b); and 3) an open-label, mixed methods, 48-week type I hybrid trial randomizing AGYW with viral suppression on their current ART regimen to switch to 1:1 cabotegravir/ rilpivirine (intervention arm) vs. continue their oral ART regimen (Aim 2a), with a component also evaluating implementation outcomes of acceptability, feasibility, and fidelity (Aim 2b). The proposed study will be conducted in HIV treatment facilities in western Kenya within the regional Moi Teaching and Referral Hospital (MTRH).</p>\n<p>\n Impact: This study will provide foundational data for future studies and implementation plans related to addressing barriers and will critically inform follow-up studies of LA ART in other priority subpopulations. Providing an array of method options for both HIV treatment and pregnancy prevention has the potential to revolutionize personal decision-making and improve long-term outcomes for AGYWLHIV. Our real-world experiences of co-delivery will also inform future considerations for co-formulations of antiretrovirals and contraceptives for both HIV treatment and prevention. This study also directly addresses the need to find interventions that will and achieve the UNAIDS 90-90-90 goals.</p>\n
      • study_title<p>\n Co-benefits of co-delivery of long-acting antiretrovirals and contraceptives</p>\n
      • laymans_summary<p>\n Layman’s Summary</p>\n<p>\n Adolescent girls and young women (AGYW) lag behind older women in viral suppression. Long-acting antiretroviral therapy (LA ART) can increase options, patient adherence and persistence to treatment. In resource-limited settings (RLS), LA ART regimens may also ease the burden on health systems by decreasing refill visits or easing supply chain management. Unintended pregnancies greatly affect AGYW. Long-acting contraceptives (e.g., LARCs and injectables) can prevent unintended pregnancies. RLS have decades of investments in contraceptive delivery. LA ART can leverage LA contraceptive delivery platforms. We speculate that using L ART will increase the demand for LAC among AGYW, using LARCs will increase the demand for L ART among AGYW (advantages will be on both sides), that taking advantage of the LARCs platforms to provide the LART to AGYW will be highly acceptable, feasible, and deliverable to all stakeholders (e.g. the AGYW, the healthcare workers, the management and policy makers).</p>\n<p>\n Study objectives:</p>\n<p>\n 1 (a): To find out more about how the body responds to L AART (Pharmacokinetic (PK) study). This will include assessing the blood levels of the LAART, as well as the blood level of the LARCs and seeing if the two are affecting each other’s blood levels. Low blood levels of any drug in the body that is needed may reduce the effectiveness of the drug. High blood levels that is needed may increase the unexpected medical problems of the drug. Other studies have found that these two are safe when used together, as well as effective. We intend to do this so that AGYW can benefit from both drugs 1 (b): To find out what stakeholders think about the L ART (Qualitative study). This will include what stakeholders think are the strengths and challenges of providing LART to AGWY. For LART to be included for routine use, all stakeholders need to be on board. We hope to provide information for policy makers to use when planning to roll out LART for routine use by AGYW 2 (a): To compare the outcomes of using LART compared to those HIV negative but on contraceptives (comparing the contraceptive drug levels in blood) and those HIV positive but not on hormonal contraceptive (comparing HIV outcomes such as drug adherence, viral loads etc. This is the Hybrid type I effectiveness-implementation trial. 2 (b): To evaluate the impact providing L ART to AGYW: We will assess, after implementing the study, how acceptable and feasible it is providing both drugs. Study site: The proposed study will be conducted in HIV treatment facilities in western Kenya within the regional Moi Teaching and Referral Hospital (MTRH).</p>\n
      • short_titleKuwa Free! - Live free!
      • protocol_noECCT/21/09/01
      • version_no1.0
      • date_of_protocol13-04-2021
      • study_drugInjectable cabotegravir/rilpivirine
      • disease_conditionHIV/AIDS
      • product_type_biologicals1
      • product_type_proteins1
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorYes
      • comparator_nameStandard of care, ART that concurrently contains combinations of nonnucleoside reverse transcriptase inhibitors (NNRTIs), such as efavirenz, and protease-inhibitors (PIs), such as atazanavir/ritonavir or lopinavir/ritonavir, or integrase inhibitors
      • comparator_registeredYes
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addresschakieunice@gmail.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantEdwin Were
      • declaration_date107-09-2021
      • declaration_principal_investigatorEdwin Were
      • declaration_date207-09-2021
      • placebo_presentNo
      • study_objectives<p>\n Aim 1: To collect foundational data to better inform design of an effectiveness implementation trial.</p>\n<p>\n Aim 1a: To determine if combined cabotegravir/rilpivirine injectable use has bidirectional drug-drug interactions with injectable (depot medroxyprogesterone acetate [DMPA]) or implantable (etonogestrel or levonorgestrel) contraceptives.</p>\n<p>\n Aim 1b: To qualitatively explore points of convergence and divergence, preferences and values, and health systems readiness around wider-scale codelivery of LA ART and contraceptives.</p>\n<p>\n Aim 2: To evaluate the impact of clinic-provided, co-delivery of LA ART and contraceptives among AGYWLHIV.</p>\n<p>\n Aim 2a: To evaluate the impact on effectiveness outcomes of HIV treatment (viral suppression and adherence/persistence) and contraception (uptake and continuation rates).</p>\n<p>\n Aim 2b: To evaluate the impact on implementation outcomes of acceptability, feasibility, and fidelity.</p>\n
      • principal_inclusion_criteria<p>\n PK study: • Female sex, • HIV-positive (for PK groups #1-4 and hybrid trial) or HIV-uninfected (for PK group #5 only), • Age 15-24 years at the time of enrollment, • Documented or confirmed viral suppression for HIV (defined as <40 copies/mL) within 6 months prior to study screening, • Have been on the study oral drug for at least 4 weeks for the PK groups #1-4, • Have initiated and intends to use DMPA or implant for at least another three or 6 months, respectively, • Willing to undergo phlebotomy every 4-12 weeks for the duration of the study period • Able to consent or assent (with parental consent) for study participation in English or Kiswahili.</p>\n<p>\n Hybrid trial: • Female sex, • HIV-positive, • Age 15-24 years at the time of enrollment, • Documented or confirmed viral suppression for HIV (defined as <40 copies/mL) within 6 months prior to study screening, • Willing to undergo phlebotomy every 4-12 weeks for the duration of the study period, • Able to consent or assent (with parental consent) for study participation in English or Kiswahili</p>\n
      • principal_exclusion_criteria<p>\n PK study:</p>\n<p>\n • Already be on ART that concurrently contains combinations of nonnucleoside reverse transcriptase inhibitors (NNRTIs), such as efavirenz, and protease-inhibitors (PIs), such as atazanavir/ritonavir or lopinavir/ ritonavir, or integrase inhibitors (INSTIs), such as raltegravir or dolutegravir • Currently pregnant or intends to become pregnant or breastfeeding within the next 12 or 24 weeks for DMPA or implant groups, respectively, • Have had unprotected sex in the last two weeks or be currently pregnant via urine pregnancy testing, • Use or anticipated use of drugs for the duration of the study period known to interact with hormonal implants or the study ART regimen, • Current or planned concomitant use of other hormonal contraceptives, • Be obese (BMI≥30), • Evidence of Hepatitis B virus (HBV) infection based on the results of testing for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (anti-HBc), Hepatitis B surface antibody (anti-HBs) and HBV Deoxyribonucleic acid (DNA) as follows: positive for HBsAg being excluded or negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive for HBV DNA are excluded (of note, participants positive for anti-HBc (negative HBsAg status) and positive for anti-HBs (past and/or current evidence) are immune to HBV and are not excluded). • Serum ALT>5x ULN at the time of screening, • Serum creatinine >2.5x ULN at the time of screening.</p>\n<p>\n Hybrid trial:</p>\n<p>\n • Already be on ART that concurrently contains combinations of nonnucleoside reverse transcriptase inhibitors (NNRTIs), such as efavirenz, and protease-inhibitors (PIs), such as atazanavir/ritonavir or lopinavir/ ritonavir, or integrase inhibitors (INSTIs), such as raltegravir or dolutegravir. • Currently pregnant or intends to become pregnant or breastfeeding within the next one year, • Have had unprotected sex in the last two weeks or be currently pregnant via urine pregnancy testing, • Use or anticipated use of drugs for the duration of the study period known to interact with the study ART regimen, • Evidence of Hepatitis B virus (HBV) infection based on the results of testing for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (anti-HBc), Hepatitis B surface antibody (anti-HBs) and HBV Deoxyribonucleic acid (DNA) as follows: positive for HBsAg being excluded or negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive for HBV DNA are excluded (of note, participants positive for anti-HBc (negative HBsAg status) and positive for anti-HBs (past and/or current evidence) are immune to HBV and are not excluded). • Serum ALT>5x ULN at the time of screening, • Serum creatinine >2.5x ULN at the time of screening.</p>\n
      • primary_end_points<p>\n The primary endpoint for the PK study is the hormone concentrations at 12 or 24 weeks after hormonal contraception initiation.</p>\n<p>\n The primary endpoint for the hybrid trial is the proportion of participants with viral suppression ( via HIV viral load <40 copies/mL) 48 weeks after study enrollment (primary outcome) in the intervention vs. control arms (primary exposure; Aim 2a).</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety0
      • scope_efficacy0
      • scope_pharmacokinetic1
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others1
      • scope_others_specifyImplementation effectiveness
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n  </p>\n<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\">\n <tbody>\n <tr>\n <td style=\"width:153px;\">\n <p>\n NAME  </p>\n <p>\n  </p>\n </td>\n <td style=\"width:184px;\">\n <p>\n ROLE</p>\n </td>\n <td style=\"width:168px;\">\n <p>\n QUALIFICATION                                     </p>\n </td>\n <td style=\"width:133px;\">\n <p>\n START DATE</p>\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:153px;\">\n <p>\n Prof. Edwin Were</p>\n </td>\n <td style=\"width:184px;\">\n <p>\n Site Principal Investigator</p>\n </td>\n <td style=\"width:168px;\">\n <p>\n MBChB, MMed, MPH</p>\n </td>\n <td style=\"width:133px;\">\n <p>\n April 2021</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:153px;\">\n <p>\n Prof. Rena Patel</p>\n </td>\n <td style=\"width:184px;\">\n <p>\n Study Principal Investigator</p>\n </td>\n <td style=\"width:168px;\">\n <p>\n MD, MPH, MPHIL</p>\n </td>\n <td style=\"width:133px;\">\n <p>\n April 2021</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:153px;\">\n <p>\n Dr. Beatrice Jakait</p>\n </td>\n <td style=\"width:184px;\">\n <p>\n Study Pharmacist</p>\n </td>\n <td style=\"width:168px;\">\n <p>\n B Pharm, PharmD,  MSc                     </p>\n </td>\n <td style=\"width:133px;\">\n <p>\n April 2021</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:153px;\">\n <p>\n Dr. Edith Apondi</p>\n </td>\n <td style=\"width:184px;\">\n <p>\n Study Clinician  </p>\n </td>\n <td style=\"width:168px;\">\n <p>\n MBChB, MMed,                                     </p>\n </td>\n <td style=\"width:133px;\">\n <p>\n April 2021</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:153px;\">\n <p>\n Eunice Kaguiri</p>\n </td>\n <td style=\"width:184px;\">\n <p>\n Study Coordinator</p>\n </td>\n <td style=\"width:168px;\">\n <p>\n BSc, MPH</p>\n </td>\n <td style=\"width:133px;\">\n <p>\n April 2021</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"4\" style=\"width:638px;\">\n <p>\n Other facilities and resources</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:153px;\">\n <p>\n IEC/IRB</p>\n </td>\n <td colspan=\"3\" style=\"width:485px;\">\n <p>\n Moi University/Moi Teaching and Referral Hospital Institutional Research and Ethics Committee (MU/MTRH IREC) has been mandated to review and approve protocols on behalf of the National Council of Science and Technology (the national regulatory authority).</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:153px;\">\n <p>\n Study facility &Equipment</p>\n <p>\n  </p>\n </td>\n <td colspan=\"3\" style=\"width:485px;\">\n <p>\n The study offices are located at the Partners House along Lumumba Road. The available space includes Coordinator’s Office, the staff offices, Data room, Counseling/Consenting rooms, and a reception/waiting area. The facility is equipped with reliable internet, desktop & laptop computers, printers, photocopiers, and filing cabinets.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:153px;\">\n <p>\n Site Laboratory</p>\n <p>\n  </p>\n </td>\n <td colspan=\"3\" style=\"width:485px;\">\n <p>\n AMPATH Reference Laboratory will provide access to all required laboratory facilities for this study.  The laboratory is staffed by appropriately trained personnel ensuring that IATA regulations for the shipping of biological samples are adhered to.  A Quality Control system is in place that ensures all procedures are performed according to GCLP & GLP standards. The laboratory provides services to the AMPATH program and all clinical trials under Moi University College of Health Sciences.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:153px;\">\n <p>\n Study Pharmacy</p>\n </td>\n <td colspan=\"3\" style=\"width:485px;\">\n <p>\n The MUCRC study   pharmacy is located at Chandaria Centre within MTRH. It is well equipped to ensure that all study medications are stored, dispensed and returned in accordance with study requirements.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:153px;\">\n <p>\n MTRH Rafiki Center for Excellence in Adolescent Health</p>\n <p>\n  </p>\n </td>\n <td colspan=\"3\" style=\"width:485px;\">\n <p>\n MTRH Rafiki Center for Excellence in Adolescent Health  is a combined adolescent medicine, adolescent HIV care and research clinic that provides a one stop shop for free reproductive health, mental health, management of chronic diseases, HIV prevention and treatment services, and life skills for adolescents in Eldoret, Kenya.</p>\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:153px;\">\n <p>\n Emergency Facilities</p>\n <p>\n  </p>\n </td>\n <td colspan=\"3\" style=\"width:485px;\">\n <p>\n A comprehensive emergency service is accessible at Moi Teaching & Referral Hospital. The hospital has a bed capacity of 1020 specialized beds with an average number of 1300 of inpatients at any time and 1500 outpatients per day. The hospital has doctors specialized in various fields of medicine, pediatrics, obstetrics and gynecology, surgery, psychiatry, critical care and medical research.</p>\n <p>\n  </p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_explanation<p>\n This research is proposed to take place in Kenya for several reasons. First, most AGYW living with HIV reside in resource-limited settings, where the burden of HIV is disproportionately high. Therefore, it is only appropriate to conduct such a study in high HIV-burden settings, such as Kenya or other parts of sub- Saharan Africa. Furthermore, we are conducting this study within a region of Kenya with one of the highest prevalence and burden of pediatric and adult HIV within Kenya. Second, the study is more feasible to conduct in Kenya than, for example, in the US, because both the prevalence of HIV and the lack of viral suppression are more common in Kenya than in the US among AGYW. Third, we are proposing this research in the context of existing research and programmatic work, namely integration of contraception provision within routine HIV care, already underway in Eldoret, Kenya. Therefore, leveraging the considerable resources for the study site to conduct the proposed study is crucial for feasibility. For all these reasons, conducting this research in Kenya is the most appropriate, feasible, and timely way to answer the proposed research questions.</p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n None</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration5 years
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherYes
      • design_controlled_specifyThe hybrid trial is randomized whereas the PK study is non- randomized
      • design_controlled_comparatorCurrent ART regimen
      • design_controlled_other_medicinalYes
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaMoi Teaching and Referral Hospital
      • single_site_physical_addressNandi Road, Eldoret
      • single_site_contact_personProf. Edwin Were
      • single_site_telephone+254 705756103
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_site105 participants in the Pharmacokinetic study (aim 1a) and 550 in the Hybrid trial(aim 2a)
      • total_participants_worldwide105 participants in the Pharmacokinetic study (aim 1a) and 550 in the Hybrid trial(aim 2a)
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male0
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specify15-17 years
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameEdwin
      • investigator1_middle_name
      • investigator1_family_nameWere
      • investigator1_qualificationProfessor
      • investigator1_professional_addressMoi University
      • investigator1_telephone+254 705756103
      • investigator1_emaileowere@gmail.com
      • organisations_transferred_No
      • number_participants105 participants in the Pharmacokinetic study (aim 1a) and 550 in the Hybrid trial(aim 2a)
      • notification
      • approval_date16-09-2022
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted07-09-2021
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments addressed
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2023-11-16 12:52:00
      • created2021-06-30 11:51:59
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id705
        • application_id1035
        • given_nameRena
        • middle_name
        • family_namePatel
        • qualificationAssistant Professor, Department of Medicine, Division of Allergy and Infectious Diseases
        • professional_addressUniversity of Washington
        • telephone+16503530718
        • emailrcpatel@uw.edu
        • created2021-08-05 11:43:33
        • modified2021-09-07 20:32:58
      • 1(array)
        • id709
        • application_id1035
        • given_nameEdwin
        • middle_name
        • family_nameWere
        • qualificationProfessor
        • professional_addressMoi University
        • telephone+254 705756103
        • emaileowere@gmail.com
        • created2021-08-27 12:14:11
        • modified2021-09-07 20:32:58
    • SiteDetail(array)
      • 0(array)
        • id1088
        • application_id1035
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2021-08-05 11:43:33
        • modified2021-09-07 20:32:58
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id528
        • application_id1035
        • sponsorUniversity of Washington
        • sponsor_typeOthers
        • contact_personRena Patel
        • addressUniversity of Washington
        • telephone_number+16503530718
        • fax_number
        • cell_number+16503530718
        • email_addressrcpatel@uw.edu
        • created2021-08-05 11:43:33
        • modified2021-09-07 20:32:58
  • 2(array)
    • Application(array)
      • id777
      • user_id360
      • trial_status_id5
      • abstract_of_study<p>\n This study, entitled Clinical Evaluation of the FilmArray Global Fever (GF) Panel, is sponsored by BioFire Defense, LLC and aims to evaluate the clinical sensitivity and specificity of the assays comprising the FilmArray Global Fever Panel when used to test whole blood collected from individuals with acute febrile illness, when compared to a well-validated molecular-based method, in the intended use setting (reference or diagnostic laboratory). The intention is to use these performance data to support classification of the FilmArray GF Panel as an in vitro diagnostic (IVD) device by the U.S. Food and Drug Administration (FDA) and other comparable regulatory agencies. Whole blood will be collected prospectively from patients attending outpatient and inpatient departments of the health care facilities at Kisumu District Hospital, Kombewa Sub-District Hospital, Kisii District Hospital, Marigat District Hospital, Gilgil District Hospital, and Kenya Armed Forces Memorial Hospital (Mbagathi, Nairobi), where only enrollment and specimen collection will be performed. The subjects will be consented for blood draw and testing of pathogens that are commonly associated with febrile illnesses such as malaria, leishmaniasis, anthrax, leptospirosis, plague, paratyphoid fever, typhoid fever, tularemia, Crimean-Congo hemorrhagic fever, chikungunya fever, dengue fever, lassa fever, ebola virus disease, marburg virus disease, West Nile fever and Yellow fever. The collected blood sample will be labeled with only a study code number (SCN) in order to protect subject identity. However, in the event a select agent is detected twice using the Global Fever Panel, the enrollment log which links the SCN to the subject may be used to identify the subject for follow-up. The samples will be secured in refrigerators and freezers at WRP/KEMRI facilities and only study investigators and their authorized staff will have access. All safeguards ensuring privacy that are in place during this study period will also continue to be in place for the long-term storage of samples. Some tests planned for this trial will be done with our collaborating laboratories abroad. Before shipment of samples to such collaborating laboratories, authority for sample shipment and testing will be sought from KEMRI SERU. The collected specimens will either be tested fresh or will be frozen and then tested at a later date. Freezing of specimens will allow for continued collection of specimens when immediate testing is not possible. Freezing and testing of specimens will be tracked on study-specific forms. Informed consent will be obtained from eligible participants prior to specimen collection. For the study, up to 500 patients will provide 2.5-3.0 mL of whole blood and the blood sample will be labeled with a study code number (SCN). Continuous enrollment and testing are expected to last for approximately 18 months in order to achieve a required number of valid specimens. All FilmArray testing and nucleic acid extraction will occur at the Basic Science Lab, KEMRI/WRP, Kisumu. Of the 2.5-3.0 mL of whole blood collected, 500 L will be archived at ≤-70°C immediately for discrepancy testing. A 200 L aliquot of the whole blood will be used for FilmArray GF Panel testing. In addition to FilmArray testing, 800 L of the whole blood will be used to purify nucleic acid, using the provided MagNA Pure Compact system (or equivalent). The purified nucleic acids will be shipped frozen to BioFire Defense for further testing (comparator testing). Comparator assays are designed to amplify and detect pathogen nucleic acid; no genetic testing or specific amplification of human nucleic acid will be performed. The residual blood specimen will be stored refrigerated until FilmArray testing and nucleic acid extraction is complete in the event that additional testing/extraction is required. Once the required testing is completed, remaining sample (up to 2.0 mL total, which includes the 500 µl aliquot archived for discrepancy testing), will be archived at ≤-70°C for at least two years after study completion. In order to conduct future research utilizing these samples, a new sub-protocol must be written, reviewed and approved by both the WRAIR IRB and the KEMRI SERU. To maintain patient confidentiality, blood samples, blood sample aliquots and specimen nucleic acid will only be labeled with a study code number (SCN). This study will be performed according to the approved multisite protocol (attached), laboratory-specific protocols and site-specific workflow procedures, and available product literature for the FilmArray instrument and the MagNA Pure Compact system. No deviation from this protocol will be implemented without the prior review and approval of BioFire Defense and the respective sites’ IRB(s), except where it may be necessary to eliminate an immediate hazard to a research subject. The results of the FilmArray GF Panel testing will not be provided to the patients or their healthcare providers, or in any way be used to affect their standard of care except in the event that a true positive select agent detection is confirmed (see 3.4 below for full description). This study is jointly funded by the U.S. Army Medical Materiel Development Activity (USAMMDA) through contracts with BioFire Defense and managed by the Joint Program Executive Office for Chemical and Biological Defense – Medical Countermeasure Systems (JPEO-CBD-MCS), the National Institute of Allergy and Infectious Diseases (NIAID) and BioFire Defense. The clinical evaluation outlined in this protocol will be administered and managed by BioFire Defense. The Sponsor contact person(s) for this study will be at BioFire Defense, and are listed above (page i).  </p>\n
      • study_title<p>\n Clinical Evaluation of the FilmArray Gobal Fever GF Panel</p>\n
      • laymans_summary<p>\n Diseases that are associated with increased body temperature (fever more than ≥ 38 °C) and other clinical signs like headache, tiredness and muscle pain are many. They can be caused by different microorganisms that are widespread in different regions, including Kenya. Sometimes these diseases can occur as outbreaks that make many people ill. One of the big problems with these types of diseases is determining the cause of the disease because symptoms such as high temperature, headache, tiredness and muscle pain are common signs of many diseases. A machine that can quickly and correctly identify microorganisms in blood of patients with elevated temperature would make treatment decisions easier for doctors. The FilmArray Global Fever (GF) Panel has the potential to detect many of these diseases. It is a machine that works by multiplying genetic material of an organism, making such materials easier to detect. The system is able to detect bacteria, viruses, and protozoa in a single blood sample. Unlike other methods that require human intervention, the machine performs all manipulations including extraction of genetic materials, multiplication of genetic materials, and identification of microorganism. The process is fully automated and gives final results in approximately one hour. The purpose of this study is to test how good this machine is in detecting the following microorganisms in patients with fever: Leptospira spp., Plasmodium spp., Plasmodium falciparum, Plasmodium vivax/ovale, chikungunya virus, and dengue virus. To do this, the machine will be tested using blood samples that will come from an ongoing study that collects blood samples from patients with fever (KEMRI SSC #1282 and WRAIR #1402). The FilmArray test results of Detected or Not Detected will be compared to validated molecular-based methods that are performed at BioFire Defense, LLC in Salt Lake City, Utah, US. Data obtained in this study will be used to support application to license the FilmArray GF Panel as an in vitro diagnostic (IVD) device for detection of microorganisms in blood from patients with fever. If the proposed study is successful, the FilmArray GF Fever Panel may provide an effective way to obtain a quick diagnosis. The study is sponsored by a company called BioFire Defense, LLC and the study will be performed at the Basic Science Lab of the Kenya Medical Research Institute/ Walter Reed Project (KEMRI/WRP) in Kisumu.</p>\n
      • short_titleBiofire FilmArray Gobal Fever GF Panel
      • protocol_noECCT/19/03/03
      • version_noREV 05
      • date_of_protocol21-02-2018
      • study_drugBiofire FilmArray Gobal Fever GF Panel-Device
      • disease_conditionACUTE FEBRILE ILLNESS
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device1
      • product_type_chemical_name
      • product_type_medical_device_nameBiofire FilmArray Gobal Fever GF Panel-Device
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressdotigondi3@gmail.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data0
      • applicant_stability_data0
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter0
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license0
      • applicant_registration_ctr(null)
      • applicant_pan_african0
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan0
      • applicant_contractual_agreement0
      • declaration_applicantJohn Waitumbi +254 733616548
      • declaration_date115-03-2019
      • declaration_principal_investigatorJohn Waitumbi +254 733616548
      • declaration_date215-03-2019
      • placebo_presentNo
      • study_objectives<p>\n The objective of this multi-center study is to evaluate the clinical sensitivity and specificity of the assays comprising the FilmArray GF Panel when used to test whole blood specimens. It is hypothesized that the FilmArray GF Panel assays will be highly specific and give no false detections of the bacteria, viruses, and protozoa included in the panel. These data will be used to support submissions to the FDA in support of the FilmArray GF Panel as an in vitro diagnostic device.</p>\n
      • principal_inclusion_criteria<p>\n Febrile patient (>38 °C) recruited at a health facility One year or older Able to give consent (guardian if lees than 18 years) and assent if >13 years</p>\n
      • principal_exclusion_criteria<p>\n Not able to give consent or assent if of appropriate age</p>\n
      • primary_end_points<p>\n N/A</p>\n
      • scope_diagnosis1
      • scope_prophylaxis0
      • 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_other1
      • trial_other_specifyDevice
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<p>\n The KEMRI/USAMRD-K Basic Science Laboratory (BSL) at Kondele is a research laboratory that performs multi-disciplinary basic science research (molecular biology and immunology) in malaria and many other infectious diseases, including disease surveillance, diagnostic evaluations and developments. BSL has a well developed basic science research infrastructure for performing: 1) Surveillance for pathogens associated with febrile illness in diverse eco-regions of Kenya; 2) Determination of malaria parasites population structure prior and post vaccine and drug intervention; 3) Evaluation of multi-pathogen diagnostic platforms for infectious diseases of regional and global importance. To perform these functions, BSL has a well developed research infrastructure that includes state of art technologies such as: 1) Real-time and conventional PCR for diagnosis and genotyping; 2) MAGPIX for multiplexing pathogen detection, ideal for outbreak investigations and disease surveillance studies; 3) Sanger sequencer for sequence generation and fingerprinting; 4) MiSeq for unbiased sequence screening and pathogen characterization. The Lab has a workforce of 13 well trained scientist that includes: • two senior scientists with PhDs • 5 Research Officers with MScs • One certified QA/QC officer with appropriate professional certification • 4 Assistant Research Officers with BSc degree • One data entry clerk/curator with BA. To support patient recruitment, the Lab has surveillance sites in 9 hospitals, each staffed with a clinical officer or nurse and a Lab technician</p>\n
      • other_details_explanation<p>\n n/a</p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n The study has been submitted to anumber of countries and the RA in the respective countries have approved the study and the study is already ongoing in those countries. These include RA in Tanzania, Thailand , Cambodia, Uganda:Peru</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n None</p>\n
      • estimated_duration18Months
      • design_controlled_randomised
      • design_controlled_open
      • design_controlled_single_blind
      • design_controlled_double_blind
      • design_controlled_parallel_group
      • design_controlled_cross_over
      • design_controlled_other
      • design_controlled_specify
      • design_controlled_comparator
      • design_controlled_other_medicinal
      • design_controlled_placebo
      • design_controlled_medicinal_other
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKEMRI Walter Reed Project USAMRD A/K Kisumu
      • single_site_physical_addressBeside New Nyanza provincial Hospital
      • single_site_contact_personDr John Waitumbi
      • single_site_telephone+254 733616548
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states3 Africa , Asia and America
      • number_of_sites
      • multi_country_listMoshi, Tanzania\nSt Louis, USA\nBangkok, Thailand\nKampong Cham, Cambodia\nKampala, Uganda\nIquitos, Peru\n\nTegucigalpa, Honduras\nWashington, DC, USA\nNavrongo, Ghana\nTbilisi, Georgia\n
      • data_monitoring_committeeNo
      • total_enrolment_per_siteN/A
      • total_participants_worldwide1500
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenYes
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyYes
      • 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_situationYes
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameJOHN
      • investigator1_middle_name
      • investigator1_family_nameWAITUMBI
      • investigator1_qualificationPhD
      • investigator1_professional_addressP.O BOX 54 KISUMU CODE 40100
      • investigator1_telephone+254 733616548
      • investigator1_emailjohn.waitumbi@usamru-k.org
      • organisations_transferred_No
      • number_participants500
      • notification<p>\n None</p>\n
      • approval_date16-05-2019
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted28-09-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<p>\n This study, entitled Clinical Evaluation of the FilmArray Global Fever (GF) Panel aimed to evaluate the clinical sensitivity and specificity of the assays comprising the FilmArray Global Fever Panel when used to test whole blood collected from individuals with acute febrile illness, when compared to a well-validated molecular-based method, in the intended use setting (reference or diagnostic laboratory). The intention was to use these performance data to support classification of the FilmArray GF Panel as an in vitro diagnostic (IVD) device by the U.S. Food and Drug Administration (FDA) and other comparable regulatory agencies.</p>\n
      • implication_results<p>\n The Clinical Evaluation of the FilmArray Global Fever Panel in Kisumu Kenya was initiated July 10-18, 2019. A total of six (6) collections sites were trained to participate in the study as well as laboratory personnel to perform FilmArray testing and nucleic acid extractions. The last participant was recruited on 30th September 2019 bringing to a total of 163 subjects, of which 158 were enrolled and tested on FilmArray at Kisumu site. All eligible nucleic acids samples were shipped to BioFire Defense Laboratories after obtaining permission from KEMRI SERU. Comparator testing and analysis at BioFire Defense Laboratories has been completed. The first submission of Global Fever Panel results from all the participating sites was made to the FDA. The second submission with all the GFP analytes was made to FDA in October 2021. Full GFP analylates includes: Chikungunya virus, dengue virus (serotypes 1-4), Leptospira spp., Plasmodium spp., P. falciparum, and P. ovale/vivax. Crimean Congo Hemorrhagic Fever virus, Ebolavirus, Lassa virus, Marburgvirus, West Nile virus, yellow fever virus, Zika virus, Bacillus anthracis, Francisella tularensis, Salmonella enterica serovar Typhi and Paratyphi A, Yersinia pestis, and Leishmania donovani complex. A manuscript titled “Clinical evaluation of the BioFire Global Fever Panel for the identification of malaria, leptospirosis, chikungunya, and dengue from whole blood: a prospective, multicentre, cross-sectional diagnostic accuracy study by Manabe et al., The Lancet Infectious Diseases, 2022, https://doi.org/10.1016/S1473-3099(22)00290-0</p>\n
      • quantity_imported3 Film Arrays Global Fever (GF) Panel
      • quantity_dispensedN/A
      • quantity_destroyedN/A
      • quantity_exported 1 was returned to the sponsor because it was faulty
      • balance_site2 were donated to the site
      • final_date0000-00-00
      • modified2025-07-15 14:11:19
      • created2019-03-15 11:24:51
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id485
        • application_id777
        • given_nameJOHN
        • middle_name
        • family_nameWAITUMBI
        • qualificationPhD
        • professional_addressP.O BOX 54 KISUMU CODE 40100
        • telephone+254 733616548
        • emailjohn.waitumbi@usamru-k.org
        • created2019-03-15 12:18:07
        • modified2020-09-28 17:09:52
    • SiteDetail(array)
      • 0(array)
        • id631
        • application_id777
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2019-03-15 12:18:07
        • modified2020-09-28 17:09:52
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id378
        • application_id777
        • sponsorBioFire Defense, LLC
        • sponsor_typeIndustry
        • contact_personCynthia Phillips
        • address79 West 4500 South, Suite 14,
        • telephone_number(801) 262-3592 ext.1370
        • fax_number
        • cell_number(801) 262-3592 ext.1370
        • email_addressCynthia.Phillips@biofiredefense.com
        • created2019-03-15 12:18:07
        • modified2020-09-28 17:09:52
  • 3(array)
    • Application(array)
      • id884
      • user_id81
      • trial_status_id5
      • abstract_of_study<p>\n <strong>Study Title:</strong> The Chloroquine/hydroxychloroquin prevention of coronavirus disease (COVID-19) in the healthcare setting; a randomized, placebo-controlled prophylaxis study (COPCOV)</p>\n<p>\n <strong>Trial registration:</strong> NCT04303507 (PACTR registration pending)</p>\n<p>\n <strong>Study design:</strong> Randomized double-blind, placebo controlled trial</p>\n<p>\n <strong>Participants</strong>: Healthcare workers aged ≥18 years in a healthcare facility delivering direct care to patients with either proven or suspected COVID-19.</p>\n<p>\n <strong>Planned sample size:</strong> 40, 000 worldwide, maximum of 1,600 in Kenya</p>\n<p>\n <strong>Planned Study Period:</strong> 18 months; individual trial duration maximum 5 months</p>\n<p>\n <strong>Objectives:</strong></p>\n<p>\n               <u>Primary</u>: To determine if hydroxychloroquine prophylaxis prevents symptomatic COVID-19 infection in healthcare workers</p>\n<p>\n               <u>Secondary: </u></p>\n<p>\n               a) To determine if hydroxychloroquine prophylaxis attenuates COVID-19 infections</p>\n<p>\n               b) To determine if hydroxychloroquine prophylaxis prevents asymptomatic infection with SARS-CoV-2, the virus that causes COVID-19</p>\n<p>\n               c) To determine if hydroxychloroquine prophylaxis prevents all-cause symptomatic acute respiratory illnesses</p>\n<p>\n               <u>Tertiary</u></p>\n<ol>\n <li>\n To characterize genetic and baseline biochemical markers associated with symptomatic COVID-19, respiratory illness and disease severity</li>\n <li>\n To assess the impact of hydroxychloroquine prophylaxis on work and behavior during the pandemic</li>\n <li>\n To perform health economic alalyses to assess the impact of hydroxychloroquine prophylaxis on costs and quality of life measures</li>\n</ol>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n
      • study_title<p>\n Chloroquine/ hydroxychloroquine prevention of coronavirus disease (COVID-19) in the healthcare setting; a randomised, placebo-controlled prophylaxis study (COPCOV)</p>\n
      • laymans_summary<p>\n <strong>Formal Title:</strong> Chloroquine/ hydroxychloroquine prevention of coronavirus disease (COVID-19) in the healthcare setting; a randomised, placebo-controlled prophylaxis study (COPCOV)</p>\n<p>\n <strong>Lay Title:</strong> Hydroxychloroquine for prevention of COVID-19</p>\n<p>\n <strong>What is the problem/background?</strong></p>\n<p>\n Coronavirus disease (COVID-19), which is caused by the virus known as SARS-CoV-2, was first reported in Wuhan China in December 2019 and has so far affected over 2 million people globally and has been declared a global pandemic by the World Health Organisation (WHO). There is no proven effective prophylaxis, no proven treatment and no vaccine. As of writing, there are more than 200,000 deaths globally with 1,017 in Africa. We are in a race against time to find effective treatments and preventive measures as the pandemic grows. There is major concern that COVID-19 could devastate countries with limited capacity for testing and case isolation, and overwhelm their fragile healthcare systems. The high risk to healthcare workers, as seen with SARS-CoV previously, and now in Wuhan with COVID-19, could be a major threat to healthcare operations overall. People who look after patients with COVID-19 infections are at increased risk of infection. There is an urgent need to identify drugs which can prevent the spread of infection but also that prevent high-risk groups, like those working in healthcare facilities, from getting the infection, so they can continue to care for patients and protect their families.</p>\n<p>\n <strong>What questions are we trying to answer?</strong></p>\n<p>\n We are conducting a study to find out whether a drug called hydroxychloroquine may prevent development of coronavirus illness. Chloroquine, the medicine very similar to hydroxychloroquine, was used very widely for the prevention and treatment of malaria for over 50 years and also to treat rheumatoid arthritis. People have taken it for many years at a time. It is considered very safe, and it may have effects against the virus. We would also like to find out if hydroxychloroquine lessens the symptoms for those who do get corona virus infection while taking it.</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 conducted from four sites in Kenya; Kilifi, Mombasa, Nairobi and Kisumu. We aim to recruit up to 1,600  participants across all sites. We will enroll health care workers who are at high risk of exposure to SARS-CoV-2 infection.</p>\n<p>\n <strong>What does the study involve for those who are in it?</strong></p>\n<p>\n Participants will answer some questions about their medical history, provide 25 ml of blood for testing, take study tablets (hydroxychloroquine or placebo) and record temperature and respiratory symptoms via mobile phone. Participants will take the study tablets for 90 days. They will be requested to come to the study clinic on days 30,60 and 90, plus a final visit being conducted at 5 months. Those reporting respiratory symptoms during the course of the study will have nasal and throat swabs collected for testing for the presence of respiratory viruses.</p>\n<p>\n W<strong>hat are the benefits and risks/costs of the study for those involved?  </strong></p>\n<p>\n There is a potential benefit of direct protection from corona virus infection if the drug works for those who are in the hydroxychloroquine arm. Individuals in the placebo arm may also benefit from indirect protection through decreased ability of the infection to spread.Risks related to hydroxychloroquine are very low.</p>\n<p>\n <strong>How will the study benefit society?</strong></p>\n<p>\n The study may show a benefit of using hydroxychloroquine which would save many lives around the world, or alternatively may show hydroxychloroquine prophylaxis is ineffective so trials can move on to evaluate other possible interventions.</p>\n<p>\n <strong>When does the study start and finish?</strong></p>\n<p>\n Following ethical and regulatory approval, the study is expected to take 18 months.</p>\n<p>\n  </p>\n
      • short_titleCOPCOV
      • protocol_noECCT/20/05/02
      • version_no4.0
      • date_of_protocol09-04-2020
      • study_drug Hydroxychloroquine
      • disease_conditionCOVID 19
      • 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_nameHydroxychloroquine sulphate
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressregulatory@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_countries(null)
      • 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_plan0
      • applicant_contractual_agreement0
      • declaration_applicant0722417507
      • declaration_date120-05-2020
      • declaration_principal_investigatorAnthony Etyang
      • declaration_date220-05-2020
      • placebo_presentYes
      • study_objectives<p>\n         <u>Primary</u>:</p>\n<p>\n         To determine if hydroxychloroquine prophylaxis prevents symptomatic COVID-19 infection in healthcare workers</p>\n<p>\n         <u>Secondary:</u></p>\n<ol>\n <li>\n To determine if hydroxychloroquine prophylaxis attenuates COVID-19 infections</li>\n <li>\n To determine if hydroxychloroquine prophylaxis prevents asymptomatic infection with SARS-CoV-2, the virus that causes COVID-19</li>\n <li>\n To determine if hydroxychloroquine prophylaxis prevents all-cause symptomatic acute respiratory illnesses</li>\n</ol>\n<p>\n         <u>Tertiary</u></p>\n<ol>\n <li>\n To characterize genetic and baseline biochemical markers associated with symptomatic COVID-19, respiratory illness and disease severity</li>\n <li>\n To assess the impact of hydroxychloroquine prophylaxis on work and behavior during the pandemic</li>\n <li>\n To perform health economic alalyses to assess the impact of hydroxychloroquine prophylaxis on costs and quality of life measures</li>\n</ol>\n<p>\n  </p>\n
      • principal_inclusion_criteria<ol>\n <li>\n 18 years and above</li>\n <li>\n Participant is willing and able to give informed consent for participation in the study and agrees with the study and its conduct</li>\n <li>\n Agrees not to self-medicate with chloroquine, hydroxychloroquine or other potential antivirals (e.g. not on HAART that includes LPV/r as part of the regimen)</li>\n <li>\n Not previously diagnosed with COVID-19</li>\n <li>\n Not currently symptomatic with an acute respiratory infection (ARI)</li>\n <li>\n Participant works in a healthcare facility delivering direct care to patients with either proven or suspected COVID-19</li>\n <li>\n Possesses an internet-enabled smartphone (Android or iOS) or computer</li>\n</ol>\n<p>\n  </p>\n
      • principal_exclusion_criteria<ol>\n <li>\n Hypersensitivity reaction to hydroxychloroquine or 4-aminoquinolines</li>\n <li>\n Contraindication to taking hydroxychloroquine as prophylaxis, e.g. known epileptic, known creatinine clearance < 10 ml/min </li>\n <li>\n Already taking chloroquine, hydroxychloroquine or 4-aminoquinolines</li>\n <li>\n Taking a concomitant medication described in section 8.5 of the master protocol, which cannot be safely stopped</li>\n <li>\n Known retinal disease</li>\n <li>\n Inability to be followed up for the trial period</li>\n <li>\n Known prolonged QT syndrome (ECG will be required for potential participants who report having a heart condition)</li>\n <li>\n Is enrolled in another clinical trial (however participants will be allowed to participate in observational studies)</li>\n</ol>\n<p>\n  </p>\n
      • primary_end_points<p>\n The number of symptomatic COVID-19 infections will be compared between participants randomised to chloroquine or hydroxychloroquine, and placebo groups.</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_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" style=\"width:515px;\" width=\"515\">\n <tbody>\n <tr>\n <td style=\"width:84px;\">\n <p>\n <strong>Sites</strong></p>\n </td>\n <td style=\"width:195px;\">\n <p>\n <strong>KEMRI - CGMRC</strong></p>\n </td>\n <td style=\"width:235px;\">\n <p>\n <strong>KEMRI-CGHR</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:84px;\">\n <p>\n Personnel</p>\n </td>\n <td style=\"width:195px;\">\n <p>\n Medical officer-4</p>\n <p>\n Clinical officer coordinator-1</p>\n <p>\n Clinical Officers -6</p>\n <p>\n Field workers- 9</p>\n <p>\n Pharmacists-2</p>\n <p>\n Nurses -5</p>\n <p>\n Data Manager -1</p>\n <p>\n Data Supervisor-1</p>\n <p>\n Lab techs -6</p>\n <p>\n Lab managers-3</p>\n </td>\n <td style=\"width:235px;\">\n <p>\n Medical officer 2</p>\n <p>\n Clinical officer Coordinator-1</p>\n <p>\n Clinical Officers -3</p>\n <p>\n Field workers-3</p>\n <p>\n Pharmacists-1</p>\n <p>\n Data Manager -1</p>\n <p>\n Data Supervisor -1</p>\n <p>\n Lab techs-4</p>\n <p>\n  </p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">In both sites the clinical team are trained in basic life support and resuscitation facilitaties are available</span></p>\n
      • other_details_explanation<p>\n Potential trial sites include:</p>\n<p>\n  </p>\n<p>\n <strong>The Faculty of Tropical Medicine (FTM), Mahidol University, Bangkok</strong>, is affiliated and partnered with the Mahidol Oxford Tropical Medicine Research Unit (MORU), which have successfully collaborated together for more than 40 years in the management of Tropical diseases. FTM is the only faculty specialising in tropical medicine in Thailand and runs the Hospital for Tropical Diseases in Bangkok. Both FTM and MORU are fitted with state-of-the-art molecular diagnostic testing facilities.</p>\n<p>\n <strong>Sunpasithiprasong Hospital, Ubon Ratchathani</strong>. Situated in the East of Thailand on the Laos border, this long-term 1200 bed hospital and MORU collaborator for 34 years has dedicated on-site study nurses currently conducting clinical trials.</p>\n<p>\n <strong>Udon Thani Hospital, Udon Thani</strong>, (800 beds) is situated in the Northeast of Thailand adjacent to Lao’s capital, Vientiane, and has been a study site for previous trials with successful collaboration.</p>\n<p>\n <strong>Chiangrai Clinical Research Unit (CCRU)</strong> is a MORU-affiliated unit in the North of Thailand. It has a full-time team of a clinician researcher, study nurses and laboratory staff, with a laboratory based in the Prachanukroh Hospital (760 beds).</p>\n<p>\n <strong>Shoklo Malaria Research Unit (SMRU), Mae Sot</strong>, based on the Thai-Myanmar border in the West of Thailand is the largest of the MORU-affiliated sites. Originally set up to provide basic healthcare and malaria treatment to Myanmar migrants fleeing civil war in Kayin (Karen) state, this unit now supports and runs several in-patient clinics, has a fully accredited laboratory able to test for COVID-19 and other respiratory pathogens and works closely with the Thai Governmental hospital in the city.</p>\n<p>\n <strong>Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU)</strong>, a clinical research unit embedded in the 450 bed Mahosot Hospital in Lao PDR’s capital, Vientiane, conducts clinical research on diseases of regional public health importance, and has recently developed capability for testing for SARS-CoV-2, as well as other respiratory viruses and causes of febrile illness. Audrey Dubot-Pérès, the head of Virology at LOMWRU and also works at the Institut de Recherche pour le Développement (IRD) in the Unit of Emerging Viruses (Aix-Marseille Univ-IRD 190-Inserm 1207-IHU Méditerranée Infection), Marseille. Additionally LOMWRU has excellent links, and is currently collaborating in, 5 provincial hospitals, which could be potential study sites: Xieng Khuang; Luang Namtha; Salavan; Savannakhet; and Phonhong. These provinces provide health care to the provinces which have porous borders with China, Myanmar and several geographically distinct regions of Thailand and Vietnam.</p>\n<p>\n <strong>Myanmar-Oxford Clinical Research Unit (MOCRU)</strong> is a MORU-affiliated unit in Yangon, Myanmar with strong links to Medical Action Myanmar (MAM) a non-governmental organisation which runs a network of 2,000 health workers and 10 clinics as well as strong collaborative links with the Myanmar Ministry of Health and several public hospitals in Yangon and Mandalay. </p>\n<p>\n <strong>Cambodia-Oxford Medical Research Unit (COMRU)</strong> a collaboration between MORU and the Angkor Hospital for Children (AHC) in Siem Reap, Cambodia. This collaboration started in 2006 and led by Professor Paul Turner, head of COMRU, and Dr Claudia Turner, CEO of AHC, provides free, quality healthcare to approximately 450 children a day, as well as high-quality research. The laboratory is equipped to do respiratory virus testing, including COVID-19 as well as whole genome sequencing of isolates. Given the volume of children presenting with respiratory illnesses, COVID-19 could quite easily spread to healthcare providers and back out to the community.</p>\n<p>\n <strong>Hospital of Tropical Diseases (HTD), Ho Chi Minh City, Vietnam</strong> The Oxford University Clinical Research Unit (OUCRU), our sister unit based in the HTD, has a long history of conducting hospital-based clinical trials and was at the forefront of the research response to Avian Influenza in 2004 led by Professor Jeremy Farrar. HTD is a regional referral hospital serving a population of 38 million in the South of the country.</p>\n<p>\n <strong>The Christian Medical College (CMC), Vellore, India</strong>. An institution currently collaborating with MORU, Bangkok on the biggest scrub typhus trial ever conducted and the only trial on severe scrub typhus. CMC comprises 3,000 hospital beds across 6 campuses providing primary to quaternary care management of patients. CMC consistently ranks as one of the top medical institutions in India.</p>\n<p>\n <strong>Other sites including, but not limited to sites in the UK, Italy, France, Switzerland, the Netherlands, Indonesia, Bangladesh, Pakistan, Malaysia, Kenya, Uganda, Malawi, Zambia, South Africa, Cameroon, Niger and the Democratic Republic of the Congo.</strong></p>\n<p>\n  </p>\n<p>\n  </p>\n
      • other_details_regulatory_notapproved<p>\n N/A</p>\n
      • other_details_regulatory_approved<p>\n N/A</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration18 Months
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPlacebo
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states50-100 sites
      • number_of_sites2
      • multi_country_listEuropean and African sites
      • data_monitoring_committeeYes
      • total_enrolment_per_site800
      • total_participants_worldwide40000
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyYes
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsNo
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameClara
      • investigator1_middle_nameAtieno
      • investigator1_family_nameAgutu
      • investigator1_qualificationMBChB, MPH, MSc
      • investigator1_professional_addressKEMRI Wellcome Trust Research Programme, P O Box 230, 80108 Kilifi
      • investigator1_telephone0720735000
      • investigator1_emailCAgutu@kemri-wellcome.org
      • organisations_transferred_Yes
      • number_participants1600
      • notification
      • approval_date04-09-2020
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted19-12-2021
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonEdwardabwao
      • final_report<p data-pm-slice=\"1 1 []\">\n Executive Summary: COPCOV Trial</p>\n<p>\n Title: Chloroquine/ Hydroxychloroquine Prevention of Coronavirus Disease (COVID-19) in the Healthcare Setting: A Randomised, Placebo-Controlled Prophylaxis Study (COPCOV)</p>\n<p>\n  </p>\n<p>\n Introduction</p>\n<p>\n The COPCOV trial was conducted to investigate whether hydroxychloroquine (HCQ) and chloroquine (CQ) could serve as effective preventive measures against COVID-19, particularly for healthcare workers at high risk of exposure. Given the urgent need for prophylactic solutions at the onset of the COVID-19 pandemic, the study aimed to determine the efficacy and safety of these widely-used antimalarial drugs in preventing symptomatic and asymptomatic infections.</p>\n<p>\n  </p>\n<p>\n Key Findings</p>\n<p>\n Safety and Tolerability:</p>\n<p>\n Both HCQ and CQ were found to be safe and well-tolerated, with no significant adverse events recorded among participants receiving the drugs.</p>\n<p>\n  </p>\n<p>\n Efficacy:</p>\n<p>\n The trial demonstrated a 15% reduction in symptomatic COVID-19 cases among participants receiving HCQ/CQ compared to the placebo group, but there was no significant difference in asymptomatic cases.</p>\n<p>\n  </p>\n<p>\n Impact on Respiratory Illness:</p>\n<p>\n Participants in the HCQ/CQ group experienced fewer respiratory illnesses overall, with fewer workdays lost due to illness compared to the placebo group.</p>\n<p>\n  </p>\n<p>\n Limitations:</p>\n<p>\n The study faced challenges due to the smaller-than-expected sample size, influenced by the widespread rollout of COVID-19 vaccines, which diminished the urgency for chemoprevention studies. Additionally, controversies surrounding the use of HCQ contributed to delays.</p>\n<p>\n  </p>\n<p>\n Meta-Analysis:</p>\n<p>\n A meta-analysis that combined data from this and other similar studies suggested a 20% moderate protective benefit against symptomatic COVID-19, but the overall efficacy of HCQ/CQ in the context of available vaccines remains limited.</p>\n<p>\n  </p>\n<p>\n Recommendations</p>\n<p>\n While HCQ/CQ showed modest efficacy in preventing symptomatic COVID-19, it is unlikely to be recommended for widespread use due to the availability of vaccines, which provide more robust protection. However, the findings may still hold value in situations where vaccines are unavailable or in future pandemic scenarios.</p>\n<p>\n  </p>\n<p>\n Conclusion</p>\n<p>\n The COPCOV trial demonstrated that HCQ and CQ are safe, with moderate protection against symptomatic COVID-19. However, in the context of evolving COVID-19 prevention strategies, particularly with vaccine development, these drugs are not expected to play a major role. Nonetheless, the trial highlights the importance of conducting large-scale randomized controlled trials during pandemics to provide clear evidence for treatment and prevention approaches.</p>\n
      • implication_results<p data-pm-slice=\"1 1 []\">\n The results of the COPCOV trial have several implications for current medical and public health practice, especially concerning the use of hydroxychloroquine (HCQ) and chloroquine (CQ) for COVID-19 prevention:</p>\n<p>\n  </p>\n<p>\n 1. Limited Role for HCQ/CQ in Current COVID-19 Prophylaxis</p>\n<p>\n Vaccine Priority: With the development and widespread availability of highly effective COVID-19 vaccines, HCQ/CQ are no longer considered viable prophylactic options. The trial demonstrated moderate efficacy in reducing symptomatic cases (15%), but vaccines provide much higher levels of protection (up to 90% efficacy) and are now the preferred preventive measure.</p>\n<p>\n No Impact on Asymptomatic Cases: The trial showed no significant effect on asymptomatic infections, further limiting the utility of HCQ/CQ as preventive tools.</p>\n<p>\n 2. Future Pandemic Preparedness</p>\n<p>\n Exploration of Early Pandemic Treatments: Although HCQ/CQ are unlikely to be used for COVID-19 prevention in the current pandemic, their moderate efficacy and safety profile suggest they could be explored in future pandemics, especially in the early stages before vaccines are available. This underscores the importance of maintaining a pipeline of potential treatments for rapid deployment.</p>\n<p>\n 3. Emphasis on Evidence-Based Practices</p>\n<p>\n Importance of Randomized Trials: The COPCOV trial reinforced the necessity of conducting large-scale, randomized controlled trials (RCTs) to determine the efficacy of potential treatments. Early in the pandemic, HCQ was widely used based on limited evidence, leading to controversy and mixed outcomes. This study serves as a reminder that high-quality evidence must guide clinical practice to avoid unnecessary or ineffective treatments.</p>\n<p>\n 4. Healthcare Worker Safety</p>\n<p>\n Protection Through Vaccination and Other Measures: Although the trial did not provide conclusive evidence for the continued use of HCQ/CQ, it highlighted the need for adequate protection for healthcare workers. Vaccines, personal protective equipment (PPE), and infection control practices remain the primary strategies for protecting healthcare workers, rather than chemoprevention.</p>\n<p>\n 5. Reallocating Research Focus</p>\n<p>\n Shift to Vaccine-Based Solutions: The COPCOV trial’s findings signal a shift in focus from drug-based prevention (like HCQ/CQ) to vaccine-driven solutions. This emphasizes the importance of supporting vaccine development and distribution as the most effective way to manage pandemics.</p>\n<p>\n In summary, while the COPCOV trial confirmed the safety and moderate efficacy of HCQ/CQ, their role in preventing COVID-19 is minimal in the current context of vaccine availability. The findings reinforce the need for evidence-based interventions and could inform preparedness for future infectious disease outbreaks.</p>\n
      • quantity_imported
      • quantity_dispensed
      • quantity_destroyed
      • quantity_exported
      • balance_site
      • final_date0000-00-00
      • modified2024-10-02 11:34:11
      • created2020-05-02 09:29:53
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id546
        • application_id884
        • given_nameAnthony
        • middle_nameOliwa
        • family_nameEtyang
        • qualificationMBChB, MMed, MSc, PhD
        • professional_addressKEMRI Wellcome Trust Research Programme, P O Box 230, 80108 Kilifi
        • telephone0722417507
        • emailAEtyang@kemri-wellcome.org
        • created2020-05-02 09:41:01
        • modified2021-12-19 15:56:05
    • SiteDetail(array)
      • 0(array)
        • id767
        • application_id884
        • county_id3
        • site_nameKEMRI - Centre for Geographic Medicine Research Coast (CGMRC)
        • physical_addressOff Hospital Road
        • contact_detailsKEMRI Wellcome Trust Research Programme, P O Box 230, 80108 Kilifi
        • contact_personDr. Anthony Etyang
        • site_capacity(null)
        • misc(null)
        • created2020-05-02 09:41:01
        • modified2021-12-19 15:56:05
        • County(array)
          • id3
          • county_nameKilifi
          • created2012-05-31 16:15:49
          • modified2012-05-31 16:15:49
      • 1(array)
        • id768
        • application_id884
        • county_id42
        • site_nameKEMRI-Centre for Global Health Research (CGHR)
        • physical_addressKisian Campus. Opp Kisian Primary School
        • contact_details+254724464507,P O 1578, 40100 Kisumu
        • contact_personDr. Hellen Barsosio
        • site_capacity(null)
        • misc(null)
        • created2020-05-02 10:27:01
        • modified2021-12-19 15:56:05
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
    • Sponsor(array)
      • 0(array)
        • id429
        • application_id884
        • sponsorUniversity of Oxford
        • sponsor_typeResearch Institution
        • contact_personDr, William Schilling
        • addressMahidol Oxford Tropical Medicine Research Unit, Thailand
        • telephone_number+447555397128
        • fax_number
        • cell_number+447555397128
        • email_addresswilliam@tropmedres.ac
        • created2020-05-02 09:41:01
        • modified2021-12-19 15:56:05
  • 4(array)
    • Application(array)
      • id567
      • user_id81
      • trial_status_id5
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style=\"mso-bidi-font-family:\nArial\">COAST overarching objective is to address the key research gaps in the therapeutic use of oxygen in resource-limited setting in order to provide a better evidence base for future management guidelines. <span style=\"color:black;\nmso-bidi-font-weight:bold\">The trial has been designed to address the poor outcomes of children in sub-Saharan Africa, which are associated with high rates of </span>in-hospital mortality 9-10% (for those with oxygen saturations between 80% and 92%) and 26-30% case fatality for those with oxygen saturations <80%, indicating that the current recommendations and/or management strategies are not working in practice. </span></p>\n<p class=\"MsoNormal\" style=\"margin-top:6.0pt\">\n <span style=\"mso-bidi-font-family:\nArial\">Despite over two decades of investment by WHO technologies group aimed at improving systems for delivering oxygen it appears not to have been afforded a high enough priority at both a global and a country level. Although oxygen is a <span class=\"st1\"><span style=\"mso-bidi-font-weight:bold\">basic element of hospital care, </span></span>the poor implementation of current treatment recommendations also <span class=\"st1\"><span style=\"mso-bidi-font-weight:bold\">stems from the lack of availability in many hospitals, or it cannot be used routinely due to unpredictable supply, faulty cylinders or limitations and interruptions of the electricity supply. This has resulted in </span></span>mismatch between supply of, and demand for, oxygen in many rural hospitals in developing countries<span class=\"st1\"><span style=\"mso-bidi-font-weight:bold\">. </span></span>Whilst the health burden of hypoxia, including morbidity, hospital admission and death have been realised, its potential economic burden for treating children with conditions leading to hypoxia is substantial. As a result there are major gaps between current treatment policies and implementation. These largely stem from the lack of relevant research to inform clinical management; consequently current treatment recommendations are based on weak evidence. <span style=\"color:black\">Systematic and policy reviews have indicated the need for formal evaluation of the </span>hypoxaemia threshold for which oxygen should be targeted and how best to administer oxygen.</span></p>\n<p class=\"MsoNormal\" style=\"mso-pagination:none;tab-stops:47.0pt 72.0pt;\nmso-layout-grid-align:none;text-autospace:none\">\n <span style=\"mso-bidi-font-family:\nArial\">COAST aims to provide the relevant evidence for policy makers and health services by evaluating key elements of an integrated management strategy in African hospitals on the basis of clinical effectiveness and costs. </span></p>\n<p class=\"MsoNormal\" style=\"mso-pagination:none;tab-stops:47.0pt 72.0pt;\nmso-layout-grid-align:none;text-autospace:none\">\n <span style=\"mso-bidi-font-family:\nArial\">COAST is a randomised controlled trial designed to </span><span style=\"mso-fareast-font-family:"MS Mincho";mso-bidi-font-family:Arial\">provide the evidence for the most <i style=\"mso-bidi-font-style:normal\">clinically-effective</i> and <i style=\"mso-bidi-font-style:normal\">cost-efficient</i> targeted use of oxygen as a life-saving treatment with respect to the </span><span style=\"mso-bidi-font-family:Arial\">optimal oxygen saturation threshold for treatment and mode of delivery in 4200 African children, aged 2 months to 12 years, presenting to hospital with respiratory distress complicated by hypoxia (defined as oxygen saturation (SaO₂)< 92%).<span style=\"mso-spacerun:yes\">  </span></span></p>\n<p class=\"MsoNormal\" style=\"mso-pagination:none;tab-stops:47.0pt 72.0pt;\nmso-layout-grid-align:none;text-autospace:none\">\n <span style=\"mso-bidi-font-family:\nArial;color:black;mso-bidi-font-weight:bold\">Children will be enrolled at admission to hospital over 2 years from 5 sites in 2 countries (</span><span style=\"mso-bidi-font-family:Arial\">Uganda and Kenya)<span style=\"color:black;\nmso-bidi-font-weight:bold\"> and followed for 28 days.<span style=\"mso-spacerun:yes\">  </span></span>The trial has a pragmatic design, to ensure this encompasses a spectrum of high-risk children, identified largely by clinical criteria, so that the results are applicable to health services in Africa, with limited access to health technologies.</span></p>\n<h2 style=\"margin-top:10.0pt;margin-right:0cm;margin-bottom:6.0pt;margin-left:\n7.1pt;mso-list:none;tab-stops:36.0pt\">\n <a name=\"_Toc437619370\"><span style=\"font-style:normal\">Primary objectives</span></a></h2>\n<p class=\"MsoNormal\">\n To establish whether:</p>\n<p class=\"MsoListParagraphCxSpFirst\" style=\"margin-bottom:10.0pt;mso-add-space:\nauto;text-indent:-18.0pt;line-height:115%;mso-list:l2 level1 lfo2\">\n <span style=\"font-family:Symbol;mso-fareast-font-family:Symbol;mso-bidi-font-family:\nSymbol;mso-bidi-font-weight:bold\"><span style=\"mso-list:Ignore\">·<span style=\"font:7.0pt "Times New Roman"\">       </span></span></span><span style=\"mso-bidi-font-weight:bold\">liberal oxygenation will decrease mortality compared with permissive hypoxia (usual care); and</span></p>\n<p class=\"MsoListParagraphCxSpLast\" style=\"margin-bottom:10.0pt;mso-add-space:\nauto;text-indent:-18.0pt;line-height:115%;mso-list:l2 level1 lfo2\">\n <span style=\"font-family:Symbol;mso-fareast-font-family:Symbol;mso-bidi-font-family:\nSymbol;mso-bidi-font-weight:bold\"><span style=\"mso-list:Ignore\">·<span style=\"font:7.0pt "Times New Roman"\">       </span></span></span><span style=\"mso-bidi-font-weight:bold\">high flow oxygen delivery will decrease mortality compared with low flow oxygen delivery (usual care).</span></p>\n<h2 style=\"margin-top:10.0pt;margin-right:0cm;margin-bottom:6.0pt;margin-left:\n7.1pt;mso-list:none;tab-stops:36.0pt\">\n <a name=\"_Toc437619371\">Secondary objectives</a></h2>\n<p class=\"MsoNormal\">\n The secondary objectives of COAST are:</p>\n<p class=\"MsoListParagraphCxSpFirst\" style=\"margin-bottom:10.0pt;mso-add-space:\nauto;text-indent:-18.0pt;line-height:115%;mso-list:l1 level1 lfo3\">\n <span style=\"font-family:Symbol;mso-fareast-font-family:Symbol;mso-bidi-font-family:\nSymbol\"><span style=\"mso-list:Ignore\">·<span style=\"font:7.0pt "Times New Roman"\">       </span></span></span>to assess the effectiveness in the speed and success of recovery from the initial respiratory failure;</p>\n<p class=\"MsoListParagraphCxSpMiddle\" style=\"margin-bottom:10.0pt;mso-add-space:\nauto;text-indent:-18.0pt;line-height:115%;mso-list:l1 level1 lfo3\">\n <span style=\"font-family:Symbol;mso-fareast-font-family:Symbol;mso-bidi-font-family:\nSymbol\"><span style=\"mso-list:Ignore\">·<span style=\"font:7.0pt "Times New Roman"\">       </span></span></span>to assess safety and quality of life;</p>\n<p class=\"MsoListParagraphCxSpMiddle\" style=\"margin-bottom:10.0pt;mso-add-space:\nauto;text-indent:-18.0pt;line-height:115%;mso-list:l1 level1 lfo3\">\n <span style=\"font-family:Symbol;mso-fareast-font-family:Symbol;mso-bidi-font-family:\nSymbol\"><span style=\"mso-list:Ignore\">·<span style=\"font:7.0pt "Times New Roman"\">       </span></span></span>to determine long-term effects of the delivery strategies; and</p>\n<p class=\"MsoListParagraphCxSpLast\" style=\"margin-bottom:10.0pt;mso-add-space:\nauto;text-indent:-18.0pt;line-height:115%;mso-list:l1 level1 lfo3\">\n <span style=\"font-family:Symbol;mso-fareast-font-family:Symbol;mso-bidi-font-family:\nSymbol\"><span style=\"mso-list:Ignore\">·<span style=\"font:7.0pt "Times New Roman"\">       </span></span></span>to identify whether the additional costs of each of the interventions are proportionate to the health benefits and to inform future widespread implementation in terms of value for money.</p>\n<p class=\"MsoNormal\" style=\"mso-pagination:none;tab-stops:47.0pt 72.0pt;\nmso-layout-grid-align:none;text-autospace:none\">\n <span style=\"mso-bidi-font-family:\nArial\"> </span></p>\n<p class=\"MsoNormal\" style=\"mso-pagination:none;tab-stops:47.0pt 72.0pt;\nmso-layout-grid-align:none;text-autospace:none\">\n <span style=\"mso-bidi-font-family:\nArial\">The trial will have two randomisations:</span></p>\n<p class=\"MsoNormal\" style=\"line-height:12.0pt;mso-pagination:none\">\n <b><span style=\"mso-bidi-font-family:Arial\">R1: For children with a baseline SaO₂<92% but ≥80%, randomisation to l</span></b><span style=\"mso-bidi-font-family:Arial\">iberal oxygenation delivered by either high flow or low flow versus a more conservative strategy (control: no oxygen) </span></p>\n<p class=\"MsoNormal\" style=\"line-height:12.0pt;mso-pagination:none\">\n <b><span style=\"mso-bidi-font-family:Arial\">R2: For children with a baseline SaO₂<80% and for those randomised to liberal oxygenation for R1, </span></b><span style=\"mso-bidi-font-family:Arial;mso-bidi-font-weight:bold\">h</span><span style=\"mso-bidi-font-family:Arial;color:black\">igh flow versus low flow delivery (routine care)</span></p>\n<p class=\"MsoNormal\" style=\"mso-pagination:none;tab-stops:47.0pt 72.0pt;\nmso-layout-grid-align:none;text-autospace:none\">\n <b style=\"mso-bidi-font-weight:\nnormal\"><span style=\"mso-bidi-font-family:Arial\"> </span></b></p>\n<p>\n <b style=\"mso-bidi-font-weight:normal\"><span style=\"font-size:11.0pt;\nline-height:105%;font-family:Calibri;mso-ascii-theme-font:minor-latin;\nmso-fareast-font-family:"ï¼­ï¼³ 明朝";mso-fareast-theme-font:minor-fareast;\nmso-hansi-theme-font:minor-latin;mso-bidi-font-family:Arial;mso-ansi-language:\nEN-GB;mso-fareast-language:EN-GB;mso-bidi-language:AR-SA\">R1 </span></b><span style=\"font-size:11.0pt;line-height:105%;font-family:Calibri;mso-ascii-theme-font:\nminor-latin;mso-fareast-font-family:"ï¼­ï¼³ 明朝";mso-fareast-theme-font:minor-fareast;\nmso-hansi-theme-font:minor-latin;mso-bidi-font-family:Arial;mso-ansi-language:\nEN-GB;mso-fareast-language:EN-GB;mso-bidi-language:AR-SA\">addresses the question of what threshold to give oxygen in children with hypoxia (above a threshold of SaO₂<span style=\"mso-bidi-font-weight:bold\">≥</span>80%); <b style=\"mso-bidi-font-weight:normal\">R2 </b>addresses how best to give oxygen all receiving to oxygen. For <b style=\"mso-bidi-font-weight:normal\">R1</b>, a cut off of <92% assesses a range of saturations that would be consistent with international recommendations for use of oxygen in sick children - providing important additional data about those at a higher threshold than currently recommended by WHO. Children randomised to control will receive low flow oxygen if they ever develop severe hypoxia (SaO₂<80%). All randomisations will be open. </span></p>\n
      • study_title<p>\n Childrens Oxygen Administration Strategies Trial</p>\n
      • laymans_summary<p>\n Lay title<br />\n Optimising and targeting oxygen treatment in sick children: The COAST trial<br />\n What is the problem?<br />\n Although oxygen is a basic element of hospital care, there are no relevant studies to guide which level of oxygen saturation or the best method of how to administer it (low flow or high flow) to improve outcome. In practice many children in low-income countries do not receive oxygen, despite being recommended, owing to the lack of its availability due to the high cost, or supplies that are unpredictable (erratic delivery of cylinders or electricity to power oxygen concentrators) resulting in mismatch between supply and demand. The outcomes of children in sub-Saharan Africa with pneumonia, remains poor with an in-hospital mortality 9-10% (for those with oxygen saturations between 80% and 92%) and 26-30% case fatality for those with oxygen saturations <80%, indicating that the current recommendations and/or management strategies are not working in practice.<br />\n What questions are we trying to answer?<br />\n COAST has been designed to identify which children would benefit from receiving oxygen and what would be the best delivery method. Although oxygen is a basic element of hospital care, this therapy is costly and supplies are inadequate and erratic in African hospitals.<br />\n COAST will address two related questions of oxygen therapy and one about nutrition supplementation:<br />\n 1. Who to give oxygen too?<br />\n We will examine whether or not giving oxygen improves outcomes for children who have a moderately low level of oxygen it is not certain what the best level to provide oxygen is and whether this results in a better outcome – so half of the children will receive oxygen and the other half will not. Children with severe hypoxia (<80%) will all receive oxygen as we are more confident about the benefits of oxygen in this group.<br />\n 2. How best to give oxygen?<br />\n For children receiving oxygen, we will compare whether giving oxygen at a higher flow compared with a lower flow (routine care) improves outcomes. High flow oxygen provides extra pressure to the airways to prevent them from collapsing after every exhalation. This helps reduce the effort of breathing, which is vital when lung infections can often lead to respiratory exhaustion and ultimately respiratory failure in critically sick children with limited access to relevant life support i.e. mechanical ventilation (the majority of hospitals in Africa).<br />\n 3. Nutritional Support<br />\n To establish whether supplementary feeding for 56-days (8 weeks) using Ready to Use Therapeutic Feeds (RUTF) in all children versus usual standard care will improve outcome at 90-days.<br />\n Where is the study taking place?<br />\n The study will take place in 5 hospitals in 2 African countries Kilifi County Hospital and Coast Provincial General Hospital (Kenya) and Mulago (Kampala) Mbale and Soroti Hospitals in Uganda.</p>\n
      • short_titleCOAST
      • protocol_noECCT/16/11/03
      • version_no1.1
      • date_of_protocol15-09-2016
      • study_drugOxygen
      • disease_conditionSevere pneumonia
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device1
      • product_type_chemical_name
      • product_type_medical_device_nameAirVO2 Nasal Oxygen interface
      • 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_countries1
      • applicant_addendum1
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      • applicant_pan_african1
      • applicant_hard_copies(null)
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      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantPatricia Njuguna
      • declaration_date110-11-2016
      • declaration_principal_investigatorKathryn Maitland
      • declaration_date210-11-2016
      • placebo_presentNo
      • study_objectives<p>\n Primary objectives</p>\n<p>\n To establish whether:</p>\n<ul>\n <li>\n liberal oxygenation will decrease mortality compared with permissive hypoxia (usual care); and</li>\n <li>\n high flow oxygen delivery will decrease mortality compared with low flow oxygen delivery (usual care).</li>\n <li>\n Supplementing feeds with RUTF will improve anthropometric outcomes at Day 90 and Day 180.</li>\n</ul>\n<p>\n The secondary objectives of COAST are:</p>\n<ul>\n <li>\n to assess the effectiveness in the speed and success of recovery from the initial respiratory failure;</li>\n <li>\n to assess safety and quality of life;</li>\n <li>\n to determine long-term effects of the delivery strategies; and</li>\n <li>\n to identify whether the additional costs of each of the interventions are proportionate to the health benefits and to inform future widespread implementation in terms of value for money.</li>\n</ul>\n<ol>\n <li value=\"1.1\">\n ctives</li>\n</ol>\n
      • principal_inclusion_criteria<p>\n Aged between 28 days to 12 years with a</p>\n<ul>\n <li>\n History of respiratory illness (cough, upper respiratory tract symptom or any respiratory symptoms, e.g. rapid breathing or increase work of breathing)</li>\n <li>\n Hypoxia (pulse oximetry reading of SaO₂ <92% recorded in room air over 5 minutes)</li>\n <li>\n Plus <em>any one of the following</em> signs of severe pneumonia (from 2013 WHO clinical definitions for pneumonia [<a href=\"#_ENREF_55\" title=\", 2013 #71\">55</a>]):</li>\n</ul>\n<ol style=\"list-style-type:lower-alpha;\">\n <li>\n Sign of respiratory distress (any one of):\n <ul style=\"list-style-type:circle;\">\n <li>\n severe lower chest wall in-drawing</li>\n <li>\n use of auxiliary muscles</li>\n <li>\n head nodding</li>\n <li>\n inability to feed because of respiratory problems</li>\n </ul>\n </li>\n <li>\n Suspected pneumonia\n <ul style=\"list-style-type:circle;\">\n <li>\n fast breathing:\n <ul>\n <li>\n age 2–11 months: ≥ 50/minute</li>\n <li>\n age 1–5 years: ≥ 40/minute</li>\n <li>\n age 5-12 years ≥ 30/minute</li>\n </ul>\n </li>\n <li>\n chest auscultation signs:\n <ul>\n <li>\n decreased breath sounds</li>\n <li>\n bronchial breath sounds</li>\n <li>\n crackles</li>\n <li>\n abnormal vocal resonance (decreased over a pleural effusion or empyema, increased over lobar consolidation)</li>\n <li>\n pleural rub</li>\n </ul>\n </li>\n </ul>\n </li>\n <li>\n Signs of pneumonia with a general danger sign:</li>\n</ol>\n<ul style=\"list-style-type:circle;\">\n <li>\n inability to breastfeed or drink</li>\n <li>\n lethargy or unconscious</li>\n <li>\n convulsions</li>\n</ul>\n
      • principal_exclusion_criteria<ul>\n <li>\n Known uncorrected cyanotic heart disease</li>\n <li>\n Assent/consent refusal by parent/carer</li>\n <li>\n Previously recruited to COAST</li>\n <li>\n Already received oxygen for this episode of illness</li>\n</ul>\n
      • primary_end_points<p>\n Primary</p>\n<p>\n 48 hour mortality post randomisation</p>\n<p>\n Secondary</p>\n<ul>\n <li>\n Treatment failure at 48 hours</li>\n <li>\n Survival to 28 days</li>\n <li>\n Neurocognitive sequelae at 28 days</li>\n <li>\n Disability-free survival to 28 days</li>\n <li>\n Time to hypoxia (≥92%) resolution during initial hospital stay</li>\n <li>\n Length of initial hospital stay</li>\n <li>\n Re-admission to hospital by 28 days</li>\n <li>\n Anthropometric status by 28 days</li>\n</ul>\n<p>\n Resolution of neurocognitive sequelae at 90 days (for those with neurocognitive sequelae at 28 days)</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety0
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n Kenya: KEMRI Wellcome Trust Programme, Kilifi County Hospital (KCH). The clinical programme at KCH is a well-established research centre on the coast of Kenya. It has been the site of several clinical studies on severe malaria including two large phase III trials (AQUAMAT and FEAST). Coast Provincial General Hospital (CPGH) is based in the second largest city in Kenya (Mombasa) and has conducted in collaboration with KWTRP a number of research studies and Phase III clinical trials in children admitted to CPGH .</p>\n<p>\n Uganda: Mulago National Referral Hospital. Mbale Regional Referral Hospital and Soroti Regional Referral Hospital. Mulago, Mbale and Soroti hospitals have annual admissions to the paediatric ward of 18,000, 20,000 and 8000 respectively. There has been considerable research capacity development in the last five years, with these three sites involved in the FEAST trial and currently conducting a large multicentre trial of transfusion trial (TRACT).</p>\n<p>\n The five centres in Africa represent a spectrum of intensity of malaria transmission, from perennial and high (in Mbale and Soroti) to seasonal and meso-endmic (in Kampala, Mombasa and Kilifi). Mulago and CPGH are located within large urban areas, whereas the populations that utilise Mbale, Soroti and Kilifi are more typically rural; however Mbale has a few slum developments within the town.</p>\n<p>\n Central grant funding will be available for participating sites to support infrastructural upgrade to ensure basic life resuscitation, standard medications available and oxygen can be delivered continuously and sufficient staff to run the trial - each centre have 2 clinician, 5 nurses and laboratory staff. Fischer and Paykel have donated sufficient AIRVO machines (5 per site) , tubing and nasal prongs for oxygen administration.</p>\n
      • other_details_explanation<p>\n The trial is in children with  severe pneumonia in low income settings</p>\n
      • other_details_regulatory_notapproved<p>\n not applicable</p>\n
      • other_details_regulatory_approved<p>\n Uganda March 2016</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n None</p>\n
      • estimated_duration30 months
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorHigh Flow Oxygen versus L
      • design_controlled_other_medicinalYes
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherYes
      • design_controlled_medicinal_specifyAirVO oxgen nasal delivery device
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states2 countries 5 sites
      • number_of_sites2
      • multi_country_listUganda (Mbale and Soroti Regional Referral Hospitals) Mulago National Referral Hospital\nKenya (as above)
      • data_monitoring_committeeYes
      • total_enrolment_per_sitePer site a minimum of 400 and maximum of 800
      • total_participants_worldwide4200
      • 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 aged 2months-12 years admitted to hospital with severe pneumonia and hypoxia
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_namePatricia
      • investigator1_middle_name
      • investigator1_family_nameNjuguna
      • investigator1_qualificationMMed PhD
      • investigator1_professional_addressKEMRI Wellcome Trust Programme CRG, Kilifi
      • investigator1_telephone254 41 7522063
      • investigator1_emailPNjuguna@kemri-wellcome.org
      • organisations_transferred_Yes
      • number_participants1200 across 2 sites over 3 years
      • notification<p>\n None</p>\n
      • approval_date22-02-2017
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted26-02-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<p>\n The trial was stopped prematurely by the Trial Steering Committee on the grounds of feasibility. Between 14th Feb 2017 and when enrolment ceased 28th Feb 2020, 1842, eligible children were enrolled into the COAST trial and included in all analyses. In the severe hypoxemia stratum, 388 children were enrolled,194 children were randomized to High Flow Nasal Therapy, and 194 to Low Flow Oxygen. In the hypoxemia stratum,1454 children were enrolled and, 363 were randomized to HFNT, 364 to LFO, and 727 to permissive hypoxemia.</p>\n<p>\n At the point of termination, the COAST trial was unable to answer the two specific hypotheses it was designed to address. First, whether liberal oxygenation therapy for children with hypoxemia (SpO2 80–91%) is superior to permissive hypoxemia. Secondly, there were insufficient data to demonstrate that HFNT was superior to LFO.</p>\n<p>\n Across both strata, HFNT administration was also relatively oxygen-sparing, using room air/oxygen blends without any evidence of harm. In the hypoxemia stratum in many cases HFNT was provided on room air, leading to correction of hypoxemia. Although the trial does not provide definitive data to inform treatment guidelines, the knowledge acquired from the trial adds a new level of uncertainty to the liberal use of oxygen as a supportive therapy.</p>\n<p>\n In the case of severe pneumonia, pre-existing evidence demonstrating clear benefits of oxygen therapy was poor hence the trial was both ethically and scientifically sound.</p>\n<p>\n While oxygen, as a supportive therapy, has been considered the standard treatment for pneumonia for a large part of the last century, the recognition of potential oxygen toxicity is relatively recent. In several areas of emergency care and resuscitation, the use of oxygen is now being challenged by emerging evidence from clinical trials, including in pediatric populations and systematic reviews.</p>\n<p>\n Regarding demand on health services, the routine use of pulse oximetry to target oxygen therapy is poorly implemented despite having been recommended by WHO for triage of sick children. Hence, oxygen therapy is generally targeted by non-specific clinical signs that predict hypoxemia poorly, thus exposing large numbers of children without hypoxemia to oxygen therapy, and raising questions over safety, cost, and demand for a constrained health resource. Our findings indicate that hypoxemia in children with severe pneumonia can be corrected without additional oxygen.</p>\n<p>\n Recognizing the resource limitations and costs of oxygen therapy, the protocol incorporated relatively oxygen sparing strategies in the investigational groups (HFNT and permissive hypoxemia) and vital sign monitoring to ensure early weaning in both liberal (HFNT and LFO)</p>\n<p>\n strategies.</p>\n<p>\n COAST trial represents the largest trial of oxygen therapy ever conducted in children and the only multicenter controlled trial.</p>\n<p>\n We, therefore, proposed that HFNT was a feasible alternative source of respiratory support owing to its relative simplicity in implementation, humidification, low risk of nosocomial infection. In addition, the ability to blend both oxygen and room air to deliver positive end-expiratory pressure, thus, limiting exposure to high concentrations of oxygen (and potential toxicity) and with the prospect of reducing costs to health services.</p>\n<p>\n  </p>\n
      • implication_results<p>\n <span style=\"font-size: 9pt; font-family: Arial, sans-serif;\">Our findings supports the need for future trials with similar designs, particularly in settings where access to oxygen and/or mechanical respiratory support are restricted. The scale of the mortality reduction of High Flow Nasal Therapy over Low Flow Oxygen, particularly in severely hypoxaemic children warrants further investigation. Oxygen-sparing strategies potentially offer cost-effective approaches to reducing overall oxygen requirements in overburdened health services and adds to the general findings in critical care that less is more.<o:p></o:p></span></p>\n
      • quantity_importedN/A
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      • final_date0000-00-00
      • modified2025-07-25 18:54:17
      • created2016-11-02 15:20:40
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        • given_nameKathryn
        • middle_name
        • family_nameMaitland
        • qualificationMBBS FRCP Phd
        • professional_addressImperial College, London
        • telephone+4420 7594 3891
        • emailk.maitland@imperial.ac.uk
        • created2016-11-02 15:21:12
        • modified2020-02-26 10:02:14
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        • contact_detailsn/a
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        • id292
        • application_id567
        • sponsorImperial College, London
        • sponsor_typeOthers
        • contact_personGary Roper
        • addressJoint Research Office, Sir Alexander Fleming Building, Imperial College, Exhibition Road, London, United Kingdom, SW7 2AZ
        • telephone_number+44(0)2075949484
        • fax_numbern/a
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        • email_addressgary.roper@imperial.ac.uk
        • created2016-11-02 15:21:12
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    • Component(array)
      • 0Search/Controller/Component/PrgComponent.php
    • Behavior(array)
      • 0Search/Model/Behavior/SearchableBehavior.php
  • Shim(array)
    • Config(array)
      • 0Shim/Config/bootstrap.php
  • Tools(array)
    • Config(array)
      • 0Tools/Config/bootstrap.php