Pan African Clinical Trials Registry

South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: www.pactr.org
Trial no.: PACTR202009786901147 Date of Approval: 16/09/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Hydroxychloroquine for prevention of COVID-19
Official scientific title The Chloroquine/hydroxychloroquine prevention of coronavirus disease (COVID-19) in the healthcare setting; a randomized, placebo-controlled prophylaxis study (COPCOV)
Brief summary describing the background and objectives of the trial BACKGROUND 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. OBJECTIVES Primary: To determine if hydroxychloroquine prophylaxis prevents symptomatic COVID-19 infection in healthcare workers Secondary: a) To determine if hydroxychloroquine prophylaxis attenuates COVID-19 infections b) To determine if hydroxychloroquine prophylaxis prevents asymptomatic infection with SARS-CoV-2, the virus that causes COVID-19 c) To determine if hydroxychloroquine prophylaxis prevents all-cause symptomatic acute respiratory illnesses Tertiary a) To characterize genetic and baseline biochemical markers associated with symptomatic COVID-19, respiratory illness and disease severity b) To assess the impact of hydroxychloroquine prophylaxis on work and behavior during the pandemic c) To perform health economic alalyses to assess the impact of hydroxychloroquine prophylaxis on costs and quality of life measures
Type of trial RCT
Acronym (If the trial has an acronym then please provide) COPCOV
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Coronavirus disease
Purpose of the trial Prevention
Anticipated trial start date 01/10/2020
Actual trial start date
Anticipated date of last follow up 30/04/2022
Actual Last follow-up date
Anticipated target sample size (number of participants) 1600
Actual target sample size (number of participants) 1600
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using a randomization table created by a computer software program Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Placebo 1 tablet/ 15kg at Day 0 and a further 30 tablets to be taken once daily for 3 months, taken orally. 3 months The placebo will comprise identical tablets and the regimen will be the same with 1tablet/ 15kg at D0 and a further 30 tablets to be taken once daily. 800 Placebo
Experimental Group hydroxychloroquine 200mg of hydroxychloroquine sulphate On Day 0 the participant will be supervised taking 10mg base/kg (usually 3-6 tablets depending on weight) stat and they will be given a further 30 tablets of 200mg base to be taken once daily. 3 months The trial intervention is the administration of the study product. This will either be hydroxychloroquine or placebo. Hydroxychloroquine will be in the dose of 200mg of hydroxychloroquine sulphate. On D0 the participant will be supervised taking 10 mg base/kg (usually 3-6 tablets depending on weight) and they will be given a further 30 tablets of 200 mg base to be taken once daily. The placebo will comprise identical tablets and the regimen will be the same with 1 tablet/ 15 kg at D0 and a further 30 tablets to be taken once daily. Neither the participant, nor those conducting the study will know if the participant is receiving hydroxychloroquine or placebo. 800
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
• 18 years and above • Participant is willing and able to give informed consent for participation in the study and agrees with the study and its conduct • 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) • Not previously diagnosed with COVID-19 • Not currently symptomatic with an acute respiratory infection (ARI) • Possesses an internet-enabled smartphone (Android or iOS) or computer • Hypersensitivity reaction to hydroxychloroquine or 4-aminoquinolines • Contraindication to taking hydroxychloroquine as prophylaxis, e.g. known epileptic, known creatinine clearance < 10 ml/min • Already taking chloroquine, hydroxychloroquine or 4-aminoquinolines • Taking a concomitant medication described in section 8.5 of the master protocol, which cannot be safely stopped known retinal disease • Inability to be followed up for the trial period • Known prolonged QT syndrome (ECG will be required for potential participants who report having a heart condition) • Is enrolled in another clinical trial (however participants will be allowed to participate in observational studies) Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 65 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 25/08/2020 SCIENTIFIC ETHICS REVIEW UNIT
Ethics Committee Address
Street address City Postal code Country
54840 Nairobi 00200 Kenya
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 15/04/2020 Oxford Tropical Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
University of Oxford Research Services, University Offices Wellington Square, Oxford OX1 2JD Oxford OX1 2JD United Kingdom
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome The number of symptomatic COVID-19 infections will be compared between participants randomised to hydroxychloroquine, and placebo groups During the trial period
Secondary Outcome The symptoms,severity and duration of COVID-19, in those who become infected during the study will be compared between the two groups using a respiratory severity score During the trial period
Secondary Outcome The number of asymptomatic cases of COVID-19 will be determined by comparing serology in all participants at time of enrolment and at the end of follow up During the trial period
Secondary Outcome The number and severity of symptomatic acute respiratory illnesses will be compared between the hydroxychloroquine,and placebo group During the trial period
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Kenya Medical Research Institute CGMRC 230 Kilifi 80108 Kenya
Kenya Medical Research Institute CGHR 1578 Kisumu 40100 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
COVID 19 Therapeutics Accelerator Consortium Consortium United Kingdom
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Dr. William Schilling Wellington Square, Oxford OX1 2JD Oxford United Kingdom University
COLLABORATORS
Name Street address City Postal code Country
Professor Sir Nicholas White MahidolOxford Tropical Medicine Research Unit Thailand Thailand
Dr William Schilling MahidolOxford Tropical Medicine Research Unit Thailand Thailand
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Anthony Etyang AEtyang@kemri-wellcome.org +254722417507 230 80108
City Postal code Country Position/Affiliation
Kilifi Kenya Kenya Medical Research Institute CGMRC
Role Name Email Phone Street address
Scientific Enquiries Anthony Etyang AEtyang@kemri-wellcome.org +254722417507 230 80108
City Postal code Country Position/Affiliation
Kilifi Kenya Kenya Medical Research Institute CGMRC
Role Name Email Phone Street address
Public Enquiries Anthony Etyang AEtyang@kemri-wellcome.org +254722417507 230 80108
City Postal code Country Position/Affiliation
Kilifi Kenya Kenya Medical Research Institute CGMRC
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes After the study period, once the primary results are published, a de-identified copy of the data will be prepared for deposition in the KWTRP data repository (https://dataverse.harvard.edu/) under managed access through the KWTRP Data Governance Committee (Data_Governance_Committee@kemri-wellcome.org). Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol Following publication of the main study results. Access will be managed through the KWTRP Data Governance Committee (Data_Governance_Committee@kemri-wellcome.org).
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Trial description 18/05/2020 edit BACKGROUND 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. OBJECTIVES Primary: To determine if hydroxychloroquine prophylaxis prevents symptomatic COVID-19 infection in healthcare workers Secondary: a) To determine if hydroxychloroquine prophylaxis attenuates COVID-19 infections b) To determine if hydroxychloroquine prophylaxis prevents asymptomatic infection with SARS-CoV-2, the virus that causes COVID-19 c) To determine if hydroxychloroquine prophylaxis prevents all-cause symptomatic acute respiratory illnesses Tertiary a) To characterize genetic and baseline biochemical markers associated with symptomatic COVID-19, respiratory illness and disease severity b) To assess the impact of hydroxychloroquine prophylaxis on work and behavior during the pandemic c) To perform health economic alalyses to assess the impact of hydroxychloroquine prophylaxis on costs and quality of life measures BACKGROUND 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. OBJECTIVES Primary: To determine if hydroxychloroquine prophylaxis prevents symptomatic COVID-19 infection in healthcare workers Secondary: a) To determine if hydroxychloroquine prophylaxis attenuates COVID-19 infections b) To determine if hydroxychloroquine prophylaxis prevents asymptomatic infection with SARS-CoV-2, the virus that causes COVID-19 c) To determine if hydroxychloroquine prophylaxis prevents all-cause symptomatic acute respiratory illnesses Tertiary a) To characterize genetic and baseline biochemical markers associated with symptomatic COVID-19, respiratory illness and disease severity b) To assess the impact of hydroxychloroquine prophylaxis on work and behavior during the pandemic c) To perform health economic alalyses to assess the impact of hydroxychloroquine prophylaxis on costs and quality of life measures
Section Name Field Name Date Reason Old Value Updated Value
Eligibility Inclusion criteria 18/05/2020 edit • 18 years and above • Participant is willing and able to give informed consent for participation in the study and agrees with the study and its conduct • 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) • Not previously diagnosed with COVID-19 • Not currently symptomatic with an acute respiratory infection (ARI) • Possesses an internet-enabled smartphone (Android or iOS) or computer • 18 years and above • Participant is willing and able to give informed consent for participation in the study and agrees with the study and its conduct • 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) • Not previously diagnosed with COVID-19 • Not currently symptomatic with an acute respiratory infection (ARI) • Possesses an internet-enabled smartphone (Android or iOS) or computer
Section Name Field Name Date Reason Old Value Updated Value
Eligibility Exclusion criteria 18/05/2020 edit • Hypersensitivity reaction to hydroxychloroquine or 4-aminoquinolines • Contraindication to taking hydroxychloroquine as prophylaxis, e.g. known epileptic, known creatinine clearance < 10 ml/min • Already taking chloroquine, hydroxychloroquine or 4-aminoquinolines • Taking a concomitant medication described in section 8.5 of the master protocol, which cannot be safely stopped • Known retinal disease • Inability to be followed up for the trial period • Known prolonged QT syndrome (ECG will be required for potential participants who report having a heart condition) • Is enrolled in another clinical trial (however participants will be allowed to participate in observational studies) • Hypersensitivity reaction to hydroxychloroquine or 4-aminoquinolines • Contraindication to taking hydroxychloroquine as prophylaxis, e.g. known epileptic, known creatinine clearance < 10 ml/min • Already taking chloroquine, hydroxychloroquine or 4-aminoquinolines • Taking a concomitant medication described in section 8.5 of the master protocol, which cannot be safely stopped known retinal disease • Inability to be followed up for the trial period • Known prolonged QT syndrome (ECG will be required for potential participants who report having a heart condition) • Is enrolled in another clinical trial (however participants will be allowed to participate in observational studies)
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Official scientific title 21/05/2020 Administrative error (Typographical error) The Chloroquine/hydroxychloroquin prevention of coronavirus disease (COVID-19) in the healthcare setting; a randomized, placebo-controlled prophylaxis study (COPCOV) The Chloroquine/hydroxychloroquine prevention of coronavirus disease (COVID-19) in the healthcare setting; a randomized, placebo-controlled prophylaxis study (COPCOV)
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 21/05/2020 Indicated the actual date of Ethics approval submission FALSE, SCIENTIFIC ETHICS REVIEW UNIT, 54840, Nairobi, 00200, Kenya, 22 May 2020, , +254717719477, seru@kemri.org, FALSE, SCIENTIFIC ETHICS REVIEW UNIT, 54840, Nairobi, 00200, Kenya, 20 May 2020, , +254717719477, seru@kemri.org,
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 15/09/2020 Approval obtained. FALSE, SCIENTIFIC ETHICS REVIEW UNIT, 54840, Nairobi, 00200, Kenya, 20 May 2020, , +254717719477, seru@kemri.org, TRUE, SCIENTIFIC ETHICS REVIEW UNIT, 54840, Nairobi, 00200, Kenya, 20 May 2020, 25 Aug 2020, +254717719477, seru@kemri.org, 11019_11306_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Anticipated trial start date 15/09/2020 There was a delay in ethical approval and the study did not start as earlier anticipated. 01 Jul 2020 01 Oct 2020
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Anticipated date of last follow up 15/09/2020 There was a delay in ethical approval and the study did not start as earlier anticipated. 31 Dec 2021 30 Apr 2022
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 15/09/2020 Additional Ethics approval TRUE, Oxford Tropical Research Ethics Committee, University of Oxford Research Services, University Offices Wellington Square, Oxford OX1 2JD, Oxford, OX1 2JD, United Kingdom, , 15 Apr 2020, +4401865, oxtrec@admin.ox.ac.uk, 11019_11697_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD description 15/09/2020 To include IPD description After the study period, once the primary results are published, a de-identified copy of the data will be prepared for deposition in the KWTRP data repository (https://dataverse.harvard.edu/) under managed access through the KWTRP Data Governance Committee (Data_Governance_Committee@kemri-wellcome.org).
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD-Sharing time frame 15/09/2020 To include IP sharing time frame Following publication of the main study results.
Section Name Field Name Date Reason Old Value Updated Value
Reporting Key access criteria 15/09/2020 To include key access criteria Access will be managed through the KWTRP Data Governance Committee (Data_Governance_Committee@kemri-wellcome.org).
Section Name Field Name Date Reason Old Value Updated Value
Reporting Study protocol document 15/09/2020 TO include additional documents types Study Protocol, Statistical Analysis Plan, Informed Consent Form, Clinical Study Report