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.: PACTR202006537901307 Date of Approval: 24/06/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title An open-label, multicentre, randomised, adaptive platform trial of the safety and efficacy of several therapies, including antiviral therapies, versus control in mild/moderate cases of COVID-19
Official scientific title An open-label, multicentre, randomised, adaptive platform trial of the safety and efficacy of several therapies, including antiviral therapies, versus control in mild/moderate cases of COVID-19
Brief summary describing the background and objectives of the trial At present, it seems that approximately 80% of patients infected with SARS-CoV-2 remain asymptomatic while 20% develop mild to severe symptoms. Once patients progress towards severe pneumonia, i.e. in approximately 10% of cases, sophisticated supportive treatment is required including oxygen, ventilation, vasopressors and antibacterial treatment. Significant healthcare resources are therefore needed to manage and care for these patients. To date, no treatment has shown confirmed efficacy in treating severe cases. It is therefore crucial to avoid, as far as possible, progression to severe disease. From a public health perspective, the primary objective of disease management is therefore to limit the number of COVID-19-related hospitalisations for oxygen therapy and/or intensive care to a number that is practicable, i.e. to treat patients before they become critically ill and require intensive care especially in low and middle income countries. It is also likely that early treatment in the most at-risk ones will also be the best way to reduce mortality. This is study a multicentre, randomised, open-label, adaptive clinical study on the safety and efficacy of treatments for COVID-19 in patients treated on an out-patient basis. The primary objective is to compare the efficacy of alternative treatment strategies versus control on the risk of progression to severe respiratory disease The main secondary objectives are : • To compare the safety • To compare the rate of hospitalisations • To compare the time to hospitalisation • To compare the disease-free rate • To compare the death rate i • To compare worsening of clinical status • To compare the capacity to prevent severe progression between study arms • To identify risk factors for severe progression
Type of trial RCT
Acronym (If the trial has an acronym then please provide) ANTICOV
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied COVID 19
Purpose of the trial Treatment: Drugs
Anticipated trial start date 20/07/2020
Actual trial start date
Anticipated date of last follow up 31/12/2021
Actual Last follow-up date
Anticipated target sample size (number of participants) 3000
Actual target sample size (number of participants) 2800
Recruitment status 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 Dynamic (adaptive) random allocation such as minimization Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group PARACETAMOL max 3g/day 14 days One to two tablets every 4-6 hours as required 700 Active-Treatment of Control Group
Experimental Group Lopinavir Ritonavir Daily intake of lopinavir 800 mg / ritonavir 200 mg 14 days Two tablets twice daily for a total daily intake of lopinavir 800 mg / ritonavir 200 mg 700
Experimental Group Hydroxychloroquine Day 1: loading dose of 800 mg Day 2-7: maintenance dose of 400 mg daily 7 days Day 1: loading dose of 800 mg daily, divided into two daily intakes of 400 mg taken 12 hours apart Day 2-7: maintenance dose of 400 mg daily, divided into two daily intakes of 200 mg taken 12 hours apart 700
Experimental Group To be determined To be determined To be determined In the protocol we have considered the option to add a fourth arm if a new treatment is available 700
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Male or female patients, 2. Adults > or= 18 years of age at the time of screening. Children > 12 years of age may be included if recommended by the DSMB after the first analysis. 3. COVID-19 confirmed by molecular biology for SARS-Cov2 according to national guidelines, based on result within 24 hours prior to screening. 4. Viral syndrome with or without uncomplicated pneumonia, defined as blood oxygen saturation level (SpO2) > or= 94%. 5. Corrected QT interval (QTc - Fridericia) < 500 msec on ECG. 6. Signed written consent from the patient or his/her representative. 7. Accepting and having the ability to be reached by telephone throughout the study. 8. Having designated a contact person who can be contacted in case of emergency. 1. Abnormal physical examination findings: • respiratory rate > or= 25 per minute; • blood pressure < 90/60 mmHg or > 160/100 mmHg; • body weight < 45 kg for patients > or= 18 years of age and age-adapted for children > 12 years of age if inclusion is recommended by the DSMB after the first analysis; • recurrent diarrhoea or vomiting episodes (> 3 in the last 24 hours) or hypokalaemia (< 3.5 mmol/L) or hyperkalaemia (> 5 mmol/L). 2. Known glucose-6-phosphate dehydrogenase (G6PD) deficiency. 3. Feeling unwell for more than 7 days prior to screening. 4. Severe cardiopathy or history of arrhythmia, renal or liver insufficiency. 5. History of congenital or acquired long QT-interval, family history of long QT arrythmia, cardiac disease such as heart failure, myocardial infarction, family history of sudden cardiac death, sudden cardiac death, bradycardia < 50 bpm. 6. Past history of retinopathy, such as spots or dark strings floating in the field of vision (floaters), blurred or fluctuating vision, impaired colour vision, dark or empty areas in vision. 7. History of severe skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis. 8. End-organ compromise requiring admission to a resuscitation or continuous care unit or short-term life-threatening comorbidity with life expectancy < 3 months. 9. Known pregnancy or breast-feeding, unless recommended by the Data and Safety Monitoring Board after the first interim analysis. 10. Prior treatment with. lopinavir/ritonavir within 29 days prior to screening except if patients are receiving the same regimen as planned in this study. Patients randomised to lopinavir/ritonavir will stop their current treatment and switch to the IP lopinavir/ ritonavir. If randomised to other arms, patients will continue their current treatment with lopinavir/ritonavir. 11. Prior treatment with hydroxychloroquine within 29 days prior to screening or on-going at screening. 12. Use of concomitant medications that are contraindicated 80 and over: 80+ Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 100 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
No 19/06/2020 Ethics Committee for Research in Health
Ethics Committee Address
Street address City Postal code Country
Ministere de la Sante Building Lamizana Ouagadougou Ouagadougou 0970099 Burkina Faso
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 19/06/2020 Comite National Ethique pour la Recherche en Sante HUmaine
Ethics Committee Address
Street address City Postal code Country
Ministere de la sante Yaounde yaounde 00237 Cameroon
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 19/06/2020 Comite National Ethique de la Sante
Ethics Committee Address
Street address City Postal code Country
Local 5 1er niveau, Immeuble PNMLS Kasa-Vubu Kinshasa 3089 Democratic Republic of the Congo
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 19/06/2020 Equatorial Guinea National Ethics Committee
Ethics Committee Address
Street address City Postal code Country
CENGE office Viviendas Sociales of Sipopo Block 8 Portal 2 Floor 6-2 Malabo 00000 Equatorial Guinea
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 19/06/2020 National Research Ethics Review Committee
Ethics Committee Address
Street address City Postal code Country
Ministry of Science and Technology of Ethiopia Compound National Research Ethics Review Committee of Ethiopia Secretariat Addis Abeba 2490 Ethiopia
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 19/06/2020 Ghana Health Service Ethical Review Committee
Ethics Committee Address
Street address City Postal code Country
Ghana Health Service Ethical Review Committee Research and Development Division Accra 00190 Ghana
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 19/06/2020 Comite National Ethique de la Recherche en Sante
Ethics Committee Address
Street address City Postal code Country
chez Professeur Oumou Younoussa SOW Conakry 00634 Guinea
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 19/06/2020 National Ethics Committee for Life and Health Sciences
Ethics Committee Address
Street address City Postal code Country
Chez Institut Pasteur de Cocody Abidjan 00225 Cote Divoire
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 19/06/2020 Ethical Review Committee Scientific and Ethics Review Unit
Ethics Committee Address
Street address City Postal code Country
KEMRI Off Mbagathi Road NAIROBI 548400020 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
No 19/06/2020 National Committee for Bioethics in Health
Ethics Committee Address
Street address City Postal code Country
Av. Eduardo Mondlane Salvador Alende Maputo 00265 Mozambique
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 19/06/2020 Comite Consultatif National Ethique
Ethics Committee Address
Street address City Postal code Country
BP 623 Niamey Niger Niamey 00623 Niger
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 19/06/2020 National Medicines and Poisons Board
Ethics Committee Address
Street address City Postal code Country
Unnamed Road Khartoum Sudan Khartoum 11111 Sudan
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 19/06/2020 Uganda National Council for Science and Technology
Ethics Committee Address
Street address City Postal code Country
Uganda National Council for Science and Technology PO Box 6884 Kampala Uganda Kampala 06884 Uganda
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome • SpO2 < or equal to 93% on repeated measurement within 21 days after randomisation of treatment, which will be considered as failure. Death for any reasons occurring within 21 days after randomisation of treatment will be considered as failure. 21 days
Secondary Outcome • Mean number and incidence rate of serious adverse events (SAEs) • Mean number and incidence rate of severe adverse events • Mean number of discontinuations or temporary suspensions of IP 21 days
Secondary Outcome • Number of hospitalisations due to severe progression during the study
Secondary Outcome • Time to hospitalisation during the study
Secondary Outcome • Disease-free status: disease-free based on normalisation of pre-existing symptoms (based on mMRC scale, scale of Clinical progression and clinical symptoms) and SpO2 > or equal to 94 at Day 21 and no hospitalisation for COVID-19 21 days
Secondary Outcome • Occurrence of death related to COVID-19 during the study
Secondary Outcome • Time to worsening of SpO2 < or equal to 93 within 21 days 21 days
Secondary Outcome • Failure rate for each study arm (see Primary Endpoint) during the study
Secondary Outcome • Occurrence of SpO2 < 93 or death or hospitalisation due to COVID-19 during the study
Secondary Outcome • Sub-group analysis of failure rate for each study arm during the study
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Centre Hospitalier Universitaire Souro Sanou 01 Avenue du gouverneur William Ponty 01 BP 676 Bobo Dioulasso Burkina Faso
Centre Hospitalier Universitaire de Tengandogo 11 BP 104 CMS Ouagadougou Burkina Faso
Central Hospital Yaounde and annexes Rue Henri Dunan BP 87 Yaounde Cameroon
Clinique Ngaliema Gombe Avenue Papa ILEO ex des Cliniques Kinshasa BP 3089 Kinshasa Democratic Republic of the Congo
Hopital Saint Joseph Boulevard Lumumba 15 rue Residentiel A cote de la Fikin Petit Boulevard Limete Kinshasa Democratic Republic of the Congo
Malabo Clinical Research Center Rotunda Arab Malabo Equatorial Guinea
Hospital Bahir Dar University Bahir Dar University, Department of Dermato-venereology, PO Box 79, Bahir Dar Bahir Dar Ethiopia
University of Gondar Hospital Department of Internal Medicine PO Box 196, Gondar Gondar Ethiopia
Komfo Anokye Teaching Hospital Okomfo Anokye Road Kumasi Ghana
CHU Donka Donka BP 834, Conakry Conakry Guinea
Military Hospital of Abidjan Route du Zoo Abidjan Cote Divoire
Kenyatta University Teaching Referral and Research Hospital Northern Bypass Rd Kahawa West PO Box 7674-00100 GPO Nairobi Nairobi Kenya
Mbagathi Infectious Disease Unit Mbagathi County Hospital 1 Mbagathi Road, Off Mbagathi Way PO Box 40205-00200 Nairobi Kenya
Centro de Investigacao e Treino em Saude da Polana Canico Rua da Costa do Sol Polana Canico Maputo Maputo Mozambique
CISM Centro de Investigacao em Saude de Manhica Rua 12, Cambeve Vila de Manhica CP 1929 Maputo Maputo Mozambique
SOBA University Hospital Soba locality, South Khartoum, P.O Box 102 Khartoum Sudan
Bagamoyo Clinical Trial Facility Bagamoyo Clinical Trial Facility Kingani, Bagamoyo Bagamoyo Tanzania
Mbarara Regional Referral Hospital Mbarara Town Council, P.O.Box 40 Mbarra Uganda
FUNDING SOURCES
Name of source Street address City Postal code Country
DNDi 15 Chemin Louis DUnant Geneve 1202 Switzerland
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Drug for Neglected Diseases initiative Chemin Louis-Dunant 15 Geneve 1202 Switzerland NGO
Primary Sponsor INSERM ANRS 101 rue tolbiac Paris 75013 France Research Organisation
Primary Sponsor Institut Pasteur Cameroun 451 2005 street Yaounde 2 BP 1274 Yaounde Yaounde 01274 Cameroon Charities/Societies/Foundation
Primary Sponsor Ifakara Health Institute 463 Kiko avenue Box 78373 Dar-es-salaamTanzania Dar es salaam 78373 Tanzania Health Institute
Primary Sponsor Institute of Tropical Medicine Kronenburgstraat 43, 2000 Antwerpen, Belgium Antwerpen 2000 Belgium Research Institute
Primary Sponsor BERNHARD NOCHT INSTITUTE FOR TROPICAL MEDICINE Bernhard-Nocht-Strasse 74 D-20359 Hamburg Hamburg 20359 Germany Research Institute
Primary Sponsor Centre Suisse de Recherches Scientifiques Centre Suisse de Recherches Scientifiques Abidjan Cote Divoire Research Institute
Primary Sponsor ISGlobal Barcelona Institute for Global Health Hospital Clinical Universitat de Barcelona Carrer Rosello 132 5-1 E-08036 Barcelona 08036 Spain Health Institute
Primary Sponsor Epicentre 14-24 avenue Jean Jaures, 75019 Paris France Paris 75019 France NGO
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Nathalie Strub Wourgaft nstrub@dndi.org 0041798740539 15 chemin Louis DUnant
City Postal code Country Position/Affiliation
Geneve 1202 Switzerland NTD Director
Role Name Email Phone Street address
Scientific Enquiries Nathalie Strub Wourgaft nstrub@dndi.org 0041798740539 15 chemin Louis Dunant
City Postal code Country Position/Affiliation
Geneve 1202 Switzerland NTD director
Role Name Email Phone Street address
Public Enquiries James Arkinstall jarkinstall@dndi.org 0041793929823 15 chemin louis Dunant
City Postal code Country Position/Affiliation
Geneve 1202 Switzerland Head of Communications and Advocacy
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes The intent is to have summary of results available on an open access website Study Protocol within 12 months of the study completion open
URL Results Available Results Summary Result Posting Date First Journal Publication Date
to be determined 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
Eligibility Age group 23/06/2020 edit to include the full age range Adult: 19 Year-44 Year Adult: 19 Year-44 Year, Middle Aged: 45 Year(s)-64 Year(s), Aged: 65+ Year(s), 80 and over: 80+ Year
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Final no of participants 24/06/2020 We are targeting a number of patients between 2000 and 3000 patients. As it is not possible to enter this information. I am adding the average 2500 2500
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 24/06/2020 To reflect the maximum number of patients Experimental Group, To be determined, To be determined, To be determined, In the protocol we have considered the option to add a fourth arm if a new treatment is available, 700,
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Final no of participants 24/06/2020 We are targeting a number of patients between 2000 and 3000 patients with 3 to 4 arms of randomisation. As it is not possible to enter this information. I am entering the closest number to this estimation. thanks 2500 2800
Section Name Field Name Date Reason Old Value Updated Value
Funding Source FundingSources List 24/06/2020 ANTICOV study is sponsored by a consortium of 9 Sponsors. Several grants were submitted but for now we have not yet received a formal answer on the approval. DNDi, 15 Chemin Louis DUnant, Geneve, 1202, Switzerland, Self Funded,
Section Name Field Name Date Reason Old Value Updated Value
Reporting Plan to share IPD 24/06/2020 Reflect the intent of the ANTICOV consortium to share outcome of this study Undecided Yes
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD description 24/06/2020 Reflect the intent of the ANTICOV consortium to share outcome of this study The intent is to have summary of results available on an open access website
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD-Sharing time frame 24/06/2020 Reflect the intent of the ANTICOV consortium to share outcome of this study within 12 months of the study completion
Section Name Field Name Date Reason Old Value Updated Value
Reporting Key access criteria 24/06/2020 Reflect the intent of the ANTICOV consortium to share outcome of this study open
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD URL 24/06/2020 Reflect the intent of the ANTICOV consortium to share outcome of this study to be determined
Section Name Field Name Date Reason Old Value Updated Value
Reporting Study protocol document 24/06/2020 Reflect the intent of the ANTICOV consortium to share outcome of this study Study Protocol
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 22/09/2020 start recruitment Not yet recruiting Recruiting