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.: PACTR202009642148520 Date of Approval: 29/09/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Malaria as a risk factor for COVID-19 in western Kenya and Burkina Faso
Official scientific title Malaria as a risk factor for COVID-19 in western Kenya and Burkina Faso
Brief summary describing the background and objectives of the trial It is unknown whether malaria or malaria treatment affects COVID-19 severity, immune responses to SARS-CoV-2 virus, or viral loads and/or duration of shedding and therewith the onwards spread of SARS-COV-2. We will conduct a multi-site observational cohort study in 708 newly diagnosed COVID-19 patient of all ages in western Kenya and Burkina-Faso. They will be enrolled in hospitals with COVID-19 testing facilities from a source population screened for SARS-CoV-2 (N~4,720). Approximately 142 of the 708 COVID-19 patients are expected to be co-infected with malaria. They will be enrolled in the nested malaria treatment trial (the topic of this trial registration) and randomized to receive 3-days of artemether-lumefantrine (the current standard of care) or pyronaridine-artesunate, an effective antimalarial with known antiviral properties against SARS-CoV-2 in-vitro, that is newly registered and being rolled out in Africa. Disease progression will be assessed and sequential nasal swabs and blood samples taken. Signs and symptoms of COVID-19 will be assessed daily for 14 days. The antimalarial treatment response will be assessed for 42 days. Other endpoints include seroconversion, chemokine/cytokine responses, T and B cell responses, viral load and duration of viral carriage. Hospitalisation, self-isolation and home-based care will follow national guidelines.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) MALCOV
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied COVID-19,Malaria
Purpose of the trial Treatment: Drugs
Anticipated trial start date 01/11/2020
Actual trial start date
Anticipated date of last follow up 01/11/2022
Actual Last follow-up date
Anticipated target sample size (number of participants) 142
Actual target sample size (number of participants)
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 Permuted block randomization Sealed opaque envelopes Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Artemether lumefantrine Bodyweight (kg) Dose (mg) of artemether + lumefantrine given twice daily for 3 days (total, six doses) 5 to < 15 20 + 120 15 to < 25 40 + 240 25 to < 35 60 + 360 >=35 80 + 480 Twice daily for 3 days (total, six doses) Current first line treatment of malaria 71 Active-Treatment of Control Group
Experimental Group pyronaridine artesunate Body weight (kg) Dose (mg) of pyronaridine + aresunate given once daily for 3 days (total, three doses) 5 to < 8 60 + 20 8 to <15 120 + 40 15 to <20 180 + 60 20 to <24 kg 180 + 60 24 to <45 360 + 120 45 to <65 540 + 180 >=65 720 + 240 Once-daily for 3 days (total, three doses) Pyramax, antimalarial 71
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
• Laboratory confirmed SARS-CoV-2 infection, with positive molecular test results within the past 72 hours* • Aged >=6 months ** • Resident in the study area • The participant or caretaker is willing and able to give informed consent or assent with parent/guardian informed consent for participation in the study • Agrees not to self-medicate with chloroquine, hydroxychloroquine or other antimalarials with potential anti-SARS-CoV-2 properties • Not previously diagnosed with COVID-19 • Contactable by phone for follow-up permitting real-time, reliable information • Uncomplicated malaria, defined as able to take oral medication • Bodyweight ≥5kg • Confirmed malaria infection by RDT (pLDH) or microscopy • Unwilling or unable to provide informed consent/assent • The participant is judged by the Investigator to be at significant risk of failing to comply with the provisions of the protocol as to cause harm to self or seriously interfere with the validity of the study results • Inability/unlikely to be in the study area for the duration of the 28-day follow-up period • Pregnant or lactating women • Severe disease requiring parenteral treatment • Currently receiving, or recently received (within the last 28 days) pyronaridine-artesunate or artemether-lumefantrine • Received chloroquine in the last three days • Inability/unlikely to be in the study area for the duration of the 42-day follow-up period • Known hypersensitivity or specific contraindication to the use of any of the study drugs in the treatment arms • Known chronic kidney disease (signs or symptoms of stage IV renal impairment or receiving dialysis) • Known liver cirrhosis (Child-Pugh Class B or greater) or signs or symptoms of severe hepatotoxicity 80 and over: 80+ Year,Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Child: 6 Year-12 Year,Infant: 0 Month-23 Month,Infant: 1 Month-23 Month,Middle Aged: 45 Year(s)-64 Year(s),New born: 0 Day-1 Month,Preschool Child: 2 Year-5 Year 0 Day(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
Yes 17/09/2020 London School of Hygiene and Tropical Medicine
Ethics Committee Address
Street address City Postal code Country
Keppel Street London WC1E 7HT United Kingdom
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Incidence of SARS-CoV-2 clearance (defined as the proportion of participants with a negative nasal swab) by day 7
Secondary Outcome • Median viral load of SARS-CoV-2 detected from mid-nasal swabs by PCR by day 14
Secondary Outcome Cumulative incidence of SARS-CoV-2 clearance (defined as the proportion of participants with negative nasal swabs) by days 14, 21 and 28
Secondary Outcome Time to clearance of nasal SARS-CoV-2, defined as negative SARS-CoV-2 RNA PCR tests using data measured at days 1, 3, 7, 14 and 28
Secondary Outcome Cumulative seroconversion rates (IgG, IgM, IgA) by days 7, 14, 21 and 28, and IgG, IgM, IgA antibody titres against SARS-CoV-2 by day-28 expressed as the geometric mean, maximum, and change from baseline by days 7, 14, 21 and 28
Secondary Outcome Inflammatory, genomic, and cellular immune responses to SARS-CoV-2 infection by multiplex serum cytokine markers; transcriptional profiling (gene expression) of whole blood and fixed whole blood for T and B cell markers by day 28
Secondary Outcome The clinical and parasitological antimalarial treatment response expressed as the proportion with early treatment failure, late clinical failure, late parasitological failure or an adequate clinical and parasitological response. Recrudescence will be differentiated from new infection by genotyping of malaria parasites by day 42
Secondary Outcome COVID-19 disease progression and severity assessed by the duration and severity of OVID-19 symptoms, as defined by a severity index score, as well as the proportion of days with a fever after randomization, and the proportion of days with respiratory symptoms after randomization by day 28
Secondary Outcome The safety of pyronaridine-artesunate and artemether-lumefantrine in COVID-19 patient coinfected with malaria parasites assessed as the cumulative proportion of treatment-related adverse events, serious adverse events, and adverse events resulting in treatment discontinuation by day 7 by day 7
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Jaramogi Oginga Odinga Teaching and Referral Hospital Kisumu Kisumu 4010 Kenya
Kisumu County Referral Hospital Kisumu Kisumu 4010 Kenya
Ouagadougou Hospitals Ouagadougou Ouagadougou 06BP10248 Burkina Faso
Bobo Dioulasso Hospitals Sikasso Sira Bobo Dioulasso 226 Burkina Faso
FUNDING SOURCES
Name of source Street address City Postal code Country
Bill and Melinda Gates Foundation 1300 I St NW WASHINGTON DC DC 2005 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor LSTM Liverpool School of Tropical Medicine Pembroke Place Liverpool L3 5QA United Kingdom University
Primary Sponsor LSHTM London School of Hygiene and Tropical medicine Keppel Street London WC1E 7HT United Kingdom University
COLLABORATORS
Name Street address City Postal code Country
Kenya Medical Research Institute KEMRI Busia Road Kisumu 40100 Kenya
US Centers for Disease Control and Prevention CDC 1600 Clifton Road Altanta 30329 GA United States of America
Groupe de Recherche Action en Sante GRAS N3 Secteur 19 Somgande Ouagadougou 06 06BP10248 Burkina Faso
CONTACT PEOPLE
Role Name Email Phone Street address
Scientific Enquiries Feiko ter Kuile feiko.terKuile@lstmed.ac.uk +441517053287 PEMBROKE PLACE
City Postal code Country Position/Affiliation
LIVERPOOL L3 5QA United Kingdom Co Chief Investigator
Role Name Email Phone Street address
Public Enquiries Hellen Barsosio hellen.barsosio@lstmed.ac.uk +25472446450 Busia Road
City Postal code Country Position/Affiliation
KISUMU 40100 Kenya Co Principle investigator
Role Name Email Phone Street address
Principal Investigator Simon Kariuki SKariuki@kemricdc.org +254725389246 Busia Road
City Postal code Country Position/Affiliation
KISUMU 40100 Kenya Co Principal investigator
Role Name Email Phone Street address
Principal Investigator Sodiomo Sirima s.sirima@gras.bf +22670200444 Secteur 19 Somgande
City Postal code Country Position/Affiliation
Ouagadougou 06BP10248 Burkina Faso Co Principal investigator
Role Name Email Phone Street address
Scientific Enquiries Chris Drakeley Chris.Drakeley@lshtm.ac.uk +442079272289 LSHTM Keppel Street
City Postal code Country Position/Affiliation
London WC1E 7HT United Kingdom Co Chief Investigator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes We will encourage data sharing to ensure that the scientific potential of this study is maximized. The full anonymized research database will be made publicly available as soon as the full study findings have been published or based on any data requests that may occur during the study or analysis is still ongoing. For the databases, we will use a controlled access approach. Study Protocol As soon as the full study findings have been published or based on any data requests that may occur during the study or analysis is still ongoing. Data access will be provided to researchers after a proposal has been approved by an independent review committee identified for this purpose. An agreement on how to collaborate will be reached based on any overlap between the proposal and any ongoing efforts. Proposals can be directed to email addresses provided in the publications and websites. To gain access, data requesters will need to sign a data-sharing agreement. The only limits to data sharing will be to safeguard research participants’ confidentiality. External users will be bound by data-sharing agreements in line with the Data Sharing Policy from the respective Sponsors and the Gates Foundation to ensure that the privacy of individuals is protected. The agreement will prohibit any attempt to (a) identify study participants from the data or otherwise breach confidentiality, (b) make unapproved contact with study participants.
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
Eligibility Age group 29/09/2020 age categories added Infant: 1 Month-23 Month, Preschool Child: 2 Year-5 Year, Child: 6 Year-12 Year, Adolescent: 13 Year-18 Year, Adult: 19 Year-44 Year, Middle Aged: 45 Year(s)-64 Year(s), Aged: 65+ Year(s), 80 and over: 80+ Year New born: 0 Day-1 Month, Infant: 1 Month-23 Month, Infant: 0 Month-23 Month, Preschool Child: 2 Year-5 Year, Child: 6 Year-12 Year, Adolescent: 13 Year-18 Year, Adult: 19 Year-44 Year, Middle Aged: 45 Year(s)-64 Year(s), Aged: 65+ Year(s), 80 and over: 80+ Year