Malaria as a Risk Factor for COVID-19 in Western Kenya and Burkina Faso (MALCOV)
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| ClinicalTrials.gov Identifier: NCT04695197 |
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Recruitment Status :
Recruiting
First Posted : January 5, 2021
Last Update Posted : February 24, 2021
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Covid-19 Malaria | Drug: Artemether-lumefantrine (AL) Drug: Pyronaridine-artesunate (PA) | Phase 3 |
Background: In Africa, COVID-19 has the potential to cripple the continent's fragile healthcare systems and be devastating economically. It is unknown whether malaria infection worsens COVID-19, affects the acquisition of protective antibodies against the SARS-CoV-2 virus, or contributes to its onwards spread by resulting in higher viral loads and/or longer duration of viral shedding. It is also unknown if the effective clearance of malaria parasites and/or the choice of antimalarials affects any of these potential associations. His study will determine if the antimalarial pyronaridine, in the fixed-dose combination of pyronaridine-artesunate, has a positive, negative or negligible effect on COVID-19 disease progression or duration of viral carriage and the seroconversion rate to SARS-CoV-2.
Methods: A malaria treatment trial will be conducted nested within a larger observational COVID-19 cohort study in highly malaria-endemic areas in western Kenya and Burkina-Faso. The COVID-19 cohort study consists of approximately 708 newly diagnosed COVID-19 patient of all ages. They will be enrolled from a source population of approximately 4,720 individuals of all ages screened for SARS-CoV-2. It is anticipated that approximately 142 of the 708 cohort participants will be co-infected with malaria. These co-infected participants will be enrolled in the nested malaria treatment trial if they have uncomplicated malaria and are able to take oral medication. They will be randomized to receive either a standard 3-day treatment course of artemether-lumefantrine (the current first-line treatment) or pyronaridine-artesunate, a new highly effective antimalarial combination that is being rolled out as first or second-line treatment in western Kenya and Burkina Faso. All 142 patients will be followed for 42 days and nasal swabs and blood samples taken on days 1, 3, 7, 14, and 28. Malaria smears will be taken on days 3, 7, 14, 21, 28 and 42. The primary endpoint is the rate of SARS-CoV-2 clearance by day-7.
To limit the transmission of SARS-CoV-2, strict adherence to infection prevention and control (IPC) guidelines, including use of personal protection equipment (PPE), and measures for patient transport will be followed as per national guidelines in each country. Written informed consent/assent will be sought.
Partners: This 18-months study is funded by the Bill and Melinda Gates Foundation and is part of a collaboration between the Kenyan Medical Research Institute (KEMRI) in Kenya; the US Centers for Disease Control and Prevention (CDC); the Liverpool School of Tropical Medicine (LSTM); the Ministry of Health, Kenya; the Groupe de Recherche Action en Santé (GRAS), Ouagadougou, Burkina Faso; the Ministry of Health in Burkina Faso, and the London School of Hygiene and Tropical Medicine (LSHTM). LSTM and LSHTM will act as sponsors for the studies in Kenya and Burkina Faso, respectively.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 142 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | Permuted block randomization |
| Masking: | None (Open Label) |
| Masking Description: | Masking: blinding of primary outcome assessor (off-site laboratory-based staff) |
| Primary Purpose: | Treatment |
| Official Title: | Malaria as a Risk Factor for COVID-19 in Western Kenya and Burkina Faso |
| Actual Study Start Date : | January 8, 2021 |
| Estimated Primary Completion Date : | November 1, 2022 |
| Estimated Study Completion Date : | July 31, 2023 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Artemether-lumefantrine
Artemether-lumefantrine, standard 3-day antimalarial treatment regimen.
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Drug: Artemether-lumefantrine (AL)
Current first line treatment of malaria. Dose: 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)
Other Name: Coartem |
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Experimental: Pyronaridine-artesunate
Pyronaridine-artesunate, standard 3-day antimalarial treatment regimen.
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Drug: Pyronaridine-artesunate (PA)
Antimalarial; Dose: 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).
Other Name: Pyramax |
- Incidence of SARS-CoV-2 clearance [ Time Frame: by day 7 ]Defined as the proportion of participants with a negative nasal swab on Day 7 after the start of treatment
- Median viral load of SARS-CoV-2 [ Time Frame: by day 14 ]Median CT value as detected from mid-nasal swabs by PCR
- Cumulative incidence of SARS-CoV-2 clearance [ Time Frame: by days 14, 21 and 28 ]Defined as the proportion of participants with negative nasal swabs
- Time to clearance of nasal SARS-CoV-2 [ Time Frame: by days 1, 3, 7, 14 and 28 ]Defined as the number of days to a negative SARS-CoV-2 RNA PCR tests (swabs collected on days 1, 3, 7, 14, 21 and 28)
- Cumulative seroconversion rates (IgG, IgM, IgA) [ Time Frame: by days 7, 14, 21 and 28 ]proportion of antibody negative patients on enrolment who seroconvert
- IgG, IgM, IgA antibody titres against SARS-CoV-2 [ Time Frame: by days 7, 14, 21 and 28 ]Geometric mean, maximum, and change from baseline
- IL-6, IL-7, IL-10, TNF-alpha and Interferon-Gamma [ Time Frame: by days 3, 7, 14 and 28 ]median, max and change from baseline
- CRP and angiotensin-2, angiopoietin-1 and angiopoietin-2 [ Time Frame: by days 3, 7, 14 and 28 ]median, max and change from baseline
- Genomic responses to SARS-CoV-2 infection [ Time Frame: by day 28 ]Transcriptional profiling (gene expression) of whole blood and fixed whole blood for T and B cell markers
- Cellular immune responses to SARS-CoV-2 infection [ Time Frame: by day 28 ]T cell responses
- The clinical and parasitological antimalarial treatment response [ Time Frame: by day 42 ]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
- COVID-19 disease severity [ Time Frame: by day 28 ]Defined by a severity index score for COVID-19
- COVID-19 disease duration [ Time Frame: by day 28 ]The proportion of days with symptoms after randomization
- COVID-19 fever duration [ Time Frame: by day 28 ]The proportion of days with a fever after randomization
- COVID-19 respiratory symptoms duration [ Time Frame: by day 28 ]The proportion of days with respiratory symptoms after randomization
- COVID-19 disease duration in days [ Time Frame: by day 28 ]The number of days until symptom clearance
- Treatment-related adverse events, serious adverse events, and adverse events resulting in treatment discontinuation [ Time Frame: by day 7 ]The cumulative proportion of patients with any of these events after the start of treatment
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 6 Months to 100 Years (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04695197
| Contact: Feiko ter Kuile, MD, PhD | +44 151 705 3287 | Feiko.terKuile@lstmed.ac.uk | |
| Contact: Chris Drakeley, PhD | +44 207 9272 289 | Chris.Drakeley@lshtm.ac.uk |
| Burkina Faso | |
| Ouagadougou Hospitals | Recruiting |
| Ouagadougou, Burkina Faso, 06BP10248 | |
| Contact: Sodiomon B. Sirima, MD, PhD +226 7020 0444 s.sirima@gras.bf | |
| Kenya | |
| Kisumu County Referral Hospital | Not yet recruiting |
| Kisumu, Kenya, 40100 | |
| Contact: Hellen C Barsosio, MD +254724464507 hellen.barsosio@lstmed.ac.uk | |
| Contact: Simon Kariuki, PhD + 254 725 389 246 SKariuki@kemricdc.org | |
| Principal Investigator: | Kariuki Simon, PhD | Kenya Medical Research Institute | |
| Principal Investigator: | Sirima Sodiomon, MD, PhD | Groupe de Recherche Action en Santé(GRAS) |
| Responsible Party: | Liverpool School of Tropical Medicine |
| ClinicalTrials.gov Identifier: | NCT04695197 |
| Other Study ID Numbers: |
20-063 202009642148520 ( Registry Identifier: Pan African Clinical Trial Registry (PACTR) ) |
| First Posted: | January 5, 2021 Key Record Dates |
| Last Update Posted: | February 24, 2021 |
| Last Verified: | February 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | 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. |
| Supporting Materials: |
Study Protocol |
| Time Frame: | 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. |
| Access Criteria: | 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. |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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COVID-19 Malaria Respiratory Tract Infections Infections Pneumonia, Viral Pneumonia Virus Diseases Coronavirus Infections Coronaviridae Infections Nidovirales Infections RNA Virus Infections Lung Diseases Respiratory Tract Diseases Protozoan Infections Parasitic Diseases |
Vector Borne Diseases Artesunate Lumefantrine Artemether Artemether, Lumefantrine Drug Combination Pyronaridine Antimalarials Antiprotozoal Agents Antiparasitic Agents Anti-Infective Agents Antineoplastic Agents Antiviral Agents Schistosomicides Antiplatyhelmintic Agents Anthelmintics |