Malaria as a Risk Factor for COVID-19 in Western Kenya and Burkina Faso (MALCOV)
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|ClinicalTrials.gov Identifier: NCT04695197|
Recruitment Status : Recruiting
First Posted : January 5, 2021
Last Update Posted : February 24, 2021
|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|
|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)|
|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|
Active Comparator: Artemether-lumefantrine
Artemether-lumefantrine, standard 3-day antimalarial treatment regimen.
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
Pyronaridine-artesunate, standard 3-day antimalarial treatment regimen.
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
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|
|Ouagadougou, Burkina Faso, 06BP10248|
|Contact: Sodiomon B. Sirima, MD, PhD +226 7020 0444 firstname.lastname@example.org|
|Kisumu County Referral Hospital||Not yet recruiting|
|Kisumu, Kenya, 40100|
|Contact: Hellen C Barsosio, MD +254724464507 email@example.com|
|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)|