Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Malaria as a Risk Factor for COVID-19 in Western Kenya and Burkina Faso (MALCOV)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04695197
Recruitment Status : Recruiting
First Posted : January 5, 2021
Last Update Posted : February 24, 2021
Sponsor:
Collaborators:
London School of Hygiene and Tropical Medicine
Kenya Medical Research Institute
Groupe de Recherche Action en Sante
Centres for Disease Control and Prevention, Kenya.
Bill and Melinda Gates Foundation
Centers for Disease Control and Prevention
Information provided by (Responsible Party):
Liverpool School of Tropical Medicine

Brief Summary:
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. An observational cohort study will be conducted 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 and randomized to receive 3-days of artemether-lumefantrine (the current standard of care) or pyronaridine-artesunate, a highly 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 nasal swabs and blood samples will be taken during home/clinic visits on days 1, 3, 7, 14, 21, 28, and 42. Patients self-isolating will be phoned daily in between scheduled visits for the first 14 days to assess signs and symptoms. Hospitalisation, self-isolation and home-based care will follow national guidelines. The WHO clinical progression scale and FLU-PRO plus scales will be used to compare disease progression between COVID-19 patients with and without malaria, and by malaria. Other endpoints include seroconversion/reversion rates, chemokine/cytokine responses, T and B cell responses, viral load and duration of viral carriage. Infection prevention and control (IPC), including the use of personal protection equipment (PPE), and measures for patient transport will follow national guidelines in each country. Written informed consent/assent will be sought. The study is anticipated to start in January 2021 and last for approximately 18 months.

Condition or disease Intervention/treatment Phase
Covid-19 Malaria Drug: Artemether-lumefantrine (AL) Drug: Pyronaridine-artesunate (PA) Phase 3

Detailed Description:

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.

Layout table for study information
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

Arm Intervention/treatment
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

Experimental: Pyronaridine-artesunate
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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Median viral load of SARS-CoV-2 [ Time Frame: by day 14 ]
    Median CT value as detected from mid-nasal swabs by PCR

  2. 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

  3. 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)

  4. Cumulative seroconversion rates (IgG, IgM, IgA) [ Time Frame: by days 7, 14, 21 and 28 ]
    proportion of antibody negative patients on enrolment who seroconvert

  5. 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

  6. 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

  7. CRP and angiotensin-2, angiopoietin-1 and angiopoietin-2 [ Time Frame: by days 3, 7, 14 and 28 ]
    median, max and change from baseline

  8. 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

  9. Cellular immune responses to SARS-CoV-2 infection [ Time Frame: by day 28 ]
    T cell responses

  10. 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

  11. COVID-19 disease severity [ Time Frame: by day 28 ]
    Defined by a severity index score for COVID-19

  12. COVID-19 disease duration [ Time Frame: by day 28 ]
    The proportion of days with symptoms after randomization

  13. COVID-19 fever duration [ Time Frame: by day 28 ]
    The proportion of days with a fever after randomization

  14. COVID-19 respiratory symptoms duration [ Time Frame: by day 28 ]
    The proportion of days with respiratory symptoms after randomization

  15. COVID-19 disease duration in days [ Time Frame: by day 28 ]
    The number of days until symptom clearance

  16. 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



Information from the National Library of Medicine

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.


Layout table for eligibility information
Ages Eligible for Study:   6 Months to 100 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

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


Contacts
Layout table for location contacts
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

Locations
Layout table for location information
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   
Sponsors and Collaborators
Liverpool School of Tropical Medicine
London School of Hygiene and Tropical Medicine
Kenya Medical Research Institute
Groupe de Recherche Action en Sante
Centres for Disease Control and Prevention, Kenya.
Bill and Melinda Gates Foundation
Centers for Disease Control and Prevention
Investigators
Layout table for investigator information
Principal Investigator: Kariuki Simon, PhD Kenya Medical Research Institute
Principal Investigator: Sirima Sodiomon, MD, PhD Groupe de Recherche Action en Santé(GRAS)
Layout table for additonal information
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.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Malaria
Protozoan Infections
Parasitic 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