NCT04695197

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
143

participants targeted

Target at P25-P50 for phase_3 covid19

Timeline
Completed

Started Jan 2021

Longer than P75 for phase_3 covid19

Geographic Reach
2 countries

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 14, 2020

Completed
22 days until next milestone

First Posted

Study publicly available on registry

January 5, 2021

Completed
3 days until next milestone

Study Start

First participant enrolled

January 8, 2021

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2022

Completed
1.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 20, 2024

Completed
Last Updated

February 23, 2024

Status Verified

February 1, 2021

Enrollment Period

1.8 years

First QC Date

December 14, 2020

Last Update Submit

February 22, 2024

Conditions

Outcome Measures

Primary Outcomes (1)

  • Incidence of SARS-CoV-2 clearance

    Defined as the proportion of participants with a negative nasal swab on Day 7 after the start of treatment

    by day 7

Secondary Outcomes (16)

  • Median viral load of SARS-CoV-2

    by day 14

  • Cumulative incidence of SARS-CoV-2 clearance

    by days 14, 21 and 28

  • Time to clearance of nasal SARS-CoV-2

    by days 1, 3, 7, 14 and 28

  • Cumulative seroconversion rates (IgG, IgM, IgA)

    by days 7, 14, 21 and 28

  • IgG, IgM, IgA antibody titres against SARS-CoV-2

    by days 7, 14, 21 and 28

  • +11 more secondary outcomes

Study Arms (2)

Artemether-lumefantrine

ACTIVE COMPARATOR

Artemether-lumefantrine, standard 3-day antimalarial treatment regimen.

Drug: Artemether-lumefantrine (AL)

Pyronaridine-artesunate

EXPERIMENTAL

Pyronaridine-artesunate, standard 3-day antimalarial treatment regimen.

Drug: Pyronaridine-artesunate (PA)

Interventions

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)

Also known as: Coartem
Artemether-lumefantrine

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).

Also known as: Pyramax
Pyronaridine-artesunate

Eligibility Criteria

Age6 Months - 100 Years
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Ouagadougou Hospitals

Ouagadougou, 06BP10248, Burkina Faso

Location

Kisumu County Referral Hospital

Kisumu, 40100, Kenya

Location

Related Publications (1)

  • Tangara B, Barsosio HC, Marlais T, Kabore JMT, Tiono AB, Otieno K, Wanjiku M, Achieng M, Onyango ED, Ondieki ED, Aura H, Odawo T, Allen DJ, Hannan L, Tetteh KK, Soulama I, Ouedraogo A, Serme SS, Soulama BI, Barry A, Badoum ES, Matthewman J, Brazal-Monzo H, Canizales J, Drabko A, Wu W, Kariuki S, Lesosky M, Sirima SB, Drakeley C, Ter Kuile FO. Artemether-lumefantrine versus pyronaridine-artesunate for the treatment of malaria in patients with mild to moderate COVID-19 in Kenya and Burkina Faso: a randomised open-label trial (MALCOV). EClinicalMedicine. 2026 Jan 3;91:103735. doi: 10.1016/j.eclinm.2025.103735. eCollection 2026 Jan.

MeSH Terms

Conditions

COVID-19Malaria

Interventions

Artemether, Lumefantrine Drug Combinationpyronaridine tetraphosphate, artesunate drug combination

Condition Hierarchy (Ancestors)

Pneumonia, ViralPneumoniaRespiratory Tract InfectionsInfectionsVirus DiseasesCoronavirus InfectionsCoronaviridae InfectionsNidovirales InfectionsRNA Virus InfectionsLung DiseasesRespiratory Tract DiseasesProtozoan InfectionsParasitic DiseasesMosquito-Borne DiseasesVector Borne Diseases

Intervention Hierarchy (Ancestors)

ArtemetherArtemisininsReactive Oxygen SpeciesFree RadicalsInorganic ChemicalsOrganic ChemicalsLumefantrineFluorenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsSesquiterpenesTerpenesPolycyclic CompoundsDrug CombinationsPharmaceutical Preparations

Study Officials

  • Kariuki Simon, PhD

    Kenya Medical Research Institute

    PRINCIPAL INVESTIGATOR
  • Sirima Sodiomon, MD, PhD

    Groupe de Recherche Action en Sante

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Masking Details
Masking: blinding of primary outcome assessor (off-site laboratory-based staff)
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Permuted block randomization
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 14, 2020

First Posted

January 5, 2021

Study Start

January 8, 2021

Primary Completion

November 1, 2022

Study Completion

February 20, 2024

Last Updated

February 23, 2024

Record last verified: 2021-02

Data Sharing

IPD Sharing
Will share

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.

Shared Documents
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.

Locations