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

NCT ID: NCT04695197

Last Updated: 2024-02-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 143 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-08
• Study Completion Date: 2024-02-20

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.

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.

Conditions

Covid-19; Malaria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Artemether-lumefantrine

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

Group Type: ACTIVE_COMPARATOR

Artemether-lumefantrine (AL)

Intervention Type: DRUG

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)

Pyronaridine-artesunate

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

Group Type: EXPERIMENTAL

Pyronaridine-artesunate (PA)

Intervention Type: DRUG

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).

Interventions

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)

Intervention Type: 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).

Intervention Type: DRUG

Other Intervention Names

Coartem; Pyramax

Eligibility 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

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

London School of Hygiene and Tropical Medicine

OTHER

Sponsor Role: collaborator

Kenya Medical Research Institute

OTHER

Sponsor Role: collaborator

Groupe de Recherche Action en Sante

OTHER

Sponsor Role: collaborator

Centres for Disease Control and Prevention, Kenya.

OTHER

Sponsor Role: collaborator

Bill and Melinda Gates Foundation

OTHER

Sponsor Role: collaborator

Centers for Disease Control and Prevention

FED

Sponsor Role: collaborator

Liverpool School of Tropical Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kariuki Simon, PhD

Role: PRINCIPAL_INVESTIGATOR

Kenya Medical Research Institute

Sirima Sodiomon, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Groupe de Recherche Action en Sante

Locations

Ouagadougou Hospitals

Ouagadougou, , Burkina Faso

Kisumu County Referral Hospital

Kisumu, , Kenya

Countries

Burkina Faso; Kenya

Other Identifiers

202009642148520

Identifier Type: REGISTRY

Identifier Source: secondary_id

20-063

Identifier Type: -

Identifier Source: org_study_id