Test Efficacy Study on the Recommended Antimalarial Drugs in the Democratic Republic of the Congo

Phase 4

Completed

• Conditions: Uncomplicated Plasmodium Falciparum Malaria
• Interventions: Drug: Artemether-lumefantrine; Drug: Artesunate-amodiaquine

• Registration Number: NCT06076213
• Lead Sponsor: Ministry of Public Health, Democratic Republic of the Congo

Brief Summary

Malaria remains a public health concern, despite efforts that are invested in the disease control. The Democratic Republic of the Congo (DRC) is one of the most affected countries in Sub Saharan Africa. Artemisinin-based combination treatments (ACTs) are recommended for the treatment of uncomplicated malaria. However, reported cases of mutations that confer to Plasmodium falciparum resistance to artemisinin (the main component of ACTs) constitute a threat to malaria control, particularly in Sub Saharan Africa. Therefore, the recommendation of the World Health Organization to conduct regularly test efficacy studies in endemic countries is paramount.

The purpose of this trial is to assess efficacy and safety of artesunate-amodiaquine (ASAQ Winthrop®) and artemether-lumefantrine (Coartem Dispersible®) at day 28 for the treatment of uncomplicated Plasmodium falciparum malaria in eight surveillance sites around DRC.

Detailed Description

This is a phase IV, randomized, open label, 2-arm trial. It will be performed in eight malaria sentinel sites around DRC. Children aged 6 to 59 months with confirmed Plasmodium falciparum uncomplicated malaria will be enrolled after informed consent granted by a parent or guardian. They will be randomized to receive either artesunate-amodiaquine or artemether lumefrantrine during 3 days (directly observed treatment) and then followed up until day 28. At each visit, clinical examination (including collection of safety data) will be done and malaria testing as well. Dried blood spots will also be prepared whenever microscopy is performed, in order to assess resistance markers and perform the genotyping of the parasite for PCR-adjusted efficacy. Hemoglobin level will be measured on the recruitment day and then every two weeks until day 28.

Study Timeline

• Study Start: 2023-05-01
• Study First Submitted: 2023-09-24
• Study First Submitted QC: 2023-10-07
• Study First Posted: 2023-10-10
• Primary Completion: 2024-09-24
• Study Completion: 2024-09-30
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-01
• Last Update Posted: 2024-11-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1260

Inclusion Criteria

• children aged 6 to 59 months
• monoinfection with Plasmodium falciparum with asexual parasite count of 2,000 to 200,000/µL
• axillary temperature ≥ 37.5 °C
• ability to swallow oral medication
• ability and willingness to comply with the protocol for the duration of the study and to comply with the study visit schedule;
• informed consent from a parent or a guardian
• living within the study catchment area
• absence of severe manutrition
• absence of infectious diseases that can be responsible of fever
• absence of allergy to the study drugs

Exclusion Criteria

• presence of general danger signs or signs of severe falciparum malaria according to the definitions of WHO;
• body weight < 5kg
• hemoglobin level < 5g/ dL or hematocrit < 15%
• presence of severe malnutrition
• presence of febrile conditions due to diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhoea with dehydration) or other known underlying chronic or severe diseases (e.g. cardiac, renal and hepatic diseases, HIV/AIDS);
• regular medication, which may interfere with antimalarial pharmacokinetics;
• malaria treatment within 2 days prior to recruitment
• history of hypersensitivity reactions or contraindications to any of the medicines being tested or used as alternative treatment;
• body weight below 5 kg

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Artemether-lumefantrine	Artemether-lumefantrine	tablets of Coartem Dispersible®
Artesunate-amodiaquine	Artesunate-amodiaquine	tablets of ASAQ Winthrop®

Primary Outcome Measures

Name	Time	Method
PCR adjusted efficacy	day 28	Absence of fever and negative blood smear during the follow-up until day 28 or new infection occurred during the follow-up.

Secondary Outcome Measures

Name	Time	Method
Prevalence of HRP2 deletion	Baseline	Proportion of positive samples that fail to be detected by malaria rapid diagnostic tests due to the deletion of the related antigen
Quantification of Lumefantrine	day 7	Level of lumefantrine in the blood of children who will be randomized to the Artemether-lumefantrine arm
Proportion of adverse events and serious adverse events	day 28	Number of adverse events and serious adverse events that every participant will experience
Prevalence of resistance markers at baseline	Baseline	Proportion of samples containing different markers of resistance to different antimalarial drugs

Trial Locations

Locations (7)

Centre de santé Lupidi 1; 🇨🇩 Kapolowe, Haut-Katanga, Congo, The Democratic Republic of the

Centres de santé de Mikalayi et Matamba; 🇨🇩 Kazumba, Kasai Central, Congo, The Democratic Republic of the

Centre de santé de Coopération; 🇨🇩 Kimpese, Kongo Central, Congo, The Democratic Republic of the

Centre de Santé de Vanga; 🇨🇩 Vanga, Kwilu, Congo, The Democratic Republic of the

Centre de santé de Kalima; 🇨🇩 Kalima, Maniema, Congo, The Democratic Republic of the

Centres de santé Umoja et Foyer social; 🇨🇩 Kabondo, Tshopo, Congo, The Democratic Republic of the

Centre de santé Boende 2 Nsele; 🇨🇩 Boende, Tshuapa, Congo, The Democratic Republic of the