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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Efficacy and Safety of Artesunate-amodiaquine and Artemether-lumefantrine in the Treatment of Uncomplicated Plasmodium Falciparum Malaria in the Democratic Republic of the Congo: a Randomized Controlled Trial (TES2022)

Conditions
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Uncomplicated Plasmodium Falciparum Malaria

Intervention / Treatment
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* Drug: Artesunate-amodiaquine
* Drug: Artemether-lumefantrine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 59 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomization 1:1 in two treatment arms: artesunate-amodiaquine and artemether-lumefantrine
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Artesunate-amodiaquine<br>tablets of ASAQ Winthrop® | Drug: Artesunate-amodiaquine<br>* Tablets<br>* Other names: ASAQ Winthrop®;|
| Experimental: Artemether-lumefantrine<br>tablets of Coartem Dispersible® | Drug: Artemether-lumefantrine<br>* Tablets<br>* Other names: Coartem Dispersible®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PCR adjusted efficacy | Absence of fever and negative blood smear during the follow-up until day 28 or new infection occurred during the follow-up. | day 28 | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Uncomplicated malaria, Plasmodium falciparum, Artemisinin-based Combination Treatment, Artemether-lumefantrine, Artesunate-amodiaquine