Project: Clinical evaluation of ArteSunate+Amodiaquine+Atovaquone-Proguanil tri-therapy for Malaria treatment in African children
| Acronym | ASAAP (Reference Number: RIA2017MC-2022) |
| Duration | 01/03/2019 - 28/02/2023 |
| Project Topic | Background: Artemisinin-based combination therapies (ACTs) are currently the first-line treatment for malaria. Their efficacy has declined in South-East Asia because of the emergence of parasite resistance that has the potential to spread through Africa. Although susceptibility to ACTs currently remains high among the African Plasmodium falciparum population, occurrence of drug resistance against first line antimalarials has led to a dramatic increase in malaria related mortality. To mitigate the risk of resistance, more efficient ACTs need to be urgently explored for quick deployment in Africa. Objectives: - Primary objective: To assess the efficacy of a triple-therapy associating artesunate-amodiaquine (ASAQ) and atovaquone-proguanil (AP) for the treatment of uncomplicated P. falciparum malaria in African children in a non-inferiority comparator-controlled trial. - Secondary objectives: To compare ASAQ+AP with ASAQ regarding 1) safety and tolerability, 2) posttreatment prophylactic effect, 3) transmission-blocking activity, 4) pharmacokinetics and 5) selection antimalarial resistance markers. Rationale: ASAQ is widely used and shows high efficacy and favourable safety in Africa but needs to be protected to increase its useful lifespan. AP is highly efficacious, safe and registered for the use in young children and resistant parasites are not circulating in any endemic area. AP targets multiple parasite stages -liver and blood in human host, and mosquito- through an independent mode of action, limiting the risk of cross-resistance with current ACTs and providing post-treatment prophylactic efficacy and also transmission-blocking activity. Methods: An individually randomized open label comparator-controlled phase III clinical trial will be conducted to compare safety and cure rate of a 3-day treatment course with ASAQ+AP versus ASAQ in 1,504 consenting 6-59 months children experiencing uncomplicated P. falciparum malaria from Benin, Gabon, Ghana and Mali. The main outcome will be cure rate at day-42, excluding reinfections. Antimalarial pharmacokinetic parameters and posttreatment prophylactic efficacy, by recording time to first reinfection, will be estimated for the two treatments and compared. Sub-studies will look at transmission-blocking efficacy through membrane-feeding assays and gametocyte dynamics, drug resistance selection. Expected outcomes and relevance: By proofing that ASAQ+AP has safety and cure rate similar to ASAQ, this project will lead to important public health-level benefits by provision of a first candidate regimen to be deployed when ACT resistance spreads throughout Africa and by decreasing human to mosquito transmission and therefore reducing malaria transmission. The project will provide a platform for North-North, North-South and South-South networking, and infrastructure and capacity building, including training in implementation of clinical trials, and entomological assays. |
| Network | EDCTP2 |
| Call | Clinical trials and operational research studies to optimise the use of products for poverty-related diseases in mothers, newborns, children and/or adolescents |
Project partner
| Number | Name | Role | Country |
|---|---|---|---|
| 1 | Kwame Nkrumah University of Science and Technology | Coordinator | Ghana |
| 4 | Bernhard-Nocht-Institut für Tropenmedizin | Partner | Germany |
| 7 | Centre de Recherches Médicales de Lambaréné | Partner | Gabon |
| 10 | Institut de Recherche Clinique du Bénin | Partner | Benin |
| 13 | Institut de Recherche pour le Développement | Partner | France |
| 15 | Institut des Sciences et Techniques | Partner | Burkina Faso |
| 18 | Université des Sciences, des Techniques et des Technologies de Bamako | Partner | Mali |