Descripción del proyecto
Enfoque terapéutico triple para el tratamiento del paludismo sin complicaciones en niños
El paludismo sigue siendo un importante problema sanitario en África, por lo que se necesitan soluciones más eficaces y de despliegue rápido para prevenir la resistencia a los tratamiento combinado con artemisinina (TCA). Arteméter-lumefantrina (AL) se utiliza ampliamente en África, pero salvaguardar su eficacia es crucial para prolongar su vida útil. Atovacuona-proguanil (AP) presenta una alternativa altamente productiva, segura y prometedora. Se dirige a múltiples estadios del parásito y minimiza el riesgo de resistencia cruzada con los TCA actuales. El proyecto ASAAP-plus, financiado con fondos europeos, constituye un ensayo clínico de fase III diseñado para evaluar la eficacia de un enfoque terapéutico triple para tratar el paludismo por «Plasmodium falciparum» sin complicaciones en niños africanos. Este enfoque implica la combinación de AL y AP y se llevará a cabo en Benín, Gabón, Ghana y Mali. La principal medida de resultados será la tasa de curación a los cuarenta y dos días.
Objetivo
Susceptibility to Artemisinin-based combination therapies (ACTs) currently remains high among the African Plasmodium falciparum population, but resistant mutant has been detected recently. To mitigate the risk of resistance leading to a dramatic increase in malaria related mortality, more efficient ACTs need to be urgently explored for quick deployment in Africa.
Artemether-lumefantrine (AL) is widely used and shows high efficacy and favourable safety in Africa but needs to be protected to increase its useful lifespan. Atovaquone-proguanil (AP) is highly efficacious, safe 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.
The aim of the project is to assess the efficacy of a triple-therapy associating artemether-lumefantrine (AL) and atovaquone-proguanil (AP) for the treatment of uncomplicated P. falciparum malaria in African children in a non-inferiority comparator-controlled trial.
A phase III clinical trial will be conducted to compare safety and cure rate of a 3-day treatment course with AL+AP versus AL in 1,664 consenting 6 to 70 months children with uncomplicated malaria from Benin, Gabon, Ghana and Mali. The main outcome will be cure rate at day-42, excluding reinfections. Antimalarial pharmacokinetic parameters and post-treatment prophylactic efficacy 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.
By proofing that AL+AP has safety and cure rate similar to AL, 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.
Ámbito científico
Palabras clave
Programa(s)
- HORIZON.2.1 - Health Main Programme
Convocatoria de propuestas
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HORIZON-JU-RIA - HORIZON JU Research and Innovation ActionsCoordinador
20359 Hamburg
Alemania