Re-ACT

Randomisierte kontrollierte Studie zur Bewertung der Wirksamkeit von Artemisinin-Kombinationstherapien in einem Umfeld aufkommender Artemisinin-Resistenz in Afrika

01.01.2025 bis 30.04.2027

With over 2 billion people at risk and an estimated 247 million cases and 619,000 deaths worldwide, Plasmodium falciparum malaria remains a major global health challenge; more so in Africa, where over 95% of cases and deaths occur. Artemisinin combination therapies (ACTs) are critical malaria management tool. However, P. falciparum resistance threatens ACT efficacy. In southeast Asia, the emergence of artemisinin partial resistance and partner
drug resistance led to high ACT failures. In Africa, there are robust indications that parasites resistant to artemisinins have emerged, especially in Eastern- and Horn of Africa.
In Uganda, Conrad and Asua et al (2023) reported emergence of parasites carrying genetic polymorphisms associated with artemisinin partial resistance at multiple locations, with increasing prevalence and regional spread. However, the impact of artemisinin partial resistance on malaria case management is not fully understood, and therefore requires an urgent and critical assessment to provide appropriate guidance for malaria case management. The overall aim of this project is to evaluate the role of emerging partial artemisinin resistance on ACT treatment outcome in Uganda, by determining the therapeutic efficacy of artemether-lumefantrine, the current first-line treatment for the management of uncomplicated P. falciparum malaria in Uganda vs pyronaridine-artesunate in a randomized controlled clinical trial. To obtain additional data on pyronaridineartesunate and as a comparison to a location with no evidence of artemisinin partial resistance, we will assess the efficacy of the current first-line ACT artesunate-amodiaquine vs pyronaridine-artesunate in a parallel randomized clinical trial using an equivalent study protocol in Gabon. Pyronaridine-artesunate is a relatively new regimen that has received strong recommendation from WHO, but its deployment is currently limited in Africa, in part due to limited efficacy data. Of note, pyronaridine-artesunate is a prime candidate to rapidly replace current first-line ACTs as no parasite resistance to pyronaridine has been reported to date. In Uganda, a total of 600 children aged 6 months to 10 years will be enrolled from two sites; while in Gabon, 300 children aged 6 months to 10 years will be enrolled from one site. Participants will be randomised to receive either of the study drugs and be followed for 42 days to assess for cure rate per treatment group as the primary study end point.