Artesunate–pyronaridine–atovaquone–proguanil and artesunate–fosmidomycin–clindamycin compared with standard artesunate–pyronaridine for the treatment of uncomplicated malaria (MultiMal): a randomised, controlled, clinical, phase 2 trial in Gabon and Ghana
The Lancet Microbe·
- DOI
- 10.1016/j.lanmic.2025.101245
- PMID
- 41616788
- PMCID
- —
- OpenAlex
- W7125821268
- Study type
- Randomised controlled trial
- Publisher
- Elsevier BV
- Article type
- journal-article
- Integrity
- current
Why this research matters now
The authors position APAP and AFC as candidate multidrug combinations intended to address emerging artemisinin-reduced susceptibility in sub-Saharan Africa, warranting further clinical development.
Structured evidence summary
Research question
The trial evaluated whether two multidrug antimalarial regimens, artesunate–pyronaridine–atovaquone–proguanil (APAP) and artesunate–fosmidomycin–clindamycin (AFC), differ from standard artesunate–pyronaridine (AP) in safety, tolerability, and efficacy against uncomplicated malaria.
Study design
An open-label, randomised, controlled, phase 2 clinical trial conducted at sites in Lambaréné, Gabon, and Kumasi, Ghana, with 42-day follow-up and PCR-corrected per-protocol and intention-to-treat analyses of efficacy.
Population and setting
100 patients with uncomplicated P. falciparum malaria and parasitaemia of 1000–100,000 per μL were enrolled across three age strata (6 months–10 years, 11–17 years, and 18–65 years, including semi-immune adults) at two sub-Saharan African trial sites.
Main findings
PCR-corrected per-protocol ACPR at day 28 was 100% for AP and APAP and 97% for AFC, and at day 42 was 87.5%, 85.3%, and 94.4%, respectively. Treatment-emergent adverse event proportions did not differ across arms (p=0.37), and investigators reported no differential efficacy among AP, APAP, and AFC, describing APAP and AFC as safe, well tolerated, and highly efficacious in this phase 2 study.
Public-health relevance
The authors position APAP and AFC as candidate multidrug combinations intended to address emerging artemisinin-reduced susceptibility in sub-Saharan Africa, warranting further clinical development.
Important limitations
The abstract reports an open-label design, a small sample size (n=100) across multiple age strata, and 95% CIs that are wide for several day-42 estimates (e.g., AP 62–98). This summary is limited to the supplied single-article abstract/metadata and requires the original paper for decision-grade interpretation.
GIDS interpretation
Within the evidence-supply context, the article is discoverable as a phase 2 trial of multidrug antimalarial regimens indexed under Malaria, Antimicrobial resistance, and Treatment, with geographic links to Gabon and Ghana; this metadata does not by itself constitute or confirm a surveillance signal.
Related GIDS surveillance
Literature context does not validate, explain, or change a surveillance signal. Exact and contextual relationships are shown separately.
Evidence relationships
This article has 12 auditable classifier relationships to diseases, places, topics, and study design.