Efficacy and tolerability of artemether–lumefantrine and pyronaridine-artesunate for uncomplicated Plasmodium falciparum malaria in Niger

Abstract Background Following the WHO recommendation for the use of Artemisinin based combination for treatment of uncomplicated malaria endemic area, there have been a growing increase in the consumption of artemether-lumefantrine-based products in Niger. The present study aimed to evaluate the efficacy and tolerability of artemether-lumefantrine and artesunate-pyronaridine for the treatment of uncomplicated P. falciparum malaria in Niger. Methods A randomized, open-label, longitudinal, and controlled phase 4 clinical trial was conducted from November 2020 to October 2021 at Koira-Tegui in Niamey, Niger. A freely given informed consent was obtained from adult patients aged from 6 months and above with microscopically confirmed Plasmodium falciparum and/or other species malaria (1000 to 200 000 parasites per µL of blood). Eligible participants were randomized to receive either AL (Coartem®) or AP (Pyramax®). Microscopy and dry blood spot were collected from day0 to day42 to evaluate clinical and parasitological responses of the treatment and for molecular correction of parasitological failures. Appropriates statistical analysis were performed and p-value less than 0.05 was considered as statistically significant. Results Among 240 eligible participants, 123 and 117 were randomized to receive AL and AP respectively. Female patients represented 59% while under 5 years old were 32%. The median ages were 6 years in AL group and 8 years in AP. The two groups were comparable for sex and age groups. There was a significant statistical difference of PCR-unadjusted ACPR between AL and AP on day28 (82% versus 97% respectively; p = 0.0003) and day42 (77% versus 90% respectively; p = 0.0119). After PCR corrections the efficacy of both ACTs were 100% on 28 days follow up and 99.2% and 100% on 42 days for AL and AP respectively. After treatment initiation, the proportion of parasites clearances at 12 hours was comparable between AL and AP (p = 0.1197), but significantly higher in AP group compared to AL group at 36 hours, 48 hours, and 72 hours (p < 0.05). Only 5 and 2 patients vomited in AL and PA respectively while no pruritus nor allergy to treatment drugs were observed. However, no vomiting occurred on Day3. Also, no Pruritus was observed in any treatment arm. Conclusion Both the two first-line Artemisinin-based combination therapy, Artemether-Lumefantrine and Artesunate-Pyronaridine, are highly efficacy for the treatment of uncomplicated malaria in Niger. Trial registration PACTR202105706263530