Pyronaridine-artesunate granules versus artemether-lumefantrine crushed tablets in children with Plasmodium falciparum malaria: a randomized controlled trial

Abstract

Background Children are most vulnerable to malaria. A pyronaridine-artesunate paediatric granule formulation is being developed for the treatment of uncomplicated Plasmodium falciparum malaria. Methods This phase III, multi-center, comparative, open-label, parallel-group, controlled clinical trial included patients aged ≤12 years, bodyweight ≥5 to Results Of 535 patients randomized, 355 received pyronaridine-artesunate and 180 received artemether-lumefantrine. Day-28 adequate clinical and parasitological response (ACPR), corrected for re-infection using polymerase chain reaction (PCR) genotyping (per-protocol population) was 97.1% (329/339; 95% CI 94.6, 98.6) for pyronaridine-artesunate; 98.8% (165/167; 95% CI 95.7, 99.9) for artemether-lumefantrine. The primary endpoint was achieved: pyronaridine-artesunate PCR-corrected day-28 ACPR was statistically significantly >90% (P 3 times the upper limit of normal (ULN) and peak total bilirubin >2xULN (i.e. within the Hy's law definition). Conclusions The pyronaridine-artesunate paediatric granule formulation was efficacious and was noninferior to artemether-lumefantrine. The adverse event profile was similar for the two comparators. Pyronaridine-artesunate should be considered for inclusion in paediatric malaria treatment programmes