Pyronaridine–artesunate and artemether–lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Kenyan children: a randomized controlled non-inferiority trial

Abstract

BackgroundPyronaridine–artesunate is a novel artemisinin-based combination therapy. The efficacy and safety of pyronaridine–artesunate were compared with artemether–lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in children.MethodsThis phase III open-label randomized controlled non-inferiority trial was conducted in Western Kenya. Children aged 6 months to ≤ 12 years with a bodyweight > 5 kg and microscopically confirmed P. falciparum malaria were randomly assigned in a 1:1 ratio to orally receive pyronaridine–artesunate or artemether–lumefantrine, dosed according to bodyweight, for 3 days.ResultsOf 197 participants, 101 received pyronaridine–artesunate and 96 received artemether–lumefantrine. The day-28 adequate clinical and parasitological response in the per-protocol population, PCR-corrected for reinfections, was 98.9% (93/94, 95% CI 94.2–99.8) for pyronaridine–artesunate and 96.4% (81/84, 95% CI 90.0–98.8) for artemether–lumefantrine. Pyronaridine–artesunate was found to be non-inferior to artemether–lumefantrine: the treatment difference was 2.5% (95% CI − 2.8 to 9.0). Adverse events occurred in 41.6% (42/101) and 34.4% (33/96) of patients in the pyronaridine–artesunate group and the artemether–lumefantrine group, respectively. No participants were found to have alanine or aspartate aminotransferase levels > 3 times the upper limit of normal.ConclusionsPyronaridine–artesunate was well tolerated, efficacious and non-inferior to artemether–lumefantrine for the treatment of uncomplicated P. falciparum malaria in Kenyan children. Results are in line with previous reports and inclusion of pyronaridine–artesunate in paediatric malaria treatment programmes should be considered.This study is registered at clinicaltrials.gov under NCT02411994. Registration date: 8 April 2015. https://clinicaltrials.gov/ct2/show/NCT02411994?term=pyronaridine–artesunate&cond=Malaria&cntry=KE&rank=1Electronic supplementary materialThe online version of this article (10.1186/s12936-018-2340-3) contains supplementary material, which is available to authorized users.

Pyronaridine-artesunate for treating uncomplicated Plasmodium falciparum malaria

“…At day 42, the PCR‐adjusted treatment failure rate for pyronaridine‐artesunate was slightly greater than 5% in two studies (Kayentao 2012, 18 events for 275 evaluable patients, 6.5%; Roth 2018, 4 events for 77 evaluable patients, 5.2%).…”

“…We identified four studies that were not included in the previous version of this review (Nelwan 2015; Roth 2018; Sagara 2018; Shin 2011). …”

“…Sample sizes ranged from 197 participants in Roth 2018 to 1323 participants in Sagara 2018, yielding a total number of 3327 for inclusion in quantitative synthesis. Two studies were multicentred in Africa and Asia (Kayentao 2012; Tshefu 2010), one was multicentred in Africa (Sagara 2018), and one was a single‐centre in Africa (Roth 2018).…”

“…Two studies were multicentred in Africa and Asia (Kayentao 2012; Tshefu 2010), one was multicentred in Africa (Sagara 2018), and one was a single‐centre in Africa (Roth 2018). None of the studies described the P falciparum resistance profile to currently available antimalarials.…”

“…Six studies reported that the investigators performing clinical assessments were blinded to treatment allocation (Kayentao 2012; Poravuth 2011; Roth 2018; Rueangweerayut 2012; Shin 2011; Tshefu 2010). Eight studies reported that the investigators performing parasitological assessments were blinded to treatment allocation (Kayentao 2012; Nelwan 2015; Poravuth 2011; Roth 2018; Rueangweerayut 2012; Sagara 2018; Shin 2011; Tshefu 2010). …”