Efficacy and safety of pyronaridine–artesunate versus artemether–lumefantrine in the treatment of acute uncomplicated malaria in children in South-West Nigeria: an open-labelled randomized controlled trial

Malaria Journal

Research

Oluwafunmibi E. Anjorin¹  Bose E. Orimadegun²  Olugbenga A. Mokuolu³  Fiyinfoluwa I. Olusola⁴  Aduragbenro D. Adedapo⁴  Obaro S. Michael⁴  Catherine O. Falade⁵  Roland I. Funwei⁶  Abiola L. Olusanya⁷  Adebola E. Orimadegun⁸ 

[1] Department of Accident and Emergency, Obafemi Awolowo University Teaching, Hospital, Ile-Ife, Nigeria;Department of Chemical Pathology, College of Medicine, University of Ibadan, Ibadan, Nigeria;Department of Paediatrics, University of Ilorin Teaching Hospital, Ilorin, Nigeria;Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Ibadan, Nigeria;Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Ibadan, Nigeria;Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria;Department of Pharmacology, Babcock University, Ilisan, Remo, Ogun State, Nigeria;Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria;Institute of Child Health, College of Medicine, University of Ibadan, Ibadan, Nigeria;

关键词: Randomized clinical trial;    Pyronaridine–artesunate;    Artemether–lumefantrine;    Efficacy and safety;    Uncomplicated malaria;    Nigeria;   

DOI  :  10.1186/s12936-023-04574-7

 received in 2022-05-17, accepted in 2023-04-24,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundIn Nigeria, declining responsiveness to artemether–lumefantrine (AL), the artemisinin-based combination therapy (ACT) of choice since 2005, has been reported. Pyronaridine–artesunate (PA) is a newer fixed-dose ACT recently prequalified by the WHO for the treatment of uncomplicated falciparum malaria. However, PA data from the Nigerian pediatric population is scarce. Therefore, the efficacy and safety of PA and AL using the WHO 28-day anti-malarial therapeutic efficacy study protocol in Ibadan, southwest Nigeria, were compared.MethodsIn an open-labelled, randomized, controlled clinical trial, 172 children aged 3–144 months with a history of fever and microscopically confirmed uncomplicated Plasmodium falciparum malaria were enrolled in southwest Nigeria. Enrollees were randomly assigned to receive PA or AL at standard dosages according to body weight for 3 days. Venous blood was obtained for hematology, blood chemistry, and liver function tests on days 0, 3, 7, and 28 as part of the safety evaluation.Results165 (95.9%) of the enrolled individuals completed the study. About half (52.3%; 90/172) of enrollees were male. Eighty-seven (50.6%) received AL, while 85 (49.4%) received PA. Day 28, adequate clinical and parasitological response for PA was 92.7% [(76/82) 95% CI 83.1, 95.9] and 71.1% [(59/83) 95% CI 60.4, 79.9] for AL (0.001). Fever and parasite clearance were similar in both groups. Two of six and eight of 24 parasite recurrences were observed among PA- and AL-treated children, respectively. PCR-corrected Day-28 cure rates for PA were 97.4% (76/78) and 88.1% (59/67) for AL (= 0.04) in the per-protocol population after new infections were censored. Hematological recovery at day 28 was significantly better among PA-treated patients (34.9% 2.8) compared to those treated with AL (33.1% 3.0) (0.002). Adverse events in both treatment arms were mild and similar to the symptoms of malaria infection. Blood chemistry and liver function tests were mostly within normal limits, with an occasional marginal rise.ConclusionPA and AL were well-tolerated. PA was significantly more efficacious than AL in both the PCR-uncorrected and PCR-corrected per-protocol populations during this study. The results of this study support the inclusion of PA in the anti-malarial treatment guidelines in Nigeria.Retrospective trial registrationClinicaltrials.gov: NCT05192265.

【 授权许可】

CC BY   
© The Author(s) 2023

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