Efficacy of artesunate-amodiaquine and artemether-lumefantrine fixed-dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria among children aged six to 59 months in Nimba County, Liberia: an open-label randomized non-inferiority trial

Malaria Journal

Research

Pascal Houzé¹  Jean-René Kiechel²  Gwenaelle Carn²  Mehul Dhorda³  Yap Boum³  Loretxu Pinoges⁴  Timothy Sundaygar⁴  Parastou Valeh⁴  Birgit Schramm⁴  Richard Smith⁴  Elisabeth Baudin⁴  Charles S Mazinda⁴  Elizabeth A Ashley⁵  Philippe J Guérin⁵  Vincent Jullien⁶  Eric Comte⁷  Yah M Zolia⁸  Joel J Jones⁸ 

[1] AP-HP, Hôpital St-Louis, Laboratoire de Biochimie, 75010, Paris, France;Drugs for Neglected Diseases initiative, 1202, Geneva, Switzerland;Epicentre Mbarara Research Base, Mbarara, Uganda;Epicentre, 75011, Paris, France;Epicentre, 75011, Paris, France;Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, CCVTM, Oxford, UK;INSERM U663, Université Paris Descartes, 75006, Paris, France;Médecins Sans Frontières, 1211, Geneva, Switzerland;National Malaria Control Programme, Ministry of Health and Social Welfare, Monrovia, Liberia;

关键词: Malaria;    Artemisinin;    Efficacy;    Randomized trial;    Liberia;   

DOI  :  10.1186/1475-2875-12-251

 received in 2013-03-22, accepted in 2013-07-07,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundProspective efficacy monitoring of anti-malarial treatments is imperative for timely detection of resistance development. The in vivo efficacy of artesunate-amodiaquine (ASAQ) fixed-dose combination (FDC) was compared to that of artemether-lumefantrine (AL) among children aged six to 59 months in Nimba County, Liberia, where Plasmodium falciparum malaria is endemic and efficacy data are scarce.MethodsAn open-label, randomized controlled non-inferiority trial compared the genotyping adjusted day 42 cure rates of ASAQ FDC (ASAQ Winthrop®) to AL (Coartem®) in 300 children aged six to 59 months with uncomplicated falciparum malaria. Inclusion was between December 2008 and May 2009. Randomization (1:1) was to a three-day observed oral regimen (ASAQ: once a day; AL: twice a day, given with fatty food). Day 7 desethylamodiaquine and lumefantrine blood-concentrations were also measured.ResultsThe day 42 genotyping-adjusted cure rate estimates were 97.3% [95% CI: 91.6-99.1] for ASAQ and 94.2% [88.1-97.2] for AL (Kaplan-Meier survival estimates). The difference in day 42 cure rates was −3.1% [upper limit 95% CI: 1.2%]. These results were confirmed by observed proportion of patients cured at day 42 on the per-protocol population. Parasite clearance was 100% (ASAQ) and 99.3% (AL) on day 3. The probability to remain free of re-infection was 0.55 [95% CI: 0.46-0.63] (ASAQ) and 0.66 [0.57-0.73] (AL) (p = 0.017).ConclusionsBoth ASAQ and AL were highly efficacious and ASAQ was non-inferior to AL. The proportion of patients with re-infection was high in both arms in this highly endemic setting. In 2010, ASAQ FDC was adopted as the first-line national treatment in Liberia. Continuous efficacy monitoring is recommended.Trial registrationThe protocols were registered with Current Controlled Trials, under the identifier numbers ISRCTN51688713, ISRCTN40020296.

【 授权许可】

CC BY   
© Schramm et al.; licensee BioMed Central Ltd. 2013