Tolerability and safety of artesunate-amodiaquine and artemether-lumefantrine fixed dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria: two open-label, randomized trials in Nimba County, Liberia

Malaria Journal

Research

Arnaud Bruneel¹  Jean-René Kiechel²  Gwenaelle Carn²  Elizabeth A Ashley³  Loretxu Pinoges³  Timothy Sundaygar³  Parastou Valeh³  Birgit Schramm³  Richard Smith³  Elisabeth Baudin³  Charles S Mazinda³  Philippe J Guérin⁴  Vincent Jullien⁵  Eric Comte⁶  Yah M Zolia⁷  Joel J Jones⁷  Michel Branger⁸ 

[1] AP-HP, Biochimie Métabolique et Cellulaire, Hôpital Bichat, 75018, Paris, France;Drugs for Neglected Diseases initiative, 1202, Geneva, Switzerland;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;Service de Virologie, Centre Hospitalier Bichat-Claude Bernard, 75018, Paris, France;

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

DOI  :  10.1186/1475-2875-12-250

 received in 2013-03-22, accepted in 2013-06-23,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundSafety surveillance of widely used artemisinin-based combination therapy (ACT) is essential, but tolerability data in the over five years age group are largely anecdotal.MethodsTwo open-label, randomized trials were conducted in Nimba County, Liberia: i) the main tolerability trial with 1,000 Plasmodium falciparum malaria patients aged over five years (Study-T), and, ii) an efficacy trial with a secondary objective of collecting tolerability data among 300 children age six to 59 months (Study-E). In both studies patients were randomized to fixed-dose artesunate-amodiaquine (ASAQ Winthrop®) or artemether-lumefantrine (AL, Coartem®), respectively. Clinical- and laboratory-adverse events (AEs) were recorded until day 28.ResultsStudy-T: most patients experienced at least one AE. Severe AEs were few, primarily asymptomatic blood system disorders or increased liver enzyme values. No treatment or study discontinuation occurred. Mild or moderate fatigue (39.8% vs 16.3%, p < 0.001), vomiting (7.1% vs 1.6%, p < 0.001), nausea (3.2% vs 1.0%, p = 0.01), and anaemia (14.9% vs 9.8%, p = 0.01) were more frequently recorded in the ASAQ versus AL arm. Study-E: mild or moderate AEs were common, including anaemia, fatigue, vomiting or diarrhoea. The few severe events were asymptomatic blood system disorders and four clinical events (pneumonia, malaria, vomiting and stomatitis).ConclusionBoth ASAQ and AL were well tolerated in patients of all age groups. No unexpected AEs occurred. Certain mild or moderate AEs were more frequent in the ASAQ arm. Standardised safety surveillance should continue for all forms of ACT.Trial registrationThe protocols were registered with Current Controlled Trials, under the identifier numbers ISRCTN40020296, ISRCTN51688713, (http://www.controlled-trials.com).

【 授权许可】

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