Comparison of azithromycin plus chloroquine versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in children in Africa: a randomized, open-label study

Malaria Journal

Research

Alfred B Tiono¹  Ali Sie²  Jeffery Robbins³  Qinying Zhao³  Louis K Penali⁴  Issaka Sagara⁵  Abdoulaye A Djimde⁵  Patrick Ansah⁶  Richa Chandra⁷  Bernhards Ogutu⁸ 

[1] Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso;Centre de Recherche en Santé de Nouna, Nouna, Burkina Faso;Global Research and Development, Pfizer Inc, 445 Eastern Point Road, 06340, Groton, CT, USA;Institut Pasteur de Côte d’ Ivoire, Unité de Paludologie, Abidjan, Côte d’Ivoire;Malaria Research and Training Center, University of Sciences, Techniques and Technologies, Bamako, Mali;Navrongo Health Research Centre, Ghana Health Service War Memorial Hospital, Navrongo, Ghana;Novartis, Cambridge, MA, USA;Walter Reed Project, Centre for Clinical Research, Kenya Medical Research Institute, Kisumu, Kenya;

关键词: Uncomplicated malaria;    Azithromycin;    Chloroquine;    Paediatrics;    Africa;    Artemether-lumefantrine;    Azithromycin-chloroquine;    Treatment efficacy;   

DOI  :  10.1186/s12936-015-0620-8

 received in 2014-11-13, accepted in 2015-02-22,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundThis randomized, open-label study was conducted to establish the non-inferiority of a combination of azithromycin (AZ) and chloroquine (CQ) to artemether-lumefantrine (AL) for treatment of uncomplicated malaria in children from six sites in sub-Saharan Africa.MethodsChildren with uncomplicated Plasmodium falciparum malaria between six and 59 months of age were randomized 1:1 to either AZCQ (30 mg/kg AZ + 10 mg/kg CQ base) or AL per prescribing information for three days (Days 0, 1, 2). Each site could enrol in the study population once the treatment of uncomplicated malaria in five children five to 12 years of age was deemed to be effective and well tolerated. The primary efficacy evaluation was the proportion of subjects in both the modified intent-to-treat (MITT) and per-protocol (PP) populations with an adequate clinical and parasitological response (PCR corrected) at Day 28. Non-inferiority was concluded if the lower bound of the 95% confidence interval comparing the two groups was 10 percentage points or greater.ResultsA total of 255 children were enrolled in the efficacy analysis (AZCQ, n = 124; AL, n = 131). The PCR corrected clearance rates were 89% (AZCQ) versus 98% (AL) for MITT, a difference of -9.10 (95% confidence interval; -16.02, -2.18) and 93% (AZCQ) versus 99% (AL) for PP, a difference of -6.08 (-12.10, -0.05). Early and late treatment failures were more common in subjects receiving AZCQ. Adverse events were more common in subjects treated with AZCQ. Drug concentrations obtained at specified time points following AZCQ administration had a large coefficient of variation partially due to sparse sampling with sample collection time window.ConclusionsIn this study, non-inferiority of AZCQ to AL was not demonstrated.Trial registrationClinicalTrials.gov NCT00677833.

【 授权许可】

Unknown   
© Chandra et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.