A Head-to-Head Comparison of Four Artemisinin-Based Combinations for Treating Uncomplicated Malaria in African Children: A Randomized Trial



Atwine, Daniel, Balikagala, Betty, Bassat, Quique, Chalwe, Victor, D'Alessandro, Umberto, Dhorda, Mehul, Donegan, Sarah ORCID: 0000-0003-1709-2290, Garner, Paul, Gonzalez, Raquel, Guiguemde, Robert Tinga
et al (show 34 more authors) (2011) A Head-to-Head Comparison of Four Artemisinin-Based Combinations for Treating Uncomplicated Malaria in African Children: A Randomized Trial. PLOS MEDICINE, 8 (11). e1001119-.

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Abstract

<h4>Background</h4>Artemisinin-based combination therapies (ACTs) are the mainstay for the management of uncomplicated malaria cases. However, up-to-date data able to assist sub-Saharan African countries formulating appropriate antimalarial drug policies are scarce.<h4>Methods and findings</h4>Between 9 July 2007 and 19 June 2009, a randomized, non-inferiority (10% difference threshold in efficacy at day 28) clinical trial was carried out at 12 sites in seven sub-Saharan African countries. Each site compared three of four ACTs, namely amodiaquine-artesunate (ASAQ), dihydroartemisinin-piperaquine (DHAPQ), artemether-lumefantrine (AL), or chlorproguanil-dapsone-artesunate (CD+A). Overall, 4,116 children 6-59 mo old with uncomplicated Plasmodium falciparum malaria were treated (1,226 with AL, 1,002 with ASAQ, 413 with CD+A, and 1,475 with DHAPQ), actively followed up until day 28, and then passively followed up for the next 6 mo. At day 28, for the PCR-adjusted efficacy, non-inferiority was established for three pair-wise comparisons: DHAPQ (97.3%) versus AL (95.5%) (odds ratio [OR]: 0.59, 95% CI: 0.37-0.94); DHAPQ (97.6%) versus ASAQ (96.8%) (OR: 0.74, 95% CI: 0.41-1.34), and ASAQ (97.1%) versus AL (94.4%) (OR: 0.50, 95% CI: 0.28-0.92). For the PCR-unadjusted efficacy, AL was significantly less efficacious than DHAPQ (72.7% versus 89.5%) (OR: 0.27, 95% CI: 0.21-0.34) and ASAQ (66.2% versus 80.4%) (OR: 0.40, 95% CI: 0.30-0.53), while DHAPQ (92.2%) had higher efficacy than ASAQ (80.8%) but non-inferiority could not be excluded (OR: 0.35, 95% CI: 0.26-0.48). CD+A was significantly less efficacious than the other three treatments. Day 63 results were similar to those observed at day 28.<h4>Conclusions</h4>This large head-to-head comparison of most currently available ACTs in sub-Saharan Africa showed that AL, ASAQ, and DHAPQ had excellent efficacy, up to day 63 post-treatment. The risk of recurrent infections was significantly lower for DHAPQ, followed by ASAQ and then AL, supporting the recent recommendation of considering DHAPQ as a valid option for the treatment of uncomplicated P. falciparum malaria.<h4>Trial registration</h4>ClinicalTrials.gov NCT00393679; Pan African Clinical Trials Registry PACTR2009010000911750

Item Type: Article
Additional Information: ## TULIP Type: Articles/Papers (Journal) ##
Uncontrolled Keywords: Four Artemisinin-Based Combinations (4ABC) Study Group, Humans, Malaria, Falciparum, Ethanolamines, Artemisinins, Amodiaquine, Fluorenes, Drug Combinations, Antimalarials, Adult, Africa South of the Sahara, Female, Male, Artemether, Lumefantrine Drug Combination
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Population Health
Depositing User: Symplectic Admin
Date Deposited: 18 Oct 2022 07:51
Last Modified: 18 Jan 2023 20:36
DOI: 10.1371/journal.pmed.1001119
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3165573