A head-to-head comparison of four artemisinin-based combinations for treating uncomplicated malaria in african children: A randomized trial

Background: 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. methods and findings: 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. conclusions: 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. trial registration: clinicaltrials.gov nct00393679; pan african clinical trials registry pactr2009010000911750. © 2011 4abc study group.