Efficacy and safety of the six-dose regimen of artemether-lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in adolescents and adults: a pooled analysis of individual patient data from randomized clinical trials.
To demonstrate the superiority of the six-dose over the four-dose regimen of artemether-lumefantrine (co-artemether, Coartem) in patients >12 years, data from 11 randomized clinical trials were pooled and analyzed. A total of 1368 patients with uncomplicated Plasmodium falciparum malaria (six-dose: 598; four-dose: 770) were included in the analysis, together with 717 patients treated with comparators. Analysis of the 28-day cure rate based on the ITT and evaluable populations yielded corrected cure rates for the six-dose regimen of 87% and 97% compared with 74% and 87%, respectively, with the four-dose regimen (P<0.0001, for both comparisons). For mefloquine/artesunate, the most frequently used comparator, cure rates were 87% and 99%, respectively. The six-dose regimen was well tolerated and not markedly different to the four-dose regimen. The main finding of our analysis is that the six-dose regimen of co-artemether is more effective than the four-dose regimen in adolescents and adults without compromising safety.