A randomized comparison of the efficacy and tolerability of three artemisinin-based combination treatments for children with acute falciparum malaria in The Democratic Republic of Congo

An open label, randomized controlled trial was carried out in 2011-12 in the Democratic Republic of Congo to test the efficacy, safety and tolerability of the artemisinin-based combination treatments dihydroartemisinin-piperaquine, amodiaquine-artesunate and artemether-lumefantrine. 684 children aged 3 to 59 months with uncomplicated Plasmodium falciparum malaria were randomly allocated to each study arm. Children were hospitalized for three days, given supervised treatment and followed-up weekly for 42 days. All regimens were well tolerated and rapidly effective. The median parasitemia clearance half-life was 2.2 hours and similar between arms (p=0.19). The PCR-uncorrected cure rates by day 42 were 73.0% for amodiaquine-artesunate, 70.2% for artemether-lumefantrine and 86.3% for dihydroartemisinin-piperaquine (p=0.001). Early treatment failure occurred in three patients (0.5%), one in each arm. The PCR-corrected cure rates were 93.4% for amodiaquine-artesunate, 92.7% for artemether-lumefantrine, and 94.3% for dihydroartemisinin-piperaquine (p=0.78). The latter provided a longer post-treatment prophylactic effect compared with the other two treatments. The day 7 plasma concentration of piperaquine was below 30 ng/mL in 47% of the children treated with dihydroartemisinin-piperaquine and the day 7 lumefantrine concentration was below 280 ng/mL in 37.0% of children who received artemether-lumefantrine. Thus although cure rates were all satisfactory, they could be improved by increasing the dose (Trial Registration ISRCTN20984426).