Efficacy and safety of artemether-lumefantrine dispersible tablets compared with crushed commercial tablets in African infants and children with uncomplicated malaria: a randomised, single-blind, multicentre trial.
D'Alessandro, U., Abdulla, S., Premji, Z., Ubben, D., Sagara, I., Borrmann, S., González, R., Hamel, M., Ogutu, B., Mårtensson, A., Lyimo, J., Maiga, H., Sasi, P., Nahum, A., Bassat, Q., Juma, E., Otieno, L., Björkman, A., Beck, H.P., Andriano, K., Cousin, M., Lefèvre, G.
Background: Combination treatments, preferably containing an artemisinin derivative, are recommended to improve efficacy and prevent Plasmodium falciparum drug resistance. Our aim was to show non-inferiority of a new dispersible formulation of artemether-lumefantrine to the conventional crushed tablet in the treatment of young children with uncomplicated malaria. Methods: We did a randomised non-inferiority study on children weighing 5–35 kg with uncomplicated P. falciparum malaria in Benin, Kenya, Mali, Mozambique, and Tanzania. The primary outcome measure was PCR-corrected 28-day parasitological cure rate. We aimed to show non-inferiority (with a margin of –5%) of dispersible versus crushed tablet. We constructed an asymptotic one-sided 97·5% CI on the difference in cure rates. A computer-generated randomisation list was kept centrally and investigators were unaware of the study medication administered. We used a modified intention-to-treat analysis. This trial is registered with ClinicalTrials.gov, number NCT00386763. Findings: 899 children aged 12 years or younger were randomly assigned to either dispersible (n=447) or crushed tablets (n=452). More than 85% of patients in each treatment group completed the study. 812 children qualified for the modified intention-to-treat analysis (n=403 vs n=409). The PCR-corrected day-28 cure rate was 97·8% (95% CI 96·3–99·2) in the group on dispersible formulation and 98·5% (97·4–99·7) in the group on crushed formulation. The lower bound of the one-sided 97·5% CI was −2·7%. The most common drug-related adverse event was vomiting (n=33 [7%] and n=42 [9%], respectively). No signs of ototoxicity or relevant cardiotoxicity were seen. Interpretation: A six-dose regimen of artemether-lumefantrine with the new dispersible formulation is as efficacious as the currently used crushed tablet in infants and children, and has a similar safety profile.
The Lancet (2008) 372 (9652) pp. 1819-1827 [DOI:10.1016/S0140-6736(08)61492-0].