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.
- Department for International Development
- 1 January 2008
- Kenya, Tanzania, Mozambique, Mali, and Benin
- Document Type:
- Journal Article
- 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., and 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].
Published: 1 January 2008
Document Type: Journal Article
Authors: 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.