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.
RCT Entities:
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.
Authors: Selidji T Agnandji; Florian Kurth; Jose F Fernandes; Solange S Soulanoudjingar; Beatrice P Abossolo; Ghyslain Mombo-Ngoma; Arti Basra; Raquel González; Gondo Kizito; Pembe I Mayengue; Lorenz Auer-Hackenberg; Saadou Issifou; Bertrand Lell; Ayola A Adegnika; Michael Ramharter Journal: Malar J Date: 2011-12-14 Impact factor: 2.979
Authors: Marielle K Bouyou-Akotet; Michael Ramharter; Edgard Brice Ngoungou; Modeste Mabika Mamfoumbi; Mireille Pemba Mihindou; Michel A Missinou; Florian Kurth; Sabine Bélard; Selidji T Agnandji; Saadou Issifou; János L Heidecker; Sonja Trapp; Peter G Kremsner; Maryvonne Kombila Journal: Wien Klin Wochenschr Date: 2010-03 Impact factor: 1.704
Authors: Sam Salman; Madhu Page-Sharp; Susan Griffin; Kaye Kose; Peter M Siba; Kenneth F Ilett; Ivo Mueller; Timothy M E Davis Journal: Antimicrob Agents Chemother Date: 2011-08-29 Impact factor: 5.191
Authors: Kovi Bessoff; Thomas Spangenberg; Jenna E Foderaro; Rajiv S Jumani; Gary E Ward; Christopher D Huston Journal: Antimicrob Agents Chemother Date: 2014-02-24 Impact factor: 5.191