Efficacy and safety of artemether-lumefantrine compared with quinine in pregnant women with uncomplicated Plasmodium falciparum malaria: an open-label, randomised, non-inferiority trial.

Journal article

BACKGROUND: Malaria in pregnancy is associated with maternal and fetal morbidity and mortality. In 2006, WHO recommended use of artemisinin-based combination treatments during the second or third trimesters, but data on efficacy and safety in Africa were scarce. We aimed to assess whether artemether-lumefantrine was at least as efficacious as oral quinine for the treatment of uncomplicated falciparum malaria during the second and third trimesters of pregnancy in Mbarara, Uganda. METHODS: We did an open-label, randomised, non-inferiority trial between October, 2006, and May, 2009, at the antenatal clinics of the Mbarara University of Science and Technology Hospital in Uganda. Pregnant women were randomly assigned (1:1) by computer generated sequence to receive either quinine hydrochloride or artemether-lumefantrine, and were followed up weekly until delivery. Our primary endpoint was cure rate at day 42, confirmed by PCR. The non-inferiority margin was a difference in cure rate of 5%. Analysis of efficacy was for all randomised patients without study deviations that could have affected the efficacy outcome. This study was registered with ClinicalTrials.gov, number NCT00495508. FINDINGS: 304 women were randomly assigned, 152 to each treatment group. By day 42, 16 patients were lost to follow-up and 25 were excluded from the analysis. At day 42, 137 (99.3%) of 138 patients taking artemether-lumefantrine and 122 (97.6%) of 125 taking quinine were cured-difference 1.7% (lower limit of 95% CI -0.9). There were 290 adverse events in the quinine group and 141 in the artemether-lumefantrine group. INTERPRETATION: Artemisinin derivatives are not inferior to oral quinine for the treatment of uncomplicated malaria in pregnancy and might be preferable on the basis of safety and efficacy. FUNDING: Médecins Sans Frontières and the European Commission.

Authors: Piola, P; Nabasumba, C; Turyakira, E; Dhorda, M; Lindegardh, N

• Publication status: Published
• Journal: Lancet. Infectious diseases
• Volume: 10
• Issue: 11
• Pages: 762-769
• Publication date: 2010-11-01
• DOI: 10.1016/s1473-3099(10)70202-4
• EISSN: 1474-4457
• ISSN: 1473-3099
• Language: English
• Keywords: Adolescent; Pregnancy; Humans; Antimalarials; Young Adult; Treatment Outcome; Ethanolamines; Animals; Female; Fluorenes; Uganda; Malaria, Falciparum; Drug Combinations; Plasmodium falciparum; Artemisinins; Quinine; Polymerase Chain Reaction; Adult; Pregnancy Complications, Infectious