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

Abstract

Efficacy and safety of artemether-lumefantrine compared with quinine in pregnant women with uncomplicated Plasmodium falciparum malaria: an open-label, randomised, non-inferiority trial MSF Field Research SummaryBackground 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 effi cacy and safety in Africa were scarce. We aimed to assess whether artemether-lumefantrine was at least as effi cacious as oral quinine for the treatment of uncomplicated falciparum malaria during the second and third trimesters of pregnancy in Mbarara, Uganda. MethodsWe 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 artemetherlumefantrine, and were followed up weekly until delivery. Our primary endpoint was cure rate at day 42, confi rmed by PCR. The non-inferiority margin was a diff erence in cure rate of 5%. Analysis of effi cacy was for all randomised patients without study deviations that could have aff ected the effi cacy 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 followup 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-diff erence 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 effi cacy.Funding Médecins Sans Frontières and the European Commission.

Population Pharmacokinetics and Clinical Response for Artemether-Lumefantrine in Pregnant and Nonpregnant Women with Uncomplicated Plasmodium falciparum Malaria in Tanzania

“…It is currently available at a subsidized cost in most countries where malaria is endemic. AL has proved to be not inferior to quinine in East Africa for the treatment of P. falciparum infection in the second and third trimesters of pregnancy (4). ACTs are recommended by the World Health Organization (WHO) as the first-line treatment for uncomplicated malaria in the second and third trimesters of pregnancy (5).…”

Performance of a Histidine-Rich Protein 2 Rapid Diagnostic Test, Paracheck Pf®, for Detection of Malaria Infections in Ugandan Pregnant Women

“…12 The protocols for these studies were approved by the Faculty Research Ethics Committee and the Institutional Review Board of the Mbarara University of Science and Technology (Mbarara, Uganda), and the Ugandan National Council for Science and Technology (Kampala, Uganda). The MIP study protocol was also approved by the Comité de Protection des Personnes (Ile-de-France XI, Paris, France).…”

Anti‐infective use in children and pregnancy: current deficiencies and future challenges

“…However, a recent study comparing the safety of ACT and quinine found no difference in adverse pregnancy outcomes when used in the second and third trimester [49].…”