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

Hdl Handle:
http://hdl.handle.net/10144/116337
Title:
Efficacy and safety of artemether-lumefantrine compared with quinine in pregnant women with uncomplicated Plasmodium falciparum malaria: an open-label, randomised, non-inferiority trial
Authors:
Piola, Patrice; Nabasumba, Carolyn; Turyakira, Eleanor; Dhorda, Mehul; Lindegardh, Niklas; Nyehangane, Dan; Snounou, Georges; Ashley, Elizabeth A; McGready, Rose; Nosten, Francois; Guerin, Philippe J
Journal:
The Lancet Infectious Diseases
Abstract:
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.
Affiliation:
Epicentre, Paris, France; Epicentre, Mbarara, Uganda; Mbarara University of Science & Technology, Mbarara, Uganda; Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; INSERM UMR S945, Paris, France; Université Pierre & Marie Curie, Faculté de Médecine Pitié-Salpêtrière, Paris, France; Department of Microbiology, Imperial College NHS Trust, London, UK; Shoklo Malaria Research Unit, Mae Sot, Tak, Thailand
Issue Date:
5-Oct-2010
URI:
http://hdl.handle.net/10144/116337
DOI:
10.1016/S1473-3099(10)70202-4
PubMed ID:
20932805
Additional Links:
http://www.thelancet.com/journals/laninf/article/PIIS1473-3099%2810%2970202-4/abstract
Type:
Article
Language:
en
ISSN:
1474-4457
Appears in Collections:
Malaria

Full metadata record

DC FieldValue Language
dc.contributor.authorPiola, Patriceen
dc.contributor.authorNabasumba, Carolynen
dc.contributor.authorTuryakira, Eleanoren
dc.contributor.authorDhorda, Mehulen
dc.contributor.authorLindegardh, Niklasen
dc.contributor.authorNyehangane, Danen
dc.contributor.authorSnounou, Georgesen
dc.contributor.authorAshley, Elizabeth Aen
dc.contributor.authorMcGready, Roseen
dc.contributor.authorNosten, Francoisen
dc.contributor.authorGuerin, Philippe Jen
dc.date.accessioned2010-11-25T19:37:19Z-
dc.date.available2010-11-25T19:37:19Z-
dc.date.issued2010-10-05-
dc.identifier.citationLancet Infect Dis 2010;10(11):762-9en
dc.identifier.issn1474-4457-
dc.identifier.pmid20932805-
dc.identifier.doi10.1016/S1473-3099(10)70202-4-
dc.identifier.urihttp://hdl.handle.net/10144/116337-
dc.description.abstractBACKGROUND: 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.en
dc.languageENG-
dc.language.isoenen
dc.relation.urlhttp://www.thelancet.com/journals/laninf/article/PIIS1473-3099%2810%2970202-4/abstracten
dc.rightsPublished by Elsevier Reproduced on this site with permission of Elsevier Ltd. Please see [url]http://www.thelancet.com/journals/laninf[/url] for further relevant comment.en
dc.subject.meshMalariaen
dc.subject.meshPregnant Womenen
dc.subject.meshPregnancyen
dc.subject.meshTreatmenten
dc.subject.meshCoartemen
dc.subject.meshartemether-lumefantrine combinationen
dc.subject.meshArtemisininsen
dc.subject.meshQuinineen
dc.subject.meshAntimalarialsen
dc.subject.meshUgandaen
dc.subject.meshSub-Saharan Africaen
dc.titleEfficacy and safety of artemether-lumefantrine compared with quinine in pregnant women with uncomplicated Plasmodium falciparum malaria: an open-label, randomised, non-inferiority trialen
dc.typeArticleen
dc.contributor.departmentEpicentre, Paris, France; Epicentre, Mbarara, Uganda; Mbarara University of Science & Technology, Mbarara, Uganda; Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; INSERM UMR S945, Paris, France; Université Pierre & Marie Curie, Faculté de Médecine Pitié-Salpêtrière, Paris, France; Department of Microbiology, Imperial College NHS Trust, London, UK; Shoklo Malaria Research Unit, Mae Sot, Tak, Thailanden
dc.identifier.journalThe Lancet Infectious Diseasesen

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