Dihydroartemisinin-piperaquine and artemether-lumefantrine for treating uncomplicated malaria in African children: a randomised, non-inferiority trial

Hdl Handle:
http://hdl.handle.net/10144/115165
Title:
Dihydroartemisinin-piperaquine and artemether-lumefantrine for treating uncomplicated malaria in African children: a randomised, non-inferiority trial
Authors:
Bassat, Quique; Mulenga, Modest; Tinto, Halidou; Piola, Patrice; Borrmann, Steffen; Menéndez, Clara; Nambozi, Michael; Valéa, Innocent; Nabasumba, Carolyn; Sasi, Philip; Bacchieri, Antonella; Corsi, Marco; Ubben, David; Talisuna, Ambrose; D'Alessandro, Umberto
Journal:
PLoS ONE
Abstract:
BACKGROUND: Artemisinin combination therapies (ACTs) are currently the preferred option for treating uncomplicated malaria. Dihydroartemisinin-piperaquine (DHA-PQP) is a promising fixed-dose ACT with limited information on its safety and efficacy in African children. METHODOLOGY/PRINCIPAL FINDINGS: The non-inferiority of DHA-PQP versus artemether-lumefantrine (AL) in children 6-59 months old with uncomplicated P. falciparum malaria was tested in five African countries (Burkina Faso, Kenya, Mozambique, Uganda and Zambia). Patients were randomised (2:1) to receive either DHA-PQP or AL. Non-inferiority was assessed using a margin of -5% for the lower limit of the one-sided 97.5% confidence interval on the treatment difference (DHA-PQP vs. AL) of the day 28 polymerase chain reaction (PCR) corrected cure rate. Efficacy analysis was performed in several populations, and two of them are presented here: intention-to-treat (ITT) and enlarged per-protocol (ePP). 1553 children were randomised, 1039 receiving DHA-PQP and 514 AL. The PCR-corrected day 28 cure rate was 90.4% (ITT) and 94.7% (ePP) in the DHA-PQP group, and 90.0% (ITT) and 95.3% (ePP) in the AL group. The lower limits of the one-sided 97.5% CI of the difference between the two treatments were -2.80% and -2.96%, in the ITT and ePP populations, respectively. In the ITT population, the Kaplan-Meier estimate of the proportion of new infections up to Day 42 was 13.55% (95% CI: 11.35%-15.76%) for DHA-PQP vs 24.00% (95% CI: 20.11%-27.88%) for AL (p<0.0001). CONCLUSIONS/SIGNIFICANCE: DHA-PQP is as efficacious as AL in treating uncomplicated malaria in African children from different endemicity settings, and shows a comparable safety profile. The occurrence of new infections within the 42-day follow up was significantly lower in the DHA-PQP group, indicating a longer post-treatment prophylactic effect. TRIAL REGISTRATION: Controlled-trials.com ISRCTN16263443.
Affiliation:
Barcelona Centre for International Health Research (CRESIB), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain; Manhiça Health Research Centre (CISM), Manhiça, Mozambique; Tropical Disease Research Centre, Ndola, Zambia; Centre Muraz, Bobo-Dioulasso, Burkina Faso, IRSS/DRO, Bobo-Dioulasso, Burkina Faso; Epicentre/MSF, Mbarara, Uganda; Kenya Medical Research Institute, Kilifi, Kenya; University of Heidelberg, Heidelberg, Germany; Department of Clinical Pharmacology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; Sigma Tau Industrie Farmaceutiche Riunite, Pomezia, Rome, Italy; Medicines for Malaria Venture, Geneva, Switzerland; Prince Leopold Institute of Tropical Medicine, Antwerp, Belgium
Issue Date:
17-Nov-2009
URI:
http://hdl.handle.net/10144/115165
DOI:
10.1371/journal.pone.0007871
PubMed ID:
19936217
Additional Links:
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007871
Type:
Article
Language:
en
ISSN:
1932-6203
Appears in Collections:
Malaria

Full metadata record

DC FieldValue Language
dc.contributor.authorBassat, Quiqueen
dc.contributor.authorMulenga, Modesten
dc.contributor.authorTinto, Halidouen
dc.contributor.authorPiola, Patriceen
dc.contributor.authorBorrmann, Steffenen
dc.contributor.authorMenéndez, Claraen
dc.contributor.authorNambozi, Michaelen
dc.contributor.authorValéa, Innocenten
dc.contributor.authorNabasumba, Carolynen
dc.contributor.authorSasi, Philipen
dc.contributor.authorBacchieri, Antonellaen
dc.contributor.authorCorsi, Marcoen
dc.contributor.authorUbben, Daviden
dc.contributor.authorTalisuna, Ambroseen
dc.contributor.authorD'Alessandro, Umbertoen
dc.date.accessioned2010-11-09T14:46:23Z-
dc.date.available2010-11-09T14:46:23Z-
dc.date.issued2009-11-17-
dc.identifier.citationPLoS ONE 2009;4(11):e7871en
dc.identifier.issn1932-6203-
dc.identifier.pmid19936217-
dc.identifier.doi10.1371/journal.pone.0007871-
dc.identifier.urihttp://hdl.handle.net/10144/115165-
dc.description.abstractBACKGROUND: Artemisinin combination therapies (ACTs) are currently the preferred option for treating uncomplicated malaria. Dihydroartemisinin-piperaquine (DHA-PQP) is a promising fixed-dose ACT with limited information on its safety and efficacy in African children. METHODOLOGY/PRINCIPAL FINDINGS: The non-inferiority of DHA-PQP versus artemether-lumefantrine (AL) in children 6-59 months old with uncomplicated P. falciparum malaria was tested in five African countries (Burkina Faso, Kenya, Mozambique, Uganda and Zambia). Patients were randomised (2:1) to receive either DHA-PQP or AL. Non-inferiority was assessed using a margin of -5% for the lower limit of the one-sided 97.5% confidence interval on the treatment difference (DHA-PQP vs. AL) of the day 28 polymerase chain reaction (PCR) corrected cure rate. Efficacy analysis was performed in several populations, and two of them are presented here: intention-to-treat (ITT) and enlarged per-protocol (ePP). 1553 children were randomised, 1039 receiving DHA-PQP and 514 AL. The PCR-corrected day 28 cure rate was 90.4% (ITT) and 94.7% (ePP) in the DHA-PQP group, and 90.0% (ITT) and 95.3% (ePP) in the AL group. The lower limits of the one-sided 97.5% CI of the difference between the two treatments were -2.80% and -2.96%, in the ITT and ePP populations, respectively. In the ITT population, the Kaplan-Meier estimate of the proportion of new infections up to Day 42 was 13.55% (95% CI: 11.35%-15.76%) for DHA-PQP vs 24.00% (95% CI: 20.11%-27.88%) for AL (p<0.0001). CONCLUSIONS/SIGNIFICANCE: DHA-PQP is as efficacious as AL in treating uncomplicated malaria in African children from different endemicity settings, and shows a comparable safety profile. The occurrence of new infections within the 42-day follow up was significantly lower in the DHA-PQP group, indicating a longer post-treatment prophylactic effect. TRIAL REGISTRATION: Controlled-trials.com ISRCTN16263443.en
dc.language.isoenen
dc.relation.urlhttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007871en
dc.rightsPublished by Public Library of Science, [url]http://www.plosone.org/[/url] Archived on this site by Open Access permissionen
dc.subject.meshAfricaen
dc.subject.meshAntiparasitic Agentsen
dc.subject.meshArtemisininsen
dc.subject.meshChild, Preschoolen
dc.subject.meshDrug Therapy, Combinationen
dc.subject.meshEthanolaminesen
dc.subject.meshFluorenesen
dc.subject.meshHumansen
dc.subject.meshInfanten
dc.subject.meshMalariaen
dc.subject.meshMalaria, Falciparumen
dc.subject.meshPlasmodium falciparumen
dc.subject.meshPolymerase Chain Reactionen
dc.subject.meshQuinolinesen
dc.subject.meshTime Factorsen
dc.titleDihydroartemisinin-piperaquine and artemether-lumefantrine for treating uncomplicated malaria in African children: a randomised, non-inferiority trialen
dc.typeArticleen
dc.contributor.departmentBarcelona Centre for International Health Research (CRESIB), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain; Manhiça Health Research Centre (CISM), Manhiça, Mozambique; Tropical Disease Research Centre, Ndola, Zambia; Centre Muraz, Bobo-Dioulasso, Burkina Faso, IRSS/DRO, Bobo-Dioulasso, Burkina Faso; Epicentre/MSF, Mbarara, Uganda; Kenya Medical Research Institute, Kilifi, Kenya; University of Heidelberg, Heidelberg, Germany; Department of Clinical Pharmacology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; Sigma Tau Industrie Farmaceutiche Riunite, Pomezia, Rome, Italy; Medicines for Malaria Venture, Geneva, Switzerland; Prince Leopold Institute of Tropical Medicine, Antwerp, Belgiumen
dc.identifier.journalPLoS ONEen

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