Dihydroartemisinin-piperaquine and artemether-lumefantrine for treating uncomplicated malaria in African children: a randomised, non-inferiority trial
dc.contributor.author | Bassat, Quique | |
dc.contributor.author | Mulenga, Modest | |
dc.contributor.author | Tinto, Halidou | |
dc.contributor.author | Piola, Patrice | |
dc.contributor.author | Borrmann, Steffen | |
dc.contributor.author | Menéndez, Clara | |
dc.contributor.author | Nambozi, Michael | |
dc.contributor.author | Valéa, Innocent | |
dc.contributor.author | Nabasumba, Carolyn | |
dc.contributor.author | Sasi, Philip | |
dc.contributor.author | Bacchieri, Antonella | |
dc.contributor.author | Corsi, Marco | |
dc.contributor.author | Ubben, David | |
dc.contributor.author | Talisuna, Ambrose | |
dc.contributor.author | D'Alessandro, Umberto | |
dc.date.accessioned | 2010-11-09T14:46:23Z | |
dc.date.available | 2010-11-09T14:46:23Z | |
dc.date.issued | 2009-11-17 | |
dc.identifier.citation | PLoS ONE 2009;4(11):e7871 | en |
dc.identifier.issn | 1932-6203 | |
dc.identifier.pmid | 19936217 | |
dc.identifier.doi | 10.1371/journal.pone.0007871 | |
dc.identifier.uri | http://hdl.handle.net/10144/115165 | |
dc.description.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. | |
dc.language.iso | en | en |
dc.relation.url | http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007871 | en |
dc.rights | Published by Public Library of Science, [url]http://www.plosone.org/[/url] Archived on this site by Open Access permission | en |
dc.subject.mesh | Africa | en |
dc.subject.mesh | Antiparasitic Agents | en |
dc.subject.mesh | Artemisinins | en |
dc.subject.mesh | Child, Preschool | en |
dc.subject.mesh | Drug Therapy, Combination | en |
dc.subject.mesh | Ethanolamines | en |
dc.subject.mesh | Fluorenes | en |
dc.subject.mesh | Humans | en |
dc.subject.mesh | Infant | en |
dc.subject.mesh | Malaria | en |
dc.subject.mesh | Malaria, Falciparum | en |
dc.subject.mesh | Plasmodium falciparum | en |
dc.subject.mesh | Polymerase Chain Reaction | en |
dc.subject.mesh | Quinolines | en |
dc.subject.mesh | Time Factors | en |
dc.title | Dihydroartemisinin-piperaquine and artemether-lumefantrine for treating uncomplicated malaria in African children: a randomised, non-inferiority trial | en |
dc.type | Article | en |
dc.contributor.department | 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 | en |
dc.identifier.journal | PLoS ONE | en |
refterms.dateFOA | 2019-03-04T08:29:34Z | |
html.description.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. |