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Randomized Controlled Trial
. 2009 Nov 17;4(11):e7871.
doi: 10.1371/journal.pone.0007871.

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

Quique Bassat  1 , Modest Mulenga, Halidou Tinto, Patrice Piola, Steffen Borrmann, Clara Menéndez, Michael Nambozi, Innocent Valéa, Carolyn Nabasumba, Philip Sasi, Antonella Bacchieri, Marco Corsi, David Ubben, Ambrose Talisuna, Umberto D'Alessandro
Affiliations
Randomized Controlled Trial

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

Quique Bassat et al. 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.

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Conflict of interest statement

Competing Interests: David Ubben is an employee of Medicines for Malaria Venture. Ambrose Talisuna is now an employee of Medicines for Malaria Venture but at the time the study was conducted he was employed by the Institute of Tropical Medicine, Antwerp. Antonella Bacchieri and Marco Corsi are employees of Sigma-Tau. Umberto D'Alessandro has received additional research funds from Sigma Tau. The study was supported by funds from the Medicines for Malaria Venture and sponsored by Sigma-Tau I.F.R. SpA (Rome). Employees of Sigma-Tau participated in study design, data entry, collection and analysis of data. Medicines for Malaria Venture employees contributed to the preparation of the manuscript. An author independent of the sponsor, Umberto D'Alessandro, had access to the primary dataset and takes responsibility for the analyses and manuscript as a whole.

Figures

Figure 1
Figure 1. Trial profile.
Figure 2
Figure 2. PCR-corrected Adequate Clinical and Parasitological Response (ACPR) (ePP population) by country and by time point.
Figure 3
Figure 3. Kaplan Meier curve showing the cumulative proportion until day 42 of children with new infections (ITT population).
See this image and copyright information in PMC

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