Correction: An Open-Label, Randomised Study of Dihydroartemisinin-Piperaquine Versus Artesunate-Mefloquine for Falciparum Malaria in Asia

Background: The artemisinin-based combination treatment (ACT) of dihydroartemisinin (DHA) and piperaquine (PQP) is a promising novel anti-malarial drug effective against multi-drug resistant falciparum malaria. The aim of this study was to show non-inferiority of DHA/PQP vs. artesunate-mefloquine (AS+MQ) in Asia. Methods and Findings: This was an open-label, randomised, non-inferiority, 63-day follow-up study conducted in Thailand, Laos and India. Patients aged 3 months to 65 years with Plasmodium falciparum mono-infection or mixed infection were randomised with an allocation ratio of 2:1 to a fixed-dose DHA/PQP combination tablet (adults: 40 mg/160 mg; children: 20 mg/320 mg; n = 769) or loose combination of AS+MQ (AS: 50 mg, MQ: 250 mg; n = 381). The cumulative doses of study treatment over the 3 days were of about 6.75 mg/kg of DHA and 54 mg/kg of PQP and about 12 mg/kg of AS and 25 mg/kg of MQ. Doses were rounded up to the nearest half tablet. The primary endpoint was day-63 polymerase chain reaction (PCR) genotype-corrected cure rate. Results were 87.9% for DHA/PQP and 86.6% for AS+MQ in the intention-to-treat (ITT; 97.5% onesided confidence interval, CI: .22.87%), and 98.7% and 97.0%, respectively, in the per protocol population (97.5% CI: .20.39%). No country effect was observed. Kaplan-Meier estimates of proportions of patients with new infections on day 63 (secondary endpoint) were significantly lower for DHA/PQP than AS+MQ: 22.7% versus 30.3% (p = 0.0042; ITT). Overall gametocyte prevalence (days 7 to 63; secondary endpoint), measured as person-gametocyte-weeks, was significantly higher for DHA/PQP than AS+MQ (10.15% versus 4.88%; p = 0.003; ITT). Fifteen serious adverse events were reported, 12 (1.6%) in DHA/ PQP and three (0.8%) in AS+MQ, among which six (0.8%) were considered related to DHA/PQP and three (0.8%) to AS+MQ. Conclusions: DHA/PQP was a highly efficacious drug for P. falciparum malaria in areas where multidrug parasites are prevalent. The DHA/PQP combination can play an important role in the first-line treatment of uncomplicated falciparum malaria. Trial Registration: Controlled-Trials.com ISRCTN81306618 Citation: Valecha N, Phyo AP, Mayxay M, Newton PN, Krudsood S, et al. (2010) An Open-Label, Randomised Study of Dihydroartemisinin-Piperaquine Versus Artesunate-Mefloquine for Falciparum Malaria in Asia. PLoS ONE 5(7): e11880. doi:10.1371/journal.pone. 0011880 Editor: David Joseph Diemert, The George Washington University Medical Center, United States of America Received June 19, 2009; Accepted May 26, 2010; Published July 30, 2010 Copyright: 2010 Valecha et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: The development of DHA-PQP was undertaken by a public-private partnership that operated within a development agreement between the Medicines for Malaria Venture and Sigma Tau. Oxford University also joined the development team as academic partners. Dr Justin Cook was funded by Medicines for Malaria Venture. Role of the funding source: A committee representing members of the DHA-PQP Joint Development Team and study site Principal Investigators developed the protocol. Sigma Tau conducted the study, collected and analysed data. All authors had access to the primary data and take responsibility for data reporting accuracy and completeness. The corresponding author had responsibility for the final decision to submit for publication. Competing Interests: The authors declare no conflict of interest other than M Corsi and A Bacchieri who are employed by Sigma Tau and D Ubben and S Duparc who are employed by the Medicines for Malaria Venture as stated in the affiliations. * E-mail: neenavalecha@gmail.com PLoS ONE | www.plosone. org 1 July 2010 | Volume 5 | Issue 7 | e11880