Neena ValechaAung Pyae PhyoMayfong MayxayPaul N. NewtonSrivicha KrudsoodSommay KeomanyManiphone KhanthavongTiengkham PongvongsaRonnatrai RuangveerayuthChirapong UthaisilDavid UbbenStephan DuparcAntonella BacchieriMarco CorsiBappanad H.K. RaoPrabash C. BhattacharyaNagesh DubhashiSusanta K. GhoshVas DevAshwani KumarSasithon PukittayakameeNational Institute of Malaria Research IndiaShoklo Malaria Research UnitOxford University Tropical Medicine Research CollaborationUniversity of Health SciencesChurchill HospitalMahidol UniversitySalavan Provincial HospitalCentre of MalariologySavannakhet Provincial Malaria StationMae Sod HospitalMae Ramat HospitalInternational Center CointrinSigma-Tau S.p.A.Wenlock District HospitalDown Town HospitalGoa Medical CollegeNational Institute of Malaria ResearchNational Institute of Malaria Research (Field Station) (ICMR)National Institute of Malaria Research Field Unit2018-09-242018-09-242010-08-20PLoS ONE. Vol.5, No.7 (2010)193262032-s2.0-77955606614https://repository.li.mahidol.ac.th/handle/20.500.14594/28469Background: 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% one sided confidence interval, CI: >-2.87%), and 98.7% and 97.0%, respectively, in the per protocol population (97.5% CI: >-0.39%). 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 multi drug 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. © 2010 Valecha et al.video/youtubeMahidol UniversityAgricultural and Biological SciencesBiochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1371/journal.pone.0011880