A Phase III, Randomized, Non-Inferiority Trial to Assess the Efficacy and Safety of Dihydroartemisinin-Piperaquine in Comparison with Artesunate-Mefloquine in Patients with Uncomplicated Plasmodium falciparum Malaria in Southern Laos

Mayfong Mayxay Wellcome Trust, Mahosot Hospital, Oxford University Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Laos; Faculty of Postgraduate Studies, University of Health Sciences, Vientiane, Laos; Salavan Provincial Hospital, Salavan Province, Laos; Centre of Malariology, Parasitology and Entomology, Vientiane, Laos; Phalanxay District Clinic, Savannakhet Province, Laos; Savannakhet Provincial Malaria Station, Savannakhet Province, Laos; Medicines for Malaria Venture, Geneva, Switzerland; Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, University of Oxford, Oxford, United Kingdom; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; National Institute of Malaria Research, Delhi, India

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Sommay Keomany Wellcome Trust, Mahosot Hospital, Oxford University Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Laos; Faculty of Postgraduate Studies, University of Health Sciences, Vientiane, Laos; Salavan Provincial Hospital, Salavan Province, Laos; Centre of Malariology, Parasitology and Entomology, Vientiane, Laos; Phalanxay District Clinic, Savannakhet Province, Laos; Savannakhet Provincial Malaria Station, Savannakhet Province, Laos; Medicines for Malaria Venture, Geneva, Switzerland; Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, University of Oxford, Oxford, United Kingdom; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; National Institute of Malaria Research, Delhi, India

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Maniphone Khanthavong Wellcome Trust, Mahosot Hospital, Oxford University Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Laos; Faculty of Postgraduate Studies, University of Health Sciences, Vientiane, Laos; Salavan Provincial Hospital, Salavan Province, Laos; Centre of Malariology, Parasitology and Entomology, Vientiane, Laos; Phalanxay District Clinic, Savannakhet Province, Laos; Savannakhet Provincial Malaria Station, Savannakhet Province, Laos; Medicines for Malaria Venture, Geneva, Switzerland; Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, University of Oxford, Oxford, United Kingdom; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; National Institute of Malaria Research, Delhi, India

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Phoutthalavanh Souvannasing Wellcome Trust, Mahosot Hospital, Oxford University Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Laos; Faculty of Postgraduate Studies, University of Health Sciences, Vientiane, Laos; Salavan Provincial Hospital, Salavan Province, Laos; Centre of Malariology, Parasitology and Entomology, Vientiane, Laos; Phalanxay District Clinic, Savannakhet Province, Laos; Savannakhet Provincial Malaria Station, Savannakhet Province, Laos; Medicines for Malaria Venture, Geneva, Switzerland; Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, University of Oxford, Oxford, United Kingdom; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; National Institute of Malaria Research, Delhi, India

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Kasia Stepniewska Wellcome Trust, Mahosot Hospital, Oxford University Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Laos; Faculty of Postgraduate Studies, University of Health Sciences, Vientiane, Laos; Salavan Provincial Hospital, Salavan Province, Laos; Centre of Malariology, Parasitology and Entomology, Vientiane, Laos; Phalanxay District Clinic, Savannakhet Province, Laos; Savannakhet Provincial Malaria Station, Savannakhet Province, Laos; Medicines for Malaria Venture, Geneva, Switzerland; Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, University of Oxford, Oxford, United Kingdom; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; National Institute of Malaria Research, Delhi, India

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Tiengthong Khomthilath Wellcome Trust, Mahosot Hospital, Oxford University Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Laos; Faculty of Postgraduate Studies, University of Health Sciences, Vientiane, Laos; Salavan Provincial Hospital, Salavan Province, Laos; Centre of Malariology, Parasitology and Entomology, Vientiane, Laos; Phalanxay District Clinic, Savannakhet Province, Laos; Savannakhet Provincial Malaria Station, Savannakhet Province, Laos; Medicines for Malaria Venture, Geneva, Switzerland; Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, University of Oxford, Oxford, United Kingdom; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; National Institute of Malaria Research, Delhi, India

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Siamphay Keola Wellcome Trust, Mahosot Hospital, Oxford University Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Laos; Faculty of Postgraduate Studies, University of Health Sciences, Vientiane, Laos; Salavan Provincial Hospital, Salavan Province, Laos; Centre of Malariology, Parasitology and Entomology, Vientiane, Laos; Phalanxay District Clinic, Savannakhet Province, Laos; Savannakhet Provincial Malaria Station, Savannakhet Province, Laos; Medicines for Malaria Venture, Geneva, Switzerland; Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, University of Oxford, Oxford, United Kingdom; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; National Institute of Malaria Research, Delhi, India

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Tiengkham Pongvongsa Wellcome Trust, Mahosot Hospital, Oxford University Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Laos; Faculty of Postgraduate Studies, University of Health Sciences, Vientiane, Laos; Salavan Provincial Hospital, Salavan Province, Laos; Centre of Malariology, Parasitology and Entomology, Vientiane, Laos; Phalanxay District Clinic, Savannakhet Province, Laos; Savannakhet Provincial Malaria Station, Savannakhet Province, Laos; Medicines for Malaria Venture, Geneva, Switzerland; Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, University of Oxford, Oxford, United Kingdom; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; National Institute of Malaria Research, Delhi, India

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Samlane Phompida Wellcome Trust, Mahosot Hospital, Oxford University Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Laos; Faculty of Postgraduate Studies, University of Health Sciences, Vientiane, Laos; Salavan Provincial Hospital, Salavan Province, Laos; Centre of Malariology, Parasitology and Entomology, Vientiane, Laos; Phalanxay District Clinic, Savannakhet Province, Laos; Savannakhet Provincial Malaria Station, Savannakhet Province, Laos; Medicines for Malaria Venture, Geneva, Switzerland; Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, University of Oxford, Oxford, United Kingdom; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; National Institute of Malaria Research, Delhi, India

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David Ubben Wellcome Trust, Mahosot Hospital, Oxford University Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Laos; Faculty of Postgraduate Studies, University of Health Sciences, Vientiane, Laos; Salavan Provincial Hospital, Salavan Province, Laos; Centre of Malariology, Parasitology and Entomology, Vientiane, Laos; Phalanxay District Clinic, Savannakhet Province, Laos; Savannakhet Provincial Malaria Station, Savannakhet Province, Laos; Medicines for Malaria Venture, Geneva, Switzerland; Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, University of Oxford, Oxford, United Kingdom; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; National Institute of Malaria Research, Delhi, India

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Neena Valecha Wellcome Trust, Mahosot Hospital, Oxford University Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Laos; Faculty of Postgraduate Studies, University of Health Sciences, Vientiane, Laos; Salavan Provincial Hospital, Salavan Province, Laos; Centre of Malariology, Parasitology and Entomology, Vientiane, Laos; Phalanxay District Clinic, Savannakhet Province, Laos; Savannakhet Provincial Malaria Station, Savannakhet Province, Laos; Medicines for Malaria Venture, Geneva, Switzerland; Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, University of Oxford, Oxford, United Kingdom; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; National Institute of Malaria Research, Delhi, India

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Nicholas J. White Wellcome Trust, Mahosot Hospital, Oxford University Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Laos; Faculty of Postgraduate Studies, University of Health Sciences, Vientiane, Laos; Salavan Provincial Hospital, Salavan Province, Laos; Centre of Malariology, Parasitology and Entomology, Vientiane, Laos; Phalanxay District Clinic, Savannakhet Province, Laos; Savannakhet Provincial Malaria Station, Savannakhet Province, Laos; Medicines for Malaria Venture, Geneva, Switzerland; Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, University of Oxford, Oxford, United Kingdom; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; National Institute of Malaria Research, Delhi, India

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Paul N. Newton Wellcome Trust, Mahosot Hospital, Oxford University Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Laos; Faculty of Postgraduate Studies, University of Health Sciences, Vientiane, Laos; Salavan Provincial Hospital, Salavan Province, Laos; Centre of Malariology, Parasitology and Entomology, Vientiane, Laos; Phalanxay District Clinic, Savannakhet Province, Laos; Savannakhet Provincial Malaria Station, Savannakhet Province, Laos; Medicines for Malaria Venture, Geneva, Switzerland; Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, University of Oxford, Oxford, United Kingdom; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; National Institute of Malaria Research, Delhi, India

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We conducted an open, randomized clinical trial of oral dihydroartemisinin-piperaquine (DP) versus artesunate-mefloquine (AM) in 300 patients in Laos with uncomplicated Plasmodium falciparum malaria as part of a multicentre study in Asia. Survival analysis and adjustment for re-infection showed that the 63-day cure rates (95% confidence interval [CI]) were 100% for AM and 99.5% (96.4–99.8%) for DP. The 63-day cure rates per protocol were 99% (97 of 98) for AM and 99.5% (196 of 197) for DP (P = 0.55). The difference (AM minus DP) in cure rates (95% CI) was −0.5% (−5.1 to 2.0%), which is within the 5% non-inferiority margin. The median fever and parasite clearance times were also similar for AM and DP. The proportion of patients with at least one recorded potential adverse event was significantly higher in the AM group (38 of 87, 44%) than in the DP group (57 of 182, 31%) (relative risk = 0.6, 95% CI = 0.4–0.9; P = 0.04). Dihydroartemisinin-piperaquine is not inferior to AM in the treatment of uncomplicated P. falciparum malaria in Laos and is associated with fewer adverse effects. The results of this study were similar to those of the larger multicentre study.

Author Notes

*Address correspondence to Mayfong Mayxay, Microbiology Laboratory, Mahosot Hospital, Vientiane, Laos. E-mail: mayfong@tropmedres.ac

Financial support: This study was supported by the MMV and the Wellcome Trust of Great Britain.

Authors' addresses: Mayfong Mayxay, Wellcome Trust–Mahosot Hospital–Oxford Tropical Medicine Research Collaboration, Mahosot Hospital, Mahosot Road, Vientiane, Laos, Faculty of Postgraduate Studies, University of Health Sciences, Vientiane, Laos, and Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford OX3 7LJ, United Kingdom, E-mail: mayfong@tropmedres.ac. Sommay Keomany and Phoutthalavanh Souvannasing, Salavan Provincial Hospital, Salavan Province, Laos. Maniphone Khanthavong and Samlane Phompida, Centre of Malariology, Parasitology and Entomology, Vientiane, Laos, E-mail: cmpe@laotel.com. Kasia Stepniewska, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford OX3 7LJ, United Kingdom and Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. Tiengthong Khomthilath, Faculty of Postgraduate Studies, University of Health Sciences, Vientiane, Laos. Siamphay Keola, Phalanxay District Clinic, Savannakhet Province, Laos. Tiengkham Pongvongsa, Savannakhet Provincial Malaria Station, Savannakhet Province, Laos, E-mail: tpongvongsa@hotmail.com. David Ubben, Medicine for Malaria Venture, Geneva, Switzerland, E-mail: ubbend@mmv.org. Neena Valecha, National Institute of Malaria Research, 22-Sham NathMarg, Delhi-110 054, India, E-mail: neenavalecha@gmail.com. Nicholas J. White, Wellcome Trust–Mahosot Hospital–Oxford Tropical Medicine Research Collaboration, Mahosot Hospital, Mahosot Road, Vientiane, Laos, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford OX3 7LJ, United Kingdom, and Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand, 420/6 Rajvithi Road, Bangkok, 10400, Thailand, E-mail: nickw@tropmedres.ac. Paul N. Newton, Wellcome Trust–Mahosot Hospital–Oxford Tropical Medicine Research Collaboration, Mahosot Hospital, Mahosot Road, Vientiane, Laos and Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford OX3 7LJ, United Kingdom, E-mail: paul@tropmedres.ac.

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