Publication:
An open-label, randomised study of dihydroartemisinin-piperaquine versus artesunate-mefloquine for falciparum malaria in Asia

Issued Date

2010-08-20

Resource Type

Article

File Type

video/youtube

ISSN

19326203

DOI

10.1371/journal.pone.0011880

Other identifier(s)

2-s2.0-77955606614

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Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

PLoS ONE. Vol.5, No.7 (2010)

Suggested Citation

Neena Valecha, Aung Pyae Phyo, Mayfong Mayxay, Paul N. Newton, Srivicha Krudsood, Sommay Keomany, Maniphone Khanthavong, Tiengkham Pongvongsa, Ronnatrai Ruangveerayuth, Chirapong Uthaisil, David Ubben, Stephan Duparc, Antonella Bacchieri, Marco Corsi, Bappanad H.K. Rao, Prabash C. Bhattacharya, Nagesh Dubhashi, Susanta K. Ghosh, Vas Dev, Ashwani Kumar, Sasithon Pukittayakamee An open-label, randomised study of dihydroartemisinin-piperaquine versus artesunate-mefloquine for falciparum malaria in Asia. PLoS ONE. Vol.5, No.7 (2010). doi:10.1371/journal.pone.0011880 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/28469

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Title

An open-label, randomised study of dihydroartemisinin-piperaquine versus artesunate-mefloquine for falciparum malaria in Asia

Author(s)

Neena Valecha
 Aung Pyae Phyo
 Mayfong Mayxay
 Paul N. Newton
 Srivicha Krudsood
 Sommay Keomany
 Maniphone Khanthavong
 Tiengkham Pongvongsa
 Ronnatrai Ruangveerayuth
 Chirapong Uthaisil
 David Ubben
 Stephan Duparc
 Antonella Bacchieri
 Marco Corsi
 Bappanad H.K. Rao
 Prabash C. Bhattacharya
 Nagesh Dubhashi
 Susanta K. Ghosh
 Vas Dev
 Ashwani Kumar
 Sasithon Pukittayakamee

Other Contributor(s)

National Institute of Malaria Research India
 Shoklo Malaria Research Unit
 Oxford University Tropical Medicine Research Collaboration
 University of Health Sciences
 Churchill Hospital
 Mahidol University
 Salavan Provincial Hospital
 Centre of Malariology
 Savannakhet Provincial Malaria Station
 Mae Sod Hospital
 Mae Ramat Hospital
 International Center Cointrin
 Sigma-Tau S.p.A.
 Wenlock District Hospital
 Down Town Hospital
 Goa Medical College
 National Institute of Malaria Research
 National Institute of Malaria Research (Field Station) (ICMR)
 National Institute of Malaria Research Field Unit

Abstract

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% 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.

Keyword(s)

Agricultural and Biological Sciences
 Biochemistry, Genetics and Molecular Biology

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https://repository.li.mahidol.ac.th/handle/20.500.14594/28469

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Scopus 2006-2010