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

Author

Listed:
  • 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

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 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

Suggested Citation

  • Neena Valecha & Aung Pyae Phyo & Mayfong Mayxay & Paul N Newton & Srivicha Krudsood & Sommay Keomany & Maniphone Khanthavong & Tiengkham Pongvongsa & Ronnatrai Ruangveerayuth & Chirapong Uthaisil & Da, 2010. "An Open-Label, Randomised Study of Dihydroartemisinin-Piperaquine Versus Artesunate-Mefloquine for Falciparum Malaria in Asia," PLOS ONE, Public Library of Science, vol. 5(7), pages 1-13, July.
    • Handle: RePEc:plo:pone00:0011880
    DOI: 10.1371/journal.pone.0011880
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