Randomized, controlled dose-optimization studies of dihydroartemisinin-piperaquine for the treatment of uncomplicated multidrug-resistant falciparum malaria in Thailand

J Infect Dis. 2004 Nov 15;190(10):1773-82. doi: 10.1086/425015. Epub 2004 Oct 18.

Abstract

Background: Dihydroartemisinin-piperaquine (DP) is a new and relatively inexpensive artemisinin-containing fixed-combination antimalarial treatment. An adult treatment course contained 6.4 mg/kg dihydroartemisinin (DHA), which is >40% lower than the level in most artemisinin-containing combinations. This raised the possibility that the efficacy of the current coformulation may not be optimal in the treatment of multidrug-resistant falciparum malaria.

Methods: In 2 large randomized, controlled studies in Thailand, the recommended dose of DP was compared with a regimen with additional artemisinin derivative (12 mg/kg; DP+) and with mefloquine plus artesunate (MAS3).

Results: A total of 731 patients were included: 201 in a hospital-based study and 530 in a community study. Day-28 cure rates in the hospital-based study were 100% (95% confidence interval [CI], 93.9%-100%) in the MAS3 and DP+ groups and 98.3% (95% CI, 91%-99.7%) in the DP group, with a single recrudescence on day 21. In the community study, polymerase chain reaction genotyping-adjusted cure rates on day 63 were 96.1% (95% CI, 92.6%-99.7%) in the DP group, 98.3% (95% CI, 96.1%-100%) in the DP+ group, and 94.9% (95% CI, 91.2%-98.6%) in the MAS3 group (P=.2). Adverse events were few, with an excess of mild abdominal pain in the DP group.

Conclusions: The current dosage of DP (6.4 mg/kg DHA and 51.2 mg/kg piperaquine phosphate) given over the course of 48 h is highly effective, safe, and well tolerated for the treatment of multidrug-resistant falciparum malaria, and its efficacy is not improved by the addition of more DHA.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Antimalarials / administration & dosage*
  • Antimalarials / adverse effects
  • Antimalarials / therapeutic use
  • Artemisinins / administration & dosage*
  • Artemisinins / adverse effects
  • Artemisinins / therapeutic use
  • Artesunate
  • Child
  • Child, Preschool
  • Drug Combinations
  • Drug Resistance, Multiple
  • Drug Therapy, Combination
  • Female
  • Humans
  • Infant
  • Malaria, Falciparum / drug therapy*
  • Malaria, Falciparum / parasitology
  • Male
  • Mefloquine / administration & dosage
  • Mefloquine / adverse effects
  • Mefloquine / therapeutic use
  • Middle Aged
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / growth & development
  • Plasmodium falciparum / isolation & purification
  • Quinolines / administration & dosage*
  • Quinolines / adverse effects
  • Quinolines / therapeutic use
  • Sesquiterpenes / administration & dosage*
  • Sesquiterpenes / adverse effects
  • Sesquiterpenes / therapeutic use
  • Thailand

Substances

  • Antimalarials
  • Artemisinins
  • Drug Combinations
  • Quinolines
  • Sesquiterpenes
  • Artesunate
  • dihydroartemisinin
  • piperaquine
  • Mefloquine