A simplified intravenous artesunate regimen for severe malaria

J Infect Dis. 2012 Jan 15;205(2):312-9. doi: 10.1093/infdis/jir724. Epub 2011 Dec 15.

Abstract

Background: We compared a conventional empirically derived regimen with a simplified regimen for parenteral artesunate in severe malaria.

Methods: This was a randomized, double-blind, placebo-controlled comparison to assess the noninferiority of a simplified 3-dose regimen (given at 0, 24, and 48 hours) compared with the conventional 5-dose regimen of intravenous artesunate (given at 0, 12, 24, 48, and 72 hours) in African children with Plasmodium falciparum malaria with a prespecified delta of 0.2. The total dose of artesunate in each group was 12 mg/kg. The primary end point was the proportion of children clearing ≥ 99% of their admission parasitemia at 24 hours. Safety data, secondary efficacy end points, and pharmacokinetics were also analyzed.

Results: In 171 children (per protocol), 78% of the recipients (95% confidence interval [CI], 69%-87%) in the 3-dose group achieved ≥ 99% parasite clearance 24 hours after the start of treatment, compared with 85% (95% CI, 77%-93%) of those receiving the conventional regimen (treatment difference, -7.2%; 95% CI, -18.9% to 4.4%). Dihydroartemisinin was cleared slightly more slowly in those children receiving the higher 3-dose regimen (7.4 vs 8.8 L/h for a 13-kg child; P 5 .008).

Conclusions: Pharmacodynamic analysis suggests that 3 doses of artesunate were not inferior to 5 doses for the treatment of severe malaria in children.

Clinical trials registration: NCT00522132.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimalarials / administration & dosage*
  • Antimalarials / adverse effects
  • Antimalarials / pharmacokinetics
  • Artemisinins / administration & dosage*
  • Artemisinins / adverse effects
  • Artemisinins / blood
  • Artemisinins / pharmacokinetics
  • Artesunate
  • Child
  • Child, Preschool
  • Double-Blind Method
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Malaria, Falciparum / blood
  • Malaria, Falciparum / drug therapy*
  • Male
  • Parasite Load*
  • Parasitemia / drug therapy
  • Time Factors
  • Treatment Outcome

Substances

  • Antimalarials
  • Artemisinins
  • Artesunate
  • artenimol

Associated data

  • ClinicalTrials.gov/NCT00522132