Safety and tolerability of adjunctive rosiglitazone treatment for children with uncomplicated malaria

Malar J. 2017 May 23;16(1):215. doi: 10.1186/s12936-017-1858-0.

Abstract

Background: Despite the widespread use and availability of rapidly acting anti-malarials, the fatality rate of severe malaria in sub-Saharan Africa remains high. Adjunctive therapies that target the host response to malaria infection may further decrease mortality over that of anti-malarial agents alone. Peroxisome proliferator-activated receptor-gamma agonists (e.g. rosiglitazone) have been shown to act on several pathways implicated in the pathogenesis of severe malaria and may improve clinical outcome as an adjunctive intervention.

Methods: In this study, the safety and tolerability of adjunctive rosiglitazone in paediatric uncomplicated malaria infection was evaluated in Mozambique, as a prelude to its evaluation in a randomized controlled trial in paediatric severe malaria. The study was a prospective, randomized, double-blind, placebo-controlled, phase IIa trial of rosiglitazone (0.045 mg/kg/dose) twice daily for 4 days versus placebo as adjunctive treatment in addition to Mozambican standard of care (artemisinin combination therapy Coartem®) in children with uncomplicated malaria. The primary outcomes were tolerability and safety, including clinical, haematological, biochemical, and electrocardiographic evaluations.

Results: Thirty children were enrolled: 20 were assigned to rosiglitazone and 10 to placebo. Rosiglitazone treatment did not induce hypoglycaemia nor significantly alter clinical, biochemical, haematological, or electrocardiographic parameters.

Conclusions: Adjunctive rosiglitazone was safe and well-tolerated in children with uncomplicated malaria, permitting the extension of its evaluation as adjunctive therapy for severe malaria. The trial is registered with Clinicaltrials.gov, NCT02694874.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Antimalarials / therapeutic use*
  • Child
  • Child, Preschool
  • Double-Blind Method
  • Female
  • Humans
  • Infant
  • Malaria / drug therapy*
  • Male
  • Mozambique
  • Rosiglitazone
  • Thiazolidinediones / therapeutic use*

Substances

  • Antimalarials
  • Thiazolidinediones
  • Rosiglitazone

Associated data

  • ClinicalTrials.gov/NCT02694874

Grants and funding