Efficacy and safety of a fixed dose artesunate-sulphamethoxypyrazine-pyrimethamine compared to artemether-lumefantrine for the treatment of uncomplicated falciparum malaria across Africa: a randomized multi-centre trial

Malar J. 2009 Apr 14:8:63. doi: 10.1186/1475-2875-8-63.

Abstract

Background: The efficacy of artemisinin-based combination therapy has already been demonstrated in a number of studies all over the world, and some of them can be regarded as comparably effective. Ease of administration of anti-malarial treatments with shorter courses and fewer tablets may be key determinant of compliance.

Methods: Patients with uncomplicated falciparum malaria and over six months of age were recruited in Cameroon, Mali, Rwanda and Sudan. 1,384 patients were randomly assigned to receive artesunate-sulphamethoxypyrazine-pyrimethamine (AS-SMP) three-day (once daily for 3 days) regimen (N = 476) or AS-SMP 24-hour (0 h, 12 h, 24 h) regimen (N = 458) or artemether-lumefantrine (AL), the regular 6 doses regimen (N = 450). The primary objective was to demonstrate non-inferiority (using a margin of -6%) of AS-SMP 24 hours or AS-SMP three days versus AL on the PCR-corrected 28-day cure rate.

Results: The PCR corrected 28-day cure rate on the intention to treat (ITT) analysis population were: 96.0%(457/476) in the AS-SMP three-day group, 93.7%(429/458) in the AS-SMP 24-hour group and 92.0%(414/450) in the AL group. Likewise, the cure rates on the PP analysis population were high: 99.3%(432/437) in the AS-SMP three-day group, 99.5%(416/419) in the AS-SMP 24-hour group and 99.7(391/394)% in the AL group. Most common drug-related adverse events were gastrointestinal symptoms (such as vomiting and diarrhea) which were slightly higher in the AS-SMP 24-hour group.

Conclusion: AS-SMP three days or AS-SMP 24 hours are safe, are as efficacious as AL, and are well tolerated.

Trial registration: NCT00484900 http://www.clinicaltrials.gov.

Publication types

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

MeSH terms

  • Animals
  • Antimalarials / administration & dosage
  • Antimalarials / adverse effects
  • Antimalarials / therapeutic use*
  • Artemether, Lumefantrine Drug Combination
  • Artemisinins / administration & dosage
  • Artemisinins / adverse effects
  • Artemisinins / therapeutic use*
  • Artesunate
  • Child
  • Child, Preschool
  • Drug Administration Schedule
  • Drug Combinations
  • Drug Therapy, Combination
  • Ethanolamines / administration & dosage
  • Ethanolamines / adverse effects
  • Ethanolamines / therapeutic use*
  • Female
  • Fluorenes / administration & dosage
  • Fluorenes / adverse effects
  • Fluorenes / therapeutic use*
  • Humans
  • Infant
  • Malaria, Falciparum / drug therapy*
  • Malaria, Falciparum / epidemiology
  • Male
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / isolation & purification
  • Pregnancy
  • Prospective Studies
  • Pyrimethamine / administration & dosage
  • Pyrimethamine / adverse effects
  • Pyrimethamine / therapeutic use*
  • Sulfalene / administration & dosage
  • Sulfalene / adverse effects
  • Sulfalene / therapeutic use*
  • Tablets
  • Treatment Outcome

Substances

  • Antimalarials
  • Artemether, Lumefantrine Drug Combination
  • Artemisinins
  • Drug Combinations
  • Ethanolamines
  • Fluorenes
  • Tablets
  • Artesunate
  • Sulfalene
  • Pyrimethamine

Associated data

  • ClinicalTrials.gov/NCT00484900