title: Equivalence trial of melarsoprol and nifurtimox monotherapy and combination therapy for the treatment of second-stage Trypanosoma brucei gambiense sleeping sickness.
abstract: BACKGROUND
  Treatment of second-stage sleeping sickness relies mainly on melarsoprol. Nifurtimox has been successfully used to cure melarsoprol-refractory sleeping sickness caused by Trypanosoma brucei gambiense infection.
  
  
  METHODS
  An open, randomized trial was conducted to test for equivalence between the standard melarsoprol regimen and 3 other regimens, as follows: standard melarsoprol therapy (3 series of 3.6 mg/kg/day intravenously [iv] for 3 days, with 7-day breaks between the series); 10-day incremental-dose melarsoprol therapy (0.6 mg/kg iv on day 1, 1.2 mg/kg iv on day 2, and 1.8 mg/kg iv on days 3-10); nifurtimox monotherapy for 14 days (5 mg/kg orally 3 times per day); and consecutive 10-day melarsoprol-nifurtimox combination therapy (0.6 mg/kg iv melarsoprol on day 1, 1.2 mg/kg iv melarsoprol on day 2, and 1.2 mg/kg/day iv melarsoprol combined with oral 7.5 mg/kg nifurtimox twice a day on days 3-10). Primary outcomes were relapse, severe adverse events, and death attributed to treatment.
  
  
  RESULTS
  A total of 278 patients were randomized. The frequency of adverse events was similar between the standard melarsoprol regimen and the other regimens. Encephalopathic syndromes occurred in all groups and caused all deaths that were likely due to treatment. Relapses (n=48) were observed only with the 3 monotherapy regimens.
  
  
  CONCLUSIONS
  A consecutive 10-day low-dose melarsoprol-nifurtimox combination is more effective than the standard melarsoprol regimen.
authors.affiliation: Institute of Tropical Medicine, Department of Parasitology, Antwerp, B-2000 Antwerp, Belgium.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bisser
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: N'Siesi
authors.forename: Veerle
authors.initials: V
authors.lastname: Lejon
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Preux
authors.forename: Simon
authors.initials: S
authors.lastname: Van Nieuwenhove
authors.forename: Constantin
authors.initials: C
authors.lastname: Miaka Mia Bilenge
authors.forename: Philippe
authors.initials: P
authors.lastname: Būscher
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000818:Animals; D001927:Brain Diseases / Q000139:chemically induced; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008549:Melarsoprol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009547:Nifurtimox / Q000627:therapeutic use*; D012008:Recurrence; D016896:Treatment Outcome; D014344:Trypanocidal Agents / Q000627:therapeutic use*; D014347:Trypanosoma brucei gambiense; D014353:Trypanosomiasis, African / Q000188:drug therapy*
chemical_list: D014344:Trypanocidal Agents; D009547:Nifurtimox; D008549:Melarsoprol