Equivalence trial of melarsoprol and nifurtimox monotherapy and combination therapy for the treatment of second-stage Trypanosoma brucei gambiense sleeping sickness.
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.
Bisser
Sylvie
S
Institute of Tropical Medicine, Department of Parasitology, Antwerp, B-2000 Antwerp, Belgium.
N'Siesi
François-Xavier
FX
Lejon
Veerle
V
Preux
Pierre-Marie
PM
Van Nieuwenhove
Simon
S
Miaka Mia Bilenge
Constantin
C
Būscher
Philippe
P
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*
D014344:Trypanocidal Agents; D009547:Nifurtimox; D008549:Melarsoprol