Short-course eflornithine in Gambian trypanosomiasis: a multicentre randomized controlled trial

Objective A randomized controlled trial was conducted to determine whether 7 days of intravenous eflornithine (100 mg/kg every 6 h) was as effective a s the standard 14-day regimen in the treatment of late-stage Trypanosoma br ucei gambiense trypanosomiasis. Methods A total of 321 patients (274 new cases, 47 relapsing cases) were ra ndomized at four participating centres in Congo, Cote d'lvoire, the Democra tic Republic of the Congo, and Uganda to one of these treatment regimens an d followed up for 2 years. Results Six patients died during treatment, one of whom was on the 7-day re gimen, whereas the other five had been on the 14-day regimen (P = 0.2). The response to eflornithine differed markedly between Uganda and other countr ies. Among new cases in Uganda, the 2-year probability of cure was 73% on t he 14-day course compared with 62% on the 7-day regimen (hazard ratio (HR) for treatment failure, 7-day versus 14-day regimen: 1.45, 95% CI: 0.7, 3.1, P = 0.3). Among new cases in Cote d'lvoire, Congo, and the Democratic Repu blic of the Congo combined, the 2-year probability of cure was 97% on the 1 4-day course compared with 86.5% on the 7-day regimen (HR for treatment fai lure, 7-day vs 14-day. 6.72, 95% confidence interval (CI): 1.5, 31.0, P = 0 .003). Among relapsing cases in all four countries, the 2-year probability of cure was 94% with 7 days and 100% with 14 days of treatment. Factors ass ociated with a higher risk of treatment failure were: a positive lymph node aspirate (HR 4.1, 95% CI: 1.8-9.4), a cerebrospinal fluid (CSF) white cell count greater than or equal to 100/mm(3) (HR 3.5; 95% CI: 1.1-10.9), being treated in Uganda (HR 2.9; 95% CI: 1.4-5.9), and CSF trypanosomes (HR 1.9; 95% CI : 0.9-4.1). Being stuporous on admission was associated with a lowe r risk of treatment failure (HR 0.18; 95% CI: 0.02-1.4) as was increasing a ge (HR 0.977; 95% CI: 0.95-1.0, for each additional year of age). Discussion The 7-day course of eflornithine is an effective treatment of re lapsing cases of Gambian trypanosomiasis. For new cases, a 7-day course is inferior to the standard 14-day regimen and cannot be recommended.