Safety and efficacy of the 10-day melarsoprol schedule for the treatment of second stage Rhodesiense sleeping sickness.

OBJECTIVE: Assessment of the safety and efficacy of a 10-day melarsoprol schedule in second stage T.b. rhodesiense patients and the effect of suramin-pretreatment on the incidence of encephalopathic syndrome (ES) during melarsoprol therapy. DESIGN: Sequential conduct of a proof-of-concept trial (n = 60) and a utilization study (n = 78) using historic controls as comparator. SETTING: Two trial centres in the T.b. rhodesiense endemic regions of Tanzania and Uganda. PARTICIPANTS: Consenting patients with confirmed second stage disease and a minimum age of 6 years were eligible for participation. Unconscious and pregnant patients were excluded. MAIN OUTCOME MEASURES: The primary outcome measures were safety and efficacy at end of treatment. The secondary outcome measure was efficacy during follow-up after 3, 6 and 12 months. RESULTS: The incidence of ES in the trial population was 11.2% (CI 5-17%) and 13% (CI 9-17%) in the historic data. The respective case fatality rates were 8.4% (CI 3-13.8%) and 9.3% (CI 6-12.6%). All patients discharged alive were free of parasites at end of treatment. Twelve months after discharge, 96% of patients were clinically cured. The mean hospitalization time was reduced from 29 to 13 days (p<0.0001) per patient. CONCLUSIONS: The 10-day melarsoprol schedule does not expose patients to a higher risk of ES or death than does treatment according to national schedules in current use. The efficacy of the 10-day melarsoprol schedule was highly satisfactory. No benefit could be attributed to the suramin pre-treatment. TRIAL REGISTRATION: Current Controlled Trials ISRCTN40537886.