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.