Journal Article > ResearchFull Text
J Infect Dis. 1 June 2005; Volume 191 (Issue 11); DOI:10.1086/429929
Schmid C, Richer M, Bilenge CM, Josenando T, Chappuis F, et al.
J Infect Dis. 1 June 2005; Volume 191 (Issue 11); DOI:10.1086/429929
BACKGROUND: Treatment of late-stage human African trypanosomiasis (HAT) with melarsoprol can be improved by shortening the regimen. A previous trial demonstrated the safety and efficacy of a 10-day treatment schedule. We demonstrate the effectiveness of this schedule in a noncontrolled, multinational drug-utilization study. METHODS: A total of 2020 patients with late-stage HAT were treated with the 10-day melarsoprol schedule in 16 centers in 7 African countries. We assessed outcome on the basis of major adverse events and the cure rate after treatment and during 2 years of follow-up. RESULTS: The cure rate 24 h after treatment was 93.9%; 2 years later, it was 86.2%. However, 49.3% of patients were lost to follow-up. The overall fatality rate was 5.9%. Of treated patients, 8.7% had an encephalopathic syndrome that was fatal 45.5% of the time. The rate of severe bullous and maculopapular eruptions was 0.8% and 6.8%, respectively. CONCLUSIONS: The 10-day treatment schedule was well implemented in the field and was effective. It reduces treatment duration, drug amount, and hospitalization costs per patient, and it increases treatment-center capacity. The shorter protocol has been recommended by the International Scientific Council for Trypanosomiasis Research and Control for the treatment of late-stage HAT caused by Trypanosoma brucei gambiense.
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 16 February 2016; Volume 10 (Issue 2); e0004362.; DOI:10.1371/journal.pntd.0004362
Burri C, Yeramian PD, Allen JL, Merolle A, Serge KK, et al.
PLoS Negl Trop Dis. 16 February 2016; Volume 10 (Issue 2); e0004362.; DOI:10.1371/journal.pntd.0004362
BACKGROUND
Sleeping sickness (human African trypanosomiasis [HAT]) is caused by protozoan parasites and characterized by a chronic progressive course, which may last up to several years before death. We conducted two Phase 2 studies to determine the efficacy and safety of oral pafuramidine in African patients with first stage HAT.
METHODS
The Phase 2a study was an open-label, non-controlled, proof-of-concept study where 32 patients were treated with 100 mg of pafuramidine orally twice a day (BID) for 5 days at two trypanosomiasis reference centers (Angola and the Democratic Republic of the Congo [DRC]) between August 2001 and November 2004. The Phase 2b study compared pafuramidine in 41 patients versus standard pentamidine therapy in 40 patients. The Phase 2b study was open-label, parallel-group, controlled, randomized, and conducted at two sites in the DRC between April 2003 and February 2007. The Phase 2b study was then amended to add an open-label sequence (Phase 2b-2), where 30 patients received pafuramidine for 10 days. The primary efficacy endpoint was parasitologic cure at 24 hours (Phase 2a) or 3 months (Phase 2b) after treatment completion. The primary safety outcome was the rate of occurrence of World Health Organization Toxicity Scale Grade 3 or higher adverse events. All subjects provided written informed consent.
FINDINGS/CONCLUSION
Pafuramidine for the treatment of first stage HAT was comparable in efficacy to pentamidine after 10 days of dosing. The cure rates 3 months post-treatment were 79% in the 5-day pafuramidine, 100% in the 7-day pentamidine, and 93% in the 10-day pafuramidine groups. In Phase 2b, the percentage of patients with at least 1 treatment-emergent adverse event was notably higher after pentamidine treatment (93%) than pafuramidine treatment for 5 days (25%) and 10 days (57%). These results support continuation of the development program for pafuramidine into Phase 3.
AUTHOR SUMMARY
Sleeping sickness (human African trypanosomiasis [HAT]) is caused by parasites, and has a chronic progressive course that may last from several months to several years before death occurs. The present studies were done to assess the effectiveness and safety of oral pafuramidine versus intramuscular pentamidine (the standard treatment), in patients with first stage HAT. The results indicated that, several months after treatment, pafuramidine administered for 10 days was as effective as pentamidine administered for 7 days, and it had a better safety profile than pentamidine. With further study, pafuramidine could be a promising alternative for patients with first stage HAT. In addition, the design of the studies can be used a guide for future studies for identification and delivery of treatment to affected individuals in rural Africa.
Sleeping sickness (human African trypanosomiasis [HAT]) is caused by protozoan parasites and characterized by a chronic progressive course, which may last up to several years before death. We conducted two Phase 2 studies to determine the efficacy and safety of oral pafuramidine in African patients with first stage HAT.
METHODS
The Phase 2a study was an open-label, non-controlled, proof-of-concept study where 32 patients were treated with 100 mg of pafuramidine orally twice a day (BID) for 5 days at two trypanosomiasis reference centers (Angola and the Democratic Republic of the Congo [DRC]) between August 2001 and November 2004. The Phase 2b study compared pafuramidine in 41 patients versus standard pentamidine therapy in 40 patients. The Phase 2b study was open-label, parallel-group, controlled, randomized, and conducted at two sites in the DRC between April 2003 and February 2007. The Phase 2b study was then amended to add an open-label sequence (Phase 2b-2), where 30 patients received pafuramidine for 10 days. The primary efficacy endpoint was parasitologic cure at 24 hours (Phase 2a) or 3 months (Phase 2b) after treatment completion. The primary safety outcome was the rate of occurrence of World Health Organization Toxicity Scale Grade 3 or higher adverse events. All subjects provided written informed consent.
FINDINGS/CONCLUSION
Pafuramidine for the treatment of first stage HAT was comparable in efficacy to pentamidine after 10 days of dosing. The cure rates 3 months post-treatment were 79% in the 5-day pafuramidine, 100% in the 7-day pentamidine, and 93% in the 10-day pafuramidine groups. In Phase 2b, the percentage of patients with at least 1 treatment-emergent adverse event was notably higher after pentamidine treatment (93%) than pafuramidine treatment for 5 days (25%) and 10 days (57%). These results support continuation of the development program for pafuramidine into Phase 3.
AUTHOR SUMMARY
Sleeping sickness (human African trypanosomiasis [HAT]) is caused by parasites, and has a chronic progressive course that may last from several months to several years before death occurs. The present studies were done to assess the effectiveness and safety of oral pafuramidine versus intramuscular pentamidine (the standard treatment), in patients with first stage HAT. The results indicated that, several months after treatment, pafuramidine administered for 10 days was as effective as pentamidine administered for 7 days, and it had a better safety profile than pentamidine. With further study, pafuramidine could be a promising alternative for patients with first stage HAT. In addition, the design of the studies can be used a guide for future studies for identification and delivery of treatment to affected individuals in rural Africa.
Journal Article > ResearchFull Text
Trop Med Int Health. 1 February 2008; Volume 13 (Issue 2); DOI:10.1111/j.1365-3156.2007.01999.x
Robays J, Raguenaud ME, Josenando T, Boelaert M
Trop Med Int Health. 1 February 2008; Volume 13 (Issue 2); DOI:10.1111/j.1365-3156.2007.01999.x
OBJECTIVE: To compare the cost-effectiveness of eflornithine and melarsoprol in the treatment of human African trypanosomiasis. METHOD: We used data from a Médecins Sans Frontières treatment project in Caxito, Angola to do a formal cost-effectiveness analysis, comparing the efficiency of an eflornithine-based approach with melarsoprol. Endpoints calculated were: cost per death avoided; incremental cost per additional life saved; cost per years of life lost (YLL) averted; incremental cost per YLL averted. Sensitivity analysis was done for all parameters for which uncertainty existed over the plausible range. We did an analysis with and without cost of trypanocidal drugs included. RESULTS: Effectiveness was 95.6% for melarsoprol and 98.7% for eflornithine. Cost/patient was 504.6 for melarsoprol and 552.3 for eflornithine, cost per life saved was 527.5 USD for melarsoprol and 559.8 USD for eflornithine without cost of trypanocidal drugs but it increases to 600.4 USD and 844.6 USD per patient saved and 627.6 USD and 856.1 USD per life saved when cost of trypanocidal drugs are included. Incremental cost-effectiveness ratio is 1596 USD per additional life saved and 58 USD per additional life year saved in the baseline scenario without cost of trypanocidal drugs but it increases to 8169 USD per additional life saved and 299 USD per additional life year saved if costs of trypanocidal drugs are included. CONCLUSION: Eflornithine saves more lives than melarsoprol, but melarsoprol is slightly more cost-effective. Switching from melarsoprol to eflornithine can be considered as a cost-effective option according to the WHO choice criteria.