NCT00146627

Efficacy - Safety of Eflornithine-Nifurtimox Combination Versus Eflornithine to Treat Human African Trypanosomiasis

Clinical Study Comparing the Nifurtimox-Eflornithine Combination With the Standard Eflornithine Regimen for the Treatment of Trypanosoma Brucei Gambiense Human African Trypanosomiasis in the Meningoencephalitic Phase

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 280 (estimated)
• Sponsor: Drugs for Neglected Diseases · Academic / Other
• Sex: All
• Age: 15 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to compare the therapeutic combination of I.V. eflornithine + oral nifurtimox to the standard IV eflornithine regimen in terms of therapeutic efficacy and clinical safety, in patients suffering from Trypanosoma brucei gambiense (Tbg) human African trypanosomiasis (HAT) in the meningoencephalitic phase.

Detailed description

Melarsoprol is the most commonly used product for the treatment of patients suffering from human African trypanosomiasis (HAT) in the meningoencephalitic (second, late) phase. This treatment is frequently complicated by fatal reactive encephalopathy, and at the same time resistance is beginning to appear in various countries. Eflornithine is effective and better tolerated, but it is more difficult to use. Nifurtimox, registered in several South American countries for treatment of Chagas' disease but used off label since the 1970's in series of cases of meningo-encephalitic HAT, is at present the only other potential alternative for the treatment of late-stage HAT. The very limited number of compounds available, the lack of prospects for the development of new products and the emergence of resistance are arguments for the use of therapeutic combinations. Ideally, drug combinations should allow for reductions in the dosages of the drugs used in a way that, in particular in the case of toxic drugs such as those used for second stage HAT, the toxicity of the combination does not exceed that of either monotherapy. Of the three drug combinations nowadays possible: melarsoprol-nifurtimox, melarsoprol-eflornithine and eflornithine-nifurtimox, the last one has (in two different dosing regimens) shown the least treatment-associated toxicity and mortality in the 69 patients treated in one previous and this clinical trial to date. Good tolerability was also observed in a case series of 31 patients. The efficacy data to date suggest that efficacy is comparable to that of eflornithine and that of melarsoprol (in areas without high melarsoprol failure rates).

Conditions

• Trypanosomiasis, African

Interventions

Type	Name	Description
DRUG	Eflornithine
DRUG	Nifurtimox

Timeline

• Primary completion: 2008-06-01
• Completion: 2008-06-01
• First posted: 2005-09-07
• Last updated: 2016-09-29

Locations

4 sites across 2 countries: Democratic Republic of the Congo, Republic of the Congo