Randomized Clinical Trial of Three Drug Combinations for Late-Stage Gambiense Human African Trypanosomiasis

Study Overview
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Brief Summary
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The treatment human African trypanosomiasis (HAT) in the meningoencephalitic phase relies on two molecules officially registered: melarsoprol, the most commonly used, has a poor safety profile and is becoming ineffective due to parasite resistance; and eflornithine, with better tolerance but more complicated and expensive to implement in endemic countries. nifurtimox, registered only for Chagas' disease but used off-label since the 1970's in series of cases of HAT, is at present the only other available alternative. 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. This study evaluates the efficacy and safety of three drug combination therapies: melarsoprol-nifurtimox, melarsoprol-eflornithine and eflornithine-nifurtimox.

Detailed Description
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Dosages per drug are the same in either arm of the study: IV melarsoprol 1.8 mg/kg/day, daily for 10 days; IV eflornithine 400 mg/kg/day, 6-hourly for 7 days; oral nifurtimox 15 or 20 (children <15 years) mg/kg/day, 8-hourly for 10 days. For efficacy assessment, patients are followed-up for 24 months after treatment, with planned clinical and laboratory controls. The safety assessment includes clinical and hematological adverse events.

Official Title
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Clinical Trial Comparing the Therapeutic Combinations Melarsoprol-Nifurtimox, Melarsoprol-Eflornithine and Eflornithine-Nifurtimox in the Treatment of Gambiense Human African Trypanosomiasis in the Meningo-Encephalitic Phase

Conditions
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Trypanosomiasis, African

Intervention / Treatment
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* Drug: melarsoprol 1.8 mg/kg/d, 10d + nifurtimox 15/20 mg/kg/d, 10d
* Drug: melarsoprol 1.8 mg/kg/d, 10d + eflornithine 400 mg/kg/d, 7d
* Drug: nifurtimox 15/20 mg/kg/d 10d + eflornithine 400 mg/kg/d 7d


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: confirmed second-stage T.b. gambiense infection : Infection diagnosed parasitologically (blood or lymph node fluid) and white blood cells > 5/mm3 in cerebrospinal fluid (CSF) or Trypanosomes detected in the CSF with any CSF cell count and resident in the district and written consent of the patient or of one of the parents/guardians for children under 15 years of age. Exclusion Criteria: Trypanosome absent from blood (or lymph node fluid) and from CSF Or women pregnant on inclusion Or previous history of HAT confirmed treated during the last 24 months Or impossibility of regular access to the treatment centre during the 2 years following the end of the treatment Or less than 10 kg of body weight Or refugee patient

Ages Eligible for Study
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Minimum Age: 0 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: melarsoprol 1.8 mg/kg/d, 10d + nifurtimox 15/20 mg/kg/d, 10d|nan|
|Drug: melarsoprol 1.8 mg/kg/d, 10d + eflornithine 400 mg/kg/d, 7d|nan|
|Drug: nifurtimox 15/20 mg/kg/d 10d + eflornithine 400 mg/kg/d 7d|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cure rate |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events temporally associated with the treatment |  |  | 
| Major adverse events temporally associated with the treatment |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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trypanosomiasis, gambiense, combination drug therapy, sleeping sickness, Uganda