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

Epicentre

Status and phase

Terminated

Phase 3

Conditions

Trypanosomiasis, African

Treatments

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

Study type

Interventional

Funder types

Other

Identifiers

NCT00330148

EPICENTRE-BTT

Details and patient eligibility

About

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.

Full description

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.

Sex

All

Volunteers

No Healthy Volunteers

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