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

Condition(s) targeted: Trypanosomiasis, African

Intervention: 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 (Drug)

Phase: Phase 3

Status: Terminated

Sponsored by: Epicentre

Official(s) and/or principal investigator(s):
Gerardo Priotto, MD, MPH, Principal Investigator, Affiliation: Epicentre

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.

Official title: 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

Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Cure rate

Secondary outcome:

Adverse events temporally associated with the treatment

Major adverse events temporally associated with the treatment

Detailed 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.

Minimum age: N/A. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Omugo Sleeping Sickness Treatment Center, Omugo, Arua District, Uganda

Related publications:

Legros D, Ollivier G, Gastellu-Etchegorry M, Paquet C, Burri C, Jannin J, Buscher P. Treatment of human African trypanosomiasis--present situation and needs for research and development. Lancet Infect Dis. 2002 Jul;2(7):437-40. Review.

Starting date: March 2001
Ending date: June 2004
Last updated: May 24, 2006