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

NCT ID: NCT00330148

Last Updated: 2006-05-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 435 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-03-31
• Study Completion Date: 2004-06-30

Brief Summary

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

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.

Conditions

Trypanosomiasis, African

Keywords

trypanosomiasis; gambiense; combination drug therapy; sleeping sickness; Uganda

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

melarsoprol 1.8 mg/kg/d, 10d + nifurtimox 15/20 mg/kg/d, 10d

Intervention Type: DRUG

melarsoprol 1.8 mg/kg/d, 10d + eflornithine 400 mg/kg/d, 7d

Intervention Type: DRUG

nifurtimox 15/20 mg/kg/d 10d + eflornithine 400 mg/kg/d 7d

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 0 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Médecins Sans Frontières, France

OTHER

Sponsor Role: collaborator

Embassy of France in Uganda

UNKNOWN

Sponsor Role: collaborator

National Sleeping Sickness Control Program, Uganda

UNKNOWN

Sponsor Role: collaborator

Epicentre

OTHER

Sponsor Role: lead

Principal Investigators

Gerardo Priotto, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Epicentre

Locations

Omugo Sleeping Sickness Treatment Center

Omugo, Arua District, Uganda

Countries

Uganda

References

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. doi: 10.1016/s1473-3099(02)00321-3.

Reference Type: BACKGROUND

PMID: 12127356 (View on PubMed)

Other Identifiers

EPICENTRE-BTT

Identifier Type: -

Identifier Source: org_study_id