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

Trypanosomiasis, African Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00330148
• Other study ID #: EPICENTRE-BTT
• Status: Terminated
• Phase: Phase 3
• First received: May 24, 2006
• Last updated: May 24, 2006
• Start date: March 2001
• Est. completion date: June 2004

Study information

• Verified date: May 2006
• Source: Epicentre
• Contact: n/a
• Is FDA regulated: No
• Health authority: Uganda: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 435
• Est. completion date: June 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Trypanosomiasis
• Trypanosomiasis, African

Intervention

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

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

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

Locations

Country	Name	City	State
Uganda	Omugo Sleeping Sickness Treatment Center	Omugo	Arua District

Sponsors (4)

Lead Sponsor	Collaborator
Epicentre	Embassy of France in Uganda, Medecins Sans Frontieres, National Sleeping Sickness Control Program, Uganda

Country where clinical trial is conducted

Uganda, 

References & Publications (1)

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cure rate
Secondary	Adverse events temporally associated with the treatment
Secondary	Major adverse events temporally associated with the treatment