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

Sponsor:	Epicentre
Collaborators:	Medecins Sans Frontieres Embassy of France in Uganda National Sleeping Sickness Control Program, Uganda
Information provided by:	Epicentre
ClinicalTrials.gov Identifier:	NCT00330148

Purpose

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.

Condition	Intervention	Phase
Trypanosomiasis, African	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	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
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

Resource links provided by NLM:

Drug Information available for: Nifurtimox Eflornithine Melarsoprol

U.S. FDA Resources

Further study details as provided by Epicentre:

Primary Outcome Measures:

Cure rate

Secondary Outcome Measures:

Adverse events temporally associated with the treatment
Major adverse events temporally associated with the treatment

Estimated Enrollment:	435
Study Start Date:	March 2001
Estimated Study Completion Date:	June 2004

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.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00330148

Locations

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

Sponsors and Collaborators

Epicentre

Medecins Sans Frontieres

Embassy of France in Uganda

National Sleeping Sickness Control Program, Uganda

Investigators

Principal Investigator:

Gerardo Priotto, MD, MPH

Epicentre

More Information

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.

Study ID Numbers:	EPICENTRE-BTT
Study First Received:	May 24, 2006
Last Updated:	May 24, 2006
ClinicalTrials.gov Identifier:	NCT00330148 History of Changes
Health Authority:	Uganda: Ministry of Health

Keywords provided by Epicentre:

trypanosomiasis
gambiense
combination drug therapy
sleeping sickness
Uganda

Additional relevant MeSH terms:

Anti-Infective Agents
Trypanocidal Agents
Protozoan Infections
Antiprotozoal Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Trypanosomiasis, African
Mastigophora Infections
Enzyme Inhibitors

Melarsoprol
Nifurtimox
Pharmacologic Actions
Antiparasitic Agents
Eflornithine
Therapeutic Uses
Trypanosomiasis
Sarcomastigophora Infections
Parasitic Diseases

ClinicalTrials.gov processed this record on February 08, 2010