Efficacy - Safety of Eflornithine-Nifurtimox Combination Versus Eflornithine to Treat Human African Trypanosomiasis

This study has been completed.
Sponsor:
Collaborators:
Medecins Sans Frontieres
PNLTHA-DRC;
PNLTHA-RoC
Epicentre
Swiss Tropical & Public Health Institute
World Health Organization
Information provided by:
Drugs for Neglected Diseases
ClinicalTrials.gov Identifier:
NCT00146627
First received: September 6, 2005
Last updated: September 18, 2009
Last verified: September 2009
  Purpose

The purpose of this study is to compare the therapeutic combination of I.V. eflornithine + oral nifurtimox to the standard IV eflornithine regimen in terms of therapeutic efficacy and clinical safety, in patients suffering from Trypanosoma brucei gambiense (Tbg) human African trypanosomiasis (HAT) in the meningoencephalitic phase.


Condition Intervention Phase
Trypanosomiasis, African
Drug: Eflornithine
Drug: Nifurtimox
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Clinical Study Comparing the Nifurtimox-Eflornithine Combination With the Standard Eflornithine Regimen for the Treatment of Trypanosoma Brucei Gambiense Human African Trypanosomiasis in the Meningoencephalitic Phase

Resource links provided by NLM:


Further study details as provided by Drugs for Neglected Diseases:

Estimated Enrollment: 280
Study Completion Date: June 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Detailed Description:

Melarsoprol is the most commonly used product for the treatment of patients suffering from human African trypanosomiasis (HAT) in the meningoencephalitic (second, late) phase. This treatment is frequently complicated by fatal reactive encephalopathy, and at the same time resistance is beginning to appear in various countries. Eflornithine is effective and better tolerated, but it is more difficult to use. Nifurtimox, registered in several South American countries for treatment of Chagas' disease but used off label since the 1970's in series of cases of meningo-encephalitic HAT, is at present the only other potential alternative for the treatment of late-stage HAT.

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. Ideally, drug combinations should allow for reductions in the dosages of the drugs used in a way that, in particular in the case of toxic drugs such as those used for second stage HAT, the toxicity of the combination does not exceed that of either monotherapy. Of the three drug combinations nowadays possible: melarsoprol-nifurtimox, melarsoprol-eflornithine and eflornithine-nifurtimox, the last one has (in two different dosing regimens) shown the least treatment-associated toxicity and mortality in the 69 patients treated in one previous and this clinical trial to date. Good tolerability was also observed in a case series of 31 patients. The efficacy data to date suggest that efficacy is comparable to that of eflornithine and that of melarsoprol (in areas without high melarsoprol failure rates).

  Eligibility

Ages Eligible for Study:   15 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • confirmed second-stage T.b. gambiense infection : presence of the parasite in blood, lymph node fluid or CSF and >20 white blood cells/µL in CSF. In presence of blood in the CSF, lumbar puncture must be done again or the patient cannot be included in the study (see 10.9.1).
  • and of age 15 years or older.
  • and resident in __________ (each site will define boundaries or maximum distance)
  • and written informed consent of the patient or of a legally acceptable representative if the patient is a minor (<18 years for both genders in Uganda and Angola, <18 years for males and <16 years for females in the Democratic Republic of Congo) or unable to communicate.

Exclusion Criteria:

  • pregnant woman (systematic testing of women of childbearing potential)
  • treated for late-stage HAT during the last 36 months. Patients previously treated for first-stage (pentamidine) can be included.
  • unlikely to have access to the treatment centre or be accessible at their place of residence for 18 months after treatment
  • unable to take oral medication
  • suffering from conditions other than second stage HAT that seriously limit the chances of survival over 18 months time
  • Severe anemia (Hb< 5g/dl)
  • Severe underlying diseases upon admission (e.g. Active tuberculosis and/or being treated for TB; Bacterial or cryptococcal meningitis; Stages 3 or 4 HIV/AIDS according to the WHO clinical definition) (WHO, 1986).
  • Severe renal failure based on clinical examination combined with biochemistry if available: creatinine clearance <20mL/min
  • Severe hepatic failure based on clinical examination combined with biochemistry if available: total bilirubin >50 µmol/L, ALAT/GPT >70 UI/L, unless these laboratory values are determined by the investigator as likely due to conditions other than hepatic failure.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00146627

Locations
Congo
MSF-Holland
Nkayi, RoC, Congo
The Democratic Republic of the Congo
MSF-Belgium; PNLTHA, Epicentre
Isangi, The Democratic Republic of the Congo
PNLTHA, STI, Epicentre
Katanda, The Democratic Republic of the Congo
PNLTHA, STI, Epicentre
Mbuyi Maji, The Democratic Republic of the Congo
Sponsors and Collaborators
Drugs for Neglected Diseases
Medecins Sans Frontieres
PNLTHA-DRC;
PNLTHA-RoC
Epicentre
Swiss Tropical & Public Health Institute
World Health Organization
Investigators
Study Chair: Els Torreele, PhD Drugs for Neglected Diseases
Study Director: Gerardo Priotto, MD, MPH Epicentre
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00146627     History of Changes
Other Study ID Numbers: DNDi-HAT0105; Epicentre-NECT
Study First Received: September 6, 2005
Last Updated: September 18, 2009
Health Authority: Uganda: Ministry of Health

Keywords provided by Drugs for Neglected Diseases:
Human African Trypanosomiasis
Combination
Trypanosoma brucei gambiense Human African Trypanosomiasis

Additional relevant MeSH terms:
Trypanosomiasis
Trypanosomiasis, African
Euglenozoa Infections
Protozoan Infections
Parasitic Diseases
Eflornithine
Nifurtimox
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Trypanocidal Agents
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on July 29, 2014