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

Primary Purpose

Trypanosomiasis, African

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Eflornithine
Nifurtimox
Sponsored by
Drugs for Neglected Diseases
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Trypanosomiasis, African focused on measuring Human African Trypanosomiasis, Combination, Trypanosoma brucei gambiense Human African Trypanosomiasis

Eligibility Criteria

15 Years - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • MSF-Belgium; PNLTHA, Epicentre
  • PNLTHA, STI, Epicentre
  • PNLTHA, STI, Epicentre
  • MSF-Holland

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
September 6, 2005
Last Updated
September 28, 2016
Sponsor
Drugs for Neglected Diseases
Collaborators
Medecins Sans Frontieres, Netherlands, PNLTHA-DRC;, PNLTHA-RoC, Epicentre, Swiss Tropical & Public Health Institute, World Health Organization
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1. Study Identification

Unique Protocol Identification Number
NCT00146627
Brief Title
Efficacy - Safety of Eflornithine-Nifurtimox Combination Versus Eflornithine to Treat Human African Trypanosomiasis
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2009
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
June 2008 (Actual)
Study Completion Date
June 2008 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Drugs for Neglected Diseases
Collaborators
Medecins Sans Frontieres, Netherlands, PNLTHA-DRC;, PNLTHA-RoC, Epicentre, Swiss Tropical & Public Health Institute, World Health Organization

4. Oversight

5. Study Description

Brief Summary
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.
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Trypanosomiasis, African
Keywords
Human African Trypanosomiasis, Combination, Trypanosoma brucei gambiense Human African Trypanosomiasis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
280 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Eflornithine
Intervention Type
Drug
Intervention Name(s)
Nifurtimox

10. Eligibility

Sex
All
Minimum Age & Unit of Time
15 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Els Torreele, PhD
Organizational Affiliation
Drugs for Neglected Diseases
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Gerardo Priotto, MD, MPH
Organizational Affiliation
Epicentre
Official's Role
Study Director
Facility Information:
Facility Name
MSF-Belgium; PNLTHA, Epicentre
City
Isangi
Country
Congo, The Democratic Republic of the
Facility Name
PNLTHA, STI, Epicentre
City
Katanda
Country
Congo, The Democratic Republic of the
Facility Name
PNLTHA, STI, Epicentre
City
Mbuyi Maji
Country
Congo, The Democratic Republic of the
Facility Name
MSF-Holland
City
Nkayi, RoC
Country
Congo

12. IPD Sharing Statement

Citations:
PubMed Identifier
19559477
Citation
Opigo J, Woodrow C. NECT trial: more than a small victory over sleeping sickness. Lancet. 2009 Jul 4;374(9683):7-9. doi: 10.1016/S0140-6736(09)61163-6. Epub 2009 Jun 24. No abstract available.
Results Reference
background
PubMed Identifier
19559476
Citation
Priotto G, Kasparian S, Mutombo W, Ngouama D, Ghorashian S, Arnold U, Ghabri S, Baudin E, Buard V, Kazadi-Kyanza S, Ilunga M, Mutangala W, Pohlig G, Schmid C, Karunakara U, Torreele E, Kande V. Nifurtimox-eflornithine combination therapy for second-stage African Trypanosoma brucei gambiense trypanosomiasis: a multicentre, randomised, phase III, non-inferiority trial. Lancet. 2009 Jul 4;374(9683):56-64. doi: 10.1016/S0140-6736(09)61117-X. Epub 2009 Jun 24.
Results Reference
result
Links:
URL
http://www.dndi.org
Description
Sponsor website

Learn more about this trial

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

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