Trypanosomiasis, AfricanPhase 3NCT00146627
Efficacy - Safety of Eflornithine-Nifurtimox Combination Versus Eflornithine to Treat Human African Trypanosomiasis
A Phase 3 study testing Eflornithine and Nifurtimox in people with Trypanosomiasis, African, run by Drugs for Neglected Diseases at 4 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 15 to 70 years
- Conditions the study is for
- Trypanosomiasis, African
- What is being tested?
- Eflornithine and Nifurtimox
- How many people
- 280 participants
- Where
- 4 sitesin 2 countries
- Study dates
- Start not givento Jun 2008
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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)
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- 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.
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
Democratic Republic of the Congo3 sites
MSF-Belgium; PNLTHA, Epicentre
Isangi
PNLTHA, STI, Epicentre
Katanda
PNLTHA, STI, Epicentre
Mbuyi Maji
About this study
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
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.
Read the 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).
- Conditions
- Trypanosomiasis, African
- Being tested
- Eflornithine, Nifurtimox
- Keywords
- Human African Trypanosomiasis, Combination, Trypanosoma brucei gambiense Human African Trypanosomiasis
- Medical subject headings
- Trypanosomiasis, African
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EflornithineDrug
NifurtimoxDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2005 (estimated)
- Primary completionJun 2008
- Study completionJun 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Trypanosomiasis, AfricanStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 280 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Drugs for Neglected Diseases
- Sponsor type
- University, hospital or other
- Collaborators
- Medecins Sans Frontieres, Netherlands, PNLTHA-DRC;, PNLTHA-RoC, Epicentre, Swiss Tropical & Public Health Institute, World Health Organization
- Investigators
- Els Torreele, PhD, Study chair, Drugs for Neglected DiseasesGerardo Priotto, MD, MPH, Study director, Epicentre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00146627
- Sponsor's protocol ID
- DNDi-HAT0105; Epicentre-NECT
- Status last verified
- Sep 2009
- First submitted
- 6 Sep 2005
- Last updated
- 29 Sep 2016
- Results posted
- No
Publications
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.
PubMed 19559477Priotto 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.
PubMed 19559476
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00146627
- Acronym / sponsor ID
- DNDi-HAT0105; Epicentre-NECT
- Conditions
- Trypanosomiasis, African
- Keywords
- Human African Trypanosomiasis, Combination, Trypanosoma brucei gambiense Human African Trypanosomiasis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 280 participants (estimated)
- Lead sponsor
- Drugs for Neglected DiseasesUniversity, hospital or other
- Collaborators
- Medecins Sans Frontieres, Netherlands, PNLTHA-DRC;, PNLTHA-RoC, Epicentre, Swiss Tropical & Public Health Institute, World Health Organization
- Primary completion
- Jun 2008 (actual)
- Study completion
- Jun 2008 (actual)
- First posted
- 7 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 15 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Eflornithine | Drug | – |
| Nifurtimox | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2016.
- Background: PubMed 19559477Opigo 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 publication: PubMed 19559476Priotto 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.
- Sponsor websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Els Torreele, PhD study chair
Drugs for Neglected Diseases
Gerardo Priotto, MD, MPH study director
Epicentre
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Eflornithine and Nifurtimox in people with Trypanosomiasis, African, run by Drugs for Neglected Diseases at 4 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Democratic Republic of the Congo, Republic of the Congo. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00146627, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2016.