Liver TransplantationPhase 4BEFIRTHNCT00538265
Benefit of Immunoprophylaxis on Fibrosis to Reduce Viral Load After Liver Transplantation
A Phase 4 study testing tacrolimus, tacrolimus, ATG and ATG+mycophénolate mofétil+tacrolimus in people with Liver Transplantation, run by University Hospital, Toulouse at 8 sites in France.
Trial summary
An open-label randomized multicenter clinical study comparing three regimes of immunosuppression : (A) tacrolimus and steroids, (B) antithymocyte induction therapy and full dose of tacrolimus, (C) antithymocyte induction therapy with mycophenolate mofetil and a reduced dose of tacrolimus. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Transplantation
- What is being tested?
- tacrolimus, tacrolimus, ATG and ATG+mycophénolate mofétil+tacrolimus
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 8 sitesFrance
- Study dates
- May 2005to Jan 2011
- Phase
- Phase 4
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- patients who received a first liver transplantation,
- presenting with a qualitative or quantitative PCR positive for hepatitis C virus at time of transplantation, whatever the transaminase activity,
- Women of childbearing potential with a negative pregnancy test,
- Male or female patients who agree to use an effective method of contraception,
- patients who signed a written informed consent form to participate in the study,
- patients who are compliant and likely to follow the visits specified by the study protocol
Who cannot join
- • Preoperative serious renal impairment (serum creatinine levels > 200 µmol/l),
- repeat transplantation,
- multiple organ transplantation,
- transplantation performed with an organ transplant obtained from a living donor or a reduced or shared organ grafts,
- serious concomitant disorder,
- positive serology for HBs antigen or HIV positive at time of enrollment,
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- previous history of nonhepatic cancer (except for localized skin cancer),
- presence of a hepatocellular carcinoma, for which the primary lesion exceeds 5 cm or is complicated by portal thrombosis or metastatic disease,
- an investigational product or therapy administered less than one month before entry into the study.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
France8 sites
Hopital Pellegrin Tripode
Bordeaux, 33076
La CONCEPTION hospital
Marseille, 13385
Hopital Saint-Eloi
Montpellier, 34295
Hopital de L'Archet
Nice, 06200
Hôpital Cochin
Paris, 75000
Hôpital Pontchaillou
Rennes, 35
University Hospital
Toulouse, 31500
Hopital Paul Brousse
Villejuif, 94804
About this study
Official title: Evaluation of the Benefit of Antithymocyte Induction Therapy on Hepatic Fibrosis in de Novo Hepatitis C Virus Liver Transplant Patients.
An open-label randomized multicenter clinical study comparing three regimes of immunosuppression : (A) tacrolimus and steroids, (B) antithymocyte induction therapy and full dose of tacrolimus, (C) antithymocyte induction therapy with mycophenolate mofetil and a reduced dose of tacrolimus.
- Conditions
- Liver Transplantation
- Being tested
- tacrolimus, tacrolimus, ATG, ATG+mycophénolate mofétil+tacrolimus
- Keywords
- liver transplantation, hepatitis C virus, immunoprophylaxis
- Medical subject headings
- Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tacrolimusDrug
Also called PROGRAF
Tacrolimus started at 0.50 mg/kg b.i.d. starting at D0, by nasogastric tube and then 1 to 2 hours before meals. The dose of tacrolimus will be adjusted as soon as possible to obtain trough concentrations of the product between 10 and 20 µg/L between D0 and 6 months and then between 8 and 15 µg/L after 6 months
tacrolimus, ATGDrug
Also called Thymoglobuline
immunoprophylaxis allowing sparing of steroids in maintenance therapy combining induction therapy with 3 injections of antithymocyte globulins (ATG) (1.5 mg/kg/d at D0, D2 and D4) and tacrolimus at usual dosage.
In this group of patients, the first injection of ATG will be infused over a period of at least 6 hours and will be started as soon as vascular anastomosis has been completed. It will be preceded by an injection of 3 mg/kg/d methylprednisolone. The second injection of ATG at D2, post transplantation will also be infused over 6 hours and will be preceded by an injection of 1 mg/kg methylprednisolone, and then subsequently steroids will be excluded from the treatment. The third and last injection at D4 post transplantation will be administered over a 6-hour period but will not be preceded by steroids.
In this study arm, tacrolimus will be administered as in arm (A)
ATG+mycophénolate mofétil+tacrolimusDrug
Also called Mycophénolate mofétil = Cellcept
immunoprophylaxis allowing sparing of steroids in maintenance therapy combined with mycophenolate mofetil, at an initial dosage of 2 grams a day, and then adjusted to safety and tolerability in such a way so as to maintain PMN ≥ 750/mm3, and platelet counts ≥ 30000/mm3.
In this study arm, the patients will receive the same doses of ATG and steroids (and according to the same methods) as in arm B. Tacrolimus started at 0.05 mg/kg b.i.d. starting at D0 by nasogastric tube and then 1 to 2 hours before meals. In this study arm, the tacrolimus dose will be reduced: targeted trough concentrations will be between 7 and 12 µg/L between D0 and 6 months and then between 3 et 7 µg/L after 6 months.
| Study group | Role | What they receive |
|---|---|---|
| A | Active comparator | tacrolimus + steroids Receives: Drug: tacrolimus |
| B | Experimental | ATG+ tacrolimus without steroids in maintenance therapy Receives: Drug: tacrolimus, ATG |
| C | Experimental | ATG+ Mycophenolate Mofetil + tacrolimus a reduced dosage without steroids in maintenance therapy Receives: Drug: ATG+mycophénolate mofétil+tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary endpoint will be degree of fibrosis = Ishak's histological score of hepatic biopsy at 1 year
Measured: 1 year
Secondary outcomes (2)
• Ishak's degree of activity
Measured: 1 year
Ishak's degree of fibrosis
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2007 (estimated)
- Study startMay 2005
- Primary completionJan 2010
- Study completionJan 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver TransplantationStudies of the same condition, open and under way.
- More trials run by University Hospital, ToulouseThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Toulouse
- Sponsor type
- University, hospital or other
- Investigators
- Rostaing Lionel, PhD, Principal investigator, University Hospital, ToulouseCalmus Yvon, PhD, Principal investigator, UHCochin, Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00538265
- Sponsor's protocol ID
- 0404003
- Acronym
- BEFIRTH
- Status last verified
- Feb 2011
- First submitted
- 1 Oct 2007
- Last updated
- 3 Feb 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Benefit of Antithymocyte Induction Therapy on Hepatic Fibrosis in de Novo Hepatitis C Virus Liver Transplant Patients.
- ClinicalTrials.gov ID
- NCT00538265
- Acronym / sponsor ID
- BEFIRTH / 0404003
- Conditions
- Liver Transplantation
- Keywords
- liver transplantation, hepatitis C virus, immunoprophylaxis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University Hospital, ToulouseUniversity, hospital or other
- Study start
- May 2005
- Primary completion
- Jan 2010 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 2 Oct 2007 (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.
An open-label randomized multicenter clinical study comparing three regimes of immunosuppression : (A) tacrolimus and steroids, (B) antithymocyte induction therapy and full dose of tacrolimus, (C) antithymocyte induction therapy with mycophenolate mofetil and a reduced dose of tacrolimus.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| A | Active comparator | Drug: tacrolimustacrolimus + steroids |
| B | Experimental | Drug: tacrolimus, ATGATG+ tacrolimus without steroids in maintenance therapy |
| C | Experimental | Drug: ATG+mycophénolate mofétil+tacrolimusATG+ Mycophenolate Mofetil + tacrolimus a reduced dosage without steroids in maintenance therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- patients who received a first liver transplantation,
- presenting with a qualitative or quantitative PCR positive for hepatitis C virus at time of transplantation, whatever the transaminase activity,
- Women of childbearing potential with a negative pregnancy test,
- Male or female patients who agree to use an effective method of contraception,
- patients who signed a written informed consent form to participate in the study,
Key exclusion criteria (9 listed)
- • Preoperative serious renal impairment (serum creatinine levels > 200 µmol/l),
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 |
|---|---|---|
| tacrolimusAlso: PROGRAFTacrolimus started at 0.50 mg/kg b.i.d. starting at D0, by nasogastric tube and then 1 to 2 hours before meals. The dose of tacrolimus will be adjusted as soon as possible to obtain trough concentrations of the product between 10 and 20 µg/L between D0 and 6 months and then between 8 and 15 µg/L after 6 months | Drug | A |
| tacrolimus, ATGAlso: Thymoglobulineimmunoprophylaxis allowing sparing of steroids in maintenance therapy combining induction therapy with 3 injections of antithymocyte globulins (ATG) (1.5 mg/kg/d at D0, D2 and D4) and tacrolimus at usual dosage. In this group of patients, the first injection of ATG will be infused over a period of at least 6 hours and will be started as soon as vascular anastomosis has been completed. It will be preceded by an injection of 3 mg/kg/d methylprednisolone. The second injection of ATG at D2, post transplantation will also be infused over 6 hours and will be preceded by an injection of 1 mg/kg methylprednisolone, and then subsequently steroids will be excluded from the treatment. The third and last injection at D4 post transplantation will be administered over a 6-hour period but will not be preceded by steroids. In this study arm, tacrolimus will be administered as in arm (A) | Drug | B |
| ATG+mycophénolate mofétil+tacrolimusAlso: Mycophénolate mofétil = Cellceptimmunoprophylaxis allowing sparing of steroids in maintenance therapy combined with mycophenolate mofetil, at an initial dosage of 2 grams a day, and then adjusted to safety and tolerability in such a way so as to maintain PMN ≥ 750/mm3, and platelet counts ≥ 30000/mm3. In this study arm, the patients will receive the same doses of ATG and steroids (and according to the same methods) as in arm B. Tacrolimus started at 0.05 mg/kg b.i.d. starting at D0 by nasogastric tube and then 1 to 2 hours before meals. In this study arm, the tacrolimus dose will be reduced: targeted trough concentrations will be between 7 and 12 µg/L between D0 and 6 months and then between 3 et 7 µg/L after 6 months. | Drug | C |
Primary outcome
The primary endpoint will be degree of fibrosis = Ishak's histological score of hepatic biopsy at 1 year
Time frame: 1 year
2 secondary outcomes
• Ishak's degree of activity
Time frame: 1 year
Ishak's degree of fibrosis
Time frame: 2 years
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 3 Feb 2011.
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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.
Rostaing Lionel, PhD principal investigator
University Hospital, Toulouse
Calmus Yvon, PhD principal investigator
UHCochin, Paris
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing tacrolimus, tacrolimus, ATG and ATG+mycophénolate mofétil+tacrolimus in people with Liver Transplantation, run by University Hospital, Toulouse at 8 sites in France.
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 6 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 3 Feb 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in France. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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.
What does the primary outcome measure?
The primary endpoint will be degree of fibrosis = Ishak's histological score of hepatic biopsy at 1 year (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Feb 2011.