Evidence of Liver TransplantationPhase 3MMF-FKNCT00151632
Reduction of Tacrolimus Dose in Association With Mycophenolate Mofetil After Liver Transplantation
A Phase 3 study testing Mycophenolate mofetil and Tacrolimus in people with Evidence of Liver Transplantation, run by Rennes University Hospital at 8 sites in France.
Trial summary
The prevention of graft rejection after liver transplantation benefits nowadays from a variety of newly developed immunosuppressive agents. This allows more flexible and individualized immunoprophylaxis and gives an opportunity to reduce the long-term side effects (hypertension, renal failure, diabetes, etc.) of… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Evidence of Liver Transplantation
- What is being tested?
- Mycophenolate mofetil and Tacrolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 195 participants
- Where
- 8 sitesFrance
- Study dates
- May 2003to May 2009
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults over 18 years of age
- Primary liver transplantation
- Immunosuppressive treatment associating tacrolimus and steroids at low doses (< 20 mg/d)
- Written informed consent
- Non-Inclusion Criteria:
- Pregnancy or ineffective contraception
Show all 19Show fewer
- Immunosuppressive treatment
- Blood group incompatibility with the donor
- Autoimmune hepatitis
- Fulminant hepatitis
- Primary sclerosing cholangitis
- Combined transplantations
- Reduced liver
- Living donor
- Treated hypertension and/or diastolic pressure ≥ 90 mmHg and/or systolic pressure ≥ 140 mmHg,
- Acute or chronic renal failure(creatininemia ≥ 130 μmol/L) before transplantation
- Treated diabetes and/or fasting glycemia ≥ 7 mmol/L
- Treated hypercholesterolemia and/or cholesterolemia ≥ 7 mmol/L
- post-operative creatininemia ≥ 200 μmol/L
Who cannot join
None listed.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
France8 sites
Service de Chirurgie Digestive - Hôpital de la Côte de Nacre
Caen, 14033
Service d'Hépatogastroentérologie - Hôpital Beaujon
Clichy, 92110
Service d'Hépatogastroentérologie - Hôpital Henri Mondor
Créteil, 94010
Chirurgie Générale et Digestive - Hôpital de La Croix Rousse
Lyon, 69317
Service d'Hépaogastroentérologie - Hôpital Saint Eloi
Montpellier
Service de Chirurgie Générale - Hôpital Cochin
Paris, 75679
Département de Chirurgie Viscérale - Hôpital Pontchaillou
Rennes, 35033
Centre Hépato-biliaire - Hôpital Paul Brousse
Villejuif
About this study
Official title: Evaluation of the Benefit/Risk Ratio of a Reduction of Tacrolimus Dose in Association With Mycophenolate Mofetil on the Prevention of Complications in Adult Liver Transplantation
The prevention of graft rejection after liver transplantation benefits nowadays from a variety of newly developed immunosuppressive agents. This allows more flexible and individualized immunoprophylaxis and gives an opportunity to reduce the long-term side effects (hypertension, renal failure, diabetes, etc.) of immunosuppression. The purpose of this study is to evaluate, in liver transplanted patients, if low doses of tacrolimus, given in combination with mycophenolate mofetil, can result in a lower rate of long-term side effects without increasing the rate of graft rejection.
Read the detailed description
Tacrolimus and mycophenolate mofetil are currently approved immunosuppressive agents for the prevention of acute and chronic rejection in liver transplantation. Adverse effects of tacrolimus are dose-dependent and appear early after the onset of treatment. To prevent side effects, we propose to combine reduced doses of tacrolimus with another immunosuppressant, i.e. mycophenolate mofetil, administered at usual doses. This study evaluates the interest of this combination and, subsequently, the pharmacokinetics of mycophenolate mofetil in this therapeutic context. Patients undergoing liver transplantation will be randomized to tacrolimus at normal doses or to the combination of tacrolimus at half doses and mycophenolate mofetil. A corticotherapy will be associated in both groups. The safety will be evaluated on the number of graft rejections between day 1 after transplantation and week 48; the onset of complications (hypertension, renal failure, diabetes, etc.) will allow to evaluate the efficacy of both treatment schedules.
- Conditions
- Evidence of Liver Transplantation
- Being tested
- Mycophenolate mofetil, Tacrolimus
- Keywords
- Immunosuppression, Liver transplantation, Acute graft rejection, Treatment combination
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called MMF, CELLCEPT
Mycophenolate mofetil is administered at a dose of 1,5 g x 2 / day for the 6 first weeks, then 1g x 2 / day until M12.
TacrolimusDrug
Also called FK, PROGRAF
In arm 1: Tacrolimus is administered at half recommended dose: 0,040 mg/Kg x 2 , in order to maintain plasma levels between 6 and 10 ng/ml for the 6 first weeks, between 5 and 8 ng/ml from week 7 to M6 and between 4 and 6 ng/ml between M6 and M12.
In arm 2: Tacrolimus is administered at the recommended dose: 0,075 mg/Kg x 2 , in order to maintain plasma levels between 12 and 20 ng/ml for the 6 first weeks, between 10 and 15 ng/ml from week 7 to week 12, between 8 and 12 ng/ml between M4 and M6 and between 6 and 10 ng/ml between M6 and M12.
| Study group | Role | What they receive |
|---|---|---|
| MMF+FK | Experimental | Low doses of tacrolimus in association with mycophenolate mofetil Receives: Drug: Mycophenolate mofetil; Drug: Tacrolimus |
| FK | Active comparator | Full recommended doses of tacrolimus Receives: Drug: Tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Onset of acute rejection (criterion evaluating the risk)
Measured: between Day 1 and Week 48
Onset of at least one complication (hypertension, renal failure, diabetes) requiring a specific treatment (criterion evaluating the benefit)
Measured: between Week 9 and Week 48
Secondary outcomes (1)
Onset of hypertension, renal failure, diabetes, hypercholesterolemia, or of a serious adverse effect of mycophenolate mofetil
Measured: between Day 1 and Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2005 (estimated)
- Study startMay 2003
- Primary completionDec 2008
- Study completionMay 2009
Why it stopped: insufficient enrollment
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 Evidence of Liver TransplantationStudies of the same condition, open and under way.
- More trials run by Rennes University HospitalThe 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 195 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rennes University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Health, France
- Responsible party
- Sponsor
- Investigators
- Karim Boudjema, MD, PhD, Study director, Rennes University HospitalEric Bellissant, MD, PhD, Study chair, Rennes University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00151632
- Sponsor's protocol ID
- AFSSAPS 030200
- Other IDs
- PHRC/01-01, CIC0203/011
- Acronym
- MMF-FK
- Status last verified
- Jul 2012
- First submitted
- 8 Sep 2005
- Last updated
- 4 Jul 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Jain AB, Hamad I, Rakela J, Dodson F, Kramer D, Demetris J, McMichael J, Starzl TE, Fung JJ. A prospective randomized trial of tacrolimus and prednisone versus tacrolimus, prednisone, and mycophenolate mofetil in primary adult liver transplant recipients: an interim report. Transplantation. 1998 Nov 27;66(10):1395-8. doi: 10.1097/00007890-199811270-00024.
PubMed 9846530Klupp J, Glanemann M, Bechstein WO, Platz KP, Langrehr JM, Keck H, Settmacher U, Radtke C, Neuhaus R, Neuhaus P. Mycophenolate mofetil in combination with tacrolimus versus Neoral after liver transplantation. Transplant Proc. 1999 Feb-Mar;31(1-2):1113-4. doi: 10.1016/s0041-1345(98)01925-3. No abstract available.
PubMed 10083497
Study at a glance
From the registry record, last updated by the sponsor on 4 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Benefit/Risk Ratio of a Reduction of Tacrolimus Dose in Association With Mycophenolate Mofetil on the Prevention of Complications in Adult Liver Transplantation
- ClinicalTrials.gov ID
- NCT00151632
- Acronym / sponsor ID
- MMF-FK / AFSSAPS 030200
- Conditions
- Evidence of Liver Transplantation
- Keywords
- Immunosuppression, Liver transplantation, Acute graft rejection, Treatment combination
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: insufficient enrollment
- Enrolment
- 195 participants (actual)
- Lead sponsor
- Rennes University HospitalUniversity, hospital or other
- Collaborators
- Ministry of Health, France
- Study start
- May 2003
- Primary completion
- Dec 2008 (actual)
- Study completion
- May 2009 (actual)
- First posted
- 9 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 prevention of graft rejection after liver transplantation benefits nowadays from a variety of newly developed immunosuppressive agents. This allows more flexible and individualized immunoprophylaxis and gives an opportunity to reduce the long-term side effects (hypertension, renal failure, diabetes, etc.) of immunosuppression. The purpose of this study is to evaluate, in liver transplanted patients, if low doses of tacrolimus, given in combination with mycophenolate mofetil, can result in a lower rate of long-term side effects without increasing the rate of graft rejection.
Detailed description
Tacrolimus and mycophenolate mofetil are currently approved immunosuppressive agents for the prevention of acute and chronic rejection in liver transplantation. Adverse effects of tacrolimus are dose-dependent and appear early after the onset of treatment. To prevent side effects, we propose to combine reduced doses of tacrolimus with another immunosuppressant, i.e. mycophenolate mofetil, administered at usual doses. This study evaluates the interest of this combination and, subsequently, the pharmacokinetics of mycophenolate mofetil in this therapeutic context. Patients undergoing liver transplantation will be randomized to tacrolimus at normal doses or to the combination of tacrolimus at half doses and mycophenolate mofetil. A corticotherapy will be associated in both groups. The safety will be evaluated on the number of graft rejections between day 1 after transplantation and week 48; the onset of complications (hypertension, renal failure, diabetes, etc.) will allow to evaluate the efficacy of both treatment schedules.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MMF+FK | Experimental | Drug: Mycophenolate mofetil, Drug: TacrolimusLow doses of tacrolimus in association with mycophenolate mofetil |
| FK | Active comparator | Drug: TacrolimusFull recommended doses of tacrolimus |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Adults over 18 years of age
- Primary liver transplantation
- Immunosuppressive treatment associating tacrolimus and steroids at low doses (< 20 mg/d)
- Written informed consent
- Pregnancy or ineffective contraception
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| Mycophenolate mofetilAlso: MMF, CELLCEPTMycophenolate mofetil is administered at a dose of 1,5 g x 2 / day for the 6 first weeks, then 1g x 2 / day until M12. | Drug | MMF+FK |
| TacrolimusAlso: FK, PROGRAFIn arm 1: Tacrolimus is administered at half recommended dose: 0,040 mg/Kg x 2 , in order to maintain plasma levels between 6 and 10 ng/ml for the 6 first weeks, between 5 and 8 ng/ml from week 7 to M6 and between 4 and 6 ng/ml between M6 and M12. In arm 2: Tacrolimus is administered at the recommended dose: 0,075 mg/Kg x 2 , in order to maintain plasma levels between 12 and 20 ng/ml for the 6 first weeks, between 10 and 15 ng/ml from week 7 to week 12, between 8 and 12 ng/ml between M4 and M6 and between 6 and 10 ng/ml between M6 and M12. | Drug | FK, MMF+FK |
Primary outcome
Onset of acute rejection (criterion evaluating the risk)
Time frame: between Day 1 and Week 48
Onset of at least one complication (hypertension, renal failure, diabetes) requiring a specific treatment (criterion evaluating the benefit)
Time frame: between Week 9 and Week 48
1 secondary outcome
Onset of hypertension, renal failure, diabetes, hypercholesterolemia, or of a serious adverse effect of mycophenolate mofetil
Time frame: between Day 1 and Week 48
Results and safety
The study was stopped early (reason given: insufficient enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jul 2012.
- Background: PubMed 9846530Jain AB, Hamad I, Rakela J, Dodson F, Kramer D, Demetris J, McMichael J, Starzl TE, Fung JJ. A prospective randomized trial of tacrolimus and prednisone versus tacrolimus, prednisone, and mycophenolate mofetil in primary adult liver transplant recipients: an interim report. Transplantation. 1998 Nov 27;66(10):1395-8. doi: 10.1097/00007890-199811270-00024.
- Background: PubMed 10083497Klupp J, Glanemann M, Bechstein WO, Platz KP, Langrehr JM, Keck H, Settmacher U, Radtke C, Neuhaus R, Neuhaus P. Mycophenolate mofetil in combination with tacrolimus versus Neoral after liver transplantation. Transplant Proc. 1999 Feb-Mar;31(1-2):1113-4. doi: 10.1016/s0041-1345(98)01925-3. No abstract available.
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.
Karim Boudjema, MD, PhD study director
Rennes University Hospital
Eric Bellissant, MD, PhD study chair
Rennes University Hospital
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Mycophenolate mofetil and Tacrolimus in people with Evidence of Liver Transplantation, run by Rennes University Hospital 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 19 inclusion and 0 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: stopped early, as of the sponsor's last update on 4 Jul 2012. 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 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 was stopped early (reason given: insufficient enrollment). Results are not available in the source record.
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?
Onset of acute rejection (criterion evaluating the risk) (time frame: between Day 1 and Week 48). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00151632, 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 4 Jul 2012.