Liver TransplantationPhase 4MONOCEPTNCT00456235
Reduction in the Risk of Rejection by Mycophenolate Mofetil Dose Adjustment in Liver Transplant Patients With Side Effects Caused by the Calcineurine Inhibitors
A Phase 4 study testing Mycophénolate Mofétil, Ciclosporine A and Tacrolimus in people with Liver Transplantation, run by University Hospital, Limoges at 17 sites in France.
Trial summary
The aim of this project is to determine whether, in liver transplant patients with side effects due to ICN, the use of MMF in monotherapy can be optimised by dose adjustment based on the area under the curve (AUC) of mycophenolic acid (MPA). It involves a multicentre phase IV trial with direct individual benefit. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Liver Transplantation
- What is being tested?
- Mycophénolate Mofétil, Ciclosporine A and Tacrolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 92 participants
- Where
- 17 sitesFrance
- Study dates
- Sep 2006to Sep 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient with first liver transplantion or retransplantation since more than 6 months: with a post-transplant lapse of time of 2 to 10 years and showing one of the following adverse effects of ICN:
- Renal insufficiency defined by a creatinine clearance <50ml/mn (calculated or estimated according to the Cockcroft formula)
- Arterial hypertension not controlled by an anti-hypertensive bitherapy
- Diabetes mellitus (fasting glycaemia >7.0mmol/l), whether treated or not
- Neuromuscular toxicity
- Immunosuppression by cyclosporine or tacrolimus and MMF
- Hepatic biopsy performed within the 6 months preceding the inclusion for the patients with a post-transplant period of <5 years and in the 12 months preceding the inclusion for patients with a post transplant period of >5 years.
Who cannot join
- Acute rejection within the 6 months preceding the screening
- Previous history of cortico-resistant rejection
- Chronic rejection
- Significant ductopenia (absence of inter-lobule biliary canals in more than 30% of the portal tracts) on the pre-screening biopsy.
- Existence of a pre-transplantation diabetes mellitus.
- Liver transplantation for auto-immune hepatitis or primary sclerosing cholangitis
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- Patients transplanted for viral C cirrhosis with reinfection lesions of the transplanted organ, rendering treatment by ribarivine + interferon conceivable in the year following inclusion.
- Counter-indications to MMF (anaemia, leucopenia)
- Immunosuppression by sirolimus, everolimus, azathioprine or corticoids
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
France17 sites
CHU de Besançon
Besançon, 25030
CHU de Bordeaux
Bordeaux, 33076
CHU de Caen
Caen, 14033
Hôpital Beaujon
Clichy, 92000
Hôpital Henri Mondor
Créteil, 94010
CHU de Grenoble
Grenoble, 38043
CHU de Lille
Lille, 59000
Hôpital Edouard Herriot
Lyon, 69437
CHU de Marseille
Marseille, 13385
CHU de Montpellier
Montpellier, 34295
CHU de Nice
Nice, 06200
Hôpital Saint Antoine
Paris, 75012
Hôpital Cochin
Paris, 75014
CHU de Rennes
Rennes, 35033
CHU de Strasbourg
Strasbourg, 67098
CHU de Toulouse
Toulouse, 31059
Hôpital Paul Brousse
Villejuif, 94804
About this study
Official title: Interruption of the Calcineurine Inhibitors (ICN) and Introduction of Mycophenolate Mofetil (MMF) in Liver Transplant Patients With Side Effects Due to ICN: Study of the Reduction of the Risks of Rejection by Mycophenolate Mofetil Therapeutic Drug Monitoring
The aim of this project is to determine whether, in liver transplant patients with side effects due to ICN, the use of MMF in monotherapy can be optimised by dose adjustment based on the area under the curve (AUC) of mycophenolic acid (MPA). It involves a multicentre phase IV trial with direct individual benefit.
A population of 130 liver transplant patients at 2 to 10 years post-transplant, showing significant clinical ICN side effects and being given bitherapy by ICN +MMF will be included and randomised 1:1 in two arms:
Read more
- Arm 1: progressive interruption of ICN after obtaining an AUC of MPA of 50 mg.h/l, followed by MMF monotherapy with dose adjustment based on the AUC of MPA,
- Arm 2: continuation of the ICN+MMF bitherapy without MMF therapeutic drug monitoring.
The main judgement criterion will be the incidence of acute rejection in the 2 groups at 6 months. The secondary judgment criterion will be the evaluation of the benefit of stopping ICN on the side effects caused by these drugs.
- Conditions
- Liver Transplantation
- Being tested
- Mycophénolate Mofétil, Ciclosporine A, Tacrolimus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ciclosporine ADrug
TacrolimusDrug
| Study group | Role | What they receive |
|---|---|---|
| adjument MMF | Experimental | adjusting the dose according to the MMF AUC of mycophenolic acid Receives: Drug: Mycophénolate Mofétil; Drug: Ciclosporine A; Drug: Tacrolimus |
| continued treatment | Active comparator | Continued treatment empirically usual Receives: Drug: Mycophénolate Mofétil; Drug: Ciclosporine A; Drug: Tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of biopsy proven acute rejection treated
Incidence of biopsy proven acute rejection treated with corticoids or requiring a re-introduction of ICN in arm 1 -- or an increase of ICN in arm 2 -- 6 months after the interruption of ICN (arm 1) or after randomization (arm 2).
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2007 (estimated)
- Study startSep 2006
- Primary completionSep 2009
- Study completionSep 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, LimogesThe 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
- 92 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Limoges
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pierre MARQUET, MD, Principal investigator, CHU Limoges
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00456235
- Sponsor's protocol ID
- I06024
- Acronym
- MONOCEPT
- Status last verified
- Apr 2007
- First submitted
- 3 Apr 2007
- Last updated
- 17 Apr 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Interruption of the Calcineurine Inhibitors (ICN) and Introduction of Mycophenolate Mofetil (MMF) in Liver Transplant Patients With Side Effects Due to ICN: Study of the Reduction of the Risks of Rejection by Mycophenolate Mofetil Therapeutic Drug Monitoring
- ClinicalTrials.gov ID
- NCT00456235
- Acronym / sponsor ID
- MONOCEPT / I06024
- Conditions
- Liver Transplantation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 92 participants (actual)
- Lead sponsor
- University Hospital, LimogesUniversity, hospital or other
- Study start
- Sep 2006
- Primary completion
- Sep 2009 (actual)
- Study completion
- Sep 2011 (actual)
- First posted
- 4 Apr 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.
The aim of this project is to determine whether, in liver transplant patients with side effects due to ICN, the use of MMF in monotherapy can be optimised by dose adjustment based on the area under the curve (AUC) of mycophenolic acid (MPA). It involves a multicentre phase IV trial with direct individual benefit.
A population of 130 liver transplant patients at 2 to 10 years post-transplant, showing significant clinical ICN side effects and being given bitherapy by ICN +MMF will be included and randomised 1:1 in two arms:
- Arm 1: progressive interruption of ICN after obtaining an AUC of MPA of 50 mg.h/l, followed by MMF monotherapy with dose adjustment based on the AUC of MPA,
- Arm 2: continuation of the ICN+MMF bitherapy without MMF therapeutic drug monitoring.
The main judgement criterion will be the incidence of acute rejection in the 2 groups at 6 months. The secondary judgment criterion will be the evaluation of the benefit of stopping ICN on the side effects caused by these drugs.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| adjument MMF | Experimental | Drug: Mycophénolate Mofétil, Drug: Ciclosporine A, Drug: Tacrolimusadjusting the dose according to the MMF AUC of mycophenolic acid |
| continued treatment | Active comparator | Drug: Mycophénolate Mofétil, Drug: Ciclosporine A, Drug: TacrolimusContinued treatment empirically usual |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patient with first liver transplantion or retransplantation since more than 6 months: with a post-transplant lapse of time of 2 to 10 years and showing one of the following adverse effects of ICN:
- Renal insufficiency defined by a creatinine clearance <50ml/mn (calculated or estimated according to the Cockcroft formula)
- Arterial hypertension not controlled by an anti-hypertensive bitherapy
- Diabetes mellitus (fasting glycaemia >7.0mmol/l), whether treated or not
- Neuromuscular toxicity
Key exclusion criteria (9 listed)
- Acute rejection within the 6 months preceding the screening
- Previous history of cortico-resistant rejection
- Chronic rejection
- Significant ductopenia (absence of inter-lobule biliary canals in more than 30% of the portal tracts) on the pre-screening biopsy.
- Existence of a pre-transplantation diabetes mellitus.
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 |
|---|---|---|
| Mycophénolate Mofétil | Drug | adjument MMF, continued treatment |
| Ciclosporine A | Drug | adjument MMF, continued treatment |
| Tacrolimus | Drug | adjument MMF, continued treatment |
Primary outcome
Incidence of biopsy proven acute rejection treated
Time frame: 6 months
Incidence of biopsy proven acute rejection treated with corticoids or requiring a re-introduction of ICN in arm 1 -- or an increase of ICN in arm 2 -- 6 months after the interruption of ICN (arm 1) or after randomization (arm 2).
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 17 Apr 2013.
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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.
Pierre MARQUET, MD principal investigator
CHU Limoges
17 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 Mycophénolate Mofétil, Ciclosporine A and Tacrolimus in people with Liver Transplantation, run by University Hospital, Limoges at 17 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 7 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 17 Apr 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 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?
Incidence of biopsy proven acute rejection treated (time frame: 6 months). 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 17 Apr 2013.