Mycophenolate Mofetil Immunosuppression Without/With Reduced Dose Calcineurin Inhibitor Long After Liver Transplantation

This study has been completed.
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
Albert Einstein Healthcare Network
ClinicalTrials.gov Identifier:
NCT00206076
First received: September 13, 2005
Last updated: July 31, 2013
Last verified: July 2013
  Purpose

The purpose of the study is to assess the safety and efficacy of mycophenolate mofetil alone, or with reduced dose cyclosporine (CsA) or tacrolimus, for immunosuppression long-term after liver transplantation, in an attempt to reduce the potential side effects from using cyclosporine or tacrolimus.


Condition Intervention Phase
Liver Disease
Drug: mycophenolate mofetil
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: CellCept (Mycophenolate Mofetil, MMF) Maintenance Immunosuppression in Liver Transplant Recipients With Long-term Follow-up Post-transplantation for Non-Autoimmune Liver Disease - A Prospective, Randomized, Multicenter Trial.

Resource links provided by NLM:


Further study details as provided by Albert Einstein Healthcare Network:

Primary Outcome Measures:
  • Number of Biopsy Proven Rejections at 12 Months [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    assessed by liver biopsy using Banff International Consensus Schema


Secondary Outcome Measures:
  • Patient and Graft Survival at 12 Months [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Number of Participants With Adverse Events Including Infections at 12 Months [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Enrollment: 19
Study Start Date: August 2006
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
mycophenolate mofetil monotherapy
Drug: mycophenolate mofetil
mycophenolate mofetil monotherapy
Active Comparator: 2
mycophenolate mofetil and half their baseline dose of calcineurin inhibitor
Drug: mycophenolate mofetil
mycophenolate mofetil and half their baseline dose of calcineurin inhibitor

Detailed Description:

Most liver transplant recipients receive an immunosuppressive drug regimen that contains either cyclosporine or tacrolimus. Although these drugs have revolutionized transplantation, in many patients their long-term use is a major cause of serious side effects, including kidney failure, hypertension, diabetes mellitus, hyperlipidemia, and/or neurologic side effects. Stopping or reducing the dose of cyclosporine or tacrolimus can ameliorate the above side effects but may increase the risk of rejection. Mycophenolate mofetil (MMF), a safe and effective immunosuppressant that does not cause the above side effects, is typically used in combination with cyclosporine or tacrolimus. Attempts in liver transplant recipients at using mycophenolate mofetil alone or with reduced dose cyclosporine or tacrolimus have been successful but some patients developed rejection, and a few patients suffered liver failure. Most rejections after liver transplantation are easy to successfully treat with increased immunosuppression, but such treatment may carry risks such as increased susceptibility to infection. There have not yet been any large trials to adequately assess the safety and efficacy of using mycophenolate mofetil this way (alone or with reduced dose calcineurin inhibitor (CNI)).

The purpose of this trial is to evaluate whether mycophenolate mofetil as monotherapy or with reduced dose cyclosporine or tacrolimus long-term after liver transplantation is safe and decreases side effects related to calcineurin inhibitor use.

Only liver recipients expected to have a relatively low risk of developing rejection and/or liver failure are eligible for this trial. Some reasons for considering them low risk are their stable liver function, having had the transplant for over a year, having had one or fewer prior rejection episodes, having had non-autoimmune liver disease, their currently requiring low dose/level cyclosporine or tacrolimus, and the plan to use high dose mycophenolate mofetil and to exclude patients that fail to attain target values for mycophenolic acid area under the concentration-time curve (MPA AUC - MycoPhenolic Acid Area Under the Curve).

Eligible patients will be randomized to receive either mycophenolate mofetil monotherapy (MMF; CNI discontinued), or mycophenolate mofetil and half their baseline dose of calcineurin inhibitor (MMF; CNI decreased). The primary outcome is biopsy proven rejection and the secondary outcomes include patient and graft survival, adverse events, hepatic profile, blood pressure, renal function, diabetes, and lipid profile. Additionally, mycophenolic acid concentrations will be measured; a mycophenolate mofetil monotherapy trial provides unique opportunity to study the implications of such monitoring. Patients will be followed for 12 months; there will be 16 visits during the trial.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female 18 years of age or older (females who can become pregnant must use two acceptable methods of birth control while taking mycophenolate mofetil)
  • Orthotopic liver transplant more than one year prior to enrollment
  • Using calcineurin inhibitor to prevent rejection at time of screening
  • Patients must be willing to provide informed consent and abide by the requirements of the study

Exclusion Criteria:

  • Liver disease may not have been secondary to an autoimmune cause, including:

    • autoimmune hepatitis,
    • primary sclerosing cholangitis,
    • primary biliary cirrhosis
  • Patients who have had:

    • more than one prior episode of rejection,
    • rejection within the past six months,
    • any corticosteroid resistant rejection
  • Patients with a tacrolimus trough level of greater than 7 ng/ml within 90 days prior to enrollment
  • Patients with a cyclosporine trough level greater than 225 ng/ml within 90 days prior to enrollment
  • Patients taking more the 5 mg per day of prednisone within 90 days prior to enrollment
  • Patients taking any prednisone within 30 days of enrollment
  • Allograft dysfunction within 6 months of enrollment, including ALT and/or total bilirubin greater than 2x normal, and/or biopsy proven hepatitis C virus (HCV) with fibrosis greater than stage II
  • White blood cell count less than 2,500 or platelet count less than 50,000 within 60 days of enrollment
  • MPA AUC threshold: Patients are not eligible for the study if they do not attain the threshold value MPA AUC (>30 mg*h/L if on CsA, >40 mg*h/L if on tacrolimus) after 50% calcineurin inhibitor reduction, measured using a 3-sample estimate (trough, 30-min, 120-min)
  • Patients who have had a previous transplant of organ(s) other than liver
  • Patients who received a liver from a hepatitis C positive donor
  • Patients who received a liver from a living donor
  • Patients with any technical complication requiring intervention within the three months prior to screening
  • Current infection requiring treatment
  • History of post transplant lymphoproliferative disorder
  • History of malignancy other than non-melanoma skin cancer or Stage 1-2 hepatoma
  • Active or unhealed duodenal ulcer
  • Concomitant treatment with rapamycin and/or interferon
  • Known allergy or sensitivity to CellCept® or any of its components
  • Unable or unwilling to comply with the protocol requirements or considered by the investigator(s) to be unfit for the study
  • Participation in a clinical trial within 30 days prior to study entry or prior enrollment in any CellCept® clinical trial
  • Pregnant or breastfeeding woman
  • Diabetes with known, clinically significant gastroparesis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00206076

Locations
United States, Kentucky
University of Kentucky at Lexington
Lexington, Kentucky, United States
United States, Pennsylvania
Albert Einstein Medical Center
Philadelphia, Pennsylvania, United States, 19141
United States, Texas
Texas Transplant Institute
San Antonio, Texas, United States
Sponsors and Collaborators
Albert Einstein Healthcare Network
Hoffmann-La Roche
Investigators
Principal Investigator: David J Reich, MD Drexel College of Medicine
  More Information

Publications:

Responsible Party: Albert Einstein Healthcare Network
ClinicalTrials.gov Identifier: NCT00206076     History of Changes
Other Study ID Numbers: CEL350
Study First Received: September 13, 2005
Results First Received: February 23, 2012
Last Updated: July 31, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Albert Einstein Healthcare Network:
Liver transplantation
Calcineurin inhibitor withdraw
mycophenolate mofetil
Immunosuppression side effects
Graft rejection

Additional relevant MeSH terms:
Liver Diseases
Digestive System Diseases
Mycophenolic Acid
Mycophenolate mofetil
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 16, 2014