Mycophenolate Mofetil Immunosuppression Without/With Reduced Dose Calcineurin Inhibitor Long After Liver Transplantation
Condition: Liver Disease
MeSH terms: Liver Diseases
Intervention: mycophenolate mofetil; mycophenolate mofetil
Intervention description: mycophenolate mofetil and half their baseline dose of calcineurin inhibitor; mycophenolate mofetil monotherapy
Intervention MeSH terms: Mycophenolic Acid
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Liver transplantation; Calcineurin inhibitor withdraw; mycophenolate mofetil; Immunosuppression side effects; Graft rejection

Summary:

      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.
    

Eligibility 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