Gradual Withdrawal of Immune System Suppressing Drugs in Patients Receiving a Liver Transplant
Condition: Hepatitis C; Hepatitis C, Chronic; Nonimmune Nonviral Causes of Liver Failure
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Liver Failure
Intervention: calcineurin inhibitor-based immunosuppression; liver transplant; corticosteroids; immunosuppression withdrawal
Intervention description: May be cyclosporine, mycophenolate mofetil, or tacrolimus; Occurs at study entry; 3-month course of corticosteroids; One year after transplantation, participants eligible for withdrawal are randomly assigned in a 4 to 1 ratio to immunosuppression withdrawal or to maintenance.
Intervention MeSH terms: Prednisone; Calcineurin Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 275.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: hepatitis; hepatitis C; HCV; liver; liver disease; liver transplant; liver transplantation; transplant; hepatic; hepatic transplantation; immunosuppression; rejection

Summary:

      In order to prevent organ rejection, patients receiving liver transplants currently require
      life-long treatment with immune system-suppressing medications to prevent the rejection of
      the transplanted liver. However, these medications can cause long-term side effects, such as
      infection, kidney problems, diabetes, and cancer. In patients infected with hepatitis C virus
      (HCV), these medications may increase the risk of HCV infection in the transplanted liver.
      The purpose of this study is to determine whether a slow withdrawal of immune
      system-suppressing medications is safe in two groups of subjects: those who receive a liver
      transplant due to HCV, and those who receive a liver transplant due to non-immune, non-viral
      causes of liver failure. The study will also look at whether slow withdrawal will help reduce
      the long-term side effects of immune system-suppressing medications and decrease the chance
      for HCV infection of the new liver in transplant patients with HCV.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female 18 years of age or older.

          2. Necessity for liver transplant.

          3. For females of childbearing potential: a negative pregnancy test at study entry and
             agreement to use approved methods of birth control for the duration of their
             participation.

          4. Ability to provide informed consent.

          5. Availability of donor specimen(s).

          6. For individuals with hepatitis C infection, presence of hepatitis genomes in blood.

        Exclusion Criteria:

          1. Previous transplant.

          2. Multiorgan or split liver transplant other than with a right trisegment.

          3. Living donor transplant.

          4. Donor liver from a donor positive for antibody against hepatitis C.

          5. Donor liver from a non-heart-beating donor.

          6. Liver failure due to autoimmune disease.

          7. Fulminant liver failure.

          8. Hepatitis B infection as defined by the presence of HbSAg or hepatitis-C infection
             with a genome other than genome 1.

          9. Stage III or higher hepatocellular cancer.

         10. History of malignancy except hepatocellular cancer, adequately treated in situ
             cervical carcinoma,adequately treated basal or squamous cell carcinoma of skin, or
             other cancer judged to have a 5-year risk of recurrence less than 10%.

         11. Active systemic infection at the time of transplantation.

         12. Clinically significant chronic renal disease.

         13. Clinically significant cardiovascular or cerebrovascular disease.

         14. Infection with human immunodeficiency virus.

         15. Any investigational drug received within 6 weeks of study entry or any investigational
             vaccine received at any time.

         16. Hypersensitivity to tacrolimus.

         17. Unwillingness or inability to comply with study requirements.