Everolimus Monotherapy as Immunosuppression After Liver Transplant
Condition: Kidney Failure
MeSH terms: Renal Insufficiency
Intervention: Tacrolimus; Everolimus
Intervention description: Tacrolimus (FK / Prograf) titrated to a goal trough of 6 - 8 ng/ml; Everolimus monotherapy - target trough levels 4 - 8 ng/ml as maintenance immunosuppression
Intervention MeSH terms: Everolimus; Tacrolimus
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Tacrolimus as maintenance immunosuppression
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Tacrolimus is the standard immunosuppressive drug used to prevent organ rejection post liver
      transplant. One side effect of Tacrolimus is nephrotoxicity. Everolimus does not have the
      nephrotoxicity side effects of Tacrolimus.

      Replacement of Tacrolimus by Everolimus may have a reduced incidence of renal dysfunction in
      liver transplant patients who have near normal kidney function prior to liver
      transplantation. Other investigators have already shown a benefit in terms of renal function
      with introduction of Everolimus with reduced-exposure tacrolimus at 1 month after liver
      transplantation, this benefit has been shown was maintained to 3 years in patients who
      continued Everolimus therapy with comparable efficacy and no late safety concerns.
      Investigators in this trial are proposing to advance this approach further by completely
      eliminating Tacrolimus from patients' immunosuppression protocol. The rationale for this
      approach is based on a unique induction immunosuppression protocol.

      Liver transplant patients receive potent induction immunosuppression in the form of rabbit
      anti thymocyte globulin.

      Investigators believe that in conjunction with this induction regimen, patients can be
      maintained on Everolimus monotherapy without the risk of rejection. By completely eliminating
      Tacrolimus, investigators believe that there may be further benefit in terms of renal
      function. Additionally, Everolimus is known to induce tolerance in transplant recipients.
      Tolerant patients do not require immunosuppression to accept transplant organs.

      The long-term efficacy and safety of Everolimus monotherapy as the maintenance
      immunosuppression in patients receiving rATG induction is unknown.

      Primary Aim: Assess the effect of Everolimus monotherapy versus Tacrolimus monotherapy on
      long term renal function measured by Glomerular Filtration Rate (GFR).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Liver transplant recipients >= 18 years old

          -  Normal baseline renal dysfunction (GFR > 60 mL/min)

          -  Rabbit anti-thymocyte globulin (rATG) induction (cumulative dose 1.5 - 5 mg/kg)

          -  Indication for transplant: ethanol, hepatitis C, or nonalcoholic steatohepatitis or
             any combination of these

        Exclusion Criteria:

          -  Increased risk of rejection: autoimmune hepatitis, primary biliary cirrhosis, primary
             sclerosing cholangitis, positive crossmatch, retransplantation

          -  Incompletely healed incision or other wound healing issues at time of randomization

          -  Multiple or previous organ transplantation

          -  Severe, uncontrolled hypercholesterolemia (> 9mmol/L) or hypertriglyceridemia (>8.5
             mmol/L) in the 6 months prior to transplantation

          -  Insurance company unwilling to pay for the cost of the everolimus or patient does not
             qualify for the Novartis Patient Assistance Program.

          -  Pregnant women

          -  Unable to provide informed consent