RESCUE Study - Everolimus in Liver Transplantation Recipients With Renal Insufficiency
Condition: Liver Transplantation
Intervention: Everolimus; Calcineurin inhibitors (CNI); Mycophenolate acid (MPA)/ Azathioprine (AZA); Steroids
Intervention description: 1.5 mg bid adjusted in order to achieve a trough level between 3 and 8 ng/mL while in combination with CNI and between 6 and 12 ng/mL after CNI discontinuation
Intervention MeSH terms: Cyclosporine; Everolimus; Azathioprine; Tacrolimus; Cyclosporins; Calcineurin Inhibitors
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 145.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Keywords: Liver transplantation, everolimus, calcineurin inhibitor, renal function

Summary:

      The purpose of the study is to assess the effect of everolimus initiation together with
      reduction or discontinuation of calcineurin inhibitor (CNI) on renal function in maintenance
      liver transplant recipients with CNI-related renal impairment, while maintaining efficacy.
    

Eligibility criteria:

        Inclusion criteria

          -  Male or female 18 - 70 years old

          -  Patient who has undergone a primary liver transplantation 12 to 60 months ago from a
             cadaveric or a living donor

          -  Patient with a calculated GFR ≤ 60 and ≥ 20mL/min

          -  Patient receiving tacrolimus with C0-h level ≥ 3 and ≤ 8 ng/mL or Neoral® with C0-h
             level ≥ 50 and ≤ 150 ng/mL or with C2-h level ≥ 250 ng/mL and ≤ 650 ng/mL with or
             without any of the following (MPA or AZA or steroids)

          -  Patient willing and capable of giving written informed consent for study participation
             and able to participate in the study for 6 months

          -  Patient in whom an allograft biopsy will not be contraindicated

          -  Female capable of becoming pregnant must have a negative pregnancy test prior to
             randomization and are required to practice a medically approved method of birth
             control for the duration of the study

        Exclusion criteria

          -  Recipient of multiple solid organ transplants

          -  Patient on dialysis

          -  Patient with an identifiable cause of renal dysfunction other than CNI toxicity

          -  Patient with proteinuria ≥ 1.0 g/24h

          -  Patient with any acute rejection within 6 months prior to randomization

          -  Patient with platelet count of ≤ 50,000/mm³ or white blood cell count of ≤ 2,000/mm³
             or hemoglobin value ≤ 8 g/dL

          -  Undergone a liver transplantation for a hepatocellular carcinoma with sign of
             recurrence;

          -  Severe graft dysfunction;

          -  HCV positive patient who needs an active anti-viral treatment

          -  HIV positive patient

          -  Patient who is breast feeding

          -  Patient with a current severe systemic infection

          -  Patient who has received an unlicensed drug or therapy within one month prior to study
             entry

          -  Presence of any hypersensitivity to drugs similar to everolimus (e.g. macrolides)

          -  Use of any other immunosuppressive drugs than tacrolimus/cyclosporine microemulsion,
             steroids, azathioprine and mycophenolic acid

        Additional protocol-defined inclusion/exclusion criteria may apply.