A Randomized Controlled Clinical Trial of Thymoglobulin® After Liver Transplantation
Condition: Liver Failure
MeSH terms: Liver Failure
Intervention: Thymoglobulin; Placebo
Intervention description: Treatment with thymoglobulin and delayed CNI post OLT; Normal transplant immunosuppression
Intervention MeSH terms: Thymoglobulin; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 110.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      This is a 24-month, Phase II, multi-center, two-arm, randomized controlled study of adult
      patients receiving a single organ liver transplant from a deceased donor; the purpose being
      to determine the efficacy of Thymoglobulin® induction and delayed initiation of CNI in the
      long-term preservation of renal function after liver transplantation. This study is based on
      the outcomes of an earlier phase 1 pilot study which was performed at the Cleveland Clinic.

      This study will be conducted at 3 centers, with 110 subjects randomized 1:1 into two groups:
      Group 1 will receive Thymoglobulin® induction, (4.5 mg/Kg, in 3 doses of 1.5 mg/Kg/dose) with
      delayed initiation of CNI to begin on Day 10 post LT. Group 2 will receive early CNI
      initiation (to be started no later than Day 2 post LT), and no Thymoglobulin® induction (or
      any other antibody).

      All subjects will also receive a maintenance immunosuppressive regimen consisting of
      corticosteroids and mycophenolate mofetil (MMF) according to standard of practice in
      orthotopic liver transplantation (OLT).

      Subjects will be consented pre-transplant. Participation may last up to 12 months post OLT.
      There are 15 study-related visits which will be completed during standard of care (SOC)
      visits.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients undergoing deceased donor solitary liver transplantation

          -  Age 18-75 years at the time of transplantation

          -  Willingness and ability to comply with the study procedures

          -  Signed informed consent form

          -  For patients with Hepatocellular carcinoma as indication for OLT, (must be within the
             Milan Criteria)

          -  Hepatitis C, positive or negative, patients

        Exclusion Criteria:

          -  Prior kidney transplantation

          -  Congenital or iatrogenic absence of one kidney

          -  Subjects on renal replacement therapy at the time of OLT

          -  MELD score >34

          -  HIV positive patient

          -  Patient with current severe systemic infection

          -  History of bacterial peritonitis within 30 days prior to OLT

          -  Active infection or recent infection within 30 days prior to OLT

          -  Use of a calcineurin inhibitor continuously for more than 90 days within the past 6
             months

          -  History of hypersensitivity to Thymoglobulin®, rabbits or tacrolimus

          -  Pregnant and/or nursing (lactating) females.

          -  Women of childbearing age who are unwilling to use effective contraception during the
             duration of the study, and for 30 days after study participation and/or last dose of
             Study Drug.