A Randomized Controlled Clinical Trial of Thymoglobulin® After Liver Transplantation
Condition: Liver Failure
MeSH terms: Liver Failure
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      Functional recovery of renal function from acute renal failure occurs in 75% of patients at
      approximately 14 days after onset of the disease. In liver transplantation, intraoperative
      hemodynamic insults typically lead to acute renal failure which may be further worsened by
      exposure to CNI therapy in the early postoperative period. In practice, patients who
      demonstrate early evidence of acute renal failure often have their CNI therapy delayed for
      4-5 days. This duration of CNI delay is too short to have any salutary effect on the course
      or severity of acute kidney injury as less than 20% of patients experience any functional
      recovery by day 5.

      Thymoglobulin® (Sanofi, Cambridge, MA) is a polyclonal immunosuppressive agent that is
      derived from rabbits immunized with pediatric thymocytes. It contains antibodies to a wide
      variety of T-cell antigens and major histocompatibility complex (MHC) antigens and is
      approved for the treatment of kidney rejection by the FDA. Thymoglobulin® has been shown to
      be a safe and efficacious induction therapy that permits delayed exposure to CNI therapy
      while preventing the occurrence of acute rejection in kidney transplantation. The
      investigators hypothesize that any perioperative insult leading to AKI in OLT recipients is
      unlikely to be beneficially impacted by a short delay of CNI introduction. Further
      hypothesized is that avoidance of CNI for 10 days will have a beneficial effect on the course
      and severity of perioperative AKI. Since perioperative AKI is a potent risk factor for
      chronic kidney disease (CKD) in the late post-transplant period, also hypothesized is that
      minimizing the risk and severity of AKI with prolonged delayed exposure to CNI will have a
      beneficial effect on renal function late after liver transplantation.
    

Intervention name(s): Thymoglobulin; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Treatment with thymoglobulin and delayed CNI post OLT; Normal transplant immunosuppression
Other intervention name(s): Anti-thymocyte Globulin
Intervention MeSH terms: Thymoglobulin; Antilymphocyte Serum
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment