Evaluation of Thymoglobulin Induction and Reduced Doses of Calcineurin Inhibitors on Liver Transplant Rejection

A Randomized, Controlled, Multi-Center Study of Thymoglobulin Induction Therapy With a Calcineurin Inhibitor Sparing Regimen in Liver Transplant Patients

This study involves the use of a drug called Thymoglobulin, which is approved in the US to treat kidney transplant rejection and in Canada to treat and prevent kidney transplant rejection. This study will evaluate the effect of Thymoglobulin induction therapy and reduced doses of calcineurin inhibitors on the incidence of liver rejection and will provide a basis for future evaluations of Thymoglobulin as an immunosuppressive agent to help decrease the incidence of liver transplant rejection. Subjects meeting all inclusion and exclusion criteria are eligible to participate in this study. Approximately 75 study subjects from up to 18 transplant centers in the United States and Canada will be enrolled in this 12-month study.

Study Overview

• Status: Completed
• Conditions: Liver Dysfunction; Transplantation, Liver; Rejection, Transplant
• Intervention / Treatment: Biological: Thymoglobulin; Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Drug: Corticosteroid

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2N2
      • Toronto University Hospital - UHN
  • Quebec
    • Montreal, Quebec, Canada, H3A 1A1
      • Royal Victoria Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama, Birmingham
  • California
    • Los Angeles, California, United States, 90033
      • USC University Hospital
    • San Francisco, California, United States, 94143
      • University of California, San Fransisco Hospital
  • Colorado
    • Denver, Colorado, United States, 80262
      • University of Colorado Hospital and Health Sciences Center
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Jacksonville
    • Miami, Florida, United States, 33136
      • University of Miami
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Fairview University Medical Center
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University Medical Center
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati Medical Center
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio, University Hospital
  • Virginia
    • Richmond, Virginia, United States, 23298
      • VCU Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Primary liver transplant recipient with Model for End-Stage Liver Disease (MELD) criteria documentation
• Serum creatinine > 1.5mg/dL at the time of transplant, or based on the value used to calculate the most recent pre-operative MELD Score for liver allocation
• Ages greater than or equal to 18 years
• If female, must not be lactating; must have a negative serum beta-human chorionic gonadotropin (HCG) test within 7 days prior to Study Day 0 (Day of Transplant); and must agree to practice an acceptable and reliable form of contraception during the study
• Signed informed consent

Exclusion Criteria:

• Living donor or multiple organ transplants
• Prior solid organ or bone marrow transplant recipient
• Fulminant hepatic failure
• Status 1 transplants
• ABO incompatible transplants
• Transplants utilizing livers from non heart-beating donors
• Liver transplant candidates with > 6 weeks of analysis
• Donor with positive serology for hepatitis B surface antigen (HBsAg)
• Evidence of human immunodeficiency virus (HIV)
• Autoimmune hepatitis
• History of chronic steroid or immunosuppressant use in the 90 days prior to transplant, except for inhaled corticosteroids to treat asthma
• Recipient of investigational therapy within 90 days prior to transplant procedure
• Known contraindication to administration of rabbit anti-thymocyte globulin
• Acute viral illness
• History of malignancy within 5 years, with the exception of adequately treated localized squamous or basal cell carcinoma of the skin without evidence of recurrence, and/or hepatocellular carcinoma
• Illness other than primary liver disease (e.g. severe ischemic heart disease, left ventricular dysfunction, or pulmonary disease), which, in the opinion of the investigator, may significantly increase the risk of the transplantation procedure
• Current drug and alcohol abuse that, in the opinion of the investigator, puts subjects at risk for poor compliance (no drug test required)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Standard (tacrolimus based standard therapy without induction)	Biological: Thymoglobulin; Antibody inductions with tacrolimus and corticosteroid sparing maintenance therapy; Other Names: [Anti-thymocyte Globulin (rabbit)]; Drug: Tacrolimus; Between Day 3 the last dose of Thymoglobulin; Drug: Mycophenolate Mofetil; for at least 1 month posttransplant
Active Comparator: 2 Standard of Care; Thymoglobulin with tacrolimus and corticosteroid sparing maintenance therapy	Drug: Tacrolimus; Between Day 3 the last dose of Thymoglobulin; Drug: Mycophenolate Mofetil; for at least 1 month posttransplant; Drug: Corticosteroid; For a minimum of 3 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Freedom from biopsy-proven acute rejection (including humoral rejection)	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Explore the impact of Thymoglobulin on kidney function after transplant	6 months
Explore the impact of Thymoglobulin on the prevention of liver transplant rejection, transplanted liver loss, death, and safety of Thymoglobulin after transplant.	12 months

Collaborators and Investigators

• Sponsor: Genzyme, a Sanofi Company

Publications and helpful links

Helpful Links

• US FDA Approved Full Prescribing Information for Thymoglobulin®

Study record dates

Study Major Dates

• Study Start: April 1, 2005
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): December 1, 2007

Study Registration Dates

• First Submitted: June 30, 2005
• First Submitted That Met QC Criteria: July 7, 2005
• First Posted (Estimate): July 8, 2005

Study Record Updates

• Last Update Posted (Estimate): March 18, 2015
• Last Update Submitted That Met QC Criteria: March 17, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Anti-T cell antibodies; Primary Liver Transplantation and Renal Dysfunction; Liver Transplant Rejection; Induction Therapy with reduction of Calcineurin inhibitors; Primary Liver Transplantation; Primary Transplant Rejection; Transplantation, Liver; Rejection, Transplant
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Calcineurin Inhibitors; Tacrolimus; Mycophenolic Acid; Thymoglobulin; Antilymphocyte Serum
• Other Study ID Numbers: Thymo102700103