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

Study Overview
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Brief Summary
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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.

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

Conditions
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Liver Dysfunction, Rejection, Transplant, Transplantation, Liver

Intervention / Treatment
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* Biological: Thymoglobulin
* Drug: Corticosteroid
* Drug: Tacrolimus
* Drug: Mycophenolate Mofetil


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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