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

Genzyme

Status and phase: Completed; Phase 2

Conditions: Transplantation, Liver; Rejection, Transplant; Liver Dysfunction

Treatments: Biological: Thymoglobulin; Drug: Corticosteroid; Drug: Mycophenolate Mofetil; Drug: Tacrolimus

Study type: Interventional

Funder types: Industry

Identifiers

NCT00117689

Thymo102700103

Details and patient eligibility

About

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.

Enrollment: 75 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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75 participants in 2 patient groups

1

Experimental group

Description:

Standard (tacrolimus based standard therapy without induction)

Treatment:

Drug: Mycophenolate Mofetil

Drug: Tacrolimus

Biological: Thymoglobulin

2 Standard of Care

Active Comparator group

Description:

Thymoglobulin with tacrolimus and corticosteroid sparing maintenance therapy

Treatment:

Drug: Corticosteroid

Drug: Mycophenolate Mofetil

Drug: Tacrolimus