A Study of Thymoglobulin and Tacrolimus in Liver Transplant

Study Overview
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Brief Summary
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The purpose of this study is to compare kidney function, long term patient and graft survival, and incidence of acute rejection in liver transplant recipients between one group receiving thymoglobulin induction and delayed initiation of tacrolimus and another group of liver transplant recipients having immediate administration of tacrolimus without any induction immunosuppression.

Detailed Description
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Renal insufficiency following liver transplantation in adult recipients is a major cause of morbidity and a major contributor to mortality. One of the key factors contributing to this renal dysfunction is the use of calcineurin inhibitors. There is some evidence to suggest that the first 7-10 days following liver transplantation are crucial in terms of renal function and the ability to avoid the use of nephrotoxic agents such as calcineurin inhibitors may have a significant impact on long-term outcome.

Official Title
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A Study Comparing Thymoglobulin to Tacrolimus in Liver Transplant and Impact on Renal Function

Conditions
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Liver Transplantation, Liver Disease, Immunosuppression

Intervention / Treatment
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* Drug: anti-thymocyte globulin (rabbit)
* Drug: tacrolimus


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 Over 18 years of age Signed informed consent form if female of childbearing potential: Must not be lactating Must have negative serum pregnancy test on study day 0 Must have agreed on a reliable and acceptable form of contraception during the study sexually active males must be practicing an acceptable form of contraception Exclusion Criteria: Multiple organ transplants Prior solid organ or bone marrow transplant recipients Fulminant hepatic failure Status 1 transplants Liver transplant candidates with greater than 6 weeks of dialysis Patients who in the opinion of the Investigator are not eligible for thymo induction at the time of transplant Recipients of investigational therapy within 90 days prior to transplant Know contraindication to administration of rabbit anti-thymocyte globulin Patients whose medical condition is such that the physician feels it would not be in their best interest to participate in the study Patients who are unwilling to have a Glofil nuclear medicine scan at specified time points 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

Ages Eligible for Study
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Minimum Age: 19 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Patients in arm 1 will receive induction with thymoglobulin at time of transplant with delayed initiation of tacrolimus | Drug: anti-thymocyte globulin (rabbit)<br>* 1.5mg/kg per dose with the first dose initiated in the operating room prior to reperfusion of the transplanted liver. It will then be administered again on post operative day #1, 3 and 5 for a total cumulative dose of 6mg/kg.<br>* Other names: thymoglobulin;|
| Active Comparator: 2<br>patients in arm 2 will not receive thymo induction at time of transplant and will have immediate initiation of tacrolimus | Drug: tacrolimus<br>* Tacrolimus will be administered orally on post op day #1 as per standard of care.<br>* Other names: prograf;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of renal function via Glo-Fil nuclear medicine scan and laboratory parameters |  | Post operative day #1, month 6 and month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| patient and graft survival, incidence of acute rejection, incidence of active CMV disease, incidence of other infections, any adverse events or serious adverse events associated with the use of thymo induction therapy |  | post op days 1-6, months 3,6, 9, and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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liver transplant