Tacrolimus During the Implantation and the Effect on Ischemia-reperfusion Injury in Liver Transplantation

Study Overview
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Brief Summary
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The evaluation of the efficacy of an intraportal infusion with Tacrolimus, at the time of liver graft implantation, compared to a control group without immunosuppressive intraportal infusion (Placebo: Saline solution 0.9%) with respect to the initial liver function measured by the parameters of the liver function (LFP): AST (U/L), ALT (U/L), total Bilirubin (mg/dL) and the coagulation factors: NT (%), PTT (s), INR.

Official Title
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Evaluation of Tacrolimus (Prograf®) Intraportal Infusion During the Implantation and the Protective Effect on Ischemia-reperfusion Injury in Orthotopic Liver Transplant Recipients - Single Center Study

Conditions
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Ischemia Reperfusion Injury

Intervention / Treatment
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* Drug: Tacrolimus
* Other: Saline solution 0.9% (250mL)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Multi organ transplantation or retransplantation ABO incompatible donor organ recipients- Patients, who are listed on the liver transplant-waiting list at the Vienna General Hospital and who fulfill the clinical requirements (local allocation) Written informed consent Age > 18 First transplantation Exclusion Criteria: Fulminant failure of the liver Liver-Living donor recipients pregnant or nursing women Allergy/Intolerance to antimetabolites, HCO-60, EL Cremophor or similar compounds,Steroids or macrolide antibiotics HIV-positive donors or recipients Participants of another clinical study Patient has any form of substance abuse, psychiatric disorder or condition, which, in the opinion of the investigator, may invalidate communication.

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>Group A receives an intraportal Tacrolimus-infusion, ATG Induction, Tacrolimus and Steroids. | Drug: Tacrolimus<br>* Immunosuppression, intraoperative intraportal infusion of 1ml Tacrolimus with a concentration of 20 ug/mL<br>* Other names: PROGRAF;|
| Placebo Comparator: B<br>Group B receives a placebo-Saline solution (0.9%)-Infusion, ATG induction, Tacrolimus and Steroids. | Other: Saline solution 0.9% (250mL)<br>* intraoperative intraportal infusion of Saline solution 0.9% (250mL)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| initial liver function measured by the parameters of the liver function (LFP): AST (U/L), ALT (U/L), total Bilirubin (mg/dL) and the coagulation factors: NT (%), PTT(s),INR. |  | Day 1,2,3; Weeks 6 and 12 post OLT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum parameters: TNF alpha, IL1, IL6 |  | within the first 3 month | 
| Histopathology (before and after reperfusion) |  | within the first 3 month | 
| Frequency of rejection episodes |  | within the first 3 month | 
| Graft function (Serum) und graft survival at 3 months post Tx |  | within the first 3 month | 
| Patient survival at 3 months post Tx |  | within the first 3 month |