TOP-Study (Tacrolimus Organ Perfusion): Treatment of Ischemia Reperfusion Injury in Marginal Organs With an ex Vivo Tacrolimus Perfusion

Study Overview
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Brief Summary
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Utilisation of extended criteria donors due to critical organ shortage contributes to increased ischemia reperfusion injury as well as mortality following liver transplantation. Experimental data show protective effects on hepatic ischemia reperfusion injury (IRI) using the calcineurin inhibitor Tacrolimus applied intravenously or directly as a hepatic rinse. Moreover clinical data indicate a protective role of a Tacrolimus rinse in human liver transplantation when using normal, healthy grafts. The effects of Tacrolimus on hepatic injury in extended donor criteria (EDC) liver grafts remain unclear. Therefore, the aim of the present study is to examine the effects of a Tacrolimus ex vivo rinse (20 ng/ml) on cellular injury after transplantation of marginal liver grafts exhibiting 2 or more EDCs according to Eurotransplant's definition of EDC grafts.

Official Title
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TOP-Study (Tacrolimus Organ Perfusion): A Prospective Multicenter Trial for Treatment of Ischemia Reperfusion Injury in Marginal Organs With an ex Vivo Tacrolimus Perfusion

Conditions
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Terminal Liver Disease, Ischemia Reperfusion Injury, Graft Dysfunction, Graft Failure, Poor Graft Quality

Intervention / Treatment
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* Drug: Tacrolimus
* Drug: HTK/Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recipient: Chronical terminal liver failure, age > 18 years, first organ transplantation Donor: donor age > 65 Jahre macrovesicular steatosis > 40% (macroscopy or biopsy) BMI > 30 sodium >165 mmol/l ICU stay and ventilation > 7 days cold ischemia time > 13 hours AST > 99 U/l ALT > 105 U/l bilirubin > 3 mg/dl (> 51 µmol/l) application of epinephrine Exclusion Criteria: Donor: • Hepatitis B- or Hepatitis C-infection Recipient: Multi organ transplantation high urgency listing extrahepatic tumor disease pregnancy

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tacrolimus + HTK<br>Ex vivo Tacrolimus Rinse (20 ng/ml solved in 1000 ml HTK) of marginal liver grafts prior to implantation | Drug: Tacrolimus<br>* Marginal liver grafts are flushed with Tacrolimus (20ng/ml) solved in 1000 ml HTK preservation solution (duration: 15 min) ex vivo at the end of backtable preparation in the experimental group.<br>* Other names: HTK, histidin-tryptophane-ketoglurate organ preservation solution, Custodiol, Dr. Franz Köhler Chemie, Germany;|
| Placebo Comparator: HTK<br>Ex vivo Rinse (1000 ml HTK) of marginal liver grafts prior to implantation | Drug: HTK/Placebo<br>* Marginal liver grafts are flushed with 1000 ml HTK preservation solution(duration: 15 min) ex vivo at the end of backtable preparation in the placebo group.<br>* Other names: HTK, histidin-tryptophane-ketoglurate organ preservation solution, Custodiol, Dr. Franz Köhler Chemie, Germany;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum serum ALT-level |  | 48 hrs following liver transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ALT |  | 1,2,4,7 days after surgery | 
| Graft survival |  | 7 days | 
| AST |  | 1,2,4,7 days after surgery | 
| Bilirubin |  | 1,2,4,7 days after surgery | 
| Creatinin |  | 1,2,4,7 days after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver transplantation, EDC, IRI, graft survival, graft function, graft preconditioning, Tacrolimus rinse, randomised multicenter trial