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

Phase 3TerminatedNCT01564095

Ludwig-Maximilians - University of Munich25 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Conditions

Terminal Liver Disease Ischemia Reperfusion Injury Graft Dysfunction

Interventions

TacrolimusDRUG

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.

HTK/PlaceboDRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (7)

Department of General, Visceral and Transplantation Surgery, Charité Campus Virchow-Klinikum

Berlin, Germany

Department of General and Visceral Surgery, Johann Wolfgang Goethe-University

Frankfurt am Main, Germany

Department of General, Visceral and Transplantation Surgery, Ruprecht Karls University

Heidelberg, Germany

Department of Transplantation Surgery, Johannes Gutenberg University

Mainz, Germany

Ludwig-Maximilians University, Campus Grosshadern, Department of Surgery

Munich, Germany

Department of Surgery, University of Regensburg

Regensburg, Germany

Department of General, Visceral and Transplantation Surgery, Eberhard Karls University

Tübingen, Germany

Outcomes

Primary Outcomes

Maximum serum ALT-level

Time frame: 48 hrs following liver transplantation

Secondary Outcomes

ALT

Time frame: 1,2,4,7 days after surgery

Graft survival

Time frame: 7 days

AST

Time frame: 1,2,4,7 days after surgery

Bilirubin

Time frame: 1,2,4,7 days after surgery

Creatinin

Time frame: 1,2,4,7 days after surgery