Graft Dysfunction, Graft Failure, Ischemia Reperfusion Injury, Poor Graft Quality, Terminal Liver Disease
Conditions
Keywords
Liver transplantation, EDC, IRI, graft survival, graft function, graft preconditioning, Tacrolimus rinse, randomised multicenter trial
Brief summary
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.
Interventions
DRUGTacrolimus
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.
DRUGHTK/Placebo
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.
Sponsors
Ludwig-Maximilians - University of Munich
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum serum ALT-level | 48 hrs following liver transplantation |
Secondary
| Measure | 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 |
Countries
Germany
Outcome results
None listed