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

Ludwig Maximilian University of Munich

Status and phase: Terminated; Phase 3; Phase 2

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

Treatments: Drug: Tacrolimus; Drug: HTK/Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT01564095

TOP-Study

Details and patient eligibility

About

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.

Enrollment: 25 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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25 participants in 2 patient groups, including a placebo group

Tacrolimus + HTK

Experimental group

Description:

Ex vivo Tacrolimus Rinse (20 ng/ml solved in 1000 ml HTK) of marginal liver grafts prior to implantation

Treatment:

Drug: Tacrolimus

HTK

Placebo Comparator group

Description:

Ex vivo Rinse (1000 ml HTK) of marginal liver grafts prior to implantation

Treatment:

Drug: HTK/Placebo