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

Phase 2

Terminated

• Conditions: Graft Dysfunction; Ischemia Reperfusion Injury; Terminal Liver Disease; Graft Failure; Poor Graft Quality
• Interventions: Drug: HTK/Placebo; Drug: Tacrolimus

• Registration Number: NCT01564095
• Lead Sponsor: Ludwig-Maximilians - University of Munich

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2011-10
• Study First Submitted: 2012-03-14
• Study First Submitted QC: 2012-03-23
• Study First Posted: 2012-03-27
• Primary Completion: 2013-07
• Study Completion: 2013-07
• Status Verified: 2017-03
• Last Update Submitted: 2017-03-21
• Last Update Posted: 2017-03-23

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 25

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

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Exclusion Criteria

Donor:

• Hepatitis B- or Hepatitis C-infection

Recipient:

• Multi organ transplantation
• high urgency listing
• extrahepatic tumor disease
• pregnancy

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Maximum serum ALT-level	48 hrs following liver transplantation

Secondary Outcome Measures

Name	Time	Method
Bilirubin	1,2,4,7 days after surgery
ALT	1,2,4,7 days after surgery
AST	1,2,4,7 days after surgery
Creatinin	1,2,4,7 days after surgery
Graft survival	7 days

Trial Locations

Locations (7)

Department of General, Visceral and Transplantation Surgery, Ruprecht Karls University; 🇩🇪 Heidelberg, Germany

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 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