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Open Access Clinical trial protocol

Protocol TOP-Study (tacrolimus organ perfusion): a prospective randomized multicenter trial to reduce ischemia reperfusion injury in transplantation of marginal liver grafts with an ex vivo tacrolimus perfusion

Sebastian Pratschke1, Michael Eder1, Michael Heise2, Silvio Nadalin3, Andreas Pascher4, Peter Schemmer5, Marcus N Scherer6, Frank Ulrich7, Heiner Wolters8, Karl-Walter Jauch1, Dirk Wöhling9 and Martin K Angele1*

Author Affiliations

1 Department of Surgery, University of Munich Hospital, Campus Grosshadern, Ludwig-Maximilians-University, Marchioninistrasse 15, 81377 Munich, Germany

2 Department of Transplantation Surgery, University Medical Center, Johannes Gutenberg University, Langenbeckstrasse 1, 55131 Mainz, Germany

3 Department of General, Visceral and Transplantation Surgery, University Hospital Tübingen, Eberhard Karls University, Hoppe-Seyler-Strasse 3, 72076 Tübingen, Germany

4 Department of General, Visceral and Transplantation Surgery, Charité Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany

5 Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Ruprecht-Karls-University, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany

6 Department of Surgery, University Hospital Regensburg, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany

7 Department of General and Visceral Surgery, Johann Wolfgang Goethe-University Frankfurt am Main, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany

8 Department of General and Visceral Surgery, University Hospital Münster, Westphalian Wilhelms-University, Waldeyerstrasse 1, 48149 Münster, Germany

9 DABIO Gesellschaft für Auftragsforschung mbH, Altlaufstrasse 40, 85635 Höhenkirchen, Germany

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Transplantation Research 2013, 2:3  doi:10.1186/2047-1440-2-3

Published: 4 March 2013

Abstract

Background

Critical organ shortage results in the utilization of extended donor criteria (EDC) liver grafts. These marginal liver grafts are prone to increased ischemia reperfusion injury (IRI) which may contribute to deteriorated graft function and survival. Experimental data have shown that the calcineurin inhibitor tacrolimus exerts protective effects on hepatic IRI when applied intravenously or directly as a hepatic rinse. Therefore, the aim of the present study is to examine the effects of an ex vivo tacrolimus perfusion on IRI in transplantation of EDC liver grafts.

Methods/Design

The TOP-Study (tacrolimus organ perfusion) is a randomized multicenter trial comparing the ex vivo tacrolimus perfusion of marginal liver grafts with placebo. We hypothesize that a tacrolimus rinse reduces IRI, potentially improving organ survival following transplantation of EDC livers. The study includes livers with two or more EDC, according to Eurotransplant International Foundation’s definition of EDC livers. Prior to implantation, livers randomized to the treatment group are rinsed with tacrolimus at a concentration of 20 ng/ml in 1000 ml Custodiol solution and in the placebo group with Custodiol alone. The primary endpoint is the maximum serum alanine transamninase (ALT) level within the first 48 hours after surgery; however, the study design also includes a 1-year observation period following transplantation. The TOP-Study is an investigator-initiated trial sponsored by the University of Munich Hospital. Seven other German transplant centers are participating (Berlin, Frankfurt, Heidelberg, Mainz, Münster, Regensburg, Tübingen) and aim to include a total of 86 patients.

Discussion

Tacrolimus organ perfusion represents a promising strategy to reduce hepatic IRI following the transplantation of marginal liver grafts. This treatment may help to improve the function of EDC grafts and therefore safely expand the donor pool in light of critical organ shortage.

Trial register

EudraCT number: 2010-021333-31, ClinicalTrials.gov identifier: NCT01564095

Keywords:
Liver transplantation; Organ shortage; Extended donor criteria; Marginal grafts; Tacrolimus; Organ rinse; Graft function; Graft survival