title: 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.
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
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  EudraCT number: 2010-021333-31, ClinicalTrials.gov identifier: NCT01564095.
authors.affiliation: Department of Surgery, University of Munich Hospital, Campus Grosshadern, Ludwig-Maximilians-University, Marchioninistrasse 15, 81377 Munich, Germany. Martin.Angele@med.uni-muenchen.de.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Pratschke
authors.forename: Michael
authors.initials: M
authors.lastname: Eder
authors.forename: Michael
authors.initials: M
authors.lastname: Heise
authors.forename: Silvio
authors.initials: S
authors.lastname: Nadalin
authors.forename: Andreas
authors.initials: A
authors.lastname: Pascher
authors.forename: Peter
authors.initials: P
authors.lastname: Schemmer
authors.forename: Marcus N
authors.initials: MN
authors.lastname: Scherer
authors.forename: Frank
authors.initials: F
authors.lastname: Ulrich
authors.forename: Heiner
authors.initials: H
authors.lastname: Wolters
authors.forename: Karl-Walter
authors.initials: KW
authors.lastname: Jauch
authors.forename: Dirk
authors.initials: D
authors.lastname: Wöhling
authors.forename: Martin K
authors.initials: MK
authors.lastname: Angele