title: Results of the TOP Study: Prospectively Randomized Multicenter Trial of an Ex Vivo Tacrolimus Rinse Before Transplantation in EDC Livers.
abstract: BACKGROUND
  Organ shortage results in the transplantation of extended donor criteria (EDC) livers which is associated with increased ischemia-reperfusion injury (IRI). Experimental studies indicate that an organ rinse with the calcineurin inhibitor tacrolimus before implantation protects against IRI. The tacrolimus organ perfusion study was initiated to examine the effects of ex vivo tacrolimus perfusion on IRI in transplantation of EDC livers.
  
  
  METHODS
  A prospective randomized multicenter trial comparing ex vivo perfusion of marginal liver grafts (≥2 EDC according to Eurotransplant manual) with tacrolimus (20 ng/mL) or histidine-tryptophane-ketoglutarate solution (control) was carried out at 5 German liver transplant centers (Munich Ludwig-Maximilians University, Berlin, Heidelberg, Mainz, Regensburg) between October 2011 and July 2013. Primary endpoint was the maximum alanine transaminase (ALT) level within 48 hours after transplantation. Secondary endpoints were aspartate transaminase (AST), prothrombine ratio, and graft-patient survival within an observation period of 1 week. After an interim analysis, the study was terminated by the scientific committee after the treatment of 24 patients (tacrolimus n = 11, Control n = 13).
  
  
  RESULTS
  Tacrolimus rinse did not reduce postoperative ALT peaks compared with control (P = 0.207; tacrolimus: median, 812; range, 362-3403 vs control: median, 652; range, 147-2034). Moreover, ALT (P = 0.100), prothrombine ratio (P = 0.553), and bilirubin (P = 0.815) did not differ between the groups. AST was higher in patients treated with tacrolimus (P = 0.011). Survival was comparable in both groups (P > 0.05).
  
  
  CONCLUSIONS
  Contrary to experimental findings, tacrolimus rinse failed to improve the primary endpoint of the study (ALT). Because 1 secondary endpoint (AST) was even higher in the intervention group, the study was terminated prematurely. Thus, tacrolimus rinse cannot be recommended in transplantation of EDC livers.
authors: Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the Ludwig-Maximilians-University, Munich, Germany.
authors: Sebastian
authors: S
authors: Pratschke
authors: Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the Ludwig-Maximilians-University, Munich, Germany.
authors: Hannah
authors: H
authors: Arnold
authors: Münchner Studienzentrum, University Hospital Rechts der Isar, Technical University of Munich, Munich, Germany.
authors: Alfred
authors: A
authors: Zollner
authors: Department of General, Visceral and Transplantation Surgery, University Medical Center, Johannes Gutenberg University, Mainz, Germany.
authors: Michael
authors: M
authors: Heise
authors: Department of General, Visceral and Transplantation Surgery, Charité Campus Virchow-Klinikum, Berlin, Germany.
authors: Andreas
authors: A
authors: Pascher
authors: Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Ruprecht-Karls-University, Heidelberg, Germany.
authors: Peter
authors: P
authors: Schemmer
authors: Department of Surgery, University Hospital Regensburg, University of Regensburg, Regensburg, Germany.
authors: Marcus N
authors: MN
authors: Scherer
authors: Department of Anaesthesiology, Hospital of the Ludwig-Maximilians-University, Munich, Germany.
authors: Andreas
authors: A
authors: Bauer
authors: Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the Ludwig-Maximilians-University, Munich, Germany.
authors: Karl-Walter
authors: KW
authors: Jauch
authors: Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the Ludwig-Maximilians-University, Munich, Germany.
authors: Jens
authors: J
authors: Werner
authors: Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the Ludwig-Maximilians-University, Munich, Germany.
authors: Markus
authors: M
authors: Guba
authors: Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the Ludwig-Maximilians-University, Munich, Germany.
authors: Martin K
authors: MK
authors: Angele