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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tacrolimus + HTK | Experimental | Ex vivo Tacrolimus Rinse (20 ng/ml solved in 1000 ml HTK) of marginal liver grafts prior to implantation |
|
| HTK | Placebo Comparator | Ex vivo Rinse (1000 ml HTK) of marginal liver grafts prior to implantation |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tacrolimus | Drug | Marginal liver grafts are flushed with Tacrolimus (20ng/ml) solved in 1000 ml HTK preservation solution (duration: 15 min) ex vivo at the end of backtable preparation in the experimental group. |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum serum ALT-level | 48 hrs following liver transplantation |
| Measure | Description | Time Frame |
|---|---|---|
| ALT | 1,2,4,7 days after surgery | |
| Graft survival | 7 days | |
| AST |
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Inclusion Criteria:
Recipient:
Chronical terminal liver failure, age > 18 years, first organ transplantation
Donor:
Exclusion Criteria:
Donor:
• Hepatitis B- or Hepatitis C-infection
Recipient:
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| Name | Affiliation | Role |
|---|---|---|
| Martin Angele, M.D. | Ludwig-Maximilians-University, Department of Surgery, Munich, Germany | Principal Investigator |
| Sebastian Pratschke, M.D. | Ludwig-Maximilians-University, Department of Surgery, Munich, Germany | Study Director |
| Karl-Walter Jauch, M.D. | Ludwig-Maximilians-University, Department of Surgery, Munich, Germany | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of General, Visceral and Transplantation Surgery, Charité Campus Virchow-Klinikum | Berlin | 13353 | Germany | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21962731 | Background | Pratschke S, Bilzer M, Grutzner U, Angele M, Tufman A, Jauch KW, Schauer RJ. Tacrolimus preconditioning of rat liver allografts impacts glutathione homeostasis and early reperfusion injury. J Surg Res. 2012 Jul;176(1):309-16. doi: 10.1016/j.jss.2011.07.045. Epub 2011 Aug 25. | |
| 12548508 | Background | St Peter SD, Post DJ, Rodriguez-Davalos MI, Douglas DD, Moss AA, Mulligan DC. Tacrolimus as a liver flush solution to ameliorate the effects of ischemia/reperfusion injury following liver transplantation. Liver Transpl. 2003 Feb;9(2):144-9. doi: 10.1053/jlts.2003.50018. |
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|
| HTK/Placebo | Drug | Marginal liver grafts are flushed with 1000 ml HTK preservation solution(duration: 15 min) ex vivo at the end of backtable preparation in the placebo group. |
|
|
| 1,2,4,7 days after surgery |
| Bilirubin | 1,2,4,7 days after surgery |
| Creatinin | 1,2,4,7 days after surgery |
| Department of General and Visceral Surgery, Johann Wolfgang Goethe-University |
| Frankfurt am Main |
| 60596 |
| Germany |
| Department of General, Visceral and Transplantation Surgery, Ruprecht Karls University | Heidelberg | 69120 | Germany |
| Department of Transplantation Surgery, Johannes Gutenberg University | Mainz | 55131 | Germany |
| Ludwig-Maximilians University, Campus Grosshadern, Department of Surgery | Munich | 81377 | Germany |
| Department of Surgery, University of Regensburg | Regensburg | 93053 | Germany |
| Department of General, Visceral and Transplantation Surgery, Eberhard Karls University | Tübingen | 72076 | Germany |
| 21672049 | Background | Kristo I, Wilflingseder J, Kainz A, Marschalek J, Wekerle T, Muhlbacher F, Oberbauer R, Bodingbauer M. Effect of intraportal infusion of tacrolimus on ischaemic reperfusion injury in orthotopic liver transplantation: a randomized controlled trial. Transpl Int. 2011 Sep;24(9):912-9. doi: 10.1111/j.1432-2277.2011.01284.x. Epub 2011 Jun 14. |
| 27500266 | Result | Pratschke S, Arnold H, Zollner A, Heise M, Pascher A, Schemmer P, Scherer MN, Bauer A, Jauch KW, Werner J, Guba M, Angele MK. Results of the TOP Study: Prospectively Randomized Multicenter Trial of an Ex Vivo Tacrolimus Rinse Before Transplantation in EDC Livers. Transplant Direct. 2016 May 4;2(6):e76. doi: 10.1097/TXD.0000000000000588. eCollection 2016 Jun. |
| 23497558 | Derived | Pratschke S, Eder M, Heise M, Nadalin S, Pascher A, Schemmer P, Scherer MN, Ulrich F, Wolters H, Jauch KW, Wohling D, Angele MK. 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. Transplant Res. 2013 Mar 4;2(1):3. doi: 10.1186/2047-1440-2-3. |
| ID | Term |
|---|---|
| D015427 | Reperfusion Injury |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D016559 | Tacrolimus |
| D036224 | Receptor, EphB4 |
| ID | Term |
|---|---|
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D036081 | Receptors, Eph Family |
| D020794 | Receptor Protein-Tyrosine Kinases |
| D011505 | Protein-Tyrosine Kinases |
| D011494 | Protein Kinases |
| D017853 | Phosphotransferases (Alcohol Group Acceptor) |
| D010770 | Phosphotransferases |
| D014166 | Transferases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |
| D047908 | Intracellular Signaling Peptides and Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011956 | Receptors, Cell Surface |
| D008565 | Membrane Proteins |
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