Clinical trial NCT01564095: TOP-Study (Tacrolimus Organ Perfusion): Treatment of Ischemia Reperfusion Injury in Marginal Organs With an ex Vivo Tacrolimus Perfusion
Official title: TOP-Study (Tacrolimus Organ Perfusion): A Prospective Multicenter Trial for Treatment of Ischemia Reperfusion Injury in Marginal Organs With an ex Vivo Tacrolimus Perfusion
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Terminal Liver Disease
Ischemia Reperfusion Injury
Graft Dysfunction
Graft Failure
Poor Graft Quality
Keywords: Liver transplantation
EDC
IRI
graft survival
graft function
graft preconditioning
Tacrolimus rinse
randomised multicenter trial
Lead sponsor: Ludwig-Maximilians - University of Munich
Sponsor class: OTHER
First posted: 2012-03-27
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Exclusion Criteria:

Donor:

• Hepatitis B- or Hepatitis C-infection

Recipient:

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

Primary outcomes:
measure: Maximum serum ALT-level
timeFrame: 48 hrs following liver transplantation
Secondary outcomes:
measure: ALT
timeFrame: 1,2,4,7 days after surgery
measure: Graft survival
timeFrame: 7 days
measure: AST
timeFrame: 1,2,4,7 days after surgery
measure: Bilirubin
timeFrame: 1,2,4,7 days after surgery
measure: Creatinin
timeFrame: 1,2,4,7 days after surgery
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Department of General, Visceral and Transplantation Surgery, Charité Campus Virchow-Klinikum
city: Frankfurt am Main
country: Germany
facility: Department of General and Visceral Surgery, Johann Wolfgang Goethe-University
city: Heidelberg
country: Germany
facility: Department of General, Visceral and Transplantation Surgery, Ruprecht Karls University
city: Mainz
country: Germany
facility: Department of Transplantation Surgery, Johannes Gutenberg University
city: Munich
country: Germany
facility: Ludwig-Maximilians University, Campus Grosshadern, Department of Surgery
city: Regensburg
country: Germany
facility: Department of Surgery, University of Regensburg
city: Tübingen
country: Germany
facility: Department of General, Visceral and Transplantation Surgery, Eberhard Karls University
Study officials:
affiliation: Ludwig-Maximilians-University, Department of Surgery, Munich, Germany
name: Martin Angele, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Ludwig-Maximilians-University, Department of Surgery, Munich, Germany
name: Sebastian Pratschke, M.D.
role: STUDY_DIRECTOR
affiliation: Ludwig-Maximilians-University, Department of Surgery, Munich, Germany
name: Karl-Walter Jauch, M.D.
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.