TOP-Study (Tacrolimus Organ Perfusion): Treatment of Ischemia Reperfusion Injury in Marginal Organs With an ex Vivo Tacrolimus Perfusion

Ischemia Reperfusion Injury Clinical Trial

— TOP  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01564095
• Other study ID #: TOP-Study
• Status: Terminated
• Phase: Phase 2/Phase 3
• First received: March 14, 2012
• Last updated: March 21, 2017
• Start date: October 2011
• Est. completion date: July 2013

Study information

• Verified date: March 2017
• Source: Ludwig-Maximilians - University of Munich
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 25
• Est. completion date: July 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Graft Dysfunction
• Graft Failure
• Ischemia
• Ischemia Reperfusion Injury
• Liver Diseases
• Poor Graft Quality
• Reperfusion Injury
• Terminal Liver Disease
• Wounds and Injuries

Intervention

Drug:
• Tacrolimus
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.
• HTK/Placebo
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.

Locations

Country	Name	City	State
Germany	Department of General, Visceral and Transplantation Surgery, Charité Campus Virchow-Klinikum	Berlin
Germany	Department of General and Visceral Surgery, Johann Wolfgang Goethe-University	Frankfurt am Main
Germany	Department of General, Visceral and Transplantation Surgery, Ruprecht Karls University	Heidelberg
Germany	Department of Transplantation Surgery, Johannes Gutenberg University	Mainz
Germany	Ludwig-Maximilians University, Campus Grosshadern, Department of Surgery	Munich
Germany	Department of Surgery, University of Regensburg	Regensburg
Germany	Department of General, Visceral and Transplantation Surgery, Eberhard Karls University	Tübingen

Sponsors (1)

Lead Sponsor	Collaborator
Ludwig-Maximilians - University of Munich

Country where clinical trial is conducted

Germany, 

References & Publications (4)

Kristo I, Wilflingseder J, Kainz A, Marschalek J, Wekerle T, Mühlbacher 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. — View 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 — View Citation

Pratschke S, Bilzer M, Grützner 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum serum ALT-level		48 hrs following liver transplantation
Secondary	ALT		1,2,4,7 days after surgery
Secondary	Graft survival		7 days
Secondary	AST		1,2,4,7 days after surgery
Secondary	Bilirubin		1,2,4,7 days after surgery
Secondary	Creatinin		1,2,4,7 days after surgery