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

NCT ID: NCT01564095

Last Updated: 2017-03-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

25 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-10-31

Study Completion Date

2013-07-31

Brief Summary

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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.

Detailed Description

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Conditions

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Terminal Liver Disease Ischemia Reperfusion Injury Graft Dysfunction Graft Failure Poor Graft Quality

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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Tacrolimus + HTK

Ex vivo Tacrolimus Rinse (20 ng/ml solved in 1000 ml HTK) of marginal liver grafts prior to implantation

Group Type EXPERIMENTAL

Tacrolimus

Intervention Type 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.

HTK

Ex vivo Rinse (1000 ml HTK) of marginal liver grafts prior to implantation

Group Type PLACEBO_COMPARATOR

HTK/Placebo

Intervention Type 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.

Interventions

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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.

Intervention Type DRUG

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.

Intervention Type DRUG

Other Intervention Names

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Tacrolimus, Prograf; Astellas Germany HTK, histidin-tryptophane-ketoglurate organ preservation solution, Custodiol, Dr. Franz Köhler Chemie, Germany HTK, histidin-tryptophane-ketoglurate organ preservation solution, Custodiol, Dr. Franz Köhler Chemie, Germany

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ludwig-Maximilians - University of Munich

OTHER

Sponsor Role lead

Responsible Party

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Prof. Dr. M. Angele

Prof. Dr. med. Martin Angele

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Martin Angele, M.D.

Role: PRINCIPAL_INVESTIGATOR

Ludwig-Maximilians-University, Department of Surgery, Munich, Germany

Sebastian Pratschke, M.D.

Role: STUDY_DIRECTOR

Ludwig-Maximilians-University, Department of Surgery, Munich, Germany

Karl-Walter Jauch, M.D.

Role: STUDY_CHAIR

Ludwig-Maximilians-University, Department of Surgery, Munich, Germany

Locations

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Department of General, Visceral and Transplantation Surgery, Charité Campus Virchow-Klinikum

Berlin, , Germany

Site Status

Department of General and Visceral Surgery, Johann Wolfgang Goethe-University

Frankfurt am Main, , Germany

Site Status

Department of General, Visceral and Transplantation Surgery, Ruprecht Karls University

Heidelberg, , Germany

Site Status

Department of Transplantation Surgery, Johannes Gutenberg University

Mainz, , Germany

Site Status

Ludwig-Maximilians University, Campus Grosshadern, Department of Surgery

Munich, , Germany

Site Status

Department of Surgery, University of Regensburg

Regensburg, , Germany

Site Status

Department of General, Visceral and Transplantation Surgery, Eberhard Karls University

Tübingen, , Germany

Site Status

Countries

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Germany

References

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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.

Reference Type BACKGROUND
PMID: 21962731 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12548508 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21672049 (View on PubMed)

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.

Reference Type RESULT
PMID: 27500266 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23497558 (View on PubMed)

Other Identifiers

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TOP-Study

Identifier Type: -

Identifier Source: org_study_id

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