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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01564095
Recruitment Status : Terminated (Missing evidence of the effectiveness of the study medication)
First Posted : March 27, 2012
Last Update Posted : March 23, 2017
Sponsor:
Information provided by (Responsible Party):
Prof. Dr. M. Angele, Ludwig-Maximilians - University of Munich

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.

Condition or disease Intervention/treatment Phase
Terminal Liver Disease Ischemia Reperfusion Injury Graft Dysfunction Graft Failure Poor Graft Quality Drug: Tacrolimus Drug: HTK/Placebo Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
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
Actual Study Start Date : October 2011
Actual Primary Completion Date : July 2013
Actual Study Completion Date : July 2013

Resource links provided by the National Library of Medicine

Drug Information available for: Tacrolimus

Arm Intervention/treatment
Experimental: Tacrolimus + HTK
Ex vivo Tacrolimus Rinse (20 ng/ml solved in 1000 ml HTK) of marginal liver grafts prior to implantation
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.
Other Names:
  • Tacrolimus, Prograf; Astellas Germany
  • HTK, histidin-tryptophane-ketoglurate organ preservation solution, Custodiol, Dr. Franz Köhler Chemie, Germany

Placebo Comparator: HTK
Ex vivo Rinse (1000 ml HTK) of marginal liver grafts prior to implantation
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.
Other Name: HTK, histidin-tryptophane-ketoglurate organ preservation solution, Custodiol, Dr. Franz Köhler Chemie, Germany




Primary Outcome Measures :
  1. Maximum serum ALT-level [ Time Frame: 48 hrs following liver transplantation ]

Secondary Outcome Measures :
  1. ALT [ Time Frame: 1,2,4,7 days after surgery ]
  2. Graft survival [ Time Frame: 7 days ]
  3. AST [ Time Frame: 1,2,4,7 days after surgery ]
  4. Bilirubin [ Time Frame: 1,2,4,7 days after surgery ]
  5. Creatinin [ Time Frame: 1,2,4,7 days after surgery ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01564095


Locations
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Germany
Department of General, Visceral and Transplantation Surgery, Charité Campus Virchow-Klinikum
Berlin, Germany, 13353
Department of General and Visceral Surgery, Johann Wolfgang Goethe-University
Frankfurt am Main, Germany, 60596
Department of General, Visceral and Transplantation Surgery, Ruprecht Karls University
Heidelberg, Germany, 69120
Department of Transplantation Surgery, Johannes Gutenberg University
Mainz, Germany, 55131
Ludwig-Maximilians University, Campus Grosshadern, Department of Surgery
Munich, Germany, 81377
Department of Surgery, University of Regensburg
Regensburg, Germany, 93053
Department of General, Visceral and Transplantation Surgery, Eberhard Karls University
Tübingen, Germany, 72076
Sponsors and Collaborators
Ludwig-Maximilians - University of Munich
Investigators
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Principal Investigator: Martin Angele, M.D. Ludwig-Maximilians-University, Department of Surgery, Munich, Germany
Study Director: Sebastian Pratschke, M.D. Ludwig-Maximilians-University, Department of Surgery, Munich, Germany
Study Chair: Karl-Walter Jauch, M.D. Ludwig-Maximilians-University, Department of Surgery, Munich, Germany
Publications of Results:
Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Prof. Dr. M. Angele, Prof. Dr. med. Martin Angele, Ludwig-Maximilians - University of Munich
ClinicalTrials.gov Identifier: NCT01564095    
Other Study ID Numbers: TOP-Study
First Posted: March 27, 2012    Key Record Dates
Last Update Posted: March 23, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Prof. Dr. M. Angele, Ludwig-Maximilians - University of Munich:
Liver transplantation
EDC
IRI
graft survival
graft function
graft preconditioning
Tacrolimus rinse
randomised multicenter trial
Additional relevant MeSH terms:
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Liver Diseases
Reperfusion Injury
Ischemia
Wounds and Injuries
Pathologic Processes
Digestive System Diseases
Vascular Diseases
Cardiovascular Diseases
Postoperative Complications
Tryptophan
Pharmaceutical Solutions
Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs