Back to resultsTOP-Study (Tacrolimus Organ Perfusion): Treatment of Ischemia Reperfusion Injury in Marginal Organs With an ex Vivo Tacrolimus Perfusion (TOP)
Primary Purpose
Terminal Liver Disease, Ischemia Reperfusion Injury, Graft Dysfunction
Status
Terminated
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Tacrolimus
HTK/Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Terminal Liver Disease focused on measuring Liver transplantation, EDC, IRI, graft survival, graft function, graft preconditioning, Tacrolimus rinse, randomised multicenter trial
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
Sites / Locations
- Department of General, Visceral and Transplantation Surgery, Charité Campus Virchow-Klinikum
- Department of General and Visceral Surgery, Johann Wolfgang Goethe-University
- Department of General, Visceral and Transplantation Surgery, Ruprecht Karls University
- Department of Transplantation Surgery, Johannes Gutenberg University
- Ludwig-Maximilians University, Campus Grosshadern, Department of Surgery
- Department of Surgery, University of Regensburg
- Department of General, Visceral and Transplantation Surgery, Eberhard Karls University
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Tacrolimus + HTK
HTK
Arm Description
Ex vivo Tacrolimus Rinse (20 ng/ml solved in 1000 ml HTK) of marginal liver grafts prior to implantation
Ex vivo Rinse (1000 ml HTK) of marginal liver grafts prior to implantation
Outcomes
Primary Outcome Measures
Maximum serum ALT-level
Secondary Outcome Measures
ALT
Graft survival
AST
Bilirubin
Creatinin
Full Information
NCT ID
NCT01564095
First Posted
March 14, 2012
Last Updated
March 21, 2017
Sponsor
Ludwig-Maximilians - University of Munich
1. Study Identification
Unique Protocol Identification Number
NCT01564095
Brief Title
TOP-Study (Tacrolimus Organ Perfusion): Treatment of Ischemia Reperfusion Injury in Marginal Organs With an ex Vivo Tacrolimus Perfusion
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2017
Overall Recruitment Status
Terminated
Why Stopped
Missing evidence of the effectiveness of the study medication
Study Start Date
October 2011 (Actual)
Primary Completion Date
July 2013 (Actual)
Study Completion Date
July 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ludwig-Maximilians - University of Munich
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
25 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tacrolimus + HTK
Arm Type
Experimental
Arm Description
Ex vivo Tacrolimus Rinse (20 ng/ml solved in 1000 ml HTK) of marginal liver grafts prior to implantation
Arm Title
HTK
Arm Type
Placebo Comparator
Arm Description
Ex vivo Rinse (1000 ml HTK) of marginal liver grafts prior to implantation
Intervention Type
Drug
Intervention Name(s)
Tacrolimus
Other Intervention Name(s)
Tacrolimus, Prograf; Astellas Germany, HTK, histidin-tryptophane-ketoglurate organ preservation solution, Custodiol, Dr. Franz Köhler Chemie, Germany
Intervention Description
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
Intervention Name(s)
HTK/Placebo
Other Intervention Name(s)
HTK, histidin-tryptophane-ketoglurate organ preservation solution, Custodiol, Dr. Franz Köhler Chemie, Germany
Intervention Description
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.
Primary Outcome Measure Information:
Title
Maximum serum ALT-level
Time Frame
48 hrs following liver transplantation
Secondary Outcome Measure Information:
Title
ALT
Time Frame
1,2,4,7 days after surgery
Title
Graft survival
Time Frame
7 days
Title
AST
Time Frame
1,2,4,7 days after surgery
Title
Bilirubin
Time Frame
1,2,4,7 days after surgery
Title
Creatinin
Time Frame
1,2,4,7 days after surgery
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Martin Angele, M.D.
Organizational Affiliation
Ludwig-Maximilians-University, Department of Surgery, Munich, Germany
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Sebastian Pratschke, M.D.
Organizational Affiliation
Ludwig-Maximilians-University, Department of Surgery, Munich, Germany
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Karl-Walter Jauch, M.D.
Organizational Affiliation
Ludwig-Maximilians-University, Department of Surgery, Munich, Germany
Official's Role
Study Chair
Facility Information:
Facility Name
Department of General, Visceral and Transplantation Surgery, Charité Campus Virchow-Klinikum
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Department of General and Visceral Surgery, Johann Wolfgang Goethe-University
City
Frankfurt am Main
ZIP/Postal Code
60596
Country
Germany
Facility Name
Department of General, Visceral and Transplantation Surgery, Ruprecht Karls University
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Department of Transplantation Surgery, Johannes Gutenberg University
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Facility Name
Ludwig-Maximilians University, Campus Grosshadern, Department of Surgery
City
Munich
ZIP/Postal Code
81377
Country
Germany
Facility Name
Department of Surgery, University of Regensburg
City
Regensburg
ZIP/Postal Code
93053
Country
Germany
Facility Name
Department of General, Visceral and Transplantation Surgery, Eberhard Karls University
City
Tübingen
ZIP/Postal Code
72076
Country
Germany
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
21962731
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.
Results Reference
background
PubMed Identifier
12548508
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.
Results Reference
background
PubMed Identifier
21672049
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.
Results Reference
background
PubMed Identifier
27500266
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.
Results Reference
result
PubMed Identifier
23497558
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.
Results Reference
derived
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TOP-Study (Tacrolimus Organ Perfusion): Treatment of Ischemia Reperfusion Injury in Marginal Organs With an ex Vivo Tacrolimus Perfusion
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