Ignite Creation Date:
2025-12-17 @ 2:50 PM
Ignite Modification Date:
2025-12-23 @ 7:05 PM
Study NCT ID:
NCT01564095
Status:
TERMINATED
Last Update Posted:
2017-03-23
First Post:
2012-03-14
Is Possible Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
TOP-Study (Tacrolimus Organ Perfusion): Treatment of Ischemia Reperfusion Injury in Marginal Organs With an ex Vivo Tacrolimus Perfusion
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-22'}, 'conditionBrowseModule': {'meshes': [{'id': 'D015427', 'term': 'Reperfusion Injury'}], 'ancestors': [{'id': 'D014652', 'term': 'Vascular Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D011183', 'term': 'Postoperative Complications'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D016559', 'term': 'Tacrolimus'}, {'id': 'D036224', 'term': 'Receptor, EphB4'}], 'ancestors': [{'id': 'D018942', 'term': 'Macrolides'}, {'id': 'D007783', 'term': 'Lactones'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D036081', 'term': 'Receptors, Eph Family'}, {'id': 'D020794', 'term': 'Receptor Protein-Tyrosine Kinases'}, {'id': 'D011505', 'term': 'Protein-Tyrosine Kinases'}, {'id': 'D011494', 'term': 'Protein Kinases'}, {'id': 'D017853', 'term': 'Phosphotransferases (Alcohol Group Acceptor)'}, {'id': 'D010770', 'term': 'Phosphotransferases'}, {'id': 'D014166', 'term': 'Transferases'}, {'id': 'D004798', 'term': 'Enzymes'}, {'id': 'D045762', 'term': 'Enzymes and Coenzymes'}, {'id': 'D047908', 'term': 'Intracellular Signaling Peptides and Proteins'}, {'id': 'D011506', 'term': 'Proteins'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D011956', 'term': 'Receptors, Cell Surface'}, {'id': 'D008565', 'term': 'Membrane Proteins'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2', 'PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['PARTICIPANT']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 25}}, 'statusModule': {'whyStopped': 'Missing evidence of the effectiveness of the study medication', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2011-10', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2017-03', 'completionDateStruct': {'date': '2013-07', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2017-03-21', 'studyFirstSubmitDate': '2012-03-14', 'studyFirstSubmitQcDate': '2012-03-23', 'lastUpdatePostDateStruct': {'date': '2017-03-23', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2012-03-27', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2013-07', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Maximum serum ALT-level', 'timeFrame': '48 hrs following liver transplantation'}], 'secondaryOutcomes': [{'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'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Liver transplantation', 'EDC', 'IRI', 'graft survival', 'graft function', 'graft preconditioning', 'Tacrolimus rinse', 'randomised multicenter trial'], 'conditions': ['Terminal Liver Disease', 'Ischemia Reperfusion Injury', 'Graft Dysfunction', 'Graft Failure', 'Poor Graft Quality']}, 'referencesModule': {'references': [{'pmid': '21962731', 'type': 'BACKGROUND', '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.'}, {'pmid': '12548508', 'type': 'BACKGROUND', '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.'}, {'pmid': '21672049', 'type': 'BACKGROUND', '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.'}, {'pmid': '27500266', 'type': 'RESULT', '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.'}, {'pmid': '23497558', 'type': 'DERIVED', '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.'}]}, 'descriptionModule': {'briefSummary': "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."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\nRecipient:\n\nChronical terminal liver failure, age \\> 18 years, first organ transplantation\n\nDonor:\n\n* donor age \\> 65 Jahre\n* macrovesicular steatosis \\> 40% (macroscopy or biopsy)\n* BMI \\> 30\n* sodium \\>165 mmol/l\n* ICU stay and ventilation \\> 7 days\n* cold ischemia time \\> 13 hours\n* AST \\> 99 U/l\n* ALT \\> 105 U/l\n* bilirubin \\> 3 mg/dl (\\> 51 µmol/l)\n* application of epinephrine\n\nExclusion Criteria:\n\nDonor:\n\n• Hepatitis B- or Hepatitis C-infection\n\nRecipient:\n\n* Multi organ transplantation\n* high urgency listing\n* extrahepatic tumor disease\n* pregnancy'}, 'identificationModule': {'nctId': 'NCT01564095', 'acronym': 'TOP', 'briefTitle': 'TOP-Study (Tacrolimus Organ Perfusion): Treatment of Ischemia Reperfusion Injury in Marginal Organs With an ex Vivo Tacrolimus Perfusion', 'organization': {'class': 'OTHER', 'fullName': 'Ludwig-Maximilians - University of Munich'}, 'officialTitle': 'TOP-Study (Tacrolimus Organ Perfusion): A Prospective Multicenter Trial for Treatment of Ischemia Reperfusion Injury in Marginal Organs With an ex Vivo Tacrolimus Perfusion', 'orgStudyIdInfo': {'id': 'TOP-Study'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Tacrolimus + HTK', 'description': 'Ex vivo Tacrolimus Rinse (20 ng/ml solved in 1000 ml HTK) of marginal liver grafts prior to implantation', 'interventionNames': ['Drug: Tacrolimus']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'HTK', 'description': 'Ex vivo Rinse (1000 ml HTK) of marginal liver grafts prior to implantation', 'interventionNames': ['Drug: HTK/Placebo']}], 'interventions': [{'name': 'Tacrolimus', 'type': 'DRUG', 'otherNames': ['Tacrolimus, Prograf; Astellas Germany', 'HTK, histidin-tryptophane-ketoglurate organ preservation solution, Custodiol, Dr. Franz Köhler Chemie, Germany'], '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.', 'armGroupLabels': ['Tacrolimus + HTK']}, {'name': 'HTK/Placebo', 'type': 'DRUG', 'otherNames': ['HTK, histidin-tryptophane-ketoglurate organ preservation solution, Custodiol, Dr. Franz Köhler Chemie, Germany'], '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.', 'armGroupLabels': ['HTK']}]}, 'contactsLocationsModule': {'locations': [{'zip': '13353', 'city': 'Berlin', 'country': 'Germany', 'facility': 'Department of General, Visceral and Transplantation Surgery, Charité Campus Virchow-Klinikum', 'geoPoint': {'lat': 52.52437, 'lon': 13.41053}}, {'zip': '60596', 'city': 'Frankfurt am Main', 'country': 'Germany', 'facility': 'Department of General and Visceral Surgery, Johann Wolfgang Goethe-University', 'geoPoint': {'lat': 50.11552, 'lon': 8.68417}}, {'zip': '69120', 'city': 'Heidelberg', 'country': 'Germany', 'facility': 'Department of General, Visceral and Transplantation Surgery, Ruprecht Karls University', 'geoPoint': {'lat': 49.40768, 'lon': 8.69079}}, {'zip': '55131', 'city': 'Mainz', 'country': 'Germany', 'facility': 'Department of Transplantation Surgery, Johannes Gutenberg University', 'geoPoint': {'lat': 49.98185, 'lon': 8.28008}}, {'zip': '81377', 'city': 'Munich', 'country': 'Germany', 'facility': 'Ludwig-Maximilians University, Campus Grosshadern, Department of Surgery', 'geoPoint': {'lat': 48.13743, 'lon': 11.57549}}, {'zip': '93053', 'city': 'Regensburg', 'country': 'Germany', 'facility': 'Department of Surgery, University of Regensburg', 'geoPoint': {'lat': 49.01513, 'lon': 12.10161}}, {'zip': '72076', 'city': 'Tübingen', 'country': 'Germany', 'facility': 'Department of General, Visceral and Transplantation Surgery, Eberhard Karls University', 'geoPoint': {'lat': 48.52266, 'lon': 9.05222}}], 'overallOfficials': [{'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', 'affiliation': 'Ludwig-Maximilians-University, Department of Surgery, Munich, Germany'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Ludwig-Maximilians - University of Munich', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Prof. Dr. med. Martin Angele', 'investigatorFullName': 'Prof. Dr. M. Angele', 'investigatorAffiliation': 'Ludwig-Maximilians - University of Munich'}}}}