Ignite Creation Date:
2025-12-24 @ 5:33 PM
Ignite Modification Date:
2026-01-05 @ 6:09 PM
Study NCT ID:
NCT06236568
Status:
RECRUITING
Last Update Posted:
2024-02-07
First Post:
2024-01-24
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Impact of Graft Reconditioning With Hypothermic Machine Perfusion on HCC Recurrence After Liver Transplantation
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D006528', 'term': 'Carcinoma, Hepatocellular'}, {'id': 'D015427', 'term': 'Reperfusion Injury'}], 'ancestors': [{'id': 'D000230', 'term': 'Adenocarcinoma'}, {'id': 'D002277', 'term': 'Carcinoma'}, {'id': 'D009375', 'term': 'Neoplasms, Glandular and Epithelial'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D008113', 'term': 'Liver Neoplasms'}, {'id': 'D004067', 'term': 'Digestive System Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}, {'id': 'D008107', 'term': 'Liver Diseases'}, {'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': 'D016031', 'term': 'Liver Transplantation'}], 'ancestors': [{'id': 'D016378', 'term': 'Tissue Transplantation'}, {'id': 'D064987', 'term': 'Cell- and Tissue-Based Therapy'}, {'id': 'D001691', 'term': 'Biological Therapy'}, {'id': 'D013812', 'term': 'Therapeutics'}, {'id': 'D013505', 'term': 'Digestive System Surgical Procedures'}, {'id': 'D013514', 'term': 'Surgical Procedures, Operative'}, {'id': 'D016377', 'term': 'Organ Transplantation'}, {'id': 'D014180', 'term': 'Transplantation'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'PREVENTION', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 40}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2024-02-06', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-02', 'completionDateStruct': {'date': '2030-12-31', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2024-02-06', 'studyFirstSubmitDate': '2024-01-24', 'studyFirstSubmitQcDate': '2024-01-24', 'lastUpdatePostDateStruct': {'date': '2024-02-07', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2024-02-01', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-12-31', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Survival', 'timeFrame': '5 years after surgery', 'description': 'Recurrence free survival and overall survival after LT for HCC according to the use of MP This aim will be realized at the Hepato-pancreato-biliary Surgery and Liver Transplantation Unit of Policlinico University Hospital of Modena - University of Modena and Reggio Emilia, supervised by Dr Paolo Magistri. Patients included in the trial according to the following criteria will be treated and followed-up according to the standard of care (SOC). All eligible patients have an indication to LT beyond the aims of this study, and will undergo LT according to National indications. LT is the gold standard treatment for patients affected by HCC inside Milan criteria, however biological features of the tumor may modify the expected recurrence pattern.\n\nThis aim will be focused on the potential role for MP in the modulation of tumor recurrence pattern.\n\nSA1 Deliverables:\n\nModulation of HCC recurrence pattern after MP'}], 'secondaryOutcomes': [{'measure': 'Prognostic markers - MiRNA', 'timeFrame': '5 years after surgery', 'description': 'Identification of microRNAs from liquid biopsy derived extracellular vesicles, as source of prognostic information on IRI favoring HCC recurrence. This aim will be realized by Research Laboratory at Policlinico University Hospital of Modena - University of Modena and Reggio Emilia, supervised by Dr Valentina Masciale.\n\nSA2 Deliverables:\n\n1\\) miRNAs transcriptomic profile of pre transplanted-patients.'}, {'measure': 'Prognostic markers - metabolipiodomics', 'timeFrame': '5 years after surgery', 'description': 'Identification of at least 1 prognostic markers from the promising miRNA selected on the bases of the transcriptomic analysis.\n\nSA3: Identification of prognostic markers of IRI and HCC by MS-based metabolipidomics:\n\nThis aim will be realized by UNIT2, Unisa-Difarma, Dr. Eduardo Maria Sommella'}, {'measure': 'Graft survival', 'timeFrame': '1 month after surgery', 'description': 'Reduction of early allograft disfunction'}]}, 'oversightModule': {'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Hepatocellular carcinoma', 'Liver Transplantation', 'Metabolomics', 'Liquid biopsy', 'Machine perfusion', 'Ischemia reperfusion injury'], 'conditions': ['Hepatocellular Carcinoma', 'Liver Transplant; Complications']}, 'descriptionModule': {'briefSummary': 'The use of devices for liver grafts perfusion before transplantation, either hypothermic (HOPE) or normothermic (NMP), is rapidly spreading thanks to the promising results obtained so far in terms of graft survival and post-operative morbidity. Besides the well-established ability to increase the rate of transplantability of extended criteria donors (ECD) and donors after cardiac death (DCD), the use of machine perfusion (MP) may also improve the oncological outcomes of patients affected by hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). The underlying mechanism is represented by the modulation of the ischemia-reperfusion injury (IRI)-related cellular damage obtained by the liver graft perfusion with HOPE before LT. The identification of biomarkers able to predict graft outcomes and highlight the mechanism of graft injury before transplantation rapidly and in non-invasive manner is therefore needed. Mass spectrometry-based metabolomics has already shown its potential by using perfusion liquids or pre-implantation biopsies.\n\nThe aim of the investigators is to run an open-label, randomised, controlled trial to study the impact of treating standard liver grafts from brain dead donors (DBD) with HOPE before liver transplant in patients affected by HCC. Patients aged 18-75 years presenting with HCC Milan-in at listing will be considered for inclusion. Presence of extra-hepatic disease and general contraindications to liver transplantation as defined by the local tumor board are considered as exclusion criteria. Eligible patients will be randomly assigned (1:1) with the use of a dedicated software to MP (intervention group) or no-MP (control group) before liver transplantation. Untargeted mass spectrometry metabolomics (UHPLC-HRMS) will be performed on liver graft perfusate, liver graft biopsy and recipient blood samples, to identify by classification methods, novel predictive markers of IRI. Furthermore, rapid targeted MS approaches will be performed on VIP metabolites and known key compounds (such as TCA, aminoacids, energy metabolism) to rapidly assess graft function as well as post-operative outcome.\n\nBlood samples of the recipient will be collected at two checkpoints (listing, and 3 months after liver transplant) to evaluate exosomes and miRNA expression fluctuations (liquid biopsy).\n\nPrimary outcomes of the study will be overall survival, graft survival and recurrence-free survival at 1- and 2-years. Survival results will be compared to those expected based on the Metroticket 2.0 score to assess the impact of MP in reducing the risk of HCC recurrence. Patients will remain in follow-up as for clinical practice to assess 3- and 5-years survival. Secondary end-point will be to define liquid biopsy efficacy to predict HCC recurrence and to define the correlation between metabolomic observations and HCC recurrence pattern.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Patients with HCC within Milan criteria at listing candidate for liver transplantation\n* ECOG 0-2\n* DBD donors\n* capability to sign an informed consent\n\nExclusion Criteria:\n\n* pediatric patients\n* DCD donors\n* DBD extended criteria requiring machine perfusion (no ethical randomization)\n* living donor liver transplantation\n* split liver'}, 'identificationModule': {'nctId': 'NCT06236568', 'briefTitle': 'Impact of Graft Reconditioning With Hypothermic Machine Perfusion on HCC Recurrence After Liver Transplantation', 'organization': {'class': 'OTHER', 'fullName': 'Azienda Ospedaliero-Universitaria di Modena'}, 'officialTitle': 'Impact of Graft Reconditioning With Hypothermic Machine Perfusion on HCC Recurrence After Liver Transplantation', 'orgStudyIdInfo': {'id': '561/2023/SPER/AOUMO.'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Machine perfusion', 'description': 'The liver graft to be transplanted is treated with 90 minutes of D-HOPE machine perfusion', 'interventionNames': ['Device: D-HOPE machine perfusion', 'Procedure: Liver transplantation']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'No machine perfusion', 'description': 'Standard liver transplantation', 'interventionNames': ['Procedure: Liver transplantation']}], 'interventions': [{'name': 'D-HOPE machine perfusion', 'type': 'DEVICE', 'description': 'use of the device', 'armGroupLabels': ['Machine perfusion']}, {'name': 'Liver transplantation', 'type': 'PROCEDURE', 'description': 'Liver transplantation for HCC within Milan criteria', 'armGroupLabels': ['Machine perfusion', 'No machine perfusion']}]}, 'contactsLocationsModule': {'locations': [{'zip': '41124', 'city': 'Modena', 'state': 'MO', 'status': 'RECRUITING', 'country': 'Italy', 'contacts': [{'name': 'Paolo Magistri, MD FACS', 'role': 'CONTACT', 'email': 'paolo.magistri@unimore.it', 'phone': '+390594225178'}], 'facility': 'AOU di Modena', 'geoPoint': {'lat': 44.64783, 'lon': 10.92539}}], 'centralContacts': [{'name': 'Paolo Magistri, MD FACS', 'role': 'CONTACT', 'email': 'paolo.magistri@unimore.it', 'phone': '+390594225265'}], 'overallOfficials': [{'name': 'Fabrizio Di Benedetto', 'role': 'STUDY_CHAIR', 'affiliation': 'University of Modena and Reggio Emilia'}, {'name': 'Massimo Dominici', 'role': 'STUDY_CHAIR', 'affiliation': 'University of Modena and Reggio Emilia'}, {'name': 'Pietro Campiglia', 'role': 'STUDY_CHAIR', 'affiliation': 'University of Salerno'}, {'name': 'Eduardo M Sommella', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Salerno'}, {'name': 'Valentina Masciale', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Modena and Reggio Emilia'}, {'name': 'Ilenia Mastrolia', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Modena and Reggio Emilia'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Azienda Ospedaliero-Universitaria di Modena', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Assistant Professor of Surgery', 'investigatorFullName': 'Paolo Magistri', 'investigatorAffiliation': 'Azienda Ospedaliero-Universitaria di Modena'}}}}