Impact of Graft Reconditioning With Hypothermic Machine Perfusion on HCC Recurrence After Liver Transplantation

NCT06236568 | Recruiting

• 1 other identifier: 561/2023/SPER/AOUMO.
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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. The 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. Blood 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). Primary 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.

Conditions

Hepatocellular Carcinoma; Liver Transplant; Complications

Keywords

Hepatocellular carcinoma; Liver Transplantation; Metabolomics; Liquid biopsy; Machine perfusion; Ischemia reperfusion injury

Outcome Measures

Primary Outcomes (1)

• Survival

  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. This aim will be focused on the potential role for MP in the modulation of tumor recurrence pattern. SA1 Deliverables: Modulation of HCC recurrence pattern after MP

  5 years after surgery

Secondary Outcomes (3)

• Prognostic markers - MiRNA

  5 years after surgery

• Prognostic markers - metabolipiodomics

  5 years after surgery

• Graft survival

  1 month after surgery

Study Arms (2)

Machine perfusion

EXPERIMENTAL

The liver graft to be transplanted is treated with 90 minutes of D-HOPE machine perfusion

Device: D-HOPE machine perfusion; Procedure: Liver transplantation

No machine perfusion

ACTIVE COMPARATOR

Standard liver transplantation

Procedure: Liver transplantation

Interventions

D-HOPE machine perfusion DEVICE

use of the device

Machine perfusion

Liver transplantation PROCEDURE

Liver transplantation for HCC within Milan criteria

Machine perfusion; No machine perfusion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with HCC within Milan criteria at listing candidate for liver transplantation
• ECOG 0-2
• DBD donors
• capability to sign an informed consent

You may not qualify if:

• pediatric patients
• DCD donors
• DBD extended criteria requiring machine perfusion (no ethical randomization)
• living donor liver transplantation
• split liver

Sponsors & Collaborators

• Azienda Ospedaliero-Universitaria di Modena: lead

Study Sites (1)

AOU di Modena

Modena, MO, 41124, Italy

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Reperfusion Injury

Interventions

Liver Transplantation

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tissue Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Digestive System Surgical Procedures; Surgical Procedures, Operative; Organ Transplantation; Transplantation

Study Officials

• Fabrizio Di Benedetto

  University of Modena and Reggio Emilia

  STUDY CHAIR

• Massimo Dominici

  University of Modena and Reggio Emilia

  STUDY CHAIR

• Pietro Campiglia

  University of Salerno

  STUDY CHAIR

• Eduardo M Sommella

  University of Salerno

  PRINCIPAL INVESTIGATOR

• Valentina Masciale

  University of Modena and Reggio Emilia

  PRINCIPAL INVESTIGATOR

• Ilenia Mastrolia

  University of Modena and Reggio Emilia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Paolo Magistri, MD FACS

CONTACT

+390594225265; paolo.magistri@unimore.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Surgery

Study Record Dates

• First Submitted: January 24, 2024
• First Posted: February 1, 2024
• Study Start: February 6, 2024
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2030
• Last Updated: February 7, 2024

Record last verified: 2024-02

Locations

IT (1)