Clinical trial NCT06236568: Impact of Graft Reconditioning With Hypothermic Machine Perfusion on HCC Recurrence After Liver Transplantation
Official title: Impact of Graft Reconditioning With Hypothermic Machine Perfusion on HCC Recurrence After Liver Transplantation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Hepatocellular Carcinoma
Liver Transplant; Complications
Keywords: Hepatocellular carcinoma
Liver Transplantation
Metabolomics
Liquid biopsy
Machine perfusion
Ischemia reperfusion injury
Lead sponsor: Azienda Ospedaliero-Universitaria di Modena
Sponsor class: OTHER
First posted: 2024-02-01
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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

Primary outcomes:
measure: Survival
timeFrame: 5 years after surgery
Secondary outcomes:
measure: Prognostic markers - MiRNA
timeFrame: 5 years after surgery
measure: Prognostic markers - metabolipiodomics
timeFrame: 5 years after surgery
measure: Graft survival
timeFrame: 1 month after surgery
Other outcomes:
Locations:
city: Modena
country: Italy
facility: AOU di Modena
state: MO
Study officials:
affiliation: University of Modena and Reggio Emilia
name: Fabrizio Di Benedetto
role: STUDY_CHAIR
affiliation: University of Modena and Reggio Emilia
name: Massimo Dominici
role: STUDY_CHAIR
affiliation: University of Salerno
name: Pietro Campiglia
role: STUDY_CHAIR
affiliation: University of Salerno
name: Eduardo M Sommella
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Modena and Reggio Emilia
name: Valentina Masciale
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Modena and Reggio Emilia
name: Ilenia Mastrolia
role: PRINCIPAL_INVESTIGATOR
References: