HOPE to Reduce Tumour Recurrence After LT In Patients With HCC (POTERE)

University of Bologna

Status: Not yet enrolling

Conditions: Ex-vivo Hypothermic Perfusion; Liver Transplantation; Hepatocellular Carcinoma; Tumor Recurrence; Liver Cancer

Treatments: Device: Hypothermic oxygenated Perfusion - HOPE

Study type: Interventional

Funder types: Other

Identifiers

NCT05876052

POTERE

Details and patient eligibility

About

Hypothermic oxygenated ex-situ machine perfusion (HOPE) is a dynamic preservation method that has been developed to reduce the incidence and severity of ischaemia-reperfusion injury and to improve outcomes after liver transplantation. Whit this study Pi and collaborators hypothesize that the application of ex-situ liver perfusion before LT in HCC recipients leads to an optimization of graft function, with a decrease in ischaemia-reperfusion injury and a possible decrease in tumor cell growth. This is multicentre, prospective, two-arm, randomized, controlled, clinical trial, that will will involve patients with HCC candidate to LT. The liver grafts will be randomized in two groups to compare HOPE and static cold storage (SCS) preservation before transplantation. For each group evaluation of clinical outcomes, graft function tests, histologic findings, perfusate, tumor characteristics, and recurrence will be done.

Full description

Tumor recurrence after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) is a major complication leading to decreased long-term survival of patients. However, the mechanisms leading to tumor emergence and growth remain incompletely understood. Several factors, can promote cancer growth or recurrence. Ischemia-reperfusion injury (IRI) has been recognized as an important early driver of microvascular dysfunction resulting in tissue hypoxia and inflammation, which promotes tumor cell growth.

A recent therapeutic strategy used to reduce the incidence and severity of IRI and to improve outcomes after transplantation is ex vivo HOPE. Which allows to redirect anaerobic metabolism to aerobic metabolism under hypothermic conditions, protect grafts from oxidative species-related damage, improve graft function and may potentially reduce cancer recurrence after liver transplantation.

A multicentre, prospective, two-arm, randomized, controlled, clinical trial will be performed; four Italian centres (Bologna, Palermo, Pisa e Torino) will be involved. A total of 192 patients with a history of HCC or active HCC, already present or about to be placed in the liver transplantation waiting list of the four transplantation center will be enroll. The liver grafts will be randomized in two groups to compare HOPE and SCS preservation before transplantation. For each group evaluation of clinical outcomes, graft function tests, histologic findings, perfusate, tumor characteristics, and recurrence will be done during follow up visit; 1-3-6 and 12 months after transplantation.

Livers assigned to HOPE group will be perfused by machine perfusion with cold Belzer solution (4°-10°C) and with continuous oxygenation (partial pressure of oxygen = 500-600 mmHg). Organs will be perfused from the start of the back-table procedure until implantation, without increasing cold ischemia time (CIT).

In the control group livers undergoing SCS will be steeped in cold Celsior or Belzer solutions and stored in ice. Presence of bacterial and/or fungal contamination will be tested by setting up microbiological cultures from the preservation fluid, before and after treatment in both groups.

Enrollment: 192 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• all patients with HCC medical history or active HCC
• Donation after circulatory death (DBD) donor with standard or extended criteria

Exclusion criteria

• Living transplantation
• Split Transplantation
• Combined Transplantation
• Donation after cardiac death (DCD)Transplantation
• Re-transplantation
• Patient whose liver graft will undergo ex-vivo machine perfusion for medical decision, regardless the study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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192 participants in 2 patient groups

Hypothermic oxygenated Perfusion - HOPE

Experimental group

Description:

Belzer machine perfusion solution at 4°C-10°C in sterile conditions and continuous oxygenation (partial pressure of oxygen=500-600 mmHg) will be used for perfusion, 3000 ml for livers, 1-3 hours. Liver perfusion will be performed through the portal vein at a 5 mmHg pressure. Flow, pressure and temperature will be monitored and registered on REDCap software during organ perfusion. Gas analysis of the effluent perfusate (partial pressure O2 and CO2, pH, lactate and glutamate production) will be accomplished every 15 minutes.

Treatment:

Device: Hypothermic oxygenated Perfusion - HOPE

Static Cold Storage - SCS

No Intervention group

Description:

Livers undergoing SCS will be stored in sterile organ bags with Belzer or Celsior solution and cooled in ice until transplant.