Clinical trial NCT05876052: HOPE to Reduce Tumour Recurrence After LT In Patients With HCC
Official title: Hypothermic Oxygenated Perfusion To Reduce Tumour Recurrence After Liver Transplantation In Patients With Hepatocarcinoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Liver Cancer
Tumor Recurrence
Hepatocellular Carcinoma
Liver Transplantation
Ex-vivo Hypothermic Perfusion
Lead sponsor: University of Bologna
Sponsor class: OTHER
Collaborators: name: Azienda Ospedaliero, Universitaria Pisana
name: The Mediterranean Institute for Transplantation and Advanced Specialized Therapies
name: A.O.U. Città della Salute e della Scienza
name: IRCCS Azienda Ospedaliero-Universitaria di Bologna
First posted: 2023-05-25
Enrollment: 192
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of liver recurrence
timeFrame: 1 year after LT
Secondary outcomes:
measure: Incidence of early allograft disfunction (EAD)
timeFrame: starting 24 hours after LT until 7 days after LT
Other outcomes:
measure: Changes in circulating tumor DNA (ctDNA) level
timeFrame: 1 day before LT/ until 12 months after LT
Locations:
city: Bologna
country: Italy
facility: IRCCS Azienda Ospedaliero-Universitaria di Bologna
Study officials:
References:
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