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

Primary Purpose

Liver Cancer, Tumor Recurrence, Hepatocellular Carcinoma

Status
Not yet recruiting
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
Hypothermic oxygenated Perfusion - HOPE
Sponsored by
University of Bologna
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Liver Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • IRCCS Azienda Ospedaliero-Universitaria di Bologna

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Hypothermic oxygenated Perfusion - HOPE

Static Cold Storage - SCS

Arm 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.

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

Outcomes

Primary Outcome Measures

Incidence of liver recurrence
Present/Non present; Diagnosis with abdominal ultrasound and serum tumor markers analysis Date of recurrence and location

Secondary Outcome Measures

Incidence of early allograft disfunction (EAD)
Present/Non present; Diagnosis with analysis of serum values of : Aspartate transaminase (AST), Alanine transaminase (ALT), Bilirubin and International Normalised Ratio (INR)

Full Information

First Posted
April 21, 2023
Last Updated
May 16, 2023
Sponsor
University of Bologna
Collaborators
Azienda Ospedaliero, Universitaria Pisana, The Mediterranean Institute for Transplantation and Advanced Specialized Therapies, Azienda Ospedaliera Città della Salute e della Scienza di Torino, IRCCS Azienda Ospedaliero-Universitaria di Bologna
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1. Study Identification

Unique Protocol Identification Number
NCT05876052
Brief Title
HOPE to Reduce Tumour Recurrence After LT In Patients With HCC
Acronym
POTERE
Official Title
Hypothermic Oxygenated Perfusion To Reduce Tumour Recurrence After Liver Transplantation In Patients With Hepatocarcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
May 2023 (Anticipated)
Primary Completion Date
May 2024 (Anticipated)
Study Completion Date
May 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Bologna
Collaborators
Azienda Ospedaliero, Universitaria Pisana, The Mediterranean Institute for Transplantation and Advanced Specialized Therapies, Azienda Ospedaliera Città della Salute e della Scienza di Torino, IRCCS Azienda Ospedaliero-Universitaria di Bologna

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Cancer, Tumor Recurrence, Hepatocellular Carcinoma, Liver Transplantation, Ex-vivo Hypothermic Perfusion

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
192 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Hypothermic oxygenated Perfusion - HOPE
Arm Type
Experimental
Arm 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.
Arm Title
Static Cold Storage - SCS
Arm Type
No Intervention
Arm Description
Livers undergoing SCS will be stored in sterile organ bags with Belzer or Celsior solution and cooled in ice until transplant.
Intervention Type
Device
Intervention Name(s)
Hypothermic oxygenated Perfusion - HOPE
Intervention Description
HOPE will start by flushing the organ at low flow values (30 ml/min) with new oxygenated perfusion fluid during back-table preparation. Organ will be treated with continuous HOPE until transplant. Organ perfusion will be continuously monitored. Minimal perfusion time will be 1 hour for livers.
Primary Outcome Measure Information:
Title
Incidence of liver recurrence
Description
Present/Non present; Diagnosis with abdominal ultrasound and serum tumor markers analysis Date of recurrence and location
Time Frame
1 year after LT
Secondary Outcome Measure Information:
Title
Incidence of early allograft disfunction (EAD)
Description
Present/Non present; Diagnosis with analysis of serum values of : Aspartate transaminase (AST), Alanine transaminase (ALT), Bilirubin and International Normalised Ratio (INR)
Time Frame
starting 24 hours after LT until 7 days after LT
Other Pre-specified Outcome Measures:
Title
Changes in circulating tumor DNA (ctDNA) level
Description
Blood and tissue samples collection, ctDNA extraction and quantification via Next Generation Sequencing (NGS)
Time Frame
1 day before LT/ until 12 months after LT

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Matteo Ravaioli, Professor
Phone
0512144810
Email
matteo.ravaioli6@unibo.it
Facility Information:
Facility Name
IRCCS Azienda Ospedaliero-Universitaria di Bologna
City
Bologna
ZIP/Postal Code
40138
Country
Italy

12. IPD Sharing Statement

Citations:
PubMed Identifier
27433914
Citation
Bodzin AS, Lunsford KE, Markovic D, Harlander-Locke MP, Busuttil RW, Agopian VG. Predicting Mortality in Patients Developing Recurrent Hepatocellular Carcinoma After Liver Transplantation: Impact of Treatment Modality and Recurrence Characteristics. Ann Surg. 2017 Jul;266(1):118-125. doi: 10.1097/SLA.0000000000001894.
Results Reference
background
PubMed Identifier
30697517
Citation
Boteon YL, Afford SC. Machine perfusion of the liver: Which is the best technique to mitigate ischaemia-reperfusion injury? World J Transplant. 2019 Jan 16;9(1):14-20. doi: 10.5500/wjt.v9.i1.14.
Results Reference
background
PubMed Identifier
29018070
Citation
Czigany Z, Schoning W, Ulmer TF, Bednarsch J, Amygdalos I, Cramer T, Rogiers X, Popescu I, Botea F, Fronek J, Kroy D, Koch A, Tacke F, Trautwein C, Tolba RH, Hein M, Koek GH, Dejong CHC, Neumann UP, Lurje G. Hypothermic oxygenated machine perfusion (HOPE) for orthotopic liver transplantation of human liver allografts from extended criteria donors (ECD) in donation after brain death (DBD): a prospective multicentre randomised controlled trial (HOPE ECD-DBD). BMJ Open. 2017 Oct 10;7(10):e017558. doi: 10.1136/bmjopen-2017-017558.
Results Reference
background
PubMed Identifier
26583664
Citation
Dutkowski P, Polak WG, Muiesan P, Schlegel A, Verhoeven CJ, Scalera I, DeOliveira ML, Kron P, Clavien PA. First Comparison of Hypothermic Oxygenated PErfusion Versus Static Cold Storage of Human Donation After Cardiac Death Liver Transplants: An International-matched Case Analysis. Ann Surg. 2015 Nov;262(5):764-70; discussion 770-1. doi: 10.1097/SLA.0000000000001473.
Results Reference
background
PubMed Identifier
32269237
Citation
Ravaioli M, De Pace V, Angeletti A, Comai G, Vasuri F, Baldassarre M, Maroni L, Odaldi F, Fallani G, Caraceni P, Germinario G, Donadei C, Malvi D, Del Gaudio M, Bertuzzo VR, Siniscalchi A, Ranieri VM, D'Errico A, Pasquinelli G, Morelli MC, Pinna AD, Cescon M, La Manna G. Hypothermic Oxygenated New Machine Perfusion System in Liver and Kidney Transplantation of Extended Criteria Donors:First Italian Clinical Trial. Sci Rep. 2020 Apr 8;10(1):6063. doi: 10.1038/s41598-020-62979-9. Erratum In: Sci Rep. 2020 Sep 1;10(1):14658.
Results Reference
background
PubMed Identifier
31673538
Citation
Schlegel A, Muller X, Dutkowski P. Machine perfusion strategies in liver transplantation. Hepatobiliary Surg Nutr. 2019 Oct;8(5):490-501. doi: 10.21037/hbsn.2019.04.04.
Results Reference
background
PubMed Identifier
3282347
Citation
Belzer FO, Southard JH. Principles of solid-organ preservation by cold storage. Transplantation. 1988 Apr;45(4):673-6. doi: 10.1097/00007890-198804000-00001. No abstract available.
Results Reference
background
PubMed Identifier
20677285
Citation
Olthoff KM, Kulik L, Samstein B, Kaminski M, Abecassis M, Emond J, Shaked A, Christie JD. Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors. Liver Transpl. 2010 Aug;16(8):943-9. doi: 10.1002/lt.22091.
Results Reference
background
PubMed Identifier
29564206
Citation
Schlegel A, Muller X, Dutkowski P. Hypothermic Machine Preservation of the Liver: State of the Art. Curr Transplant Rep. 2018;5(1):93-102. doi: 10.1007/s40472-018-0183-z. Epub 2018 Jan 22. Erratum In: Curr Transplant Rep. 2018;5(1):103.
Results Reference
background
PubMed Identifier
35671067
Citation
Ravaioli M, Germinario G, Dajti G, Sessa M, Vasuri F, Siniscalchi A, Morelli MC, Serenari M, Del Gaudio M, Zanfi C, Odaldi F, Bertuzzo VR, Maroni L, Laurenzi A, Cescon M. Hypothermic oxygenated perfusion in extended criteria donor liver transplantation-A randomized clinical trial. Am J Transplant. 2022 Oct;22(10):2401-2408. doi: 10.1111/ajt.17115. Epub 2022 Jun 21.
Results Reference
background

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HOPE to Reduce Tumour Recurrence After LT In Patients With HCC

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