HOPE to Reduce Tumour Recurrence After LT In Patients With HCC

NCT ID: NCT05876052

Last Updated: 2023-05-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

192 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-05-31

Study Completion Date

2025-05-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

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

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Hypothermic oxygenated Perfusion - HOPE

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.

Group Type EXPERIMENTAL

Hypothermic oxygenated Perfusion - HOPE

Intervention Type DEVICE

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.

Static Cold Storage - SCS

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

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Hypothermic oxygenated Perfusion - HOPE

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.

Intervention Type DEVICE

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Azienda Ospedaliero, Universitaria Pisana

OTHER

Sponsor Role collaborator

The Mediterranean Institute for Transplantation and Advanced Specialized Therapies

OTHER

Sponsor Role collaborator

A.O.U. Città della Salute e della Scienza

OTHER

Sponsor Role collaborator

IRCCS Azienda Ospedaliero-Universitaria di Bologna

OTHER

Sponsor Role collaborator

University of Bologna

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Matteo Ravaioli, Professor

Clinical Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

IRCCS Azienda Ospedaliero-Universitaria di Bologna

Bologna, , Italy

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Italy

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Matteo Ravaioli, Professor

Role: CONTACT

0512144810

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 27433914 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30697517 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29018070 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26583664 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32269237 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31673538 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 3282347 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20677285 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29564206 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 35671067 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

POTERE

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.