NCT05876052

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
192

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started May 2023

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 21, 2023

Completed
10 days until next milestone

Study Start

First participant enrolled

May 1, 2023

Completed
24 days until next milestone

First Posted

Study publicly available on registry

May 25, 2023

Completed
11 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2024

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2025

Completed
Last Updated

May 25, 2023

Status Verified

May 1, 2023

Enrollment Period

1 year

First QC Date

April 21, 2023

Last Update Submit

May 16, 2023

Conditions

Outcome Measures

Primary Outcomes (1)

  • Incidence of liver recurrence

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

    1 year after LT

Secondary Outcomes (1)

  • Incidence of early allograft disfunction (EAD)

    starting 24 hours after LT until 7 days after LT

Other Outcomes (1)

  • Changes in circulating tumor DNA (ctDNA) level

    1 day before LT/ until 12 months after LT

Study Arms (2)

Hypothermic oxygenated Perfusion - HOPE

EXPERIMENTAL

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.

Device: Hypothermic oxygenated Perfusion - HOPE

Static Cold Storage - SCS

NO INTERVENTION

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

Interventions

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.

Hypothermic oxygenated Perfusion - HOPE

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

IRCCS Azienda Ospedaliero-Universitaria di Bologna

Bologna, 40138, Italy

Location

Related Publications (10)

  • 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.

    PMID: 27433914BACKGROUND
  • 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.

    PMID: 30697517BACKGROUND
  • 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.

    PMID: 29018070BACKGROUND
  • 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.

    PMID: 26583664BACKGROUND
  • 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.

    PMID: 32269237BACKGROUND
  • 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.

    PMID: 31673538BACKGROUND
  • 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.

    PMID: 3282347BACKGROUND
  • 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.

    PMID: 20677285BACKGROUND
  • 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.

    PMID: 29564206BACKGROUND
  • 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.

    PMID: 35671067BACKGROUND

MeSH Terms

Conditions

Liver NeoplasmsRecurrenceCarcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Digestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesLiver DiseasesDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsAdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic Type

Central Study Contacts

Matteo Ravaioli, Professor

CONTACT

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Clinical Professor

Study Record Dates

First Submitted

April 21, 2023

First Posted

May 25, 2023

Study Start

May 1, 2023

Primary Completion

May 1, 2024

Study Completion

May 1, 2025

Last Updated

May 25, 2023

Record last verified: 2023-05

Locations