NCT06717919

Brief Summary

Liver transplantation is often performed to treat liver cancer, or hepatocellular carcinoma (HCC), in patients with impaired liver function due to cirrhosis. A shortcoming, however, is tumor recurrence after transplantation. Approximately 15 % of patients receiving livers develop recurrence and this depends on the quality of the liver received. Machine liver perfusion, for example, hypothermic oxygenated liver perfusion (HOPE), which means that the organ is perfused with an oxygen-rich fluid in a cold environment before transplantation, is a novel method to improve the quality of livers before implantation. The standard of care is cold storage without perfusion. The objective of this study is to compare the survival after tumor recurrence of patients after liver transplantation for HCC between perfused and not perfused livers. This study's hypothesis is that survival without tumor recurrence is improved when the liver is perfused before implantation. The study involves transplant centers worldwide, and adults with HCC waiting for liver transplantation are included. 220 Patients will be recruited within 12 months and then observed for at least 2 years after transplantation. To provide the most valid results, the patients will be randomly allocated to either the organ perfusion group or a control group with standard-of-care cold storage of the organ.

Trial Health

88
On Track

Trial Health Score

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

Enrollment
220

participants targeted

Target at P75+ for phase_4

Timeline
21mo left

Started Aug 2025

Typical duration for phase_4

Geographic Reach
17 countries

37 active sites

Status
recruiting

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

Study Progress31%
Aug 2025Jan 2028

First Submitted

Initial submission to the registry

November 27, 2024

Completed
8 days until next milestone

First Posted

Study publicly available on registry

December 5, 2024

Completed
8 months until next milestone

Study Start

First participant enrolled

August 1, 2025

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 31, 2028

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 31, 2028

Last Updated

December 16, 2025

Status Verified

December 1, 2025

Enrollment Period

2.5 years

First QC Date

November 27, 2024

Last Update Submit

December 15, 2025

Conditions

Keywords

HOPErandomised controlled trialmulticentrehepatocellular carcinomaliver transplantation

Outcome Measures

Primary Outcomes (1)

  • Recurrence free survival

    Post transplant HCC recurrence free survival, i.e. the time interval a patient is alive without HCC recurrence after transplantation, i.e., until either HCC recurrence is observed, or the patient dies from any cause.

    24 months

Secondary Outcomes (10)

  • HCC recurrence (while alive)

    24 months

  • HCC recurrence (while alive)

    24 months

  • HCC-related death

    24 months

  • HCC-related death

    24 months

  • Death from any other causes than HCC

    24 months

  • +5 more secondary outcomes

Study Arms (2)

Conventional cold storage

ACTIVE COMPARATOR

Conventional cold storage at 4°C will be performed with precooled preservation solution according to local standard of care. For cold storage at the Swiss centres, IGL-1 (Institute George Lopez) is used for cold storage. Liver transplant centres in other European countries, use mainly three other storage solutions (Histidine trypophan-ketoglutarat, HTK and University of Wisconsin, UW solution, Celsior) in accordance to their national guidelines.

Procedure: Conventional cold storage

Hypothermic oxygenated perfusion

EXPERIMENTAL

All study centres will use either VitaSmart, Liver assist or Perlife devices for machine liver perfusion, with a pressure controlled hypothermic oxygenated liver perfusion through the portal vein (HOPE) or through the portal vein and the hepatic artery (DHOPE), targeting a flow rate between 200-250 ml/min at a pressure of 3 mmHg, and a perfusate temperature between 8-12°C. The perfusate consists of 3L re-circulating Belzer MPS® (Bridge to Life Ltd.) with an active oxygenation (70-110 kPa). The minimum perfusion duration is defined at 2 hours, while perfusion is generally continued until the recipient hepatectomy is completed. The perfusion will exclusively be performed in the recipient centre after initial cold storage and bench preparation of the liver for implantation. The perfusion devices are routinely used in all participating centres (VitaSmart, Bridge to Life®, Liver Assist, XVIVO®, Perlife, Aferitica®).

Procedure: Hypothermic oxygenated perfusion

Interventions

All study centres will use either VitaSmart, Liver assist or Perlife devices for machine liver perfusion, with a pressure controlled hypothermic oxygenated liver perfusion through the portal vein (HOPE) or through the portal vein and the hepatic artery (DHOPE), targeting a flow rate between 200-250 ml/min at a pressure of 3 mmHg, and a perfusate temperature between 8-12°C. The perfusate consists of 3L re-circulating Belzer MPS® (Bridge to Life Ltd.) with an active oxygenation (70-110 kPa). The minimum perfusion duration is defined at 2 hours, while perfusion is generally continued until the recipient hepatectomy is completed. The perfusion will exclusively be performed in the recipient centre after initial cold storage and bench preparation of the liver for implantation. The perfusion devices are routinely used in all participating centres.

Hypothermic oxygenated perfusion

Conventional cold storage at 4°C will be performed with precooled preservation solution according to local standard of care. For cold storage at the Swiss centres, IGL-1 (Institute George Lopez) is used for cold storage. Liver transplant centres in other European countries, use mainly three other storage solutions (Histidine trypophan-ketoglutarat, HTK and University of Wisconsin, UW solution, Celsior) in accordance to their national guidelines.

Conventional cold storage

Eligibility Criteria

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

You may qualify if:

  • Adult recipients (\>18y), listed for liver transplantation with documented HCC (Liver Imaging Reporting and Data System (LIRADS) 5 lesion in magnetic resonance imaging or computer tomography of the liver or biopsy proven),
  • within up to seven criteria, i.e. HCC with seven as the sum of the diameter of the largest tumour (in cm) and the number of tumours at the time point of liver transplantation,
  • written informed consent for the trial. This also includes patients beyond the up to seven criteria after successful downsizing of the HCC

You may not qualify if:

  • Donation after circulatory death (DCD) liver grafts
  • Combined liver transplants
  • Partial liver transplants
  • Combined or mixed hepatocellular cholangiocarcinoma (cHCC-CCC) or pure cholangiocarcinoma or other malignancies in histopathology of the liver explant
  • Systemic antitumoural medical treatment with checkpoint inhibitors or multikinase inhibitors
  • Post-transplant treatment with mTOR inhibitors
  • Acute and unexpected medical contraindications
  • Pregnancy
  • Cold storage time of \> 10 hours (both study arms)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (37)

Rutgers New Jersey Medical School (New York)

New York, New York, 07103, United States

NOT YET RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

NOT YET RECRUITING

Medical University of Innsbruck

Innsbruck, 6020, Austria

RECRUITING

Medical University of Vienna

Vienna, 1090, Austria

RECRUITING

University Hospitals Leuven

Leuven, 3000, Belgium

RECRUITING

Institut de Recherche Expérimentale et Clinique (IREC) UCLouvain (Brussels)

Woluwe-Saint-Lambert, 1200, Belgium

RECRUITING

Institute for Clinical and Experimental Medicine (IKEM) (Prague)

Prague, 14021, Czechia

RECRUITING

Copenhagen University Hospital

Copenhagen, 2100, Denmark

RECRUITING

Hôpital de la Croix-Rousse (Lyon)

Lyon, 69004, France

NOT YET RECRUITING

Universitätsklinikum Essen

Essen, 45122, Germany

NOT YET RECRUITING

University Medical Centre Hamburg-Eppendorf

Hamburg-Eppendorf, 20246, Germany

NOT YET RECRUITING

Hannover Medical School

Hanover, 30626, Germany

NOT YET RECRUITING

University of Heidelberg

Heidelberg, 69120, Germany

NOT YET RECRUITING

University of Mainz

Mainz, 55131, Germany

NOT YET RECRUITING

University of Munich Grosshadern

München, 81377, Germany

NOT YET RECRUITING

Milano Institutio Nazionale dei Tumori (Milan)

Milan, 20133, Italy

NOT YET RECRUITING

ASST Grande Ospedale Metropolitano Niguarda (Milan)

Milan, 20162, Italy

NOT YET RECRUITING

Padova University Hospital

Padua, 35128, Italy

NOT YET RECRUITING

Gemelli University Hospital

Rome, 00168, Italy

NOT YET RECRUITING

University of Udine

Udine, 33100, Italy

RECRUITING

Lithuanian University of Health Sciences

Kaunas, 50009, Lithuania

NOT YET RECRUITING

University of Groningen and University Medical Centre Groningen

Groningen, 9713, Netherlands

NOT YET RECRUITING

University Medical Centre Rotterdam - Erasmus University Medical Center

Rotterdam, 3015, Netherlands

NOT YET RECRUITING

Oslo University Hospital

Oslo, 0450, Norway

NOT YET RECRUITING

Department of Surgical Oncology, Transplant Surgery and General Surgery, Medical University of Gdańsk

Gdansk, 80-210, Poland

RECRUITING

Medical University of Warsaw

Warsaw, 02-097, Poland

NOT YET RECRUITING

Centro Hepato-Bilio-Pancreático e de Transplantação (CHBPT)

Lisbon, 1069-166, Portugal

NOT YET RECRUITING

Vall d'Hebron Barcelona Hospital Campus

Barcelona, 08035, Spain

NOT YET RECRUITING

Karolinska Institutet (Stockholm)

Stockholm, 17177, Sweden

RECRUITING

Clarunis - University Digestive Health Care

Basel, Canton of Basel-City, 4031, Switzerland

NOT YET RECRUITING

University Hospital Zurich

Zurich, Canton of Zurich, 8091, Switzerland

NOT YET RECRUITING

Hôpitaux universitaires de Genève

Geneva, 1205, Switzerland

RECRUITING

University Hospitals Birmingham

Birmingham, B15 2GW, United Kingdom

NOT YET RECRUITING

Leeds Teaching Hospitals NHS Trust

Leeds, LS97TF, United Kingdom

NOT YET RECRUITING

The Royal Free Hospital (London)

London, NW3 2QG, United Kingdom

NOT YET RECRUITING

King's College Hospital (London)

London, SE5 9RS, United Kingdom

NOT YET RECRUITING

Freeman Hospital (Newcastle)

Newcastle, NE7 7DN, United Kingdom

NOT YET RECRUITING

Related Publications (1)

  • Eden J, Muller PC, Kuemmerli C, Peters F, Litke T, Kranich A, Kremer AE, von Felten S, Dutkowski P; HOPE4Cancer Trial Investigators. Hypothermic oxygenated perfusion (HOPE) against cancer recurrence after liver transplantation for hepatocellular carcinoma-study protocol for an international multicenter randomized controlled trial (HOPE4Cancer). Trials. 2025 Sep 26;26(1):369. doi: 10.1186/s13063-025-09120-1.

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsLiver NeoplasmsDigestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesLiver Diseases

Central Study Contacts

Philipp Dutkowski, Professor

CONTACT

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Sponsor representative and Principal Investigator

Study Record Dates

First Submitted

November 27, 2024

First Posted

December 5, 2024

Study Start

August 1, 2025

Primary Completion (Estimated)

January 31, 2028

Study Completion (Estimated)

January 31, 2028

Last Updated

December 16, 2025

Record last verified: 2025-12

Data Sharing

IPD Sharing
Will not share

Locations