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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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®). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hypothermic oxygenated perfusion | Procedure | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| HCC recurrence (while alive) | Number of HCC recurrences | 24 months |
| HCC recurrence (while alive) | Time to recurrence of HCC | 24 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Philipp Dutkowski, Professor | Contact | 0041 61 777 73 06 | philipp.dutkowski@clarunis.ch |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rutgers New Jersey Medical School (New York) | Not yet recruiting | New York | New York | 07103 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41013675 | Derived | 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. |
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| Conventional cold storage | Procedure | 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. |
|
| HCC-related death | Death related to HCC | 24 months |
| HCC-related death | Time to HCC related death | 24 months |
| Death from any other causes than HCC | Death not related to HCC | 24 months |
| Death from any other causes than HCC | Time to death not related to HCC | 24 months |
| Mean number of circulating tumour deoxyribonucleic acid (DNA) in blood | This will be measured before transplantation (baseline), at discharge and at 6 months after transplantation. This endpoint will add information on the risk of tumour recurrence by seeding circulating cells. | 6 months |
| Mean number of high-mobility-group-protein B1 (HMGB-1) in blood | This will be measured at the time of transplantation (baseline) and 1 week after transplantation. This endpoint will add information on danger signalling in both study arms during early and late reperfusion. | 1 week |
| Median Rejection Activity Index | The Rejection Activity Index (RAI) in liver histology (biopsy) is performed at 6 months after transplantation. This endpoint assessed in liver histology (biopsy) will show endothelial and T cell activation in implanted livers within the first months after 6 months. The RAI can be used to score liver allograft biopsies with acute rejection. The scale is from 1 to 9, higher scores mean more severe signs of rejection. | 6 months |
| Liver related complications | This endpoint will allow to assess the association between initial graft injury and liver specific complications in both study arms. | 24 months |
| Cleveland Clinic | Not yet recruiting | Cleveland | Ohio | 44195 | United States |
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| Medical University of Innsbruck | Recruiting | Innsbruck | 6020 | Austria |
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| Medical University of Vienna | Recruiting | Vienna | 1090 | Austria |
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| University Hospitals Leuven | Recruiting | Leuven | 3000 | Belgium |
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| Institut de Recherche Expérimentale et Clinique (IREC) UCLouvain (Brussels) | Recruiting | Woluwe-Saint-Lambert | 1200 | Belgium |
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| Institute for Clinical and Experimental Medicine (IKEM) (Prague) | Recruiting | Prague | 14021 | Czechia |
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| Copenhagen University Hospital | Recruiting | Copenhagen | 2100 | Denmark |
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| Hôpital de la Croix-Rousse (Lyon) | Not yet recruiting | Lyon | 69004 | France |
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| Universitätsklinikum Essen | Not yet recruiting | Essen | 45122 | Germany |
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| University Medical Centre Hamburg-Eppendorf | Not yet recruiting | Hamburg-Eppendorf | 20246 | Germany |
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| Hannover Medical School | Not yet recruiting | Hanover | 30626 | Germany |
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| University of Heidelberg | Not yet recruiting | Heidelberg | 69120 | Germany |
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| University of Mainz | Not yet recruiting | Mainz | 55131 | Germany |
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| University of Munich Grosshadern | Not yet recruiting | München | 81377 | Germany |
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| Milano Institutio Nazionale dei Tumori (Milan) | Not yet recruiting | Milan | 20133 | Italy |
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| ASST Grande Ospedale Metropolitano Niguarda (Milan) | Not yet recruiting | Milan | 20162 | Italy |
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| Padova University Hospital | Not yet recruiting | Padova | 35128 | Italy |
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| Gemelli University Hospital | Not yet recruiting | Rome | 00168 | Italy |
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| University of Udine | Recruiting | Udine | 33100 | Italy |
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| Lithuanian University of Health Sciences | Not yet recruiting | Kaunas | 50009 | Lithuania |
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| University of Groningen and University Medical Centre Groningen | Not yet recruiting | Groningen | 9713 | Netherlands |
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| University Medical Centre Rotterdam - Erasmus University Medical Center | Not yet recruiting | Rotterdam | 3015 | Netherlands |
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| Oslo University Hospital | Not yet recruiting | Oslo | 0450 | Norway |
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| Department of Surgical Oncology, Transplant Surgery and General Surgery, Medical University of Gdańsk | Recruiting | Gdansk | 80-210 | Poland |
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| Medical University of Warsaw | Not yet recruiting | Warsaw | 02-097 | Poland |
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| Centro Hepato-Bilio-Pancreático e de Transplantação (CHBPT) | Not yet recruiting | Lisbon | 1069-166 | Portugal |
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| Vall d'Hebron Barcelona Hospital Campus | Not yet recruiting | Barcelona | 08035 | Spain |
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| Karolinska Institutet (Stockholm) | Recruiting | Stockholm | 17177 | Sweden |
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| Clarunis - University Digestive Health Care | Not yet recruiting | Basel | Canton of Basel-City | 4031 | Switzerland |
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| University Hospital Zurich | Not yet recruiting | Zurich | Canton of Zurich | 8091 | Switzerland |
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| Hôpitaux universitaires de Genève | Recruiting | Geneva | 1205 | Switzerland |
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| University Hospitals Birmingham | Not yet recruiting | Birmingham | B15 2GW | United Kingdom |
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| Leeds Teaching Hospitals NHS Trust | Not yet recruiting | Leeds | LS97TF | United Kingdom |
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| The Royal Free Hospital (London) | Not yet recruiting | London | NW3 2QG | United Kingdom |
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| King's College Hospital (London) | Not yet recruiting | London | SE5 9RS | United Kingdom |
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| Freeman Hospital (Newcastle) | Not yet recruiting | Newcastle | NE7 7DN | United Kingdom |
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| ID | Term |
|---|---|
| D006528 | Carcinoma, Hepatocellular |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008113 | Liver Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D008107 | Liver Diseases |
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