Hepatocellular CarcinomaNCT06236568
Impact of Graft Reconditioning With Hypothermic Machine Perfusion on HCC Recurrence After Liver Transplantation
A study testing D-HOPE machine perfusion and Liver transplantation in people with Hepatocellular Carcinoma and Liver Transplant; Complications, run by Azienda Ospedaliero-Universitaria di Modena at 1 site in Italy.
Trial summary
The use of devices for liver grafts perfusion before transplantation, either hypothermic (HOPE) or normothermic (NMP), is rapidly spreading thanks to the promising results obtained so far in terms of graft survival and post-operative morbidity. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma, Liver Transplant; Complications
- What is being tested?
- D-HOPE machine perfusion and Liver transplantation
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteItaly
- Study dates
- 6 Feb 2024to 31 Dec 2030
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with HCC within Milan criteria at listing candidate for liver transplantation
- ECOG 0-2
- DBD donors
- capability to sign an informed consent
Who cannot join
- pediatric patients
- DCD donors
- DBD extended criteria requiring machine perfusion (no ethical randomization)
- living donor liver transplantation
- split liver
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
AOU di Modena
Modena, MO, 41124
Paolo Magistri, MD FACS, +390594225178, paolo.magistri@unimore.it
About this study
The use of devices for liver grafts perfusion before transplantation, either hypothermic (HOPE) or normothermic (NMP), is rapidly spreading thanks to the promising results obtained so far in terms of graft survival and post-operative morbidity. Besides the well-established ability to increase the rate of transplantability of extended criteria donors (ECD) and donors after cardiac death (DCD), the use of machine perfusion (MP) may also improve the oncological outcomes of patients affected by hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). The underlying mechanism is represented by the modulation of the ischemia-reperfusion injury (IRI)-related cellular damage obtained by the liver graft perfusion with HOPE before LT. The identification of biomarkers able to predict graft outcomes and highlight the mechanism of graft injury before transplantation rapidly and in non-invasive manner is therefore needed. Mass spectrometry-based metabolomics has already shown its potential by using perfusion liquids or pre-implantation biopsies.
The aim of the investigators is to run an open-label, randomised, controlled trial to study the impact of treating standard liver grafts from brain dead donors (DBD) with HOPE before liver transplant in patients affected by HCC. Patients aged 18-75 years presenting with HCC Milan-in at listing will be considered for inclusion. Presence of extra-hepatic disease and general contraindications to liver transplantation as defined by the local tumor board are considered as exclusion criteria. Eligible patients will be randomly assigned (1:1) with the use of a dedicated software to MP (intervention group) or no-MP (control group) before liver transplantation. Untargeted mass spectrometry metabolomics (UHPLC-HRMS) will be performed on liver graft perfusate, liver graft biopsy and recipient blood samples, to identify by classification methods, novel predictive markers of IRI. Furthermore, rapid targeted MS approaches will be performed on VIP metabolites and known key compounds (such as TCA, aminoacids, energy metabolism) to rapidly assess graft function as well as post-operative outcome.
Read more
Blood samples of the recipient will be collected at two checkpoints (listing, and 3 months after liver transplant) to evaluate exosomes and miRNA expression fluctuations (liquid biopsy).
Primary outcomes of the study will be overall survival, graft survival and recurrence-free survival at 1- and 2-years. Survival results will be compared to those expected based on the Metroticket 2.0 score to assess the impact of MP in reducing the risk of HCC recurrence. Patients will remain in follow-up as for clinical practice to assess 3- and 5-years survival. Secondary end-point will be to define liquid biopsy efficacy to predict HCC recurrence and to define the correlation between metabolomic observations and HCC recurrence pattern.
- Being tested
- D-HOPE machine perfusion, Liver transplantation
- Keywords
- Hepatocellular carcinoma, Liver Transplantation, Metabolomics, Liquid biopsy, Machine perfusion, Ischemia reperfusion injury
- Medical subject headings
- Carcinoma, Hepatocellular, Reperfusion Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
D-HOPE machine perfusionDevice
use of the device
Liver transplantationProcedure or surgery
Liver transplantation for HCC within Milan criteria
| Study group | Role | What they receive |
|---|---|---|
| Machine perfusion | Experimental | The liver graft to be transplanted is treated with 90 minutes of D-HOPE machine perfusion Receives: Device: D-HOPE machine perfusion; Procedure: Liver transplantation |
| No machine perfusion | Active comparator | Standard liver transplantation Receives: Procedure: Liver transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival
Recurrence free survival and overall survival after LT for HCC according to the use of MP This aim will be realized at the Hepato-pancreato-biliary Surgery and Liver Transplantation Unit of Policlinico University Hospital of Modena - University of Modena and Reggio Emilia, supervised by Dr Paolo Magistri. Patients included in the trial according to the following criteria will be treated and followed-up according to the standard of care (SOC). All eligible patients have an indication to LT beyond the aims of this study, and will undergo LT according to National indications. LT is the gold standard treatment for patients affected by HCC inside Milan criteria, however biological features of the tumor may modify the expected recurrence pattern.
This aim will be focused on the potential role for MP in the modulation of tumor recurrence pattern.
SA1 Deliverables:
Modulation of HCC recurrence pattern after MP
Measured: 5 years after surgery
Secondary outcomes (3)
Prognostic markers - MiRNA
Identification of microRNAs from liquid biopsy derived extracellular vesicles, as source of prognostic information on IRI favoring HCC recurrence. This aim will be realized by Research Laboratory at Policlinico University Hospital of Modena - University of Modena and Reggio Emilia, supervised by Dr Valentina Masciale.
SA2 Deliverables:
- miRNAs transcriptomic profile of pre transplanted-patients.
Measured: 5 years after surgery
Prognostic markers - metabolipiodomics
Identification of at least 1 prognostic markers from the promising miRNA selected on the bases of the transcriptomic analysis.
SA3: Identification of prognostic markers of IRI and HCC by MS-based metabolipidomics:
This aim will be realized by UNIT2, Unisa-Difarma, Dr. Eduardo Maria Sommella
Measured: 5 years after surgery
Graft survival
Reduction of early allograft disfunction
Measured: 1 month after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2024
- Study start6 Feb 2024
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Azienda Ospedaliero-Universitaria di Modena
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Paolo Magistri, Azienda Ospedaliero-Universitaria di Modena
- Investigators
- Fabrizio Di Benedetto, Study chair, University of Modena and Reggio EmiliaMassimo Dominici, Study chair, University of Modena and Reggio EmiliaPietro Campiglia, Study chair, University of SalernoEduardo M Sommella, Principal investigator, University of SalernoValentina Masciale, Principal investigator, University of Modena and Reggio EmiliaIlenia Mastrolia, Principal investigator, University of Modena and Reggio Emilia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06236568
- Sponsor's protocol ID
- 561/2023/SPER/AOUMO.
- Status last verified
- Feb 2024
- First submitted
- 24 Jan 2024
- Last updated
- 7 Feb 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Graft Reconditioning With Hypothermic Machine Perfusion on HCC Recurrence After Liver Transplantation
- ClinicalTrials.gov ID
- NCT06236568
- Acronym / sponsor ID
- 561/2023/SPER/AOUMO.
- Keywords
- Hepatocellular carcinoma, Liver Transplantation, Metabolomics, Liquid biopsy, Machine perfusion, Ischemia reperfusion injury
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Azienda Ospedaliero-Universitaria di ModenaUniversity, hospital or other
- Study start
- 6 Feb 2024 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2030 (estimated)
- First posted
- 1 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The use of devices for liver grafts perfusion before transplantation, either hypothermic (HOPE) or normothermic (NMP), is rapidly spreading thanks to the promising results obtained so far in terms of graft survival and post-operative morbidity. Besides the well-established ability to increase the rate of transplantability of extended criteria donors (ECD) and donors after cardiac death (DCD), the use of machine perfusion (MP) may also improve the oncological outcomes of patients affected by hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). The underlying mechanism is represented by the modulation of the ischemia-reperfusion injury (IRI)-related cellular damage obtained by the liver graft perfusion with HOPE before LT. The identification of biomarkers able to predict graft outcomes and highlight the mechanism of graft injury before transplantation rapidly and in non-invasive manner is therefore needed. Mass spectrometry-based metabolomics has already shown its potential by using perfusion liquids or pre-implantation biopsies.
The aim of the investigators is to run an open-label, randomised, controlled trial to study the impact of treating standard liver grafts from brain dead donors (DBD) with HOPE before liver transplant in patients affected by HCC. Patients aged 18-75 years presenting with HCC Milan-in at listing will be considered for inclusion. Presence of extra-hepatic disease and general contraindications to liver transplantation as defined by the local tumor board are considered as exclusion criteria. Eligible patients will be randomly assigned (1:1) with the use of a dedicated software to MP (intervention group) or no-MP (control group) before liver transplantation. Untargeted mass spectrometry metabolomics (UHPLC-HRMS) will be performed on liver graft perfusate, liver graft biopsy and recipient blood samples, to identify by classification methods, novel predictive markers of IRI. Furthermore, rapid targeted MS approaches will be performed on VIP metabolites and known key compounds (such as TCA, aminoacids, energy metabolism) to rapidly assess graft function as well as post-operative outcome.
Blood samples of the recipient will be collected at two checkpoints (listing, and 3 months after liver transplant) to evaluate exosomes and miRNA expression fluctuations (liquid biopsy).
Primary outcomes of the study will be overall survival, graft survival and recurrence-free survival at 1- and 2-years. Survival results will be compared to those expected based on the Metroticket 2.0 score to assess the impact of MP in reducing the risk of HCC recurrence. Patients will remain in follow-up as for clinical practice to assess 3- and 5-years survival. Secondary end-point will be to define liquid biopsy efficacy to predict HCC recurrence and to define the correlation between metabolomic observations and HCC recurrence pattern.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Machine perfusion | Experimental | Device: D-HOPE machine perfusion, Procedure: Liver transplantationThe liver graft to be transplanted is treated with 90 minutes of D-HOPE machine perfusion |
| No machine perfusion | Active comparator | Procedure: Liver transplantationStandard liver transplantation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients with HCC within Milan criteria at listing candidate for liver transplantation
- ECOG 0-2
- DBD donors
- capability to sign an informed consent
Key exclusion criteria (5 listed)
- pediatric patients
- DCD donors
- DBD extended criteria requiring machine perfusion (no ethical randomization)
- living donor liver transplantation
- split liver
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| D-HOPE machine perfusionuse of the device | Device | Machine perfusion |
| Liver transplantationLiver transplantation for HCC within Milan criteria | Procedure or surgery | Machine perfusion, No machine perfusion |
Primary outcome
Survival
Time frame: 5 years after surgery
Recurrence free survival and overall survival after LT for HCC according to the use of MP This aim will be realized at the Hepato-pancreato-biliary Surgery and Liver Transplantation Unit of Policlinico University Hospital of Modena - University of Modena and Reggio Emilia, supervised by Dr Paolo Magistri. Patients included in the trial according to the following criteria will be treated and followed-up according to the standard of care (SOC). All eligible patients have an indication to LT beyond the aims of this study, and will undergo LT according to National indications. LT is the gold standard treatment for patients affected by HCC inside Milan criteria, however biological features of the tumor may modify the expected recurrence pattern. This aim will be focused on the potential role for MP in the modulation of tumor recurrence pattern. SA1 Deliverables: Modulation of HCC recurrence pattern after MP
3 secondary outcomes
Prognostic markers - MiRNA
Time frame: 5 years after surgery
Prognostic markers - metabolipiodomics
Time frame: 5 years after surgery
Graft survival
Time frame: 1 month after surgery
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2024.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Fabrizio Di Benedetto study chair
University of Modena and Reggio Emilia
Massimo Dominici study chair
University of Modena and Reggio Emilia
Pietro Campiglia study chair
University of Salerno
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing D-HOPE machine perfusion and Liver transplantation in people with Hepatocellular Carcinoma and Liver Transplant; Complications, run by Azienda Ospedaliero-Universitaria di Modena at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 7 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Paolo Magistri, MD FACS (+390594225265, paolo.magistri@unimore.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Survival (time frame: 5 years after surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Feb 2024.