Liver TransplantationCyto-HOPENCT04203004
HOPE With Cytokine Filtration in Liver Transplantation (Cyto-HOPE)
A study testing HOPE with cytokine filtration by CytoSorb in people with Liver Transplantation and Post-Reperfusion Syndrome, run by Papa Giovanni XXIII Hospital at 1 site in Italy.
Trial summary
Ischemia-reperfusion injury (IRI) is unavoidably typical of solid organ transplantation. Post-reperfusion syndrome (PRS), characterized by hemodynamic instability at reperfusion of the implanted graft, is a possible complication of liver transplantation. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Liver Transplantation, Post-Reperfusion Syndrome, Ischaemia-Reperfusion Injury
- What is being tested?
- HOPE with cytokine filtration by CytoSorb
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteItaly
- Study dates
- 23 Sep 2021to 31 Dec 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
RECIPIENTS
- Inclusion criteria: age ≥18 years, signed informed consent form
- Exclusion criteria: age <18 years, combined liver-other organ transplantation, pre-transplant treatment with plasmapheresis, refusal to consent to the study
GRAFTS ELIGIBILITY CRITERIA TO HOPE:
- grafts from extended criteria donors with any combination of the following characteristics: age ≥70 years; macrosteatosis ≥35%; diabetes mellitus; severe vasculopathy; anti-HCV or HBsAg positivity (upon biopsy)
- grafts from donors with hemodynamic instability
- graft from DCD (occasionally)
- grafts with an anticipated long cold ischemia time
- PARTIAL GRAFTS ARE EXCLUDED FROM THE STUDY
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Papa Giovanni XXIII Hospital
Bergamo, 24127
Stefania Camagni, MD, scamagni@asst-pg23.it
About this study
Official title: Hypothermic Oxygenated Perfusion With Cytokine Filtration in Clinical Liver Transplantation: a Randomised Controlled Trial
Ischemia-reperfusion injury (IRI) is unavoidably typical of solid organ transplantation.
Post-reperfusion syndrome (PRS), characterized by hemodynamic instability at reperfusion of the implanted graft, is a possible complication of liver transplantation. For sure, IRI plays a fundamental role in the multifactorial pathogenesis of PRS.
Read more
IRI and PRS are associated with a higher risk of early allograft dysfunction (EAD) and, consequently, graft failure.
Liver grafts from both extended criteria donors (ECD) and donation after circulatory death (DCD) are particularly susceptible to IRI and, accordingly, are at higher risk of PRS, EAD and graft failure. Anyway, in the present scenario of organ shortage, such donors greatly contribute to enlarge the organ pool. So, various strategies have been developed for the purpose of a safer use of this kind of grafts. Among them, ex vivo hypothermic oxygenated perfusion (HOPE) reduces IRI and is beneficial for high-risk liver grafts.
The pathogenesis of IRI is an extremely complex downstream inflammation process, involving many different cytokines, chemokines and growth factors. In particular, tumor necrosis factor-alfa (TNF-alfa), interleukin-6 (IL-6), IL-8 and endothelin-1 (ET-1) are crucial in the development of IRI in liver transplantation.
In experimental models, cytokine filtration during ex vivo lung perfusion (EVLP) was proved to be safe and effective in reducing inflammatory response and, thus, pulmonary edema development.
Since
- in liver transplantation, IRI and PRS are associated with a higher risk of EAD and graft failure
- liver grafts from ECD and DCD are particularly susceptible to IRI and are at higher risk of PRS, EAD and graft failure
- HOPE of high-risk liver grafts reduces IRI
- in solid organ transplantation, various cytokines, chemokines and growth factors are involved in the pathogenesis of IRI
- in experimental models of EVLP, cytokine filtration was proved to reduce inflammatory response and subsequent organ damage, our hypothesis is that cytokine filtration during HOPE of high-risk liver grafts may potentiate the beneficial effects of HOPE, further reducing IRI and, consequently, further decreasing the incidence of PRS and EAD.
So, the aim of this study is to verify the feasibility and safety of cytokine filtration during end-ischemic HOPE of liver grafts.
Read the detailed description
This is a monocentric, pilot, randomized controlled study. Each eligible transplant candidate will be enrolled once an eligible graft has been allocated to him/her. Each enrolled patient will be randomized to either the experimental arm (HOPE-CytoSorb) or the control arm (HOPE-standard).
End-ischemic HOPE will be performed at our center after standard procurement of the graft at the donor hospital, static cold storage preservation during transport and back-table preparation. Dual HOPE, by portal continuous flow and arterial pulsatile flow, will be pressure controlled: portal pressure will be ≤5 mmHg and mean arterial pressure will be ≤30 mmHg. HOPE will be performed in an open system, so the graft will swim in the perfusate flowing out of the vena cava. The recirculating perfusion solution will have the same composition of University of Wisconsin Machine Perfusion Solution. HOPE will be maintained for 4 hours. CytoSorb will be included in the circuit only in the experimental arm.
Scheduled samples of both the perfusate and patient's blood will be analyzed for the levels of TNF-alfa, IL-6, IL-8 and ET-1. A biopsy of the implanted graft will be taken 2 hours after its reperfusion. The patient will be followed for 1 year after transplantation.
Once 10 patients have been enrolled, an interim analysis will be performed by an independent Clinical Endpoint Committee.
- Conditions
- Liver Transplantation, Post-Reperfusion Syndrome, Ischaemia-Reperfusion Injury, Early Allograft Dysfunction
- Being tested
- HOPE with cytokine filtration by CytoSorb
- Keywords
- Hypothermic oxygenated perfusion (HOPE), Cytokine filtration, Liver transplantation
- Medical subject headings
- Reperfusion Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HOPE with cytokine filtration by CytoSorbProcedure or surgery
Cytokine filtration during HOPE
| Study group | Role | What they receive |
|---|---|---|
| HOPE-CytoSorb | Experimental | Patients transplanted with livers preserved by HOPE with cytokine filtration by CytoSorb, a CE approved medical device for extracorporeal cytokine removal Receives: Procedure: HOPE with cytokine filtration by CytoSorb |
| HOPE-standard | No intervention | Patients transplanted with livers preserved by HOPE without cytokine filtration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of post-reperfusion syndrome
Aggarwal definition: a decrease in mean arterial pressure >30% below the baseline value, for at least 1 minute, occurring during the first 5 minutes after reperfusion of the liver graft
Measured: Intraoperatively, during the first 5 minutes after reperfusion of the liver graft
Secondary outcomes (2)
Entity of ischemia-reperfusion injury
Assessment of liver biopsy according to Suzuki histological grading system modified by UCLA group [Sosa RA et al. JCI Insight 2016; 1(20): e89679]
Measured: 2 hours after reperfusion of the liver graft
Incidence of early allograft dysfunction
Olthoff definition: presence of almost one of the following variables: bilirubin ≥10 mg/dl on postoperative day 7, INR ≥1.6 on postoperative day 7, ALT or AST >2000 UI/ml within the first 7 postoperative days
Measured: Postoperative day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2019
- Study start23 Sep 2021
- Primary completion31 Dec 2023 (estimated)
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver TransplantationStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Papa Giovanni XXIII Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Stefania Camagni, Papa Giovanni XXIII Hospital
- Investigators
- Michele Colledan, MD, FEBS, Study director, Papa Giovanni XXIII Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04203004
- Sponsor's protocol ID
- HOPE-2
- Acronym
- Cyto-HOPE
- Status last verified
- May 2023
- First submitted
- 16 Dec 2019
- Last updated
- 23 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hypothermic Oxygenated Perfusion With Cytokine Filtration in Clinical Liver Transplantation: a Randomised Controlled Trial
- ClinicalTrials.gov ID
- NCT04203004
- Acronym / sponsor ID
- Cyto-HOPE / HOPE-2
- Conditions
- Liver Transplantation, Post-Reperfusion Syndrome, Ischaemia-Reperfusion Injury, Early Allograft Dysfunction
- Keywords
- Hypothermic oxygenated perfusion (HOPE), Cytokine filtration, Liver transplantation
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Papa Giovanni XXIII HospitalUniversity, hospital or other
- Study start
- 23 Sep 2021 (actual)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 18 Dec 2019 (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.
Ischemia-reperfusion injury (IRI) is unavoidably typical of solid organ transplantation.
Post-reperfusion syndrome (PRS), characterized by hemodynamic instability at reperfusion of the implanted graft, is a possible complication of liver transplantation. For sure, IRI plays a fundamental role in the multifactorial pathogenesis of PRS.
IRI and PRS are associated with a higher risk of early allograft dysfunction (EAD) and, consequently, graft failure.
Liver grafts from both extended criteria donors (ECD) and donation after circulatory death (DCD) are particularly susceptible to IRI and, accordingly, are at higher risk of PRS, EAD and graft failure. Anyway, in the present scenario of organ shortage, such donors greatly contribute to enlarge the organ pool. So, various strategies have been developed for the purpose of a safer use of this kind of grafts. Among them, ex vivo hypothermic oxygenated perfusion (HOPE) reduces IRI and is beneficial for high-risk liver grafts.
The pathogenesis of IRI is an extremely complex downstream inflammation process, involving many different cytokines, chemokines and growth factors. In particular, tumor necrosis factor-alfa (TNF-alfa), interleukin-6 (IL-6), IL-8 and endothelin-1 (ET-1) are crucial in the development of IRI in liver transplantation.
In experimental models, cytokine filtration during ex vivo lung perfusion (EVLP) was proved to be safe and effective in reducing inflammatory response and, thus, pulmonary edema development.
Since
- in liver transplantation, IRI and PRS are associated with a higher risk of EAD and graft failure
- liver grafts from ECD and DCD are particularly susceptible to IRI and are at higher risk of PRS, EAD and graft failure
- HOPE of high-risk liver grafts reduces IRI
- in solid organ transplantation, various cytokines, chemokines and growth factors are involved in the pathogenesis of IRI
- in experimental models of EVLP, cytokine filtration was proved to reduce inflammatory response and subsequent organ damage, our hypothesis is that cytokine filtration during HOPE of high-risk liver grafts may potentiate the beneficial effects of HOPE, further reducing IRI and, consequently, further decreasing the incidence of PRS and EAD.
So, the aim of this study is to verify the feasibility and safety of cytokine filtration during end-ischemic HOPE of liver grafts.
Detailed description
This is a monocentric, pilot, randomized controlled study. Each eligible transplant candidate will be enrolled once an eligible graft has been allocated to him/her. Each enrolled patient will be randomized to either the experimental arm (HOPE-CytoSorb) or the control arm (HOPE-standard).
End-ischemic HOPE will be performed at our center after standard procurement of the graft at the donor hospital, static cold storage preservation during transport and back-table preparation. Dual HOPE, by portal continuous flow and arterial pulsatile flow, will be pressure controlled: portal pressure will be ≤5 mmHg and mean arterial pressure will be ≤30 mmHg. HOPE will be performed in an open system, so the graft will swim in the perfusate flowing out of the vena cava. The recirculating perfusion solution will have the same composition of University of Wisconsin Machine Perfusion Solution. HOPE will be maintained for 4 hours. CytoSorb will be included in the circuit only in the experimental arm.
Scheduled samples of both the perfusate and patient's blood will be analyzed for the levels of TNF-alfa, IL-6, IL-8 and ET-1. A biopsy of the implanted graft will be taken 2 hours after its reperfusion. The patient will be followed for 1 year after transplantation.
Once 10 patients have been enrolled, an interim analysis will be performed by an independent Clinical Endpoint Committee.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HOPE-CytoSorb | Experimental | Procedure: HOPE with cytokine filtration by CytoSorbPatients transplanted with livers preserved by HOPE with cytokine filtration by CytoSorb, a CE approved medical device for extracorporeal cytokine removal |
| HOPE-standard | No intervention | –Patients transplanted with livers preserved by HOPE without cytokine filtration |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| HOPE with cytokine filtration by CytoSorbCytokine filtration during HOPE | Procedure or surgery | HOPE-CytoSorb |
Primary outcome
Incidence of post-reperfusion syndrome
Time frame: Intraoperatively, during the first 5 minutes after reperfusion of the liver graft
Aggarwal definition: a decrease in mean arterial pressure >30% below the baseline value, for at least 1 minute, occurring during the first 5 minutes after reperfusion of the liver graft
2 secondary outcomes
Entity of ischemia-reperfusion injury
Time frame: 2 hours after reperfusion of the liver graft
Incidence of early allograft dysfunction
Time frame: Postoperative day 7
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2023.
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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. This study is not recruiting at the moment.
Michele Colledan, MD, FEBS study director
Papa Giovanni XXIII Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing HOPE with cytokine filtration by CytoSorb in people with Liver Transplantation and Post-Reperfusion Syndrome, run by Papa Giovanni XXIII Hospital 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?
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: status not confirmed, as of the sponsor's last update on 23 May 2023. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Stefania Camagni, MD (0352674771 ext. 0039, scamagni@asst-pg23.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of post-reperfusion syndrome (time frame: Intraoperatively, during the first 5 minutes after reperfusion of the liver graft). 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 23 May 2023; AzTrials last refreshed its copy on 8 Nov 2026.