HOPE With Cytokine Filtration in Liver Transplantation (Cyto-HOPE)

NCT ID: NCT04203004

Last Updated: 2023-05-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-23
• Study Completion Date: 2023-12-31

Brief 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. 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.

Conditions

Liver Transplantation; Post-Reperfusion Syndrome; Ischaemia-Reperfusion Injury; Early Allograft Dysfunction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

HOPE-CytoSorb

Patients transplanted with livers preserved by HOPE with cytokine filtration by CytoSorb, a CE approved medical device for extracorporeal cytokine removal

Group Type: EXPERIMENTAL

HOPE with cytokine filtration by CytoSorb

Intervention Type: PROCEDURE

Cytokine filtration during HOPE

HOPE-standard

Patients transplanted with livers preserved by HOPE without cytokine filtration

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

HOPE with cytokine filtration by CytoSorb

Cytokine filtration during HOPE

Intervention Type: PROCEDURE

Eligibility Criteria

Exclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Papa Giovanni XXIII Hospital

OTHER

Sponsor Role: lead

Responsible Party

Stefania Camagni

MD, Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michele Colledan, MD, FEBS

Role: STUDY_DIRECTOR

Papa Giovanni XXIII Hospital

Locations

Papa Giovanni XXIII Hospital

Bergamo, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Stefania Camagni, MD

Role: CONTACT

scamagni@asst-pg23.it

0352674771 ext. 0039

Facility Contacts

Stefania Camagni, MD

Role: primary

scamagni@asst-pg23.it

Other Identifiers

HOPE-2

Identifier Type: -

Identifier Source: org_study_id