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

NCT04203004 | Unknown DMC

• 1 other identifier: HOPE-2
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Hypothermic oxygenated perfusion (HOPE); Cytokine filtration; Liver transplantation

Outcome Measures

Primary Outcomes (1)

• 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

  Intraoperatively, during the first 5 minutes after reperfusion of the liver graft

Secondary Outcomes (2)

• Entity of ischemia-reperfusion injury

  2 hours after reperfusion of the liver graft

• Incidence of early allograft dysfunction

  Postoperative day 7

Study Arms (2)

HOPE-CytoSorb

EXPERIMENTAL

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

Procedure: HOPE with cytokine filtration by CytoSorb

HOPE-standard

NO INTERVENTION

Patients transplanted with livers preserved by HOPE without cytokine filtration

Interventions

HOPE with cytokine filtration by CytoSorb PROCEDURE

Cytokine filtration during HOPE

HOPE-CytoSorb

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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

Sponsors & Collaborators

• Papa Giovanni XXIII Hospital: lead

Study Sites (1)

Papa Giovanni XXIII Hospital

Bergamo, 24127, Italy

RECRUITING

MeSH Terms

Conditions

Reperfusion Injury

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Michele Colledan, MD, FEBS

  Papa Giovanni XXIII Hospital

  STUDY DIRECTOR

Central Study Contacts

Stefania Camagni, MD

CONTACT

0352674771; scamagni@asst-pg23.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Principal Investigator

Study Record Dates

• First Submitted: December 16, 2019
• First Posted: December 18, 2019
• Study Start: September 23, 2021
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: May 23, 2023

Record last verified: 2023-05

Locations

IT (1)