Clinical Trials Logo

Clinical 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. 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.


Clinical Trial 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


Related Conditions & MeSH terms


NCT number NCT04203004
Study type Interventional
Source Papa Giovanni XXIII Hospital
Contact Stefania Camagni, MD
Phone 0352674771
Email scamagni@asst-pg23.it
Status Recruiting
Phase N/A
Start date September 23, 2021
Completion date December 31, 2023

See also
  Status Clinical Trial Phase
Completed NCT04180735 - Intestinal Perforation in Patients Receiving an Orthtopic Liver Transplantation in the Montpellier University Hospital
Completed NCT01011205 - Phase 3b Study to Evaluate Advagraf in Combination With Mycophenolate Mofetil and Basiliximab in Liver Transplantation Phase 3
Completed NCT01888432 - Efficacy and Safety of Everolimus in Liver Transplant Recipients of Living Donor Liver Transplants Phase 3
Recruiting NCT04564313 - Safety and Efficacy of Camrelizumab (Anti-PD-1 Antibody) in Recurrent HCC After Liver Transplantation Phase 1
Withdrawn NCT03596970 - Study of the Effect of Everolimus Immunosuppressive Combination Therapies on Renal Function When Used as a Maintenance Treatment for Liver Transplant Patients. Phase 3
Not yet recruiting NCT02544906 - Propofol Versus Dexmedetomidine for Prevention of Sevoflurane Agitation in Recipients of Living Donor Liver Transplantation N/A
Completed NCT03133065 - Early Treatment of Recurrent HCV- Infection Post Liver Transplantation in the Era of DAAs Phase 4
Recruiting NCT01705015 - Organ Transplantation Rehabilitation: Effect of Bedside Exercise Device and Activity Reinforcement N/A
Completed NCT01425385 - Autoregulation Assessment During Liver Transplantation N/A
Terminated NCT01445236 - Pilot Study of Immunosuppression Drug Weaning in Liver Recipients Exhibiting Biomarkers of High Likelihood of Tolerance N/A
Completed NCT01655563 - Pharmacogenetic Trial of Tacrolimus After Pediatric Transplantation Phase 2
Completed NCT00938860 - Sustained Virological Response (SVR) to Antiviral Treatment of Liver Transplant Recipients With Recurrent Hepatitis C Phase 4
Completed NCT00531921 - Effects of Donor and Recipient Genetic Expression on Heart, Lung, Liver, or Kidney Transplant Survival N/A
Completed NCT00456235 - Reduction in the Risk of Rejection by Mycophenolate Mofetil Dose Adjustment in Liver Transplant Patients With Side Effects Caused by the Calcineurine Inhibitors Phase 4
Withdrawn NCT00585429 - Evaluation of Kidney Disease in Liver Transplant Recipients N/A
Terminated NCT00585858 - Cytokine Kinetics Test to Assess the Presence or Absence of Tolerance in Organ Transplant N/A
Recruiting NCT00147459 - Immunogenicity of Booster Hepatitis B Vaccines in Children After Liver Transplantation N/A
Withdrawn NCT00167492 - Enteric Coated Myfortic for Liver Transplant Recipients Phase 4
Terminated NCT00161356 - Ambisome in Liver Transplant Patients Phase 4
Completed NCT00170131 - MMF Influence on HCV Viral Evolution After Liver Transplantation Phase 4