An interventional study of HOPE with cytokine filtration by CytoSorb in Liver Transplantation, Post-Reperfusion Syndrome and Ischaemia-Reperfusion Injury, sponsored by Papa Giovanni XXIII Hospital. Recruiting at 1 site in Italy. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2023-05-23.
Sponsored by Papa Giovanni XXIII Hospital · Not applicable, Interventional, and Treatment
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
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.
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.
260 studies on the registry are indexed under Reperfusion Injury; 43 are open to participants now.
This study's planned enrollment of 20 is below the median of 60 across 212 interventional studies indexed under Reperfusion Injury.
Browse Reperfusion Injury studies →Papa Giovanni XXIII Hospital is the lead sponsor of 22 studies on the registry; 6 are open to participants now.
Counted across the registry records on this site, refreshed daily.
RECIPIENTS
GRAFTS ELIGIBILITY CRITERIA TO HOPE:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
Patients transplanted with livers preserved by HOPE without cytokine filtration
Cytokine filtration during HOPE
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
Time frame: Intraoperatively, during the first 5 minutes after reperfusion of the liver graft
Entity of ischemia-reperfusion injury
Assessment of liver biopsy according to Suzuki histological grading system modified by UCLA group \[Sosa RA et al. JCI Insight 2016; 1(20): e89679\]
Time frame: 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
Time frame: Postoperative day 7
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Papa Giovanni XXIII Hospital