Comparison of Hypothermic Versus Normothermic Ex-vivo Preservation.

Phase

N/A

Condition

Primary Biliary Cholangitis

Treatment

N/A

Clinical Study ID

NCT04744389

D52F20000740002

Ages 18-75
All Genders

Study Summary

Study groups:

The study is a multicenter (Pisa and Milan), prospective, randomized study comparing D-HOPE (HMP) vs NMP in DCD and ECD-DBD (extended criteria brain-dead donors). Once a DCD or a DBD with extended criteria (ECD-DBD) meets the inclusion criteria, they are randomized as follow:

20 liver grafts from DCD after normothermic regional perfusion (NRP) matching the inclusion criteria are randomized 1:1 to hypothermic machine perfusion (HMP) vs normothermic machine perfusion (NMP) and then transplanted.
40 liver grafts from ECD-DBD matching the inclusion criteria are randomized 1:1 to hypothermic machine perfusion (HMP) vs normothermic machine perfusion (NMP) and then transplanted

Eligibility Criteria

Inclusion

GRAFT: Inclusion criteria: DCD:

no absolute contraindications as per Italian National Transplant center (CNT)
donor age ≤70 years
witnessed and documented cardiac arrest
macro-vescicular steatosis <30% at liver biopsy
necrosis <5% at liver biopsy
fibrosis <2 as per Ishak's score at liver biopsy
arteriolar thickening <60% at liver biopsy
WIT ≤160 minutes
ALT <1000 UI/L during NRP
downward trend lactate during NRP DBD:
no absolute contraindications as per Italian National Transplant center (CNT)
donor age > 70 years
macro-steatosis between 30 and 50% at liver biopsy

Exclusion

Exclusion criteria: DCD:

absolute contraindications as per Italian National Transplant center (CNT)
donor age >70 years
macro-vescicular steatosis >30% at liver biopsy
necrosis >5% at liver biopsy
fibrosis >2 as per Ishak's score at liver biopsy
severe macroangiopathy (arteriolar thickening >60% at liver biopsy)
WIT >160 minutes
ALT >1000 UI/L during NRP
uptrend lactate during NRP DBD:
absolute contraindications as per Italian National Transplant center (CNT)
donor age < 70 years
macro-steatosis between > 50% at liver biopsy RECIPIENTS Inclusion criteria:
Subject must be greater than or equal to 18 years of age.
Subject with end-stage liver disease who is actively listed for primary livertransplantation
Subject, or a legally authorized representative, has given informed consent toparticipate in the study Exclusion criteria:
Subject is currently listed as a UNOS status 1A.
Subject is requiring oxygen therapy via ventilator/respiratory support.
Subject is planned to undergo simultaneous solid organ transplant.
Subject is pregnant at the time of transplant.
Subject MELD score 25 or higher
Subject receives re-transplantation of liver.
Any medical conditions contro-indicating the use of DCD grafts at transplantsurgeon/hepatologist evaluation

Study Design

December 15, 2020

March 31, 2023

Study Description

The persistent mismatch between patients waiting for a liver transplant (LT) and grafts availability promoted the use of donation after circulatory death (DCD). Italian law requires 20 minutes of continous flatline electrocardiogram to declared individual's circulatory death and such a long period of warm ischemia time forced the development of protocols using abdominal normothermic regional perfusion (NRP) followed by ex-vivo graft reperfusion by means of machine perfusion technology (MP) for its potential to minimize ischemia/reperfusion damage and promote organ repair and reconditioning prior to transplantation. An extensive evaluation of all DCD donors might increase donation rate by 30%, but, while kidney transplant from DCD donors is well implemented, no definitive data exist on the optimal use of NRP and MP in liver and pancreas transplantation and an organizational model is far to be implemented. Moreover, a randomized trial comparing hypothermic vs normothermic ex-vivo perfusion has never been performed. The proposed project will perform a pilot, open, randomized, prospective trials to evaluate the sequential use of NRP followed by ex-vivo MP (hypothermic (HMP) vs normothermic (NMP)) by measuring several indicators of organ damage and recovery with the target to set up the optimal organizational model for DCD donation:

Twenty LT from DCD donors after NRP (considered transplantable for the acceptance criteria in use) will be randomized 1:1 to ex-vivo HMP or NMP (multicenter study together with the center in Milan)
40 liver grafts from ECD-DBD matching the inclusion criteria are randomized 1:1 to hypothermic machine perfusion (HMP) vs normothermic machine perfusion (NMP) and then transplanted To assess organ damage and repair capacity, the following investigations will be performed: -biomarkers of apoptosis, necrosis, innate-mediated inflammation and its resolution, angiogenesis and thrombosis during NRP -circulating biomarkers indicating damage, proliferation, angiogenetic and tissue remodelling factors; a targeted-metabolomic and lipidomic profiling during ex-vivo HMP or NMP in the perfusate and on blood samples in the peri and post-operative period; bile composition on graft subjected to NMP. Evaluation of necrosis, apoptosis and proliferation, immunohistochemical analysis, a targeted-metabolomic and lipidomic profiling, ATP measurement, and electronic microscopy investigations will be performed on liver tissue and bile duct biopsies after NRP, before and after ex-vivo reperfusion, and immediately after reperfusion in the recipient (only for transplantable grafts) Based on the collected data a new algorithm of organ evaluation, procurement, preservation and reconditioning will be formulated and disseminated.

Connect with a study center

Daniele Dondossola
Milan,
Italy
Site Not Available
UO Chirurgia Epatica e del Trapianto di Fegato
Pisa, 56124
Italy
Active - Recruiting

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