Comparison of Hypothermic Versus Normothermic Ex-vivo Preservation.

NCT04744389 | Unknown

• 1 other identifier: D52F20000740002
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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:

1. 1.20 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.
2. 2.40 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

Conditions

End Stage Liver DIsease

Keywords

ex-situ perfusion; organ preservation; normothermic perfusion; hypothermic perfusion

Outcome Measures

Primary Outcomes (2)

• Rate of graft loss

  Death of patient, relisting or Retransplantation. Composite Outcome

  at 6 months postoperatively

• Rate of Ischemic Type Biliary Lesions (ITBL)

  ITBL as assessed by MRI / MRCP. Composite Outcome

  at 6 months postoperatively

Secondary Outcomes (5)

• 1-year graft survival

  1-year postoperatively

• 1-year patients survival

  1-year postoperatively

• level of BCL-2/BAX at the liver histology

  after 2 hours of perfusion

• level of Soluble Keratin 18 in the perfusate

  after 2 hours of perfusion

• level of HMGB1in the perfusate

  after 2 hours of perfusion

Study Arms (2)

Hypothermic Machine Perfusion

EXPERIMENTAL

uDCD and cDCD after Normothermic Regional Perfusion matching the inclusion criteria, ECD matching the inclusion criteria, uDCD and cDCD exceeding the inclusion criteria.

Device: Hypothermic Machine Perfusion

Normothermic Machine Perfusion

EXPERIMENTAL

uDCD and cDCD after Normothermic Regional Perfusion matching the inclusion criteria, ECD matching the inclusion criteria, uDCD and cDCD exceeding the inclusion criteria.

Device: Normothermic Machine Perfusion

Interventions

Hypothermic Machine Perfusion DEVICE

The perfusion system was primed with 4 L of Belzer machine perfusion solution University of Wisconsin Machine Perfusion Solution (Bridge for Life, Ltd., Columbia, SC). The arterial and portal pressures were set at 25 mm Hg with a flow and at 3-4 mm Hg with a continuous flow, respectively. The oxygen flow was set at 0.25 L/minute. The target liver temperature was between 4°C and 10°C.

Also known as: Hypothermic machine perfusion (HMP)

Hypothermic Machine Perfusion

Normothermic Machine Perfusion DEVICE

Grafts were perfused at 37°C in an OR next to the transplant OR and under medical supervision using a blood-based perfusate. Initial perfusate temperature was set at 20°C and raised by 1°C every 2 minutes. Oxygenation was provided by an anesthesia ventilator initially set at 4 L/minute with 30% fraction of inspired oxygen, and later adjusted based on perfusate pH, partial pressure of oxygen, and partial pressure of carbon dioxide. Blood gas analyses were drawn every 20 minutes during the first hour and every 30 minutes thereafter with the aim to maintain a physiological pH and ionogram result, and a partial pressure of oxygen between 200 and 250 mm Hg. Perfusate glucose, transaminases, and lactate were measured during NMP as were bile production and quality (pH, sodium, glycemia, lactate, and HCO3)

Also known as: Normothermic machine perfusion (NMP)

Normothermic Machine Perfusion

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Azienda Ospedaliero, Universitaria Pisana: lead
• Fondazione C.N.R./Regione Toscana "G. Monasterio", Pisa, Italy: collaborator
• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: collaborator

Study Sites (1)

UO Chirurgia Epatica e del Trapianto di Fegato

Pisa, 56124, Italy

RECRUITING

Related Publications (4)

• Ghinolfi D, Rreka E, De Tata V, Franzini M, Pezzati D, Fierabracci V, Masini M, Cacciatoinsilla A, Bindi ML, Marselli L, Mazzotti V, Morganti R, Marchetti P, Biancofiore G, Campani D, Paolicchi A, De Simone P. Pilot, Open, Randomized, Prospective Trial for Normothermic Machine Perfusion Evaluation in Liver Transplantation From Older Donors. Liver Transpl. 2019 Mar;25(3):436-449. doi: 10.1002/lt.25362.

  PMID: 30362649 BACKGROUND

• Ghinolfi D, Dondossola D, Rreka E, Lonati C, Pezzati D, Cacciatoinsilla A, Kersik A, Lazzeri C, Zanella A, Peris A, Maggioni M, Biancofiore G, Reggiani P, Morganti R, De Simone P, Rossi G. Sequential Use of Normothermic Regional and Ex Situ Machine Perfusion in Donation After Circulatory Death Liver Transplant. Liver Transpl. 2021 Feb;27(3):385-402. doi: 10.1002/lt.25899. Epub 2020 Nov 8.

  PMID: 32949117 BACKGROUND

• Lazzeri C, Ghinolfi D, Santini LE, Procissi APO, Cultrera D, Peris A. Improved Utilization Rate in Solid Organ Donors >/=80 Years: The 7-Year Tuscany Experience. Clin Transplant. 2025 Apr;39(4):e70142. doi: 10.1111/ctr.70142.

  PMID: 40145941 DERIVED

• Tingle SJ, Thompson ER, Figueiredo RS, Moir JA, Goodfellow M, Talbot D, Wilson CH. Normothermic and hypothermic machine perfusion preservation versus static cold storage for deceased donor kidney transplantation. Cochrane Database Syst Rev. 2024 Jul 9;7(7):CD011671. doi: 10.1002/14651858.CD011671.pub3.

  PMID: 38979743 DERIVED

MeSH Terms

Conditions

End Stage Liver Disease

Condition Hierarchy (Ancestors)

Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases

Central Study Contacts

Davide Ghinolfi, MD, PhD

CONTACT

00393282185278; d.ghinolfi@ao-pisa.toscana.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 18, 2021
• First Posted: February 9, 2021
• Study Start: December 15, 2020
• Primary Completion: September 30, 2022
• Study Completion: March 31, 2023
• Last Updated: July 26, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)