Post-Static Cold Storage Hypothermic Oxygenated Perfusion in Bergamo Liver Transplant Program

Post-Static Cold Storage Hypothermic Oxygenated Perfusion in Bergamo Liver Transplant Program: a Prospective Observational Study

In light of the widespread organ shortage, dynamic preservation by means of Machine Perfusion (MP) has been proposed as a strategy to increase the pool of suitable grafts for liver transplantation. Reproducing more physiological conditions than traditional Static Cold Storage (SCS), MP may allow a better preservation and evaluation and perhaps even the resuscitation of high risk grafts. As a consequence, unnecessary discard of organs could be avoided and quality and safety of transplantation could be improved as well.

Hypothermic MP (HMP) seems to reduce ischemia-reperfusion injury. In fact, hypothermia slows down the metabolic rate and the oxygenation of the perfusate leads to re-synthesis of Adenosine TriPhosphate (ATP), which results in the restoration of cellular energy.

Four series about the use of HMP in the clinical setting has been published so far. They all report acceptable outcomes after transplantation of human liver grafts from extended criteria Brain Dead Donors (BDD) and from Donation after Circulatory Death (DCD) donors preserved by HMP, thus proving its feasibility and safety. The efficacy of HMP, instead, is still under investigation in a phase II randomized trial.

This is an observational, prospective, monocentric study aiming at verifying the feasibility and safety of post-SCS Hypothermic Oxygenated PErfusion (HOPE) in the setting of our liver transplant program. Extended criteria grafts from BDD and grafts from DCD donors will be preserved by post-SCS HOPE prior to transplantation. The recipients of these grafts will be followed-up for at least 1 year.

Study Overview

• Status: Unknown
• Conditions: Liver Transplantation

Detailed Description

This is an observational, prospective, monocentric study aiming at verifying the feasibility and safety of post-SCS HOPE in the setting of our liver transplant program.

20 consecutive patients with written informed consent will be enrolled. They will be transplanted with grafts from extended criteria BDD or from DCD donors preserved by post-SCS HOPE.

The HOPE procedure will be performed in our operating room after regular procurement, transport and back-table preparation. University of Wisconsin Machine Perfusion Solution (UW-MPS) will be used. Two pumps will provide dual pressure-controlled perfusion through the portal vein and the hepatic artery. Portal flow will be continuous and will be adjusted to keep portal pressure below 5 mmHg. Instead, arterial flow will be pulsatile and will be regulated to maintain arterial pressure between 25 mmHg and 30 mmHg. The perfusate will be oxygenated with the goal of a partial Pressure of Oxygen (PO2) of 50-70 kilopascal. The perfusate temperature will be kept between 4°C and 12°C by a heat exchanger. pH, PO2 and partial Pressure of Carbon Dioxide (PCO2) of the perfusate pumped to the graft and drained from the vena cava will be monitored. HOPE will be maintained for 3 to 4 hours.

Patients will be followed-up for at least 1 year according to a scheduled timetable.

Data about HOPE and transplant procedure, about donors and recipients' characteristics and about patients' follow-up will be collected in a dedicated electronic Case Report Form (eCRF) according to Good Clinical Practice.

• Study Type: Observational
• Enrollment (Anticipated): 20

Contacts and Locations

Study Locations

• Italy
  • Bergamo, Italy, 24127
    • Recruiting
    • Papa Giovanni XXIII Hospital
    • Contact: Stefania Camagni, MD; Phone Number: 00390352674347; Email: scamagni@asst-pg23.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 weeks to 70 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All the patients on the waiting list for liver transplantation at Bergamo transplant centre, except for those who are candidates to combined en bloc liver and pancreas transplantation

Description

Grafts inclusion criteria:

• extended criteria BDD with a mix of the following: age ≥70 years, liver macrosteatosis ≥35%, anti-Hepatitis C Virus (HCV) positivity, Hepatitis B surface Antigen (HBsAg) positivity, hemodynamic instability
• DCD donors category IVB (on ExtraCorporeal Membrane Oxygenation (ECMO) support) with a mix of the above-mentioned characteristics and/or with undetermined hepatocellular necrosis
• DCD donors category I-IVA on normothermic regional ECMO support
• different donors characteristics from the above-mentioned ones but organisational set-up including prolonged total ischemic time.

Grafts exclusion criteria: living donors.

Recipients' inclusion criteria:

• liver transplant candidates who are going to be transplanted with a graft preserved by post-SCS HOPE
• liver transplant candidates who consent to participate in the study by signing the informed consent form.

Recipients' exclusion criteria:

• liver transplant candidates who are going to be transplanted with a graft preserved by SCS
• liver transplant candidates who are going to be transplanted with a graft preserved by post-SCS HOPE but refuse consent for their participation in the study.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of early allograft dysfunction (safety endpoint)	Occurrence of one or more of the following: bilirubin >170 µmol/L on Post-Operative Day (POD) 7, International Normalized Ratio (INR) >1,6 on POD 7, Alanine AminoTransferase (ALT) peak >2000 U/L within the first post-operative week	Post-operative day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year patient survival	Patient survival rate 1 year after transplantation	1 year after transplantation
Rate of complications grade ≥IIIa	Dindo-Clavien classification of surgical complications	1 year after transplantation
Incidence of ischemic cholangiopathy	Radiological or endoscopic diagnosis of unifocal or multifocal intrahepatic strictures in the absence of any arterial complication	6 months after transplantation
Length of intensive care unit and hospital stay	Length of intensive care unit and hospital stay after transplantation (days)	1 year after transplantation
30-day patient survival	Patient survival rate 30 days after transplantation	Post-operative day 30
30-day graft survival	Graft survival rate 30 days after transplantation	Post-operative day 30
1-year graft survival	Graft survival rate 1 year after transplantation	1 year after transplantation

Collaborators and Investigators

• Sponsor: Papa Giovanni XXIII Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 5, 2017
• Primary Completion (ANTICIPATED): December 3, 2021
• Study Completion (ANTICIPATED): December 3, 2021

Study Registration Dates

• First Submitted: March 26, 2017
• First Submitted That Met QC Criteria: March 26, 2017
• First Posted (ACTUAL): March 31, 2017

Study Record Updates

• Last Update Posted (ACTUAL): November 26, 2019
• Last Update Submitted That Met QC Criteria: November 25, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Hypothermic machine perfusion; Donation after circulatory death; Extended criteria liver grafts
• Additional Relevant MeSH Terms: Body Temperature Changes; Hypothermia
• Other Study ID Numbers: Post-SCS Liver HOPE Bg

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No