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Interest of Oxygenated Hypothermic Perfusion (PHO) in Preservation of Hepatic Grafts From Expanded Criteria Donors (PERPHO)

Primary Purpose

Hepatocellular Injury

Status
Completed
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Hypothermic oxygenated perfusion (HOPE)
Conventional cold storage
Sponsored by
Rennes University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Injury focused on measuring liver transplantation, hypothermic machine liver perfusion, extended criteria liver grafts

Eligibility Criteria

18 Months - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients older than 18 years
  • Candidates for a first orthotopic liver transplantation, without transplantation of another associated organ (kidney, pancreas, heart, lung, intestine)
  • With cirrhosis whatever its etiology and gravity
  • With or without hepatocarcinoma
  • Having given free, informed and written consent
  • LT made from a whole graft, harvested from a brain-dead donor with ECD criteria, defined as the presence of at least one of the following criteria:

    • Age> 65 years
    • BMI> 30 kg / m2
    • Duration of hospitalization in intensive care unit> 7 days
    • Natremia> 155 mmol / l
    • AST> 150 IU / ml
    • ALT> 170 IU / ml
    • Occurrence of cardiac arrest before harvesting
    • Macrovacuolar steatosis> 30% on liver histology

Exclusion Criteria:

  • History of organ transplantation
  • Transplantation in emergency
  • Transplantation from a living donor, a reduced graft or a graft from a deceased donor by cardiac arrest (DCD)
  • Major persons subject to legal protection (safeguard of justice, guardianship), persons deprived of their liberty

Sites / Locations

  • CHU de Rennes

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Hypothermic oxygenated perfusion (HOPE)

Conventional cold storage

Arm Description

Application of HOPE for 2 hours

Outcomes

Primary Outcome Measures

Evaluation of the performance of HOPE in the preservation of ECD liver grafts on graft function recovery
Occurrence of early allograft dysfunction and / or primary non function

Secondary Outcome Measures

Evaluation of the impact of PHO during the conservation of ECD liver grafts on intraoperative morbidity
Number of intraoperative transfusions
Evaluation of the impact of PHO during the conservation of ECD liver grafts on intraoperative morbidity
Incidence of reperfusion syndrome defined as a 30 % decrease of mean arterial pressure, for at least 1 minute, during the 5 minutes following revascularization
Evaluation of the impact of PHO during the conservation of ECD liver grafts on postoperative morbidity
Evaluation of graft's survival
Occurrence of a vascular and biliary complication
Number of days of hospitalization (initial stay) after transplantation
Number of days of hospitalization after transplantation
Cost of the initial stay
Cost of the hospitalization stay

Full Information

First Posted
December 7, 2017
Last Updated
March 8, 2019
Sponsor
Rennes University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03376074
Brief Title
Interest of Oxygenated Hypothermic Perfusion (PHO) in Preservation of Hepatic Grafts From Expanded Criteria Donors
Acronym
PERPHO
Official Title
Interest of Oxygenated Hypothermic Perfusion in Preservation of Hepatic Grafts From Expanded Criteria Donors. A Prospective Monocentric Study.
Study Type
Interventional

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
February 19, 2018 (Actual)
Primary Completion Date
February 7, 2019 (Actual)
Study Completion Date
February 7, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rennes University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Interest of oxygenated hypothermic perfusion in preservation of hepatic grafts from expanded criteria donors.
Detailed Description
The excellent results of liver transplantation (LT) have led to a significant increase in the number of patients awaiting transplantation. At the same time, the number of grafts remains stable. To extend the donor pool, the use of Extended Criteria Donor (ECD) donors graft increased each year despite the fact that these graft are known to be more vulnerable to ischemia-reperfusion injuries induced by cold storage preservation (CS). Their use is therefore associated with a greater risk of postoperative dysfunction of the graft. This risk can be reduced by improving preservation quality. The preservation by hypothermic oxygenated perfusion (HOPE) consists of keeping the graft in hypothermia (4 to 12 °C) on an machine perfusion (MP) using a specific solution, saturated with oxygen. In kidney transplantation, the use of MP has been shown to improve graft function as well as graft survival, especially for ECD grafts. In liver transplantation, experimental studies on animal models have demonstrated the superiority of HOPE over CS regarding graft function and survival. These results have been confirmed in humans on small retrospective series. As HOPE is an expensive procedure, obtaining evidence of its effectiveness could result in a reimbursement of the additional cost.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Injury
Keywords
liver transplantation, hypothermic machine liver perfusion, extended criteria liver grafts

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Hypothermic oxygenated perfusion (HOPE)
Arm Type
Experimental
Arm Description
Application of HOPE for 2 hours
Arm Title
Conventional cold storage
Arm Type
Active Comparator
Intervention Type
Device
Intervention Name(s)
Hypothermic oxygenated perfusion (HOPE)
Intervention Description
25 patients: Application of HOPE for 2 hours, perfusion rate 100-150 ml/min, pressure controlled, perfusion pressure < 3 mm Hg, perfusion route portal vein, recirculating system, perfusion volume 2 L, perfusate solution (UWMP®), perfusate temperature 4-12 °C, perfusate oxygenation 40 KPa
Intervention Type
Other
Intervention Name(s)
Conventional cold storage
Intervention Description
75 patients transplanted in Rennes between 2010 and 2015 with a cold stored grafts, matched (ratio 1: 3) using a propensity score calculated according to some parameters
Primary Outcome Measure Information:
Title
Evaluation of the performance of HOPE in the preservation of ECD liver grafts on graft function recovery
Description
Occurrence of early allograft dysfunction and / or primary non function
Time Frame
Day 7
Secondary Outcome Measure Information:
Title
Evaluation of the impact of PHO during the conservation of ECD liver grafts on intraoperative morbidity
Description
Number of intraoperative transfusions
Time Frame
Day 1
Title
Evaluation of the impact of PHO during the conservation of ECD liver grafts on intraoperative morbidity
Description
Incidence of reperfusion syndrome defined as a 30 % decrease of mean arterial pressure, for at least 1 minute, during the 5 minutes following revascularization
Time Frame
Day 1
Title
Evaluation of the impact of PHO during the conservation of ECD liver grafts on postoperative morbidity
Time Frame
Day 7
Title
Evaluation of graft's survival
Description
Occurrence of a vascular and biliary complication
Time Frame
Month 3
Title
Number of days of hospitalization (initial stay) after transplantation
Time Frame
Postoperative course
Title
Number of days of hospitalization after transplantation
Time Frame
Month 3
Title
Cost of the initial stay
Time Frame
Postoperative course
Title
Cost of the hospitalization stay
Time Frame
Month 3

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients older than 18 years Candidates for a first orthotopic liver transplantation, without transplantation of another associated organ (kidney, pancreas, heart, lung, intestine) With cirrhosis whatever its etiology and gravity With or without hepatocarcinoma Having given free, informed and written consent LT made from a whole graft, harvested from a brain-dead donor with ECD criteria, defined as the presence of at least one of the following criteria: Age> 65 years BMI> 30 kg / m2 Duration of hospitalization in intensive care unit> 7 days Natremia> 155 mmol / l AST> 150 IU / ml ALT> 170 IU / ml Occurrence of cardiac arrest before harvesting Macrovacuolar steatosis> 30% on liver histology Exclusion Criteria: History of organ transplantation Transplantation in emergency Transplantation from a living donor, a reduced graft or a graft from a deceased donor by cardiac arrest (DCD) Major persons subject to legal protection (safeguard of justice, guardianship), persons deprived of their liberty
Facility Information:
Facility Name
CHU de Rennes
City
Rennes
ZIP/Postal Code
35033
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33237618
Citation
Rayar M, Beaurepaire JM, Bajeux E, Hamonic S, Renard T, Locher C, Desfourneaux V, Merdrignac A, Bergeat D, Lakehal M, Sulpice L, Houssel-Debry P, Jezequel C, Camus C, Bardou-Jacquet E, Meunier B. Hypothermic Oxygenated Perfusion Improves Extended Criteria Donor Liver Graft Function and Reduces Duration of Hospitalization Without Extra Cost: The PERPHO Study. Liver Transpl. 2021 Feb;27(3):349-362. doi: 10.1002/lt.25955.
Results Reference
derived

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Interest of Oxygenated Hypothermic Perfusion (PHO) in Preservation of Hepatic Grafts From Expanded Criteria Donors

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