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
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
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
NCT ID
NCT03376074
First Posted
December 7, 2017
Last Updated
March 8, 2019
Sponsor
Rennes University Hospital
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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