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

Interest of Oxygenated Hypothermic Perfusion in Preservation of Hepatic Grafts From Expanded Criteria Donors. A Prospective Monocentric Study.

Interest of oxygenated hypothermic perfusion in preservation of hepatic grafts from expanded criteria donors.

Study Overview

• Status: Completed
• Conditions: Hepatocellular Injury
• Intervention / Treatment: Device: Hypothermic oxygenated perfusion (HOPE); Other: Conventional cold storage

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.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Rennes, France, 35033
    • CHU de Rennes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hypothermic oxygenated perfusion (HOPE); Application of HOPE for 2 hours	Device: Hypothermic oxygenated perfusion (HOPE); 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
Active Comparator: Conventional cold storage	Other: Conventional cold storage; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the impact of PHO during the conservation of ECD liver grafts on intraoperative morbidity	Number of intraoperative transfusions	Day 1
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	Day 1
Evaluation of the impact of PHO during the conservation of ECD liver grafts on postoperative morbidity		Day 7
Evaluation of graft's survival	Occurrence of a vascular and biliary complication	Month 3
Number of days of hospitalization (initial stay) after transplantation		Postoperative course
Number of days of hospitalization after transplantation		Month 3
Cost of the initial stay		Postoperative course
Cost of the hospitalization stay		Month 3

Collaborators and Investigators

• Sponsor: Rennes University Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 19, 2018
• Primary Completion (Actual): February 7, 2019
• Study Completion (Actual): February 7, 2019

Study Registration Dates

• First Submitted: December 7, 2017
• First Submitted That Met QC Criteria: December 12, 2017
• First Posted (Actual): December 18, 2017

Study Record Updates

• Last Update Posted (Actual): March 11, 2019
• Last Update Submitted That Met QC Criteria: March 8, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: liver transplantation; extended criteria liver grafts; hypothermic machine liver perfusion
• Additional Relevant MeSH Terms: Body Temperature Changes; Hypothermia
• Other Study ID Numbers: 35RC16_9792_PERPHO; 2017-A00085-48 (Other Identifier: ID-RCB number)

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