APHP Plateform of Normothermic Perfusion for Rehabilitation of Hepatic Grafts

Overview

This study aimed to evaluate fatty liver grafts, considered as unsuitable for upfront liver transplantation, by using normothermic perfusion. Grafts have to be allocated to one of 3 liver transplantation centres of Paris. After evidence of viability while on perfusion, these grafts will be transplanted to recipients with an estimated waiting time > 6 months.

Full Title of Study: “APHP Plateform for Assessement of Hepatic Grafts Initialy Discarded by Normothermic Perfusion”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: July 1, 2021

Detailed Description

In this study, the coordinator investigator proposes to build a platform for perfusing in normothermic conditions all grafts with histologically proven macrosteatosis ≥ 30% that will be considered as unsuitable for upfront LT. These grafts have to be alloacted to one of the 3 liver transplantation centers of Assistance Publique des Hôpitaux de Paris. Eligible grafts (macrosteatosis ≥ 30%, no severe fibrosis or cirrhosis) will be shipped to the platform for normothermic perfusion. Perfusion will be started provided that cold ischemia time do not exceed 8 hours. Parameters of grafts viability (lactates, bile production, flow) will be monitored. After a minimum of 4 hours of normothermic perfusion (not exceeding 16 hours), grafts fulfilling strict criteria (homogeneous aspect of the liver without any necrotic regions, lactates < 2.5 mmol/l and continuous production of bile with at least one of the following criteria: pH of perfusate > 7.3, arterial flow > 150 ml/min and portal flow > 500 ml/min, homogeneous perfusion of the graft) will be considered suitable for transplantation. Recipient will be transferred to the operating room, and first phase of LT (i.e, laparotomy and total hepatectomy) will be started. Simultaneously, grafts will be shipped to the center of initial allocation. Perfusion will be pursued during the transport from the platform to the recipient. Recipients (≥18 years and ≤ 70 years) have to be enlisted for LT with an estimated waiting time > 6 months (i.e., MELD score < 25) and who signed an informed consent.

Interventions

  • Procedure: Liver transplantation of a graft after assessment by normothermic perfusion
    • Liver transplantation of a graft after assessment by normothermic perfusion

Arms, Groups and Cohorts

  • Experimental: Normothermic perfusion of a graft

Clinical Trial Outcome Measures

Primary Measures

  • To determine the proportion of grafts that can be transplanted after evaluation by normothermic perfusion (Hypothesis 50%) with a 3-year graft survival ≥ 90%
    • Time Frame: 3 months
    • Graft survival

Secondary Measures

  • Proportion of hepatic grafts allocated to the 3 transplant centres of Paris and considered as initially not transplantable during the study period
    • Time Frame: 36 months
    • Proportion of hepatic grafts allocated to the 3 transplant centres of Paris and considered as initially not transplantable during the study period
  • Proportion of fatty grafts allocated to the 3 transplant centres of Paris and considered as initially not transplantable during the study period eligible for normothermic perfusion
    • Time Frame: 36 months
    • Proportion of fatty grafts allocated to the 3 transplant centres of Paris and considered as initially not transplantable during the study period eligible for normothermic perfusion
  • Proportion of grafts perfused
    • Time Frame: 36 months
    • Proportion of grafts perfused
  • Proportion of grafts that were transplanted after perfusion
    • Time Frame: 36 months
    • Proportion of grafts that were transplanted after perfusion
  • Time interval until liver function recovery while on normothermic perfusion (according to viability criteria defined above)
    • Time Frame: 15 hours
    • Time interval until liver function recovery while on normothermic perfusion (according to viability criteria defined above)
  • Proportions of grafts transplanted after normotheric perfusion wthout early allograft dysfunction (according to Olthoff definition)
    • Time Frame: one month
    • Proportions of grafts transplanted after normotheric perfusion wthout early allograft dysfunction (according to Olthoff definition)
  • Time interval until liver function recovery after transplantation
    • Time Frame: one day
    • Time interval until liver function recovery after transplantation
  • One-month overall survival (without retransplantation or graft dysfunction)
    • Time Frame: one month
    • One-month overall survival (without retransplantation or graft dysfunction)
  • One -year graft survival
    • Time Frame: one year
    • One -year graft survival
  • Comparison of 3-months graft survival with a control group of graft considered as initially transplantable
    • Time Frame: 3 months
    • Comparison of 3-months graft survival with a control group of graft considered as initially transplantable
  • Waiting time between the two groups
    • Time Frame: 36 months
  • Incidence of biliary stenosis (anastomotic or non anastomotic) defined by cholangio MRI at one year
    • Time Frame: 12 months
    • Incidence of biliary stenosis (anastomotic or non anastomotic) defined by cholangio MRI at one year

Participating in This Clinical Trial

Inclusion Criteria

  • patients enlisted for liver transplantation for liver disease or HCC (AFP score≤ 2);
  • Ongoing cotraception in women of reproductive age ;
  • Patient with social security ;
  • informed signed consent

Exclusion Criteria

  • Extra-hepatic tumor disease;
  • Re-transplantation ;
  • Pregnancy or brest-feeding;
  • Patients participting in another study;
  • Patients under psychiatric treatment;
  • Patients under tutorship or curatorship

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 70 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Assistance Publique – Hôpitaux de Paris
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Contact(s)
    • René ADAM, Pr, + 33 1 45 59 30 49, rene.adam@aphp.fr

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.