APHP Plateform of Normothermic Perfusion for Rehabilitation of Hepatic Grafts

Not Applicable

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

• Registration Number: NCT04154696
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

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.

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.

Study Timeline

• Status Verified: 2019-08
• Study First Submitted: 2019-08-21
• Study Start: 2019-10-28
• Study First Submitted QC: 2019-11-04
• Last Update Submitted: 2019-11-04
• Study First Posted: 2019-11-06
• Last Update Posted: 2019-11-06
• Primary Completion: 2021-07-01
• Study Completion: 2022-04-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Normothermic perfusion of a graft	Liver transplantation of a graft after assessment by normothermic perfusion	-

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

AP-HP, Paul Brousse Hospital; 🇫🇷 Villejuif, France