Clinical trial NCT04154696: APHP Plateform of Normothermic Perfusion for Rehabilitation of Hepatic Grafts
Official title: APHP Plateform for Assessement of Hepatic Grafts Initialy Discarded by Normothermic Perfusion
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Liver Diseases
Keywords: Steatotic liver graft
Liver transplantation
Normothermic perfusion
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2019-11-06
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Liver transplantation of a graft after assessment by normothermic perfusion
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: To determine the proportion of grafts that can be transplanted after evaluation by normothermic perfusion (Hypothesis 50%) with a 3-year graft survival ≥ 90%
timeFrame: 3 months
Secondary outcomes:
measure: Proportion of hepatic grafts allocated to the 3 transplant centres of Paris and considered as initially not transplantable during the study period
timeFrame: 36 months
measure: 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
timeFrame: 36 months
measure: Proportion of grafts perfused
timeFrame: 36 months
measure: Proportion of grafts that were transplanted after perfusion
timeFrame: 36 months
measure: Time interval until liver function recovery while on normothermic perfusion (according to viability criteria defined above)
timeFrame: 15 hours
measure: Proportions of grafts transplanted after normotheric perfusion wthout early allograft dysfunction (according to Olthoff definition)
timeFrame: one month
measure: Time interval until liver function recovery after transplantation
timeFrame: one day
measure: One-month overall survival (without retransplantation or graft dysfunction)
timeFrame: one month
measure: One -year graft survival
timeFrame: one year
measure: Comparison of 3-months graft survival with a control group of graft considered as initially transplantable
timeFrame: 3 months
measure: Waiting time between the two groups
timeFrame: 36 months
measure: Incidence of biliary stenosis (anastomotic or non anastomotic) defined by cholangio MRI at one year
timeFrame: 12 months
Other outcomes:
Locations:
city: Villejuif
country: France
facility: AP-HP, Paul Brousse Hospital
Study officials:
References: