APCext : Effect of Temporary Porto-caval Shunt During Liver Transplantation on Function of Liver Graft From Extended Criteria Donor (APCext)

The success of orthotopic liver transplantation (OLT) in treatment of liver malignancy and endstage liver disease has led to an increase in the gap between patients on waiting-lists and available liver grafts. In order to compensate for this scarcity, use of liver grafts harvested from extended criteria donors (ECD) has become more and more frequent.

However, these ECD grafts are known to be associated with a higher rate of primary non function (PNF) or early allograft dysfunction (EAD) because of a greater vulnerability to ischemia-reperfusion injury (IRI).

During OLT, the clamping of the portal vein induces blood congestion in the splanchnic territory leading to increased gut permeability, bacterial translocation and release of endotoxin and pro-inflammatory cytokines at revascularisation, which exacerbate IRI.

Realisation of a temporary porto-caval shunt (TPCS) (i.e. end to side anastomosis between the portal vein and infrahepatic vena cava) during the anhepatic phase, avoids splanchnic congestion and could therefore decrease IRI and improve liver graft function. However, TPCS remains poorly used as no randomised trial succeeds to show its benefit on liver function due to lack of power.

Study Overview

• Status: Recruiting
• Conditions: Liver Transplantation
• Intervention / Treatment: Procedure: temporary porto-caval shunt

• Study Type: Interventional
• Enrollment (Estimated): 214
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Michel RAYAR, MD, PhD; Phone Number: 02 99 28 42 65; Email: michel.rayar@chu-rennes.fr
• Study Contact Backup: Name: Anne Ganivet; Phone Number: 02 99 28 25 55; Email: anne.ganivet@chu-rennes.fr

Study Locations

• France
  • Bordeaux, France
    • Recruiting
    • CHU Bordeaux
    • Principal Investigator: Laurence CHICHE, MD, PhD
  • Lyon, France
    • Recruiting
    • Hospices Civils Lyon
    • Principal Investigator: Jean-Yves MABRUT, MD, PhD
  • Rennes, France
    • Recruiting
    • CHU Rennes
    • Principal Investigator: Michel RAYAR, Md, PhD
    • Sub-Investigator: Karim BOUDJEMA, Md, PhD
    • Sub-Investigator: Laurent SULPICE, Md, PhD
    • Sub-Investigator: Christophe CAMUS, Md, PhD
    • Sub-Investigator: Pauline HOUSSEL-DEBRY, Md, PhD
  • Toulouse, France
    • Recruiting
    • CHU Toulouse
    • Principal Investigator: Fabrice MUSCARI, MD, PhD
  • Tours, France
    • Recruiting
    • Chu Tours
    • Principal Investigator: Louise BARBIER

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years old
• Candidate of liver transplantation
• With cirrhosis from any etiology
• Model For End-Stage Liver Disease (MELD) score < 25

• Transplanted with a liver graft harvested from an extended criteria donor defined as presence of at least one of the following criteria:

  • Donor age > 65 years old
  • Intensive care unit stay > 7 days
  • BMI > 30
  • Natremia > 155 mmol/L
  • Aspartate aminotransferase (ASAT) > 150 IU/mL
  • Alanine aminotransferase (ALAT) > 170 IU/mL
  • Occurrence of a cardiac arrest before graft harvesting
  • Proven biopsy macrosteathosis > 30%
• Non-opposition from the patient

Non Inclusion Criteria:

• Fulminant hepatitis
• Retransplantation
• Combined organ transplantation (kidney, pancreas, heart, lung)
• Non heart beating donor
• Complete portal vein thrombosis on preoperative imaging finding

Exclusion Criteria:

• Complete portal vein thrombosis found during procedure
• Split liver graft
• Realisation of a bilio-enteric anastomosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: temporary porto-caval shunt; patients in whom temporary porto-caval shunt is performed during orthotopic liver transplantation	Procedure: temporary porto-caval shunt; temporary porto-caval shunt
No Intervention: no temporary porto-caval shunt; patients in whom temporary porto-caval shunt is not performed during orthotopic liver transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of early allograft dysfunction	defined by the presence of at least one of the following criteria: Bilirubin level > 10 mg/dL (i.e. 171 µmol/L); International Normalized Ratio > 1.6	on postoperative day 7
Incidence of early allograft dysfunction	defined by the presence of at least one of the following criteria: • ASAT or ALAT level > 2000 IU/mL	within the 7 first postoperative day
Incidence of primary non function	defined by the presence of at least one of the following criteria: Graft's death or retransplantation; Patient's death	within the 7 first postoperative day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of surgery		at day 0
Realisation of intra-operative transfusion	defined by the transfusion needs of fresh frozen plasma, red blood cell and platelet pool	during the operation
Incidence of reperfusion syndrome	defined as decrease of 30% of the median arterial pressure	during the 5 minutes following revascularisation
Liver graft function	evaluated by the Model for Early Allograft Function (MEAF) score	within 3 months
Occurrence of a severe postoperative complication	defined as a Clavien-Dindo classification > 2	within 3 months
Evaluation of urinary function	defined by: Measuring postoperative creatinine level (mg/L); Need of renal dialysis	within the first 7 days
Graft's survival	defined by graft's death or retransplantation	at 3 months
Patient's survival	defined by patient's death	at 3 months

Collaborators and Investigators

• Sponsor: Rennes University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2017
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: May 19, 2016
• First Submitted That Met QC Criteria: May 23, 2016
• First Posted (Estimated): May 26, 2016

Study Record Updates

• Last Update Posted (Actual): October 6, 2023
• Last Update Submitted That Met QC Criteria: October 5, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: extended criteria donor; temporary porto-caval shunt; liver graft
• Other Study ID Numbers: 2016-A00612-49; 35RC15_8975 (Other Identifier: CHU Rennes)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No