Efficacy of Ex-situ Normothermic Perfusion Versus Cold Storage in the Transplant With Steatotic Liver Graft. (ORGANOXLAFE)

September 27, 2023 updated by: Instituto de Investigacion Sanitaria La Fe

Clinical Trial to Compare the Efficacy of Ex-situ Normothermic Perfusion With Cold Storage in the Transplant With Steatotic Liver Graft.

Prospective, randomized, controlled clinical trial to determine the overall efficacy of normothermic machine perfusion (NMP) for steatotic liver preservation versus traditional static cold storage (SCS), in 50 liver transplant recipients with 1-year follow-up.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

This is a prospective, randomized, controlled clinical trial comparing static cold storage (SCS) versus normothermic machine perfusion (NMP) for organ preservation before liver transplantation with steatotic livers (between 30 % and 60% of histologic macrovesicular steatosis), in order to:

Main Objective:

To compare the effect of NMP versus SCS in preventing preservation injury and graft dysfunction, as measured by highest transaminase levels during the first week after liver transplantation.

Secondary Objectives:

  • To compare graft and patient survival between the NMP and SCS steatotic livers.
  • To compare the liver biochemical function between the NMP and SCS steatotic livers.
  • To compare the physiological response to the reperfusion between the NMP and SCS steatotic livers.
  • To compare the evidence of reperfusion injury between the NMP and SCS steatotic livers.
  • To compare the evidence of ischemic cholangiopathy between the NMP and SCS steatotic livers.

Study Type

Interventional

Enrollment (Actual)

7

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Valencia, Spain
        • Hospital Universitario y Politécnico La Fe

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

LIVER DONOR:

  • Donors older than 16 years
  • Liver donation grafts due to brain death
  • Steatosis confirmed by histological study (between 30% and 60% of macrovesicular steatosis)

LIVER RECIPIENT:

  • Adult patients (18 years or older)
  • Active liver transplant waiting list candidate
  • Able to give informed consent

Exclusion Criteria:

LIVER DONOR:

  • Living donors
  • Liver destined to the transplant "split"
  • Donor age <16 years
  • Donation after death due to asystole.
  • When the biopsy establishes a steatosis ≥ 50%, patients who fulfill at least 3 of the following 5 risk factors will be excluded: Transaminases (AST and ALT) ≥ 200 U / L; Age ≥ 55 years; Hypernatremia ≥ 155 mEq / L; Cardiovascular risk factors, at least 2 of the following 5: DM, HTA, IMC ≥ 35, Active smoking, ischemic stroke; Days of stay in ICU ≥ 4 days with vasoactive drugs (noradrenaline or dobutamine at any dose)

LIVER RECIPIENT:

  • Age under 18
  • Acute/fulminant hepatic failure
  • Transplant of more than one organ (for example, liver and kidney)
  • Rejection of informed consent
  • Unable to give informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Static cold storage (SCS)
Traditional method of organ preservation which involves flushing of cold preservation solution following complete dissection and interruption of blood supply to the donor organ. Although cold preservation slows metabolism by 10- to 12-fold, substantial anaerobic activity continues even at ice temperature. This lead to the generation of reactive oxygen species that are the basis of ischaemia-reperfusion injury, when the organ is re-exposed to oxygenated blood at the time of transplantation. This damage, exacerbated by any prior injury, limits the maximum safe preservation time of the donor organ.
Procedure: Static cold storage (SCS)
The liver is flushed and cooled with specialist preservation fluid, then stored in an icebox.
Experimental: Normothermic machine perfusion (NMP)
The main goal of NMP is to optimize graft preservation by mimicking physiological conditions. The perfused organ is supplied with nutrients and oxygen to maintain metabolic hemostasis. Under these conditions, ATP and glycogen reserves can be maintained or actively restored. At the same time, toxic products from the cellular milieu are continuously eliminated, so the cell-mediated injury phase of reperfusion injury can be minimized. Thus, ischemic injury is avoided and the activation of cell death cascades is prevented. This allows both hepatocellular and biliary protection.
Device: Normothermic machine perfusion (NMP)
During NMP, the liver is perfused with oxygenated blood, medications and nutrients at normal body temperature to maintain a physiological milieu.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Peak of transaminases (AST and ALT)
Time Frame: Day 1 post-transplant.
Day 1 post-transplant.
Peak of transaminases (AST and ALT)
Time Frame: Day 3 post-transplant.
Day 3 post-transplant.
Peak of transaminases (AST and ALT)
Time Frame: Day 5 post-transplant.
Day 5 post-transplant.
Peak of transaminases (AST and ALT) l
Time Frame: Day 7 post-transplant.
Day 7 post-transplant.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Primary graft failure
Time Frame: Day 10 post-transplant.
Primary graft failure: irreversible graft dysfunction that requires emergency hepatic replacement during the first 10 days after liver transplantation, in the absence of technical or immunological causes.
Day 10 post-transplant.
Graft survival
Time Frame: Day 30 post-transplant, month 6 post-transplant, month 12 post-transplant.
Day 30 post-transplant, month 6 post-transplant, month 12 post-transplant.
Patient survival
Time Frame: Day 30 post-transplant, month 6 post-transplant, month 12 post-transplant.
Day 30 post-transplant, month 6 post-transplant, month 12 post-transplant.
Post-reperfusion syndrome, measured by mean arterial pressure (MAP) levels
Time Frame: During the first 5 minutes after reperfusion
Post-reperfusion syndrome is defined as a decrease in mean arterial pressure (MAP) of more than 30% of the baseline value for more than one minute during the first five minutes after reperfusion. This will be evaluated in the context of the use of vasopressors.
During the first 5 minutes after reperfusion
Biochemical function of the liver measured by Bilirubin post-transplant levels
Time Frame: Day 1, day 3, day 5, day 7, day 30, month 6, month 12 post- transplant
Day 1, day 3, day 5, day 7, day 30, month 6, month 12 post- transplant
Biochemical function of the liver measured by GGT post-transplant levels
Time Frame: Day 1, day 3, day 5, day 7, day 30, month 6, month 12 post- transplant
Day 1, day 3, day 5, day 7, day 30, month 6, month 12 post- transplant
Biochemical function of the liver measured by AST post-transplant levels
Time Frame: Day 1, day 3, day 5, day 7, day 30, month 6, month 12 post- transplant
Day 1, day 3, day 5, day 7, day 30, month 6, month 12 post- transplant
Biochemical function of the liver measured by ALT post-transplant levels
Time Frame: Day 1, day 3, day 5, day 7, day 30, month 6, month 12 post- transplant
Day 1, day 3, day 5, day 7, day 30, month 6, month 12 post- transplant
Biochemical function of the liver measured by INR post-transplant levels
Time Frame: Day 1, day 3, day 5, day 7, day 30, month 6, month 12 post- transplant
Day 1, day 3, day 5, day 7, day 30, month 6, month 12 post- transplant
Early graft dysfunction
Time Frame: 7 days post-transplant

Defined by:

  1. Bilirubin > 10 mg / dl daily 7 after transplant
  2. INR > 1.6 on day 7 after transplantation.
  3. Peak AST and ALT > 2000 IU / L in the first 7 days after transplantation
7 days post-transplant
Intensive care stay duration
Time Frame: Day 30
Day 30
Hospital stay duration
Time Frame: Day 30
Day 30
Renal replacement therapy need
Time Frame: Day 30, month 6, month 12 post- transplant
Day 30, month 6, month 12 post- transplant
Intraoperative thromboelastogram result
Time Frame: In transplant surgery
In transplant surgery
Histological evidence of reperfusion injury
Time Frame: In transplant surgery
Post-reperfusion biopsies will be compared with baseline pre-reperfusion biopsies and classified according to standard histological criteria (blind comparison to third parties).
In transplant surgery
Evidence of biliary stenosis in magnetic resonance cholangiography (MRS).
Time Frame: 6 months after transplantation.
6 months after transplantation.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Instituto de Investigacion Sanitaria La Fe

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 26, 2019

Primary Completion (Actual)

April 4, 2023

Study Completion (Actual)

April 4, 2023

Study Registration Dates

First Submitted

April 23, 2019

First Submitted That Met QC Criteria

April 25, 2019

First Posted (Actual)

April 29, 2019

Study Record Updates

Last Update Posted (Actual)

September 29, 2023

Last Update Submitted That Met QC Criteria

September 27, 2023

Last Verified

August 1, 2019

More Information

Terms related to this study

Other Study ID Numbers

  • ORGANOXLAFE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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