WP01 - Normothermic Liver Preservation

A Multicenter Randomized Controlled Trial to Compare the Efficacy of Ex-vivo Normothermic Machine Perfusion With Static Cold Storage in Human Liver Transplantation

A multicenter randomized controlled trial to compare the efficacy of ex-vivo normothermic machine profusion with static cold storage in human liver transplantation.

Study Overview

• Status: Completed
• Conditions: Liver Transplantation
• Intervention / Treatment: Device: Normothermic Machine Perfusion (NMP); Other: Standard of Care (Ice)

• Study Type: Interventional
• Enrollment (Actual): 267
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic - Phoenix
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California (USC)
    • Los Angeles, California, United States, 90095
      • University of California - Los Angeles (UCLA)
    • San Francisco, California, United States, 94153
      • University of California-San Francisco (UCSF)
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Madison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject is 18 years of age or greater
• Subject is registered as an active recipient on the United Network for Organ Sharing (UNOS) waiting list for liver transplantation
• Subject, or legally authorized representative, is able and willing to give informed consent and HIPAA authorization
• Subject is able and willing to comply with all study requirements

Exclusion Criteria:

• Subject requiring all of the following at the time of transplantation: oxygen therapy, inotropic support, renal replacement therapy
• Subject has acute/fulminant liver failure
• Subject undergoing simultaneous transplantation of more than one organ
• Subject is pregnant or nursing
• Concurrent enrollment in another clinical trial. Subjects enrolled in clinical trials or registries where only measurements and/or samples are taken (NO TEST DEVICE or TEST DRUG USED) are allowed to participate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Normothermic Machine Perfusion (NMP); Following the routine retrieval procedure of the liver, it will be placed on the OrganOx metra for Normothermic Machine Perfusion (NMP) for transport per the Investigational Plan and the Instructions For Use.	Device: Normothermic Machine Perfusion (NMP); Other Names: OrganOx metra® device
OTHER: Standard of Care (Ice); Following the routine retrieval procedure of the liver, it will be placed in ice-cold perfusion solution within an ice box for transport as dictated by logistics and local policy.	Other: Standard of Care (Ice)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Early Allograft Dysfunction (EAD)	EAD is a binary outcome defined by the presence of one of the following 3 outcomes: Serum bilirubin ≥ 10 mg/dL at day 7 post-transplant; International normalized ratio (INR) ≥ 1.6 at day 7 post-transplant; Alanine Aminotransferase (ALT) or Aspartate Transaminase (AST) > 2000 IU/L within the first 7 days post-transplant	7 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Primary Non-Function	Primary Non-Function is defined in this study as irreversible graft dysfunction requiring emergency liver replacement during the first 10 days after liver transplantation.	10 Days
Number of Participants With Graft Survival		6 Months
Number of Participants With Subject Survival		6 Months
Number of Participants With Post-Reperfusion Syndrome	Post-Reperfusion Syndrome is defined in this study as a decrease in mean arterial pressure (MAP) of more than 30% from the baseline value for more than one minute during the first five minutes after reperfusion.	1 Day
Measure Biochemical Liver Function Via Bilirubin		6 Months
Measure Biochemical Liver Function Via Gamma-Glutamyl Transferase (GGT)		6 Months
Measure Biochemical Liver Function Via Alanine Aminotransferase (ALT)		6 Months
Measure Biochemical Liver Function Via Aspartate Transaminase (AST)		6 Months
Measure Biochemical Liver Function Via Alkaline Phosphatase (ALP)		6 Months
Measure Biochemical Liver Function Via International Normalized Ratio (INR)	The international normalized ratio (INR) is a laboratory measurement of how long it takes blood to form a clot. It is calculated using the following formula: INR = (PT [test] / PT [control])^ISI INR = international normalized ratio PT [test] = tested prothrombin time PT [control] = control prothrombin time ISI = international sensitivity index	6 Months
Measure Biochemical Liver Function Via Lactate		Days 1-7
Number of Participants With Evidence of Ischemia-Reperfusion Injury Via Comparison of Pre-Reperfusion Biopsies to Post-Reperfusion Biopsies	Overall Degree of Ischemia Reperfusion Injury (IRI) was categorized as: None/Minimal: None or Polymorphonuclear Leukocytes (PMNs) in sinusoidal zone 3 with rare hepatocellular necrosis; Mild: Polymorphonuclear Leukocytes (PMNs) in sinusoidal zone 3 with ≥ 1 cluster of necrotic hepatocytes; Moderate/Severe: Clusters of hepatocellular necrosis in > 50% of lobules or 60% of parenchyma or panlobular necrosis in > 1 lobule	1 Day
Number of Participants With Biliary Investigations and Biliary Interventions		6 Months
Number of Livers Randomized But Not Transplanted		1 Day
Number of Livers That Did Not Experience a Safety Event	Number of livers that did not experience at least one of the following safety events: Early Allograft Dysfunction (EAD); Discard of a Retrieved Liver; Primary Non-Function (PNF)	10 Days
Assessment of the Health Economic Implications Via Length of ICU Stay and Length of Hospital Stay		6 Months
Compare Quality of Life Via the EQ-5D-5L Quality of Life Questionnaire	The EQ-5D-5L Questionnaire is the standard layout for recording an adult person's current self-reported health state. It consists of a standard format for respondents to record their health state according to the EQ-5D-5L descriptive system and the EQ Visual Analog Scale (VAS). EQ-5D-5L index scores range from 0 to 1.0 on a scale where 0 = death and 1.0 = perfect health. EQ-5D-5L is the name of the instrument and is not an acronym.	6 Months

Collaborators and Investigators

• Sponsor: OrganOx Ltd.
• Collaborators: North American Science Associates Ltd.

Publications and helpful links

General Publications

• Kubal C, Mihaylov P, Holden J. Oncologic indications of liver transplantation and deceased donor liver allocation in the United States. Curr Opin Organ Transplant. 2021 Apr 1;26(2):168-175. doi: 10.1097/MOT.0000000000000866.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 9, 2016
• Primary Completion (ACTUAL): February 10, 2020
• Study Completion (ACTUAL): February 19, 2021

Study Registration Dates

• First Submitted: March 30, 2016
• First Submitted That Met QC Criteria: May 12, 2016
• First Posted (ESTIMATE): May 17, 2016

Study Record Updates

• Last Update Posted (ACTUAL): July 29, 2022
• Last Update Submitted That Met QC Criteria: July 26, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: WP01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO