WP01 - Normothermic Liver Preservation

Not Applicable

Completed

• Conditions: Liver Transplantation
• Interventions: Device: Normothermic Machine Perfusion (NMP); Other: Standard of Care (Ice)

• Registration Number: NCT02775162
• Lead Sponsor: OrganOx Ltd.

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-03-30
• Study First Submitted QC: 2016-05-12
• Study First Posted: 2016-05-17
• Study Start: 2016-10-09
• Primary Completion: 2020-02-10
• Disposition First Submitted: 2021-01-11
• Disposition First Submitted QC: 2021-01-11
• Disposition First Posted: 2021-01-13
• Study Completion: 2021-02-19
• Results First Submitted: 2022-05-16
• Results First Submitted QC: 2022-06-28
• Status Verified: 2022-07
• Results First Posted: 2022-07-22
• Last Update Submitted: 2022-07-26
• Last Update Posted: 2022-07-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 267

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Normothermic Machine Perfusion (NMP)	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.
Standard of Care (Ice)	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Early Allograft Dysfunction (EAD)	7 Days	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

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Primary Non-Function	10 Days	Primary Non-Function is defined in this study as irreversible graft dysfunction requiring emergency liver replacement during the first 10 days after liver transplantation.
Number of Participants With Graft Survival	6 Months
Number of Participants With Subject Survival	6 Months
Number of Participants With Post-Reperfusion Syndrome	1 Day	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.
Measure Biochemical Liver Function Via Bilirubin	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)	6 Months	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
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	1 Day	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
Measure Biochemical Liver Function Via Gamma-Glutamyl Transferase (GGT)	6 Months
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	10 Days	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)
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	6 Months	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.

Trial Locations

Locations (15)

University of Southern California (USC); 🇺🇸 Los Angeles, California, United States

Indiana University; 🇺🇸 Indianapolis, Indiana, United States

Washington University; 🇺🇸 Saint Louis, Missouri, United States

Mayo Clinic - Phoenix; 🇺🇸 Phoenix, Arizona, United States

University of California-San Francisco (UCSF); 🇺🇸 San Francisco, California, United States

Ochsner; 🇺🇸 New Orleans, Louisiana, United States

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

University of California - Los Angeles (UCLA); 🇺🇸 Los Angeles, California, United States

University of Miami; 🇺🇸 Miami, Florida, United States

University of Maryland; 🇺🇸 Baltimore, Maryland, United States

University of Wisconsin Madison; 🇺🇸 Madison, Wisconsin, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Duke University; 🇺🇸 Durham, North Carolina, United States