WP01 - Normothermic Liver Preservation

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

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

Conditions
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Liver Transplantation

Intervention / Treatment
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* Device: Normothermic Machine Perfusion (NMP)
* Other: Standard of Care (Ice)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Normothermic Machine Perfusion (NMP)<br>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)<br> <br> * Other names: OrganOx metra® device;|
| Other: Standard of Care (Ice)<br>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)<br> <br> |

What is the study measuring?
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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 |