Post Static Cold Storage Normothermic Machine Liver Perfusion

Study Overview
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Brief Summary
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The aim of this study is to assess the safety and feasibility of a short period of cold storage prior to normothermic machine perfusion in adult liver transplantation.

Official Title
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A Multicentre, Single-arm, Prospective Clinical Trial to Investigate the Safety and Feasibility of Cold Storage Prior to Normothermic Machine Perfusion in Adult Human Liver Transplantation

Conditions
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Liver Transplantation

Intervention / Treatment
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* Device: Normothermic Machine Liver Perfusion


Participation Criteria
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Eligibility Criteria
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Donor Inclusion Criteria: Donors over the age of 16 years. Liver allografts from donation after brain death (DBD), standard and extended criteria donors. (SCD, ECD) and donation after circulatory death (DCD) donors. Liver must be perfused on OrganOx metra perfusion device within 8 hours of in situ cold perfusion. The perfusion should last a minimum of 4 hours and maximum of 24 hours. Donor Exclusion Criteria: Living donors. Liver being transplanted as part of a multi-organ transplant (eg liver and kidney). Liver intended for split transplant. Donor age <16 years Liver which investigator is unwilling to recruit to study. Any liver in which logistics prevent perfusion on the OrganOx metra perfusion device within 8 hours of in situ cold perfusion. Recipient Inclusion Criteria: Adult patients (18 years or more). Active on the waiting list for liver transplantation. Able to give informed consent. Recipient Exclusion Criteria: Age less than 18 years. Acute/fulminant liver failure. Transplantation of more than one organ (e.g. liver and kidney). Refusal of informed consent. Unable to give informed consent.

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Device: Normothermic Machine Liver Perfusion|Liver Preservation Method|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient and Graft Survival | Patient survival after liver transplantation and liver graft survival will be assessed at 30-days post-op as a composite outcome measure. This will be recorded as yes/no outcome. | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak serum AST (U/L) | The highest AST level recorded in the first 7 days post-transplant will be identified. This is a surrogate marker for longer-term outcome. It will be compared with matched controls of livers undergoing continuous NMP and SCS | 7 days | 
| Early allograft dysfunction (EAD) | This is a composite score which is used to predict longer-term outcome. It comprises: bilirubin >or=10mg/dL on day 7 post-transplant, international normalized ratio >or=1.6 on day 7 post-transplant, and alanine or aspartate aminotransferases >2000 IU/L within the first 7 days post-transplant. This will be compared with matched controls of livers undergoing continuous NMP and SCS | 7 days | 
| Primary non-function | This is irreversible graft dysfunction requiring emergency liver replacement during the first 10 days after liver transplantation, in the absence of technical or immunological causes. This will be compared with matched controls of livers undergoing continuous NMP and SCS | 10 days | 
| Adverse events, transplantation and organ discard rates. | This composite outcome aims to establish safety and feasibility as well as organ utilisation. It will be compared with matched controls of livers undergoing continuous NMP and SCS | 30 days | 
| Biliary investigation or intervention | In order to capture the incidence of ischaemic cholangiopathy, any biliary investigation (such as magnetic resonance imaging) or intervention (such as endoscopic retrograde cholangiopancreatography) will be recorded and compared with matched controls of livers undergoing continuous NMP and SCS | 6 months | 
| Patient and Graft Survival | Patient survival after liver transplantation and liver graft survival will be assessed at 6 months post-op as a composite outcome measure. This will be recorded as yes/no outcome and compared controls undergoing continuous NMP and SCS | 6 months | 
| Patient and Graft Survival | Patient survival after liver transplantation and liver graft survival will be assessed at 12 months post-op as a composite outcome measure. This will be recorded as yes/no outcome and compared controls undergoing continuous NMP and SCS | 12 months |