Safety and Feasibility of Normothermic Machine Perfusion to Preserve and Evaluate Orphan Livers

Study Overview
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Brief Summary
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Orphan livers are organs that have been declined for clinical use by all centers due to their marginality. The current standard of care of liver preservation before transplant is cold storage. NMP may allow these livers to be evaluated before transplantation. NMP has already been used in a clinical setting with promising results. The advantage to utilizing NMP is that it would attenuate the incidence and clinical impact of classical preservation injury, allow liver function assessment before implantation and thus improve donor pool and outcomes for high risk ECD liver transplants performed at our center.

Detailed Description
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This will be a single center prospective cohort pilot study. 30 livers that have been declined for clinical use by all centers due to their marginality will be preserved with NMP in 1-18 hours after cross clamp and cold flush. The liver grafts at NMP will be at Physiological temperature and have oxygen and nutrient supply with continuous perfusion. Once the liver grafts have been evaluated and determined to be transplantable, the transplantation and post-transplant care will follow the standard of care. The follow-up period is 12 months after transplantation. The primary end point will be the rate of patient survival and primary non function (PNF) within 30 days after transplantation, while the secondary end points will be: Early Allograft Dysfunction (EAD), 6 months patient and graft survival, peak liver function tests in the first 7 days after transplantation, surgical outcomes (operative time, transfusion requirement etc.), rate of post-transplant kidney failure, assessment of histological ischemia reperfusion (liver and bile duct), rate of vascular complications, rate of biliary complications, hospital and ICU length of stay, rejection rate, infection rate, the ability to predict function based on on-pump viability markers, and the incidence of adverse effect (AE).

Official Title
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Pilot Study to Assess Safety and Feasibility of Normothermic Machine Perfusion to Preserve and Evaluate Orphan Livers

Conditions
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Liver Transplantation

Intervention / Treatment
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* Device: Normothermic Liver perfusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing primary liver transplantation Age 18-75 years at the time of transplantation Willingness and ability to comply with the study procedures Signed Informed Consent Form For patients with hepatocellular carcinoma as indication for Orthoptic Liver Transplantation (OLT), tumor must be within Milan Criteria or down-staged to Milan Criteria. Exclusion Criteria: Recipient Exclusion Criteria: History of prior solid organ transplantation Patient on a respiratory and/or cardiocirculatory support at the time of transplant MELD score >35 HIV positive patient Patient with current severe systemic infection Multiorgan transplant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Normothermic Liver perfusion<br>This group has the liver grafts preserved using the Normothermic Liver perfusion Device | Device: Normothermic Liver perfusion<br>* The liver grafts will be preserved and evaluated at physiological temperature and have continuous perfusion with oxygen and nutrient supply in the ex vivo organ preservation phase<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rate of patient survival |  | 30 days post-transplantation | 
| The rate of primary non-function | primary non-function is defined as non life sustaining liver function requiring retransplantation or leading to death with 30 days after transplantation | 30 days post-transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rate of Early Allograft Dysfunction post-transplantation | The presence of at least one of the following at post-transplant 7 days: serum bilirubin >= 10 mg/dL, international normalized ratio (INF) >= 1.6; and/or aspartate aminotransferase (AST) > 2000 U/L at any time in the first 7 posttransplant days (POD) | 7 days post-transplantation | 
| graft survival | The allograft will be considered lost if a patient has a liver re-transplant or in the event of patient death. | 6 months post-transplantation | 
| peak aspartate aminotransferase (AST) in the first 7 days post-transplantation | CLINICAL LABORATORY TEST | in the first 7 days post-transplantation | 
| peak Alanine Aminotransferase (ALT) in the first 7 days post-transplantation | CLINICAL LABORATORY TEST | in the first 7 days post-transplantation | 
| peak bilirubin in the first 7 days post-transplantation | CLINICAL LABORATORY TEST | in the first 7 days post-transplantation |