Normothermic Machine Perfusion of Steatotic Livers for Expansion of Donor Organ Pool

Study Overview
=================
Brief Summary
-----------------
The goal of this clinical trial is to assess the ability of Normothermic Machine Perfusion (NMP) to resuscitate moderately steatotic livers for transplantation in patients. This will be a single-site clinical trial placing donor livers with 30-60% macrosteatosis on NMP, and then transplanting those that meet commonly accepted viability criteria. The results of this study could lead to a trial extending NMP transplantation to severely steatotic livers, further expanding the donor organ pool.

Official Title
-----------------
Normothermic Machine Perfusion of Steatotic Livers for Expansion of Donor Organ Pool

Conditions
-----------------
Liver Transplant

Intervention / Treatment
-----------------
* Device: Normothermic machine perfusion (NMP) of steatotic liver


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18-80 years Listed for liver transplantation at MGH Calculated MELD-Na score <= 25 Able to consent Exclusion Criteria: Status 1a Cardiac or pulmonary disease Prior liver transplant Requiring pressors at the time of liver offer MELD<15 and asymptomatic from liver disease

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Liver Transplantation with Steatotic Liver<br>Graft will be selected if 30-60% macrosteatosis and transplanted into liver transplant recipient with MELD of 15-25. | Device: Normothermic machine perfusion (NMP) of steatotic liver<br>* Steatotic liver grafts that are selected will be run on NMP to assess quality of graft and determine whether it meets criteria for transplantation<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early allograft dysfunction | Number of participants with initial poor function of liver allograft: measured by presence of 1 or more of the following: aspartate aminotransferase (AST) level higher than 2000 IU/L (to convert to microkatals per liter, multiply by 0.0167) within the first 7 postoperative days; bilirubin 10 mg/dL or higher (to convert to micromoles per liter, multiply by 17.104) on postoperative day 7; international normalized ratio (INR) of 1.6 or higher on postoperative day 7; or graft primary nonfunction within the first 7 days, defined as irreversible graft dysfunction leading to recipient death or emergency retransplant, in the absence of immunologic or surgical causes | First week after transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intraoperative inotropic support | Number of participants in need of inotropic support to maintain hemodynamics intraoperatively after reperfusion of liver allograft | At reperfusion, 15 minutes, 1 hour, 2 hours, and 3 hours after reperfusion | 
| Need for post-operative inotropic support | Number of participants in need of inotropic support upon admission to the ICU | First 30 days post-transplantation | 
| Length of post-operative inotropic support | Length of inotropic support used after admission to the ICU, if needed | First 30 days post-transplantation | 
| Need for post-operative mechanical ventilation | Number of participants in need of mechanical ventilation upon admission to ICU | First 30 days post-transplantation | 
| Length of post-operative mechanical ventilation | Length of intubation after admission to ICU, if mechanical ventilation needed | First 30 days post-transplantation | 
| ICU length of stay | Length of stay in ICU post-transplant | First 30 days post-transplantation | 
| Renal replacement therapy requirement | Number of participants who require renal replacement therapy during the first 10 days after liver transplantation, if not on renal replacement prior to transplant | First 30 days post-transplantation | 
| Peak AST and ALT | Concentration of peak AST and ALT | First 7 days post-transplantation | 
| Internal Normalized Ratio (INR) | INR measurements for each participant until post-op day 7 or discharge | First 7 days post-transplantation or within first 30 days post-op if discharge is longer than 7 days out | 
| Total bilirubin | Total bilirubin measurement (mg/dl) on post-op day 7 or day of discharge | First 7 days post-transplantation or within first 30 days post-op if discharge is longer than 7 days out | 
| 30-day patient survival | 30-day patient survival (percentage) | First 30 days post-transplantation | 
| Re-listing for transplantation | Number of participants who require re-listing for liver transplantation within 30 days post-op | First 30 days post-transplantation | 
| Adverse events | Incidence of any additional adverse events, not including 24-hour ICU stay post-transplant, post-transplant transfusion <=6 units pRBCs, <=2 units FFP, <=2 units 6-pack of platelets, as these are considered routine | First 30 days post-transplantation | 
| Biopsy-proven rejection episodes | Number of participants with biopsy-proven rejection episodes | Assessed at 3, 6, and 12 months post-transplant | 
| Liver function tests more than 3 times normal | Number of participants with liver function tests more than 3 times normal; liver function tests (LFTs) will measure AST/ALT, bilirubin, INR | Assessed at 3, 6, and 12 months post-transplant | 
| Additional procedures | Number of participants that require additional procedures beyond normal recovery standard of care post-liver transplant | Assessed at 3, 6, and 12 months post-transplant | 
| Re-admissions | Number of participants with re-admissions after initial discharge | Assessed at 3, 6, and 12 months post-transplant | 
| Ischemic cholangiopathy and anastomotic strictures by imaging | Number of participants with evidence of ischemic cholangiopathy and anastomotic strictures by imaging | Assessed at 3, 6, and 12 months post-transplant | 
| Vascular complications by cross-sectional imaging or angiography | Number of participants with evidence of vascular complications by cross-sectional imaging or angiography | Assessed at 3, 6, and 12 months post-transplant | 
| Presence of steatosis by imaging or histology | Number of participants with evidence of steatosis by imaging or histology | Assessed at 3, 6, and 12 months post-transplant | 
| Degree of steatosis by imaging or histology | Degree of steatosis by imaging or histology, if present | Assessed at 3, 6, and 12 months post-transplant | 
| Renal dysfunction | Presence of a decrease in GFR > 40 from pre-transplant baseline or creatinine >2 if received simultaneous liver-kidney transplant | Assessed at 3, 6, and 12 months post-transplant | 
| Hyperlipidemia | Number of participants with evidence of hyperlipidemia | Assessed at 3, 6, and 12 months post-transplant | 
| Immunosuppression medications | Types of immunosuppression medications required | Assessed at 3, 6, and 12 months post-transplant | 
| Dosage of immunosuppression medications | Dosage of immunosuppression medications required in respective unit measurement (i.e. milligrams) | Assessed at 3, 6, and 12 months post-transplant | 
| Drug levels of immunosuppression medications | Drug levels of immunosuppression medications present in blood titers drawn from participant in respective unit measurement (i.e. ng/mL) | Assessed at 3, 6, and 12 months post-transplant | 
| Re-listing for transplantation | Number of participants who require re-listing for transplantation within 1 year post-op | Assessed at 3, 6, and 12 months post-transplant | 
| Graft failure | Number of participants with evidence of graft failure | Assessed at 3, 6, and 12 months post-transplant | 
| Patient death | Number of participants with evidence of patient death | Assessed at 3, 6, and 12 months post-transplant |