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

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.

Study Overview

• Status: Recruiting
• Conditions: Liver Transplant
• Intervention / Treatment: Device: Normothermic machine perfusion (NMP) of steatotic liver

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Heidi Yeh, MD; Phone Number: 617-643-4533; Email: hyeh@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Brigham
      • Contact: Olivia Bourgeois, CRC II, BS; Phone Number: 617-724-1976; Email: obourgeois@mgb.org
      • Contact: Emily Nyhan, CRC II, MS; Phone Number: 617-643-6266; Email: enyhan@mgb.org
      • Principal Investigator: Heidi Yeh, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Liver Transplantation with Steatotic Liver; 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; Steatotic liver grafts that are selected will be run on NMP to assess quality of graft and determine whether it meets criteria for transplantation

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

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2024
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2027

Study Registration Dates

• First Submitted: September 22, 2023
• First Submitted That Met QC Criteria: October 12, 2023
• First Posted (Actual): October 18, 2023

Study Record Updates

• Last Update Posted (Estimated): November 3, 2025
• Last Update Submitted That Met QC Criteria: October 31, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: 2023P002561

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes