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

Not Applicable

Recruiting

• Conditions: Liver Transplant

• Registration Number: NCT06088758
• Lead Sponsor: Massachusetts General Hospital

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-09-22
• Study First Submitted QC: 2023-10-12
• Study First Posted: 2023-10-18
• Study Start: 2024-02-28
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-19
• Last Update Posted: 2024-11-21
• Primary Completion: 2026-02
• Study Completion: 2026-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Early allograft dysfunction	First week after transplant	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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Massachusetts General Brigham; 🇺🇸 Boston, Massachusetts, United States