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

Not Applicable
Recruiting
Conditions
Liver Transplant
Interventions
Device: Normothermic machine perfusion (NMP) of steatotic liver
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

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
Arm && Interventions
GroupInterventionDescription
Liver Transplantation with Steatotic LiverNormothermic machine perfusion (NMP) of steatotic liverGraft will be selected if 30-60% macrosteatosis and transplanted into liver transplant recipient with MELD of 15-25.
Primary Outcome Measures
NameTimeMethod
Early allograft dysfunctionFirst 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
NameTimeMethod
Intraoperative inotropic supportAt 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 supportFirst 30 days post-transplantation

Number of participants in need of inotropic support upon admission to the ICU

ICU length of stayFirst 30 days post-transplantation

Length of stay in ICU post-transplant

Renal replacement therapy requirementFirst 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

Patient deathAssessed at 3, 6, and 12 months post-transplant

Number of participants with evidence of patient death

Length of post-operative mechanical ventilationFirst 30 days post-transplantation

Length of intubation after admission to ICU, if mechanical ventilation needed

Additional proceduresAssessed 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 bilirubinFirst 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 survivalFirst 30 days post-transplantation

30-day patient survival (percentage)

Adverse eventsFirst 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-admissionsAssessed at 3, 6, and 12 months post-transplant

Number of participants with re-admissions after initial discharge

Presence of steatosis by imaging or histologyAssessed at 3, 6, and 12 months post-transplant

Number of participants with evidence of steatosis by imaging or histology

Renal dysfunctionAssessed 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 medicationsAssessed at 3, 6, and 12 months post-transplant

Types of immunosuppression medications required

Dosage of immunosuppression medicationsAssessed at 3, 6, and 12 months post-transplant

Dosage of immunosuppression medications required in respective unit measurement (i.e. milligrams)

Length of post-operative inotropic supportFirst 30 days post-transplantation

Length of inotropic support used after admission to the ICU, if needed

Biopsy-proven rejection episodesAssessed at 3, 6, and 12 months post-transplant

Number of participants with biopsy-proven rejection episodes

Liver function tests more than 3 times normalAssessed 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 ventilationFirst 30 days post-transplantation

Number of participants in need of mechanical ventilation upon admission to ICU

Peak AST and ALTFirst 7 days post-transplantation

Concentration of peak AST and ALT

Re-listing for transplantationAssessed 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 histologyAssessed at 3, 6, and 12 months post-transplant

Degree of steatosis by imaging or histology, if present

HyperlipidemiaAssessed at 3, 6, and 12 months post-transplant

Number of participants with evidence of hyperlipidemia

Graft failureAssessed at 3, 6, and 12 months post-transplant

Number of participants with evidence of graft failure

Ischemic cholangiopathy and anastomotic strictures by imagingAssessed 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 angiographyAssessed 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 medicationsAssessed 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

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