Normothermic Machine Perfusion of Steatotic Livers for Expansion of Donor Organ Pool
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Study Design
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- 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
- 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
- Length of post-operative inotropic support [First 30 days post-transplantation]
Length of inotropic support used after admission to the ICU, if needed
- Need for post-operative mechanical ventilation [First 30 days post-transplantation]
Number of participants in need of mechanical ventilation upon admission to ICU
- Length of post-operative mechanical ventilation [First 30 days post-transplantation]
Length of intubation after admission to ICU, if mechanical ventilation needed
- 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
- Peak AST and ALT [First 7 days post-transplantation]
Concentration of peak AST and ALT
- 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)
- Re-listing for transplantation [First 30 days post-transplantation]
Number of participants who require re-listing for liver transplantation within 30 days post-op
- 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
- 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
- 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
- Re-admissions [Assessed at 3, 6, and 12 months post-transplant]
Number of participants with re-admissions after initial discharge
- 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
- 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
- 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
- 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
- Hyperlipidemia [Assessed at 3, 6, and 12 months post-transplant]
Number of participants with evidence of hyperlipidemia
- 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)
- 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)
- 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
- Graft failure [Assessed at 3, 6, and 12 months post-transplant]
Number of participants with evidence of graft failure
- Patient death [Assessed at 3, 6, and 12 months post-transplant]
Number of participants with evidence of patient death
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Age 18-80 years
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Listed for liver transplantation at MGH
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Calculated MELD-Na score <= 25
-
Able to consent
Exclusion Criteria:
-
Status 1a
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Cardiac or pulmonary disease
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Prior liver transplant
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Requiring pressors at the time of liver offer
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MELD<15 and asymptomatic from liver disease
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Massachusetts General Hospital
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2023P002561