Hypothermic Machine Preservation-Phase 2 (HMP2)
Device: The Medtronic Portable Bypass System (PBS®)
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Hypothermic Machine Preservation of Extended Criteria Liver Allografts for Transplantation|
- Patient survival [ Time Frame: post-operative day 1 to 1 year ] [ Designated as safety issue: Yes ]Patient Survival at 30 days, 90 days and one year post-transplantation
- Graft survival [ Time Frame: Post operative day 1 to 1 year ] [ Designated as safety issue: Yes ]Graft Survival at 30 days, 90 days and one year post-transplantation
- Incidence of Primary Graft Nonfunction [ Time Frame: post-operative day 1 to 1 year ] [ Designated as safety issue: Yes ]
Incidence of Primary Graft Nonfunction (PNF)as follows:
- Relisted for OLT within 7 days of OLT, not for vascular thromboses
- ALT >2000 and one or both of: acidosis with pH <7.3 or lactate >2X normal
- INR >2.5
- Incidence of Early Allograft Dysfunction (EAD) [ Time Frame: Within the first 7 days post-transplantation ] [ Designated as safety issue: Yes ]
Incidence of Early Allograft Dysfunction (EAD) as defined as follows:
- Bilirubin >10 on POD#7
- INR >1.6 on POD#7
- Transaminase level (AST or ALT) >2000 within the first 7 days
- Incidence of Acute Kidney Injury First Month Post-OLT [ Time Frame: 1 month post-OLT ] [ Designated as safety issue: No ]Incidence of acute kidney injury as defined by RIFLE criteria 1 month post-OLT.
- Hospital Length of Stay of Index Admission [ Time Frame: First admission after transplant ] [ Designated as safety issue: No ]Length of transplant hospital stay post-OLT.
- Incidence of Biliary Strictures 1 year post-OLT [ Time Frame: 1 year post-OLT ] [ Designated as safety issue: No ]Incidence of biliary strictures or leaks requiring intervention or re-operation in 1 year post-OLT.
|Study Start Date:||December 2009|
|Study Completion Date:||July 2014|
|Primary Completion Date:||July 2013 (Final data collection date for primary outcome measure)|
Experimental: Medtronic Portable Bypass System
The Medtronic Portable Bypass System (PBS®) with Model 550 Bioconsole and the BioCal® blood temperature control module will be used for machine perfusion of liver grafts. These products are commercially available and used in clinical practice for cardiopulmonary bypass and extracorporeal membrane oxygenation. The Medtronic system utilizes an atraumatic centrifugal pump that can deliver the flow rates approximating portal venous flow in human livers, and it has modules for online membrane oxygenation, and electronic flow measurement.
Device: The Medtronic Portable Bypass System (PBS®)
Will be used for machine perfusion of liver grafts.
Other Name: Medtronic Portable Bypass System (PBS®)
No Intervention: Matched control group
The proposed study is a matched cohort design. Subjects will be matched with 24 historical control patients who received similar cold stored ECD grafts. Subjects will be matched on known covariates including donor age, donation after cardiac death, steatosis, both warm and cold ischemia times, recipient age, MELD score and disease etiology. Additional analyses will be performed on historical control blood and/or tissue samples previously collected and stored in the study's sample repository.
It is our hypothesis that liver machine perfusion will increase the safe utilization of the existing supply of extended criteria donor(ECD) livers by (1) increasing the quality and duration of preservation thereby reducing the clinical effects reperfusion injury (2) improving early outcomes in patients receiving ECD liver allografts (3) developing reliable markers for pretransplant assessment of the potential graft (4) giving surgeons more confidence when transplanting ECD livers and (5) allowing an avenue for ex vivo manipulation of the liver to protect or restore a transiently injured liver.
The proposed study is a matched cohort design. Potential subjects will be recruited from the CLDT active Liver Transplant Waiting List. The Principal Investigator as well as the CoInvestigators, are all actively involved in the pre transplant evaluation process. Patients who are on the Waiting List and have provided written consent to receive an ECD graft will be recruited for this trial. Subjects will be matched with 24 historical control patients who received similar cold stored ECD grafts. Subjects will be matched on known covariates including donor age, donation after cardiac death, steatosis, both warm and cold ischemia times, recipient age, Model End-Stage Liver Disease (MELD) score and disease etiology.
Subjects will be noncritically ill, not in an intensive care unit, and have a MELD < 35 in order to minimize the variability in outcome in the sickest patients. All subjects must provide written informed consent and meet the inclusion and exclusion criteria.
Subjects will be followed for one year post transplantation, in conjunction with their routine liver transplant followup appointments. Retention of subjects for this trial will not be a challenge, in that the followup visit time points (postoperative days 1 through the discharge date, 7, 14, 30, 90, 180 and 365) are all consistent with our standard of care.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01274520
|United States, New York|
|New York, New York, United States, 10032|
|Principal Investigator:||James V Guarrera, MD, FACS||Columbia University|