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Hypothermic Machine Preservation-Phase 2 (HMP2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
James V Guarrera, Columbia University
ClinicalTrials.gov Identifier:
NCT01274520
First received: November 3, 2010
Last updated: July 22, 2014
Last verified: July 2014
  Purpose

This is a study comparing a technique of continuous circulation to the liver as a means of preventing liver damage during transportation to the transplant hospital. This new technique of Machine Perfusion (MP) will be compared to the standard technique where the liver is maintained in a bag of solution on ice without circulation. The investigators will evaluate and compare the outcomes of the transplants with the new technique to the standard technique. There will be 24 MP patient's in the study. The investigators have previously used this technique with success in 20 human liver transplant patients. The investigators think there will be a benefit in terms of less damage to and better function of the donor liver which will result in faster recovery for the patients. This protective effect may allow us to successfully transplant more patients and prevent people from dying while waiting for a liver transplant.


Condition Intervention Phase
Liver Damage
Device: The Medtronic Portable Bypass System (PBS®)
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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.


Enrollment: 24
Study Start Date: December 2009
Study Completion Date: July 2014
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed written informed IRB consent by patient or patient's legally appointed representative.
  • Be at least 18 years of age; male or female.
  • Listed with UNOS for liver transplantation.
  • Organ declined by at least one transplant center
  • Extended criteria donor as defined by:

    • Presence of hepatitis C antibody
    • Donation after Cardiac Death (DCD)
    • Severe Hypernatremia: donor serum sodium >165 meq/L for at least 12 hours prior to procurement
    • Donor age ≥65 years
    • Presence of significant steatosis >25% macrovesicular by biopsy
    • Evidence of significant donor ischemic injury
    • Current donor serum AST or ALT >1000 IU/L
    • Ischemic injury evidenced by prolonged hypotension, high pressor requirement and/or rising serum liver function tests or one test more than five times the upper limit of normal (AST, ALT, or Total Bilirubin)

Exclusion Criteria:

  • Patients in whom the donor liver will be subjected to less than 4 hours of cold ischemia (surgeon desires immediate implantation)
  • Patient hospitalized in ICU at time of transplantation and/or physiologic MELD score >35
  • Dual organ recipient
  • ABO incompatibility
  • Retransplantation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01274520

Locations
United States, New York
Columbia University
New York, New York, United States, 10032
Sponsors and Collaborators
James V Guarrera
Investigators
Principal Investigator: James V Guarrera, MD, FACS Columbia University
  More Information

No publications provided

Responsible Party: James V Guarrera, Assistant Professor of Surgery, Columbia University
ClinicalTrials.gov Identifier: NCT01274520     History of Changes
Other Study ID Numbers: AAAD6236
Study First Received: November 3, 2010
Last Updated: July 22, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Columbia University:
ECD liver transplant allografts
Hypothermic machine perfusion
Cold storage preservation
liver transplant
portable bypass system
machine perfusion preservation
extended criteria liver

Additional relevant MeSH terms:
Hypothermia
Body Temperature Changes
Signs and Symptoms

ClinicalTrials.gov processed this record on November 20, 2014