Hypothermic Machine Preservation-Phase 2

NCT ID: NCT01274520

Last Updated: 2020-07-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-19
• Study Completion Date: 2014-07-31

Brief Summary

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.

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 Center for Liver Disease and Transplantation (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.

Conditions

Liver Damage

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental: Hypothermic Machine Perfusion Group

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.

Group Type: EXPERIMENTAL

The Medtronic Portable Bypass System (PBS®)

Intervention Type: DEVICE

Will be used for machine perfusion of liver grafts.

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

The Medtronic Portable Bypass System (PBS®)

Will be used for machine perfusion of liver grafts.

Intervention Type: DEVICE

Other Intervention Names

Medtronic Portable Bypass System (PBS®)

Eligibility 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 aspartate aminotransferase (AST) or alanine aminotransferase (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 intensive care unit (ICU) at time of transplantation and/or physiologic MELD score >35
• Dual organ recipient
• ABO incompatibility
• Retransplantation

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Columbia University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

James V Guarrera, MD, FACS

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Columbia University

New York, New York, United States

Countries

United States

References

Guarrera JV, Henry SD, Samstein B, Reznik E, Musat C, Lukose TI, Ratner LE, Brown RS Jr, Kato T, Emond JC. Hypothermic machine preservation facilitates successful transplantation of "orphan" extended criteria donor livers. Am J Transplant. 2015 Jan;15(1):161-9. doi: 10.1111/ajt.12958. Epub 2014 Dec 17.

Reference Type: DERIVED

PMID: 25521639 (View on PubMed)

Other Identifiers

AAAD6236

Identifier Type: -

Identifier Source: org_study_id