Clinical trial NCT01274520: Hypothermic Machine Preservation-Phase 2
Official title: Hypothermic Machine Preservation of Extended Criteria Liver Allografts for Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Liver Damage
Keywords: ECD liver transplant allografts
Hypothermic machine perfusion
Cold storage preservation
liver transplant
portable bypass system
machine perfusion preservation
extended criteria liver
Lead sponsor: Columbia University
Sponsor class: OTHER
First posted: 2011-01-11
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Patient Survival at One Year Post-Transplantation
timeFrame: Post-Operative Day 1 to Day 365
measure: Graft Survival at One Year Post-Transplantation
timeFrame: Post-Operative Day 1 to Day 365
Secondary outcomes:
measure: Incidence of Primary Graft Nonfunction
timeFrame: Post-Operative Day 1 to Day 7
measure: Incidence of Early Allograft Dysfunction (EAD)
timeFrame: Within the first 7 days post-transplantation
measure: Incidence of Post-Operative Complications
timeFrame: 1 Month Post-Transplantation
measure: Incidence of Bile Leaks
timeFrame: Post-Operative Day 1 to Day 365
measure: Incidence of Re-Operation For Bleeding
timeFrame: Post-Operative Day 1 to Day 365
measure: Incidence of Hernia Events Within 1 Year Post-Transplantation
timeFrame: Post-Operative Day 1 to Day 365
measure: Hospital Length of Stay (Index Transplant Hospitalization)
timeFrame: First admission after transplant
measure: Time With Stent (Days)
timeFrame: Post-Operative Day 1 to Day 365
measure: Incidence of Biliary Strictures
timeFrame: Post-Operative Day 1 to Day 365
measure: Incidence of Endoscopic Retrograde Cholangiopancreatographies (ERCPs)
timeFrame: Post-Operative Day 1 to Day 365
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University
state: New York
Study officials:
affiliation: Columbia University
name: James V Guarrera, MD, FACS
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.