Clinical trial NCT03089840: Normothermic Liver Preservation Trial
Official title: Assessing the Safety and Efficacy of a Portable Ex Vivo Oxygenated, Normothermic Liver Perfusion System (OrganOx Metra™ ) Prior to Liver Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: End Stage Liver Disease
Liver Diseases
Keywords: normothermic perfusion
liver transplantation
Lead sponsor: University of Alberta
Sponsor class: OTHER
First posted: 2017-03-24
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Non-randomized, open-label, single arm, prospective trial using retrospective matched controls
Primary purpose: TREATMENT

Brief summary: This trial is to assess the safety and efficacy of normothermic machine perfusion (NMP) as an organ preservation method prior to transplantation using the OrganOx metra™ device.

Detailed description: The standard approach for storage and transportation of livers for transplantation involves cold perfusion with Histidine-tryptophan-ketoglutarate (HTK) or alternative solutions, and storage in sterile bags surrounded by preservation solution in a box by ice. The prolonged cold ischemic injury substantially compounds pre-existing donor liver graft injury, further exacerbating potential risk for recipients. Normothermic perfusion may eliminate cold ischemic injury, and provide a unique opportunity to further assess ex vivo function of the most marginal organs before they are transplanted. Being able to select or eliminate organs in this manner would provide additional livers for transplantation while at the same time minimizing risk for recipients.

This non-randomized, open-label, single arm, prospective trial is to assess safety and preliminary efficacy of normothermic machine perfusion on livers accepted under standard and expanded criteria for standard liver transplantation (n=50). Following assessment of donor and recipient eligibility and confirmation of consent, the liver will be preserved on OrganOx metra™ either at the donor hospital or where more practical transported to the University of Alberta hospital with ≤ 6 hours of cold storage and then placed on the metra™ for ≥ 4 hours ('back to base' sub-analysis). At the end of preservation, the liver will be transplanted and the patient managed according to standard local practice and protocols. 100 anonymized patient data from the University of Alberta Hospital Liver Transplant database will be utilized for the matched controls. Enrolled subjects will participate in the study for 30 days (the accrued period to capture primary and secondary end-points: graft and patient survival, graft function, NMP perfusion parameters). Additional routine (non-research) biochemical and survival data will be collected and documented at 3, 6, 9 and 12 months post-transplant. Primary outcomes will be analyzed and reported 30 days following transplantation of the last subject in the study.

Eligibility criteria: Inclusion Criteria:

Recipient inclusion criteria:

Adult subjects (age ≥18 years); active on the waiting list for liver transplantation at the University of Alberta Hospital; informed/deferred consent provided.

Donor liver inclusion criteria:

Whole livers from deceased donors ≥ 40kg in weight, that are deemed suitable for transplantation as per local and international practice, and at the discretion of the transplanting surgeon.

Donor livers will be placed on the metra™ device either at the donor hospital, or where more practical, transported to the University of Alberta hospital with ≤ 6 hours of cold storage and then reperfused on metra™ for ≥ 4 hours ('back-to-base' sub-analysis).

Expanded criteria grafts may include, but not be restricted to the following graft qualities. Such grafts will only be transplanted at the recipient transplant surgeon's discretion, if judged to be safe and appropriate for that individual recipient.

Donation after Neurological Determination of Death (NDD) Expanded Criteria livers may include: ≥60% macro/micro steatosis; cold ischemia \> 10 hours; combined steatosis 30-60% and \>6hr cold storage; significant liver trauma.

Donation after Cardio-Circulatory Death (DCD) Expanded Criteria livers may include: Age up to 75; mild steatosis (30%); DCD offers from distant centres; warm time up to 60 min.

As per standard clinical practice, the on-call recipient transplant surgeon will evaluate donor and graft information, weigh the risks and benefits of graft utilization for a particular recipient, and make the final decision about whether or not to proceed to transplantation. Based on preliminary experience with the metraTM, perfusion parameters may additionally be considered in reaching a decision:

* Normal, stable portal vein flow (≥800-1000ml/minute) and artery flow (≥200ml/minute)
* Falling lactate levels
* Stable perfusate pH within the normal range (7.2 - 7.4) after bicarbonate correction
* Evenly perfused graft on the device

Exclusion Criteria:

Recipient exclusion criteria: Age less than 18 years, allergic to required components of the perfusion solution, refusal of informed consent.

Donor liver exclusion criteria: Livers from living donors.

Primary outcomes:
measure: Graft survival rate
timeFrame: Day 30
Secondary outcomes:
measure: Patient survival rate
timeFrame: Day 30
measure: Early Allograft Dysfunction (EAD) rate
timeFrame: Up to Day 7
measure: Peak aspartate transaminase (AST) levels
timeFrame: Up to Day 7
measure: Daily lactate levels
timeFrame: Up to Day 7
measure: Perfusate AST levels
timeFrame: Day -1 and Day 0
measure: Perfusate alanine transaminase (ALT) levels
timeFrame: Day -1 and Day 0
measure: Perfusate bilirubin levels
timeFrame: Day -1 and Day 0
measure: Perfusate lactate levels
timeFrame: Day -1 and Day 0
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
Study officials:
affiliation: University of Alberta
name: James Shapiro, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: