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Normothermic Liver Preservation Trial

Primary Purpose

End Stage Liver Disease, Liver Diseases

Status

Active

Phase

Phase 1

Locations

Canada

Study Type

Interventional

Intervention

OrganOx metra

About this trial

This is an interventional treatment trial for End Stage Liver Disease focused on measuring normothermic perfusion, liver transplantation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

University of Alberta

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Normothermic Machine Perfusion (OrganOx metra)

Arm Description

Donor livers will be placed on the OrganOx metra device for normothermic perfusion before transplantation.

Outcomes

Primary Outcome Measures

Graft survival rate

Secondary Outcome Measures

Patient survival rate

Early Allograft Dysfunction (EAD) rate

EAD rate

Peak aspartate transaminase (AST) levels

Peak AST levels in the blood

Daily lactate levels

Daily lactate levels in the blood

Perfusate AST levels

AST levels in perfusate blood

Perfusate alanine transaminase (ALT) levels

ALT levels in perfusate blood

Perfusate bilirubin levels

Bilirubin levels in perfusate blood

Perfusate lactate levels

Lactate levels in perfusate blood

Full Information

NCT ID

NCT03089840

First Posted

March 11, 2017

Last Updated

October 3, 2023

Sponsor

University of Alberta

1. Study Identification

Unique Protocol Identification Number

NCT03089840

Brief Title

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

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

February 24, 2017 (Actual)

Primary Completion Date

June 30, 2025 (Anticipated)

Study Completion Date

June 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Alberta

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

End Stage Liver Disease, Liver Diseases

Keywords

normothermic perfusion, liver transplantation

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Model Description

Non-randomized, open-label, single arm, prospective trial using retrospective matched controls

Masking

None (Open Label)

Allocation

N/A

Enrollment

106 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Normothermic Machine Perfusion (OrganOx metra)

Arm Type

Experimental

Arm Description

Donor livers will be placed on the OrganOx metra device for normothermic perfusion before transplantation.

Intervention Type

Device

Intervention Name(s)

OrganOx metra

Intervention Description

Following the routine retrieval procedure at the donor hospital the liver will be flushed with cold preservation solution and prepared for cannulation. The donor organ is then placed on the OrganOx metra device and will be perfused with warmed solution. The OrganOx metra device containing the donor organ is then transported to the recipient transplant centre. The donor liver is then removed from the device and flushed with standard of care preservation solution. Alternatively, where more practical, the livers will be transported to the University of Alberta hospital with ≤ 6 hours of cold storage and then placed on the metra™ for ≥ 4 hours. Implantation and reperfusion of the liver proceed as per the usual practice of the recipient transplant centre.

Primary Outcome Measure Information:

Title

Graft survival rate

Description

Graft survival rate

Time Frame

Day 30

Secondary Outcome Measure Information:

Title

Patient survival rate

Description

Patient survival rate

Time Frame

Day 30

Title

Early Allograft Dysfunction (EAD) rate

Description

EAD rate

Time Frame

Up to Day 7

Title

Peak aspartate transaminase (AST) levels

Description

Peak AST levels in the blood

Time Frame

Up to Day 7

Title

Daily lactate levels

Description

Daily lactate levels in the blood

Time Frame

Up to Day 7

Title

Perfusate AST levels

Description

AST levels in perfusate blood

Time Frame

Day -1 and Day 0

Title

Perfusate alanine transaminase (ALT) levels

Description

ALT levels in perfusate blood

Time Frame

Day -1 and Day 0

Title

Perfusate bilirubin levels

Description

Bilirubin levels in perfusate blood

Time Frame

Day -1 and Day 0

Title

Perfusate lactate levels

Description

Lactate levels in perfusate blood

Time Frame

Day -1 and Day 0

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

James Shapiro, MD, PhD

Organizational Affiliation

University of Alberta

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Alberta

City

Edmonton

State/Province

Alberta

ZIP/Postal Code

T6G2C8

Country

Canada

12. IPD Sharing Statement

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Normothermic Liver Preservation Trial

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