Using Ex-vivo Normothermic Machine Perfusion With the Organox Metra™ Device to Store Human Livers for Transplantation

A Single Centre Study of the Feasibility and Safety of Using Ex-vivo Normothermic Machine Perfusion With the Organox Metra™ Device to Store Human Livers for Transplantation

This trial will examine the safety and feasibility of using the OrganOx Metra device to transport and store donor livers under normothermic conditions prior to transplantation. Participants will be followed for 3 months following transplantation and their outcomes recorded.

Study Overview

• Status: Enrolling by invitation
• Conditions: End-stage Liver Disease
• Intervention / Treatment: Device: OrganOx Metra

Detailed Description

Liver transplantation is a life-saving procedure but its success has been limited by a shortage of suitable donor organs. Much emphasis is now placed on optimising the condition of those organs that are available, to enable more higher risk organs to be transplanted safely. An effective means of pre-transplant viability assessment would not only allow greater use of higher risk donors but also minimise the risk of primary non-function by identifying and excluding non-viable organs before subjecting a patient to the risk of surgery. Organ storage under normothermic perfusion conditions enables organ function to be evaluated prior to transplantation and further has been shown to prevent organ injury which is sustained during standard cold storage. This trial will examine the safety and feasibility of using the OrganOx Metra device to transport and store donor livers under normothermic conditions prior to transplantation. This study will evaluate liver function post-transplantation using standard clinical parameters. Participants will be followed for 3 months following transplantation and their outcomes recorded. Participants will undergo no other study procedures. Feasibility will be measured using the ratio of actual / eligible candidate donors recruited to the study and will also encompass logistical issues with respect to transportation, and ease of use. Safety will be assessed by rates of device failures resulting in organ discard, primary graft non-function, re-transplantation, and recipient death.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2N2
      • Toronto General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients (18 years or more)
• Active on the waiting list for liver transplantation
• Able to give informed consent

Exclusion Criteria:

• Age less than 18 years
• Acute/fulminant liver failure
• Transplantation of more than one organ (e.g. liver and kidney)
• Refusal of informed consent
• Unable to give informed consent
• Re-transplantation Diagnosis of Hepatopulmonary Syndrome

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OrganOx Metra; OrganOx Metra Device	Device: OrganOx Metra; Normothermic machine perfusion (NMP) Metra device

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rates of primary graft non-function	3 months
Rates of re-transplantation	3 months
Rates of recipient death	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of device failures resulting in organ discard		3 months
Recruitment rates to the study	Measured by the ratio of actual / eligible candidate donors recruited to the study	3 months
Ischemia- reperfusion injury associated with organ storage	Assessed by a post-perfusion biopsy	7 days
Ischemia- reperfusion injury associated with organ storage	Assessed by measuring the peak serum aspartate transaminase level (AST) within 7 days post-transplant	7 days
The function of liver grafts stored with the Metra™ device	Measured by bilirubin, alkaline phosphatase, AST and INR levels at days 1-7 post-transplant. The measure is a composite.	3 months
The function of liver grafts stored with the Metra™ device	Measured by bilirubin, alkaline phosphatase, AST and INR levels at day 30 post-transplant. The measure is a composite.	3 months
The function of liver grafts stored with the Metra™ device	Measured by bilirubin, alkaline phosphatase, AST and INR levels at month 3 post-transplant. The measure is a composite.	3 months
The function of liver grafts stored with the Metra™ device	Measured by Lactate at days 1-3 post-transplant. The measure is a composite.	3 months
The ability of perfusion parameters to predict clinical outcomes following transplantation	Perfusion flows and pressures will be studied to determine their correlation with graft injury and function. The measure is a composite.	3 months
The ability of perfusion parameters to predict clinical outcomes following transplantation	Perfusate blood gas parameters will be studied to determine their correlation with graft injury and function. The measure is a composite.	3 months
The ability of perfusion parameters to predict clinical outcomes following transplantation	Bile production will be studied to determine their correlation with graft injury and function	3 months

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Investigators: Principal Investigator: David R Grant, MD, University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2015
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): March 31, 2023

Study Registration Dates

• First Submitted: December 1, 2014
• First Submitted That Met QC Criteria: June 17, 2015
• First Posted (Estimate): June 23, 2015

Study Record Updates

• Last Update Posted (Actual): April 12, 2022
• Last Update Submitted That Met QC Criteria: April 8, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Normothermic machine perfusion; Deceased donor liver transplant
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Failure; Hepatic Insufficiency; Liver Diseases; End Stage Liver Disease
• Other Study ID Numbers: 14-8132-B