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

• ClinicalTrials.gov Identifier: NCT02478151
• Recruitment Status: Enrolling by invitation
• First Posted: June 23, 2015
• Last Update Posted: April 12, 2022
• Sponsor: University Health Network, Toronto
• Information provided by (Responsible Party): University Health Network, Toronto

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
End-stage Liver Disease	Device: OrganOx Metra	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: 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
• Actual Study Start Date: July 2015
• Estimated Primary Completion Date: December 2022
• Estimated Study Completion Date: March 31, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Rates of primary graft non-function [ Time Frame: 3 months ]
2. Rates of re-transplantation [ Time Frame: 3 months ]
3. Rates of recipient death [ Time Frame: 3 months ]

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Canada, Ontario

Toronto General Hospital

Toronto, Ontario, Canada, M5G 2N2

Sponsors and Collaborators

University Health Network, Toronto

Investigators

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

More Information

• Responsible Party: University Health Network, Toronto
• ClinicalTrials.gov Identifier: NCT02478151
• Other Study ID Numbers: 14-8132-B
• First Posted: June 23, 2015
• Last Update Posted: April 12, 2022
• Last Verified: April 2022

Keywords provided by University Health Network, Toronto:

Deceased donor liver transplant; Normothermic machine perfusion

Additional relevant MeSH terms:

Liver Diseases; End Stage Liver Disease; Digestive System Diseases; Liver Failure; Hepatic Insufficiency