Extending Preservation and Assessment Time of Donor Lungs Using the Toronto EVLP System™ at a Dedicated EVLP Facility

A Phase 2, Multicenter, Open-label Study to Measure the Safety of Extending Preservation and Assessment Time of Donor Lungs Using Normothermic Ex Vivo Lung Perfusion and Ventilation (EVLP) as Administered by the SPONSOR Using the Toronto EVLP System™

This is a safety study to compare the safety of receiving a lung treated with the Toronto EVLP System™ by SPONSOR in SPONSOR's dedicated facility against standard lung transplantation.

Human donor lungs allocated to a participating study transplant center (Study Center) for a specific recipient and meeting study EVLP donor lung inclusion/exclusion criteria will be assessed by SPONSOR for inclusion into the study.

Upon retrieval, donor lung(s) will be packaged and transported on ice to the SPONSOR's EVLP facility in Silver Spring, Maryland, no differently than when lungs are recovered, packaged, and transported to any transplant center for implantation.

The EVLP procedure will be performed by Certified Ex Vivo Lung Specialists using the Toronto EVLP System™ for up to 6 hours, collecting and relaying lung function assessment data hourly or as requested by the Study Center transplant surgeon. Additionally, the Study Center surgeon will have the capability to evaluate lung function data and monitor the procedure remotely through a dedicated video link.

Upon acceptance of an EVLP donor lung by the Study Center, the single lung or lung block is cooled down by the Toronto EVLP System™ to 10 degrees C. Thereafter, perfusion and ventilation are stopped and the lung is prepared for hypothermic storage and transport to the accepting Study Center.

Subject Inclusion Criteria:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

• Male or female patients
• All patients, 18 years of age or older
• Patient already on or added to the active waiting list for a single or bilateral lung transplant
• Patient or patient's representative provides informed consent for participation in the study at the time of study commencement or time of listing for transplant
• Patient or patient's representative reconfirms informed consent for the study on the day of lung transplant

Subject Exclusion Criteria:

A subject who meets any of the following criteria will be excluded from participation:

• Patients listed for same-side lung re-transplantation
• Patients listed for multiple organ transplantation including lung and any other organ
• Patients listed for live donor lobar transplant
• Patients with HIV, active Hepatitis B/C, or Burkholderia Cepacia
• Patients not initially consented into the study prior to the time of lung transplant
• Patients in the ICU at the time of initial lung offer requiring mechanical ventilation, ECMO or other Extracorporeal life support (ECLS).

Donor Lung Inclusion Criteria for EVLP Assessment:

The donor lung must meet at least one of the following criteria to proceed with EVLP:

• At the time of the clinical evaluation, the donor PaO2/FiO2 < 300 mmHg
• Donor received ≥ 10 units of blood transfusions
• Donation after Cardiac Death (DCD) donor
• Expected cold ischemic time > 6 hours
• Donor age ≥ 55 years old
• Study Center Investigator requires additional assessment ex vivo and/or extended preservation time

Donor Lung Exclusion Criteria for EVLP Assessment:

The donor lung is excluded from EVLP if at least one of the following criteria have been met:

• The donor lung has confirmed pneumonia and/or persistent purulent secretions identified via bronchoscopy
• Non-persistent purulent secretions that do not clear by hour 3 on EVLP
• The donor lung has confirmed evidence of aspiration
• The donor lung has significant mechanical lung injury or trauma
• The cold ischemic time, starting at donor aortic cross clamp/ initial flush (CIT-1), required to transport the lung from the donor site to start of the EVLP procedure at SPONSOR's facility > 10 hours

EVLP Lung Inclusion Criteria for Transplantation:

The donor lung must meet each of the following conditions post-EVLP for transplant suitability consideration by the Study Center Investigator:

• PvO2/FiO2 ≥ 350 mmHg at final EVLP evaluation time period

• and < 15% increase from baseline value (defined as the first hour collection point) to final value of pulmonary vascular resistance (PVR)

• and < 15% increase from baseline value to final value of peak airway pressure (PawP)

• and < 15% decrease from baseline value to final value of static lung compliance (Cstat)

• and the total preservation time (TPT) does not exceed the following:

  • the initial CIT-1 time from donor to EVLP > 1 hour and ≤ 10 hours
  • the EVLP time > 3 hours and ≤ 6 hours
  • the second CIT-2 from EVLP cool down to beginning of recipient implantation must be > 1 hour and ≤ 6 hours for the first lung
  • the second CIT-2 from EVLP cool down to beginning of recipient implantation must be > 1 hour and ≤ 10 hours for the second lung

• and Study Center Investigator deems lung function suitable for intended subject

EVLP Lung Exclusion Criteria for Transplantation:

The donor lung is excluded from transplant inclusion if at least one of the following criteria have been met:

• PvO2/FiO2 < 350 mmHg at final EVLP evaluation time period

• or ≥ 15% increase from baseline value to final value of pulmonary vascular resistance (PVR)

• or ≥ 15% increase from baseline value to final value of peak airway pressure (PawP)

• or ≥ 15% decrease from baseline value to final value of static lung compliance (Cstat)

• or TPT exceeds any of the following conditions:

  • CIT-1 < 1 hour or > 10 hours
  • EVLP < 3 hours or > 6 hours
  • CIT-2 < 1 hour or > 6 hours for first lung or > 10 hours for second lung

• or Study Center investigator deems lung function unsuitable for intended subject