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™
Phase: NA
Conditions: Lung Disease
Sponsor: Lung Bioengineering Inc.

Clinical Trial Protocol: PXUS 14-001 
Study Title: 
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 
Study Number: 
PXUS 14-001 
Study Type: 
Traditional Feasibility 
Product Name: 
Toronto EVLP System 
IDE Number: 
G140021 
Indication: 
Normothermic ex vivo ventilation and perfusion of lungs for 
transplantation 
Investigators: 
Multicenter 
Sponsor: 
Lung Bioengineering Inc. 
Medical Director 
Jordan Shin, MD 
Sponsor Contact: 
Michael Roberts 
Date 
Original Protocol (v1.0) 
31 January 2014 
Amendment 1 (v2.0) 
04 May 2014 
Amendment 2 (v2.2) 
22 May 2014 
Amendment 3 (v2.4) 
24 July 2014 
Amendment 4 (v2.5) 
05 March 2015 
Amendment 5 (v5.0) 
02 May 2016 
Amendment 6 (v6.0) 
03 November 2017 
Statement of Compliance 
The study will be conducted in accordance with the International Conference on Harmonisation (ICH) 
guidelines for Good Clinical Practice (GCP) (ICH E6), the Code of Federal Regulations (CFR) on the 
Protection of Human Subjects (21 CFR Part 50), the Investigational Device Exemption (IDE) requirements 
under 21 CFR 812, and the SPONSOR Clinical Terms of Award. All personnel involved in the conduct of this 
study have completed human subjects protection training. 
Confidentiality Statement 
The concepts and information contained herein are confidential and proprietary and shall not be disclosed in 
whole or part without the express written consent of Lung Bioengineering, Inc. 
NCT Number NCT02234128

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List of Sponsor Contacts 
Study Sponsor Medical 
Director: 
Jordan Shin, MD, PhD 
1040 Spring Street 
Silver Spring, MD 20910 
Phone: 301.578.1438 
Email: jshin@lungbiotechnology.com  
 
Sponsor Contact: 
Michael Roberts 
Director, Regulatory Affairs 
Lung Bioengineering, Inc. 
1015 Spring Street 
Silver Spring, MD 20910 
Phone:  240.650.2261 
Email:  mroberts@lungbioengineering.com 
 
EVLP Facility:  
Lung Bioengineering - 1 (“LB-1”) EVLP Facility 
1015 Spring Street 
Silver Spring, MD 20910 
Phone:  844.367.3857 
 
 
See Appendix 2 for other key study personnel contacts. 
 
 
 

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Clinical Trial Protocol:  PXUS 14-001, v6.0 
 
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SYNOPSIS 
Sponsor: 
 Lung Bioengineering Inc. 
Description of Intervention: 
Normothermic EVLP for extended preservation, assessment and transplantation of donor lungs.  
Study Title: 
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 
Study Number: 
PXUS 14-001 
Study Type:  Traditional Feasibility 
Primary Objective(s):  
The primary objective of this study is to evaluate the short-term safety of subjects receiving a lung transplant, 
where the lung(s) was perfused by the Sponsor using the Toronto EVLP System (TES). Assessment of Primary 
Graft Dysfunction (PGD) Grade 3 at 72 hours post-transplant (T72) and 30-day mortality will represent the 
outcome measures, and the primary endpoints are the following two measures: 
• The proportion of recipients with PGD Grade 3 (PGD3) assessed at T72 
• 30-day mortality post-transplant. 
 
The above information will also be collected on patients enrolled in a contemporaneous control group to provide 
context for EVLP results and to inform control measures for future research. 
Secondary Objective(s): 
The secondary objectives of this study are to evaluate the short-term safety of subjects receiving a lung transplant 
where the lung(s) has been perfused via the TES performed by the Sponsor by assessment of the following: 
• PGD Score (Grades 0-3) measured at 0, 24, 48 and 72 hours post-transplant 
• Time to first extubation 
• Intensive care unit (ICU) length of stay (LOS), measured as total number of days post-transplant in the ICU 
until first hospital discharge, inclusive of ICU readmissions during that hospitalization.  
• Hospital LOS measured as total number of days in the hospital prior to discharge post-transplant 
• Total preservation time (TPT), defined as the elapsed time between first allograft lung removal from cold 
storage time prior to transplant in the recipient and the donor aortic cross clamp time at procurement 
• Assessment of the overall safety of TES lung transplants during subject's participation in the study, as 
reported through adverse events (AEs). 
 
The above information will also be collected on patients enrolled in a contemporaneous control group to provide 
context for EVLP results and to inform control measures for future research. 
 
Study Design: 
This is a Phase 2, unblinded, non-randomized, traditional feasibility study to evaluate the safety of subjects 
undergoing lung transplant using lungs after EVLP, and performed exclusively by the Sponsor at the Sponsor’s 
facility using the Toronto EVLP System (TES).  
 
Once the donor lung is accepted following EVLP, the eligible recipient, who has provided written informed 
consent, and receives the lung transplant, is enrolled into the study. Patients who consent for the current EVLP 

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study (PXUS 14-001) but receive a conventional (i.e., non-EVLP) lung transplant will be considered for a 
contemporaneous control group matched to the EVLP treatment group (66 subjects each). This matching will take 
place on a patient-by-patient basis and only after an EVLP subject has been enrolled at that Study Center. 
Investigators and their team will be notified by the Sponsor on a real-time basis of the specific matching criteria 
required for a control subject as EVLP subjects are enrolled. In order to be considered for eligibility, the control 
patient must “match” a priori to at least one EVLP subject who has already been enrolled at that Study Center 
based on the following criteria:  SLT versus DLT and Lung Allocation Score Disease Diagnosis Group 
(LASDDG). 
The post-intervention phase of the study will then be split into two phases:  1) the Analysis Phase, which includes 
follow-up within one year post-intervention and 2) Long-term Follow-up, which will capture outcome data 
annually from 1-year post-intervention until 5-years post intervention. Although the study will continue after one 
year, the database will be locked for analyses of endpoints after the last subject has his/her study visit at 1 Year. 
The Long-term Follow-up data will be summarized when the study has completed in support of long-term 
evaluation. 
Analysis Phase 
Following transplantation, subjects will be admitted to the ICU, and the initial PaO2 and PGD Score will be 
recorded. The subject’s PGD Score will be recorded every 24 hrs for the next 72 hrs. The ICU discharge date will 
be documented. Study visits will occur 30 days (±5), 90 days (±10), 6 months (±2 weeks), and 1 year (±4 weeks) 
post-transplant. Study assessments will be performed as outlined in the Schedule of Events (Appendix 1, Table 
3). 
 
Long-term Follow-up 
Although the database will be locked and analyses of endpoints performed after the last subject has his/her study 
visit at 1 Year, the Sponsor will continue to collect specified outcome parameters that are required to be reported 
by transplant centers to OPTN/ United Network for Organ Sharing (UNOS). Collection will be annually for 5-
years post-intervention; outcome collection is outlined in the Schedule of Events (Appendix 1, Table 4). 
 
Study Population:  
The study will be open to all eligible male and female patients, aged 18 years or older, with end-stage lung 
disease listed for lung transplantation at a participating Study Center. These participants may not be receiving 
mechanical ventilation, ECMO or ECLS, at the time of initial lung offer prior to EVLP. 
 
A sample size of 132 subjects, receiving either SLT or DLT, is planned for this study, where 66 subjects receive 
donor lung(s) after EVLP (EVLP Group) and 66 subjects are in a contemporaneous control group (Control 
Group). No more than two-thirds of the subjects who are enrolled (44 subjects per group) will have received a 
single-lung transplant (SLT) or double-lung transplant (DLT). 
 
Subject (recipient) Inclusion Criteria 
 
Each patient must meet the following criteria to be enrolled in this study: 
1. Male or female patients. 
2. All patients, 18 years of age or older. 
3. Patient already on or added to the active waiting list for a single or bilateral lung transplant. 
4. Patient or patient’s representative provides informed consent for participation in the study prior to 
participating in any study-related assessments or procedures. 
5. Patient or patient’s representative reconfirms informed consent for the study on the day of lung transplant if 
initial consent is > 24 hrs. 
6. Patient matches with and undergoes a transplant with a Donor Lung. 
 
Subject (recipient) Exclusion Criteria 

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Patients who meet any of the following criteria will be excluded from the study: 
1. Patients listed for same-side lung re-transplantation. 
2. Patients listed for multiple organ transplantation including lung and any other organ. 
3. Patients listed for live donor lobar transplant. 
4. Patients positive for human immunodeficiency virus, active Hepatitis B or C, or Burkholderia cepacia 
infection.  
5. Patients in the ICU at the time of the initial lung offer requiring ventilation, ECMO or other extracorporeal 
life support (ECLS). [Note: The decision to place the recipient on ECMO or other ECLS for post-transplant 
prophylaxis at time of or immediately prior to transplant is not considered an exclusion] 
6. Patient receives a conventional (non-EVLP) lung transplant but does NOT match to an EVLP subject based 
on the criteria for control matching outlined above. 
 
Study Intervention:  
EVLP is a novel technology that allows extended assessment of lungs whose suitability for transplantation is 
initially uncertain. By protocol design, EVLP-treated lungs undergo a longer period of total preservation, 
including an initial cold ischemic time (CIT-1), a period of normothermic EVLP assessment, and a final round of 
CIT (CIT-2). The extended donor lung preservation time may enable better logistical coordination of the recipient 
and donor hospital transplant teams. 
 
Upon retrieval, donor lungs will be packaged and transported to the Sponsor’s EVLP facility. The EVLP 
procedure will be performed by specifically-trained Ex Vivo Lung Specialists under remote video supervision by 
one of the Sponsor’s Expert Medical Consultants. The Sponsor will perfuse the lung using the TES for up to 6 
hrs, collecting and relaying lung function assessment data hourly, or as requested by the Study Center 
Investigator/team. Additionally, the Study Center surgeon will have access to remote monitoring capabilities at 
the Sponsor EVLP Center for evaluating lung function data and monitoring the procedure through a dedicated 
audio/video link. 
 
The Study Center Investigator/team, together with the Sponsor’s Expert Medical Consultants, will monitor the 
donor lung(s) for EVLP inclusion criteria and collaborate to determine the timing of EVLP termination. However, 
final decisions reside with the Study Center Investigator/team. Upon acceptance of an EVLP donor lung by the 
Study Center, the single lung or lung block is cooled according to TES methodology to 10°C, and perfusion and 
ventilation are stopped. This point marks the start of CIT-2. The end of CIT-2 is defined as the time the organ is 
removed from cold storage to begin the implantation phase of the transplantation procedure. The time between 
the organ’s removal from cold storage to reperfusion in the recipient is known as warm ischemic time (WIT). 
Total preservation time for the first lung transplanted from donor lung retrieval to the end of CIT-2 must not be 
greater than a combined 22 hrs and individual phase limits as follows:  
(≤ 10 hrs CIT-1) + (3 - 6 hrs EVLP) + (≤ 6 hrs CIT-2) ≤ 22 hrs 
Total preservation time for the second lung transplanted from donor lung retrieval to the end of CIT-2 must not be 
greater than a combined 26 hrs and individual phase limits as follows:  
(≤ 10 hrs CIT-1) + (3 - 6 hrs EVLP) + (≤ 10 hrs CIT-2) ≤ 26 hrs 
Duration of Subject Participation:  
Data will be collected from the organ donor, EVLP procedure (if applicable), and each subject from the time of 
lung transplantation and up to one year post-transplant for the Analysis Phase. In addition, outcome data will be 
collected annually up to 5 years post-transplant. 
 
The study duration for the Analysis Phase (from first patient, first visit [FPFV] to last patient, last visit [LPLV] 
prior to database lock) is expected to be 3 years. The estimated time to complete enrollment is approximately 24 
months. 
 

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Safety Assessments: 
Medical History and concomitant medications will be collected for each subject. Physical examinations, including 
specific tests to assess lung function, will be performed at Baseline, Day 30, and Month 6. Vital signs will be 
assessed at each study visit.  
 
The subject’s PGD Score is to be determined by the Investigator at Baseline (Day 0) after transplantation and 
upon admission to the ICU, as well as 24, 48, and 72 hrs post-transplant. Subject arterial blood gases must be 
determined by the Investigator, in order to calculate PGD grade. Graft survival will be evaluated by the 
Investigator (or his/her designee) at Day 30, Day 90, Month 6, Year 1 post-transplant, and premature termination 
(if applicable). 
 
Subject survival, measured as living or dead, will be recorded Day 30, Day 90, Month 6, and Year 1 
post-transplant. If the subject expires within first year post-transplant, the date of death and primary cause of 
death will be collected. 
 
Evaluation of Bronchiolitis Obliterans Syndrome (BOS), physical capacity, and work status will be conducted at 
Day 90, Month 6, Year 1 post-transplant, and premature termination (if applicable). 
 
In addition, after completion of the Analysis Phase, survival will be recorded annually until 5-year post-
transplant. If survival is confirmed, then FEV1 and oxygen at rest will be collected annually, along with BOS, 
physical capacity, work status, graft survival, by the Sponsor for the Long-term Follow-up Phase (Year 2, 3, 4, 
and 5). 
Statistical Methods:  
Statistical analysis will be performed primarily on data collected during the Analysis Phase (1 year 
post-intervention). The database will be locked for analysis of endpoints after the last subject completes his/her 
study visit at Year 1, and all queries have been resolved.  
 
All subjects are included in the analyses to the extent data are available. 
 
The primary endpoint of PGD3 T72 will be calculated from PGD T72 as follows:  PGD T72 = {0, 1, & 2} will be 
coded to PGD3 T72 = 0 and PGD T72 = {3} will be coded to PGD3 T72 = 1. The primary analysis will be 
descriptive as the proportion of subjects with PGD3 T72 by Transplant Group (EVLP and Control). A one-sided 
95% CI will be calculated around the proportion. A two-sided 95% CI will also be calculated. 
 
The primary endpoint of 30-Day mortality will be derived as follows:  Living at Day 30 will be coded to 0, and 
Dead before or on Day 30 will be coded to 1. The primary analysis will be descriptive as the proportion of 
subjects with 30-Day mortality, summarized by Transplant Group. A one-sided 95% CI will be calculated around 
the proportion. A two-sided 95% CI will also be calculated. 
 
All secondary endpoints will be presented using descriptive statistics along with two sided 95% CIs by Transplant 
Group. Other supportive endpoints may be provided to supplement the secondary analyses.  
Results may be displayed graphically. There will be no inferential testing conducted. 
 
All exploratory endpoints will be presented using descriptive statistics along with two sided 95% CIs by 
Transplant Group. There will be no inferential testing conducted.  
 
A contemporaneous Control group will be entered into this study. This Control group will provide context of the 
EVLP results and estimation of Control group parameters for design of future studies. All analyses of the Control 
group will be descriptive and no formal statistical comparison will be made between the EVLP and Control 
groups.  
Date of Original Approved Protocol:  31 January 2014 
Date of Most Recent Protocol Amendment:  02 May 2015 
Prepared in: Microsoft Word 2010 
 

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Table of Contents 
List of Sponsor Contacts ...............................................................................................................2 
Synopsis ...........................................................................................................................................3 
List of In-Text Tables ..................................................................................................................11 
List of In-Text Figures .................................................................................................................11 
List of Appendices ........................................................................................................................11 
List of Abbreviations and Definitions of Terms ........................................................................12 
1 
Introduction ..........................................................................................................................15 
1.1 
Lung Transplantation and Ex Vivo Lung Perfusion Background ...............................15 
1.1.1 Toronto Clinical Experience:  Toronto EVLP System ....................................16 
1.1.2 Sponsor Clinical Experience:  Toronto EVLP System ....................................17 
1.1.3 Report of Prior Investigations ..........................................................................17 
1.2 
Potential Risks and Benefits ........................................................................................17 
1.2.1 Potential Risks .................................................................................................18 
1.2.2 Potential Benefits .............................................................................................18 
1.2.2.1 
Increased Donor Lung Utilization ..........................................................18 
1.2.2.2 
Shorter Recipient Waiting Times ...........................................................19 
2 
Study Objectives ...................................................................................................................20 
2.1 
Primary Objective(s) ....................................................................................................20 
2.2 
Secondary Objective(s) ................................................................................................20 
2.3 
Other Objective(s) ........................................................................................................21 
3 
Investigational Plan .............................................................................................................22 
3.1 
Overall Study Design and Plan ....................................................................................22 
3.1.1 Lung Collection and EVLP Procedure ............................................................24 
3.1.1.1 
Lung Referral ..........................................................................................24 
3.1.1.2 
Lung Retrieval ........................................................................................25 
3.1.1.3 
Transfer of EVLP Data to the Study Center ...........................................26 
3.1.1.4 
Acceptance of EVLP Lung for Transplant .............................................27 
3.1.1.5 
Request for Reallocation of Lungs After EVLP .....................................28 
3.2 
Rationale for Study Design and Control Group ...........................................................29 
3.3 
Study Duration and Dates ............................................................................................30 
4 
Study Population Selection ..................................................................................................31 
4.1 
Study Population ..........................................................................................................31 
4.2 
Inclusion Criteria .........................................................................................................31 
4.3 
Exclusion Criteria ........................................................................................................31 
4.4 
Strategies for Recruitment and Retention ....................................................................32 
5 
Study Intervention ...............................................................................................................33 
5.1 
Description of Intervention ..........................................................................................33 
5.2 
Lung Transplantation ...................................................................................................34 
5.2.1 Donor Lung Inclusion Criteria (Pre-EVLP) ....................................................34 
5.2.2 Donor Lung Exclusion Criteria (Pre-EVLP) ...................................................35 
5.2.3 Donor Lung Criteria Post-EVLP Assessment..................................................35 
5.2.3.1 
Donor Lung Inclusion Criteria (Post-EVLP) ..........................................35 

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5.3 
Method of Assigning Patients to Intervention .............................................................36 
5.4 
Blinding........................................................................................................................37 
5.5 
Restrictions ..................................................................................................................37 
5.6 
Intervention and Study Procedure Compliance ...........................................................37 
5.7 
Packaging and Labeling ...............................................................................................37 
5.8 
Storage and Accountability ..........................................................................................37 
5.8.1 STEEN Solution...............................................................................................38 
5.8.2 EVLP Disposables ...........................................................................................38 
5.9 
Investigational Product Retention at Study Center ......................................................38 
6 
Study Procedures .................................................................................................................39 
6.1 
Donor and Donor Lung Information ............................................................................39 
6.2 
Informed Consent.........................................................................................................39 
6.3 
Medical History ...........................................................................................................39 
6.4 
Concomitant Medications ............................................................................................40 
6.5 
Physical Examination...................................................................................................40 
6.6 
Vital Signs ....................................................................................................................40 
6.7 
Primary Graft Dysfunction Score ................................................................................40 
6.8 
Survival ........................................................................................................................41 
6.9 
Bronchiolitis Obliterans Syndrome Grade ...................................................................41 
6.10 Physical Capacity .........................................................................................................42 
6.11 Work Status ..................................................................................................................42 
6.12 Clinical Laboratory Tests .............................................................................................43 
6.12.1 Laboratory Parameters .....................................................................................43 
6.12.2 Sample Collection, Storage, and Shipping ......................................................43 
6.13 Safety Reporting ..........................................................................................................43 
6.13.1 Definitions........................................................................................................43 
6.13.2 Performing Adverse Events Assessments or Recording of Adverse Events ...47 
6.13.3 Timing of Adverse Event Collection ...............................................................47 
6.13.4 Severity ............................................................................................................47 
6.13.5 Relationship .....................................................................................................48 
6.13.6 Expectedness ....................................................................................................48 
6.13.7 Reporting Procedures .......................................................................................48 
6.13.7.1 Reporting Serious Adverse Events .........................................................48 
6.13.7.2 Reporting Procedure for Serious Adverse Events ..................................49 
6.13.8 Initial Safety Review........................................................................................49 
6.13.9 Halting Rules ...................................................................................................50 
6.14 Removal of Subjects from the Study ...........................................................................50 
6.15 Premature Termination or Suspension of the Study ....................................................50 
6.16 Appropriateness of Measurements ...............................................................................51 
7 
Study Activities .....................................................................................................................52 
7.1 
Screening Visit (Days –365 to -1 [-24 hours]).............................................................52 
7.2 
Intervention ..................................................................................................................52 
7.2.1 Lung Assessment, Recipient Baseline, and Lung Transplant (Day 0) ............52 
7.2.1.1 
Donor Lung Screening (Day 0, within 24 hours prior to transplant) ......52 
7.2.1.2 
Recipient Screening (Day 0, within 24 hours before transplant) ............52 

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7.2.1.3 
Donor Lung EVLP Evaluation (at completion) ......................................53 
7.2.1.4 
Lung Transplantation (Day 0).................................................................53 
7.3 
Post-intervention Period; Analysis Phase (Day 1 to 1 Year Post-Transplant).............53 
7.3.1 Visit 1 Procedures (24 Hours post-transplant) .................................................53 
7.3.2 Visit 2 Procedures (48 Hours post-transplant) .................................................54 
7.3.3 Visit 3 Procedures (72 Hours post-transplant) .................................................54 
7.3.4 Visit 4 Procedures (Day 30 post-transplant) ....................................................54 
7.3.5 Visit 5 Procedures (Day 90 post-transplant) ....................................................54 
7.3.6 Visit 6 Procedures (Month 6 post-transplant) ..................................................55 
7.3.7 Visit 7 Procedures/ Final Visit (1 year post-transplant)...................................55 
7.4 
Post-intervention Period; Long-term Follow-up Phase (1 to 5 Years Post-
Transplant) ...................................................................................................................55 
7.5 
Early Termination Procedures .....................................................................................56 
7.6 
Unscheduled Visits ......................................................................................................56 
8 
Quality Control and Assurance ..........................................................................................57 
8.1 
Sponsor’s Quality Process ...........................................................................................57 
8.2 
Training for Study Interventionalists ...........................................................................57 
8.2.1 Transplant Center Research Personnel ............................................................57 
8.2.2 Lung Recovery Surgeons .................................................................................58 
8.2.3 Lung Transplant Surgeons ...............................................................................58 
8.2.4 EVLP Specialists .............................................................................................58 
9 
Planned Statistical Methods ................................................................................................60 
9.1 
General Considerations ................................................................................................60 
9.2 
Determination of Sample Size .....................................................................................60 
9.3 
Analysis Populations ....................................................................................................61 
9.4 
Demographics and Baseline Characteristics ................................................................61 
9.5 
Primary Endpoint(s) .....................................................................................................61 
9.5.1 Primary Graft Dysfunction Grade 3 at 72 hours Post-transplant .....................61 
9.5.2 30-Day Mortality .............................................................................................62 
9.6 
Secondary Endpoint(s) .................................................................................................62 
9.7 
Exploratory Endpoints .................................................................................................62 
9.8 
Missing Data ................................................................................................................63 
9.9 
Other Safety Assessments ............................................................................................64 
9.9.1 Adverse Events ................................................................................................64 
9.9.2 Physical Examination and Vital Signs .............................................................64 
9.9.3 Laboratory Data ...............................................................................................64 
9.10 Interim Analysis ...........................................................................................................64 
10 Administrative Considerations ...........................................................................................65 
10.1 Investigators and Study Administrative Structure .......................................................65 
10.2 Institutional Review Board (IRB) or Independent Ethics Committee (IEC) 
Approval ......................................................................................................................65 
10.3 Ethical Conduct of the Study .......................................................................................65 
10.4 Authorization and Consent ..........................................................................................66 
10.4.1 Donor Next of Kin Authorization ....................................................................66 
10.4.2 Subject (Recipient) Consent ............................................................................66 

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10.5 Subject Confidentiality ................................................................................................67 
10.6 Study Monitoring .........................................................................................................67 
10.6.1 Access to Centers .............................................................................................68 
10.6.2 Summary of Monitoring Procedures & Responsibilities .................................68 
10.6.3 Routine Monitoring ..........................................................................................68 
10.7 Case Report Forms and Study Records .......................................................................69 
10.8 Independent Medical Monitor......................................................................................70 
10.9 Protocol Violations/Deviations ....................................................................................70 
10.10 Access to Source Documentation ................................................................................71 
10.11 Data Generation and Analysis .....................................................................................72 
10.11.1 
Data Management Responsibilities ........................................................72 
10.11.2 
Data Capture Methods ............................................................................72 
10.11.2.1 Donor Data ..............................................................................................72 
10.11.2.2 EVLP Data ..............................................................................................72 
10.11.2.3 Subject (Recipient Data) .........................................................................72 
10.12 Retention of Data .........................................................................................................73 
10.12.1 
Retention of Study Documents ...............................................................73 
10.12.2 
Future Use of Stored Specimens and Other Identifiable Data ................73 
10.13 Financial Disclosure.....................................................................................................73 
10.14 Publication and Disclosure Policy ...............................................................................73 
10.15 Study Closure ...............................................................................................................74 
11 Reference List .......................................................................................................................75 
Non-Fluid Path Hardware ......................................................................................................82 
Single-Use Fluid Path Disposables ........................................................................................83 
 
 
 

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LIST OF IN-TEXT TABLES 
Table 1.  Single-use Device Storage and Stability Conditions ...................................................38 
Table 2.  Primary Graft Dysfunction Grading ............................................................................41 
Table 3.  Schedule of Events Within 1 Year Post-intervention ..................................................77 
Table 4.  Schedule of Events:  Long-term Follow-up .................................................................78 
Table 5.  Composition and Properties of STEEN Solution.........................................................86 
Table 6.  Medications Added to STEEN Solution during Prime ................................................87 
 
LIST OF IN-TEXT FIGURES 
Figure 1.  
2012 US Donor Lung Utilization .....................................................................19 
Figure 2.  
Lung Retrieval Process to Determine Acceptance or Rejection for 
Transplant 
23 
Figure 3.  
System Components of the Toronto EVLP System .........................................33 
Figure 4.  
Schematic of Perfusion Circuit ........................................................................85 
 
LIST OF APPENDICES 
Appendix 1 
Schedule of Events ...........................................................................................77 
Appendix 2 
Key Study Personnel Contacts .........................................................................79 
Appendix 3 
Risk and Risk Mitigation of EVLP ..................................................................81 
Appendix 4 
System Components of the Toronto EVLP System .........................................82 
Appendix 5 
Sponsor Signatures...........................................................................................88 
Appendix 6 
Investigator’s Signature ...................................................................................89 
 
 

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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
ABG 
Arterial Blood Gas 
ADL 
Activities of daily living 
AE 
Adverse Event/Adverse Effect 
ACIN 
AOPO Credentials Information Network 
ADL 
Activities of daily living 
BOS 
Bronchiolitis Obliterans Syndrome 
CI 
Confidence interval 
CIT 
Cold ischemic time 
CFR 
Code of Federal Regulations 
COP 
Colloid-osmotic pressure 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
Cstat 
Static compliance 
CMX 
Case Management Exchange 
DBD 
Donation after Brain Death 
DCD 
Donation after Circulatory (Cardiac) Death 
DLT 
Double-lung Transplant 
ECLS 
Extracorporeal life support  
ECMO 
Extracorporeal Membrane Oxygenation 
EVLP 
Ex Vivo Lung Perfusion 
FDA 
Food and Drug Administration 
FEV1 
Forced expiratory volume in one second 
FiO2 
Fraction of inspired oxygen 
FPFV 
First patient, first visit 
GCP 
Good Clinical Practice 
GERD 
Gastroesophageal Reflux Disease 
HDE 
Humanitarian Device Exemption 
HIV 
Human immunodeficiency virus 
HSA 
Human serum albumin 
IBW 
Ideal Body Weight 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
ICMJE 
International Committee of Medical Journal Editors 

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ICU 
Intensive Care Unit 
ID 
Identification 
IDE 
Investigational Device Exemption 
IRB 
Institutional Review Board 
ISHLT 
International Society for Heart and Lung Transplantation 
LAP 
Left atrial pressure 
LASDDG 
Lung Allocation Score Disease Diagnosis Group 
LAS 
Lung Allocation Score 
LOCF 
Last observation carried forward 
LOS 
Length of stay 
LPLV 
Last patient, last visit 
mAwP 
Mean airway pressure 
MedDRA 
Medical Dictionary for Regulatory Activities 
Min 
Minutes 
N 
Number (typically refers to subjects) 
OPO 
Organ Procurement Organization 
OPTN 
Organ Procurement and Transplantation Network 
PAF 
Pulmonary arterial flow 
PaO2 
Partial pressure of oxygen in arterial blood 
PAP 
Pulmonary arterial pressure 
PawP 
Peak airway pressure 
PCO2 
Carbon dioxide partial pressure 
platAwP 
Plateau airway pressure 
PO2 
Oxygen partial pressure 
PvO2 
Partial pressure of oxygen in venous blood 
PVR 
Pulmonary Vascular Resistance 
PGD 
Primary Graft Dysfunction 
PGD3 
Primary Graft Dysfunction Grade 3 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event/Serious Adverse Effect 
SAP 
Statistical Analysis Plan 
SCD 
Standard Criteria Donor 
SCP 
Stöckert Centrifugal Pump 
SCPC 
Stöckert Centrifugal Pump Console 

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SD 
Standard deviation 
SLT 
Single-lung Transplant 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
SRTR 
Scientific Registry of Transplant Recipients 
T72 
72 hours post-transplant 
TES 
Toronto EVLP System 
TGH 
Toronto General Hospital 
TPT 
Total Preservation Time 
UADE 
Unanticipated Adverse Device Effect 
UNK 
Unknown 
UNOS 
United Network for Organ Sharing 
US 
United States 
WIT 
Warm ischemic time 
 

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1 
INTRODUCTION 
1.1 
Lung Transplantation and Ex Vivo Lung Perfusion Background 
Lung transplantation is often the only available therapy for patients suffering end-stage lung 
disease, and the number of patients who can appropriately benefit by lung transplantation far 
exceeds the donor lungs available. Importantly, the mismatch between demand for transplantable 
lungs and the supply of available organs is substantially higher than other solid organs, with the 
lungs being used for transplantation among only 20% of brain dead donors who are used for 
transplanting other solid organs.[Munshi 2013; SRTR 2011] The described reason for declining 
the majority of the available donor lungs by transplant programs has been listed as being due to 
“Poor Organ Function” and “No Recipient Found.”[SRTR 2011]  
It has been suggested that over 40% of the lungs rejected by the United States (US) lung 
transplant programs could have been transplanted if better information was available at the time 
of procurement, or additional time was available to meet the complex logistical demands of 
procurement and transplantation.[Ware 2002] Introduction of technologies, such as Ex vivo Lung 
Perfusion (EVLP), might facilitate more in-depth assessment of lung condition, thereby enabling 
transplant programs to use lungs for transplant that are currently discarded.  
Evidence linking the pathophysiology of brain death to early organ dysfunction after 
transplantation continues to accumulate and seems especially relevant when considering donor 
lungs. Lung injury begins soon after a catastrophic event associated with massive brain injury 
with a massive sympathetic outflow, then an associated release of inflammatory cytokines. These 
mediators of inflammation then remain within the donor lung(s), ultimately being released into 
the recipient circulation after transplantation, potentially reflecting an important etiology of early 
graft dysfunction.[Fisher 2001]   
Also, cerebral edema leading to brain stem herniation effects irreversible cessation of brain 
function (e.g., death). This is associated with complete loss of autonomic tone with massive 
vasodilation and hypotension. This is generally treated by administration of large volumes of 
fluids to maintain adequate circulation and end organ perfusion.[Power 1995; Hayek 1990; 
Tropmann 2008] Together with neurogenic pulmonary edema, another consequence of brain 
death, the overall clinical picture can obscure assessment of pulmonary function.[Avlonitis 2007]  
Steen et al., described an ex vivo perfusion technique in 2001, seeking to better evaluate lungs 
from non-heart beating donors (Donation after Circulatory Death [DCD]).[Steen 2001]. This 
method demonstrated the proof-of-concept evidence that donor lungs could be assessed ex vivo, 
then successfully transplanted, initially into large animals, and later into humans. 
Keshavjee’s group in Toronto extended those observations, applying a modified, normothermic 
(37°C) EVLP technique,  using an acellular, albumin-based solution (STEEN Solution™), lower 
perfusion flow rates (40% of normal cardiac output), and a protective ventilation strategy to 
permit longer perfusion with excellent physiologic function after transplantation.[Cypel 2008a; 
Cypel 2008b; Cypel 2009] The method, called the Toronto EVLP System (TES) was 
demonstrated as technically feasible and safe, permitting perfusion of donor lungs for up to 

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6 hours (hrs) in clinical practice (and 18 hrs in the research setting). By permitting a longer 
preservation period, TES extended the time available for assessment of donor lungs under 
near-physiologic conditions.  
1.1.1 
Toronto Clinical Experience:  Toronto EVLP System 
Human studies were started during 2008 in Toronto with the Human Ex Vivo Lung Perfusion 
(HELP) trial. HELP was a prospective, non-randomized, single-center study of outcomes of 
lungs not meeting conventional lung donor criteria, receiving 4 hrs of extended preservation and 
assessment using EVLP. The EVLP treated lungs were compared to all other lungs transplanted 
(Control) during the same time period. In addition to the 4 hrs of extended preservation time, 
EVLP-treated lungs received an obligatory second cold ischemic period during transport after 
completion of ex vivo assessment. 
The first three HELP recipients received bilateral lung transplants from a standard criteria donor 
(SCD) with one lung preserved using conventional hypothermic cold storage, and the second 
lung using one hour of TES. After no adverse consequences were identified in this initial 
experience, declined lungs from 23 donors were then assessed using the TES. Among those 20 
lung transplants (86% utilization), 11 originated from brain-dead donors, and the remaining 9, 
from DCD cases. Selection criteria were not used to determine which recipient would receive the 
EVLP or conventional donor lung. Rather, selection was determined based on an algorithm 
where available lungs were assessed to establish if they met the standard for transplantation 
using conventional donor lung criteria. Donor lungs deemed not appropriate for transplantation 
using ‘conventional’ criteria were placed on EVLP then made available to potential recipients 
who previously provided informed consent for this study.   
Upon trial completion, Health Canada permitted ongoing access through compassionate use, 
resulting in 39 additional EVLP transplants (total of 61 EVLP transplants prior to final marketing 
approval). STEEN Solution™ received full marketing approval by Health Canada on 
06 Nov 2012 as a stand-alone device (i.e., could be used with any off-the-shelf perfusion 
equipment).  
The initial study results suggested that transplantation of donor lungs that were physiologically 
stable during 4 hrs of EVLP, resulted in similar outcomes to those obtained with conventionally 
procured and hypothermically-treated lungs.[Cypel 2011a]  
By protocol design, EVLP-treated lungs underwent a longer period of total preservation, 
including an initial cold ischemic time (CIT-1), a period of normothermic EVLP assessment, and 
a final round of CIT (CIT-2).[Cypel 2011a]  
Ethical concerns limited the study design in that it was not possible to randomize the initially 
rejected donor lungs to ‘EVLP’ or ‘no EVLP’ study groups to determine post-transplantation 
success. However, review was possible from a clinical perspective as to whether the 
post-transplant outcomes were satisfactory for both groups. After 4 hrs of EVLP, the donor lung 
was evaluated to determine a number of parameters including the difference in pulmonary 
venous and arterial oxygen partial pressure (PO2) (delta PO2 = pulmonary vein O2 - pulmonary 
artery O2), pulmonary vascular resistance (PVR), peak airway pressure (PAwP), and lung 

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compliance. Both the EVLP and conventional donor lungs demonstrated similar outcomes after 
transplantation during years 1 through 5 post-transplant.[Cypel 2012; Tikkanen 2012] 
In the first six years after the HELP study began, the overall lung utilization rate in Toronto 
increased to 36% [S Keshavjee, personal communication] without significant changes to lung 
transplant volumes in surrounding regions.[Tiwari 2014] Therefore, it seems reasonable to infer 
that EVLP played a relevant role in the observed lung transplant volume increase. Long-term 
outcomes for the lung recipients in the HELP (and compassionate extension) trial, suggest that 
the lungs transplanted after EVLP had similar long-term outcomes compared to conventionally 
procured lungs.[Cypel 2012] 
Taken together, more than 225 donor lung sets have been evaluated by the Toronto group with a 
consistent increase in the lung utilization rate approximating 80%.[C Jaynes, personal 
communication]. Overall, one-, three-, and five-year outcomes after lung transplantation have 
been similar to results obtained among lung recipients who received standard lung transplants 
without using EVLP.[Cypel 2011a; Cypel 2011b; Cypel 2012; Tikkanen 2012; Munshi 2013; 
Cypel 2013] 
 
1.1.2 
Sponsor Clinical Experience:  Toronto EVLP System 
In 2015, Lung Bioengineering Inc (the Sponsor) merged with PERFUSIX USA, the previous 
Sponsor of this study, and Study PXUS 14-001 continues under the new sponsorship. The 
Sponsor’s predecessor company, PERFUSIX USA, had considerable experience with the TES, in 
that its employees and consultants consisted of team members who developed the technology, 
validated the protocols through the HELP clinical trial,[Cypel 2011a; Cypel 2012; Tikkanen 
2012] and designed the single-use disposable products used in the EVLP procedure. 
Additionally, a separate Canadian corporation, PERFUSIX Canada, has been responsible for 
running all of the EVLP lung procedures in Ontario, Canada, as a service for Toronto General 
Hospital (TGH) since April 2013.  
1.1.3 
 Report of Prior Investigations 
A full report of prior investigations detailing the above and other EVLP studies will be provided 
to the Study Center Investigators and submitted to each reviewing IRB. One copy shall be filed 
in the Investigator Study File. 
1.2 
Potential Risks and Benefits 
For many patients who choose evaluation and listing for lung transplantation, the inherent risks 
are outweighed by the benefit that transplantation is the only life prolonging therapy for 
end-stage lung disease. Factors underlying the exaggerated imbalance between lung donor 
supply and recipient mismatch compared with other solid organs have been reviewed earlier. 
EVLP-specific potential risks and benefits are presented below.  

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1.2.1 
Potential Risks 
The specific additional risks associated with EVLP beyond those encountered in lung transplant 
generally include extending ischemia beyond the initial cold ischemic period, increased potential 
for contamination due to additional handling and manipulation of the lungs, and potential lung 
damage that might result from the perfusion process and associated procedures, such as 
cannulation, bronchoscopy, and repackaging, among others. Specific risks and mitigation 
strategies are addressed in Appendix 3.  
1.2.2 
Potential Benefits 
The potential benefits of extended evaluation provided by EVLP include: 
• Evaluation under fixed/ideal hemodynamics outside of the confounding influence of the 
pathophysiology resulting from brain death and accompanying somatic injury, 
• Extended time enabling more careful examination/evaluation of donor organs. 
 
Assessment of lung and recipient risk profiles is based largely on the individual experience of the 
transplanting surgeon, which varies program-to-program and becomes even more important 
when lungs from unconventional or DCD donors are assessed. Ex vivo assessment at the 
Sponsor’s dedicated EVLP facility can therefore add a level of consistency (and therefore safety) 
in lung assessment, removing inherent variability between centers and surgeons. The additional 
expertise provided by Sponsor’s specifically trained EVLP Specialists and Expert Medical 
Consultants can help the transplant surgeon make the most accurate judgment when evaluating 
the risk profile of an EVLP lung as compared to the risk profile of a potential recipient. 
1.2.2.1 
Increased Donor Lung Utilization 
Strategies which increase the use of lungs from currently available donors provide the best 
opportunity to meaningfully increase the availability of lungs for end stage patients currently 
waiting for transplantation. In 2012, there were 8144 eligible donors recorded in the US and a 
total of 1634 lung transplants, resulting in a donor utilization rate of 20.1% [SRTR 2012]. EVLP 
is anticipated to increase the number of donor lungs used for transplantation by both enabling 
additional evaluation and increasing preservation time. Based on the experience at TGH, the lung 
utilization rate from deceased donors has increased to 36% following the introduction of EVLP 
in the form of the TES (cf. section 1.1.1). In the event that these results were extended to the US, 
an additional 1298 lung transplants might be expected to result from the introduction of EVLP 
(for a total of 2932 transplants). Importantly, to achieve a similar increase in lung transplants by 
increasing the donor pool, 6458 additional donors would have to be identified, a 79% increase 
over the current pool. Despite targeted campaigns to increase public awareness of the importance 
of organ donation, the annual number of donors has remained static. Thus, the low likelihood of 
significantly increasing the number of lungs available to patients with end-stage lung disease 
through currently available approaches argues that novel technologies to increase donor lung 
utilization such as the TES are needed.  
 

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Figure 1.  
2012 US Donor Lung Utilization 
1.2.2.2 
Shorter Recipient Waiting Times 
Because EVLP may result in making more lungs available for transplantation, an additional 
potential benefit to lung candidates listed at a center participating in this study could be a 
shortened waiting time for a suitable donor (not typically evaluated by the center prior to EVLP) 
to become available. 
 
 

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2 
STUDY OBJECTIVES 
This traditional feasibility study will generate preliminary safety and effectiveness information, 
evaluating the TES at a central facility for extended donor lung preservation. This information 
may be used to plan an appropriate future pivotal study, as part of efforts to inform further 
development.   
2.1 
Primary Objective(s)  
The primary objective of this study is to evaluate the short-term safety of subjects receiving a 
lung transplant, where the lung(s) was perfused by the Sponsor using the TES. Assessment of 
Primary Graft Dysfunction (PGD) Grade 3 at 72 hrs post-transplant (T72) and 30-day mortality 
will represent the outcome measures, and the primary endpoints are the following two measures: 
• The proportion of recipients with PGD Grade 3 (PGD3) assessed at T72 
• 30-day mortality post-transplant. 
 
The above information will also be collected on patients enrolled in a contemporaneous control 
group to provide context for EVLP results and to inform control measures for future research. 
2.2 
Secondary Objective(s)  
The secondary objectives of this study are to evaluate the short-term safety of subjects receiving 
a lung transplant where the lung(s) has been perfused via the TES performed by the Sponsor by 
assessment of the following: 
• PGD Score (Grades 0-3) measured at 0, 24, 48 and 72 hours post-transplant 
• Time to first extubation 
• Intensive care unit (ICU) length of stay (LOS), measured as total number of days 
post-transplant in the ICU until first hospital discharge, inclusive of ICU readmissions during 
that hospitalization  
• Hospital LOS measured as total number of days in the hospital prior to discharge 
post-transplant 
• Total preservation time (TPT), defined as the elapsed time between first allograft lung 
removal from cold storage time prior to transplant in the recipient and the donor aortic cross 
clamp time at procurement 
• Assessment of the overall safety of TES lung transplants during subject’s participation in the 
study, as reported through adverse events (AEs). 
 
The above information will also be collected on patients enrolled in a contemporaneous control 
group to provide context for EVLP results and to inform control measures for future research. 

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2.3 
Other Objective(s) 
Additional objectives of this study include evaluation of intermediate and longer-term safety and 
preliminary efficacy in subjects receiving a lung transplant where the lung(s) was perfused using 
the TES performed by the Sponsor. Assessments will include the following: 
• Initial ICU partial pressure of oxygen in arterial blood (PaO2):  Evaluated as first PaO2 
measured after ICU admission. 
• Forced Expiratory Volume in one second (FEV1) evaluated at time of discharge, 30 days, 90 
days, 6 months and 1 year post-transplant. FEV1 is measured as a percentage of predicted 
normal value. 
• Oxygen requirement at rest evaluated at time of discharge, 30 days, 90 days, 6 months and 1 
year post-transplant. Oxygen required at rest is measured in liters per minute (L/min). 
• Subject survival evaluated at 90 days, 6 months, and 1 year post-transplant. Measured as 
living or dead. If the subject expires within first year post-transplant, the date of death and 
primary cause of death will be collected. 
• Graft survival evaluated at 30 days, 90 days, 6 months, and 1 year post-transplant. Measured 
as functioning or failed. If the graft fails within first year post-transplant, the date of graft 
failure will be collected. 
• Primary cause of graft failure evaluated at 30 days, 90 days, 6 months, and 1 year post-
transplant on all failed grafts.  
• Bronchiolitis Obliterans Syndrome (BOS) Grade evaluated at 90 days, 6 months, and 1 year 
post-transplant.  
• Number of re-hospitalizations after transplant evaluated at 6 months and 1 year 
post-transplant. Measured as total number of hospitalizations since initial discharge. 
• Physical capacity evaluated at 90 days, 6 months, and 1 year post-transplant. 
• Working for income after transplant evaluated at 90 days, 6 months, and 1 year 
post-transplant. 
 
The above information will also be collected on patients enrolled in a contemporaneous control 
group to provide context for EVLP results and to inform control measures for future research. 
 
 

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3 
INVESTIGATIONAL PLAN 
3.1 
Overall Study Design and Plan 
This is an unblinded, non-randomized, traditional feasibility study to evaluate the safety of 
subjects undergoing lung transplant using lungs after EVLP, performed exclusively by the 
Sponsor at the Sponsor’s facility using the TES. The study will include male and female adult 
lung transplant recipients, requiring a SLT or DLT who are at least 18 years of age, and who are 
not receiving mechanical ventilation, Extracorporeal Membrane Oxygenation (ECMO) or other 
Extracorporeal Life Support (ECLS) at the time of the initial lung offer. Subjects who have 
signed informed consent (Section 10.4), match to a donor lung offer through the standard Organ 
Procurement and Transplantation Network (OPTN) allocation system, and meet the other 
eligibility criteria (Section 4), including matching with and undergoing a transplant with a Donor 
Lung, may participate. Patients who consent for this study (PXUS 14-001) but receive a 
conventional (i.e., non-EVLP) lung transplant will be considered for a contemporaneous control 
group matched to the EVLP treatment group. The control group will be selected to best match 
the EVLP group with respect to the following criteria:  SLT/ DLT, and Lung Allocation Score 
Disease Diagnosis Group (LASDDG). LASDDG is assigned according to OPTN Policy 10.1.F.i. 
into one of four groups: 
• Group A:  Obstructive Lung Disease 
• Group B:  Pulmonary Vascular disease 
• Group C:  Cystic Fibrosis or Immunodeficient Disorders 
• Group D:  Restrictive Lung Disease 
 
The goal is to provide a control group with similar characteristics and risk as the experimental 
group receiving EVLP. 
A sample size of 132 subjects, receiving either SLT or DLT, is planned for this study, where 
66 subjects have received donor lung(s) after EVLP (EVLP Group) and 66 subjects have 
received a conventional (i.e., non-EVLP) lung transplant and qualify for a contemporaneous 
control group (Control Group). Further, no more than two-thirds of the subjects enrolled 
(44 subjects per group) will have received a SLT or DLT.  
Acceptance or rejection of donor lungs for EVLP will follow the process outlined in Figure 2 and 
detailed in Section 3.1.1.  

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Note: The red-bordered box indicates a procedural termination point. 
 
Figure 2.  
Lung Retrieval Process to Determine Acceptance or Rejection for Transplant 
Once the donor lung is transplanted following EVLP (see Section 5.2.3), the eligible recipient, 
who has provided written informed consent, is enrolled into the study. Patients who consent for 
the current EVLP study (PXUS 14-001) but receive a conventional (i.e., non-EVLP) lung 
transplant will be considered for a contemporaneous control group matched to the EVLP 
treatment group. This matching will take place on a patient-by-patient basis and only after an 
EVLP subject has been enrolled at that Study Center. Investigators and their team will be 
notified by the Sponsor on a real-time basis of the specific matching criteria required for a 
control subject as EVLP subjects are enrolled (see Section 5.3). In order to be considered for 
eligibility, the control subject must “match” a priori to an EVLP subject who has already been 
enrolled at that Study Center based on the following criteria:   
• SLT versus DLT 
• LASDDG 
 
1hr < CIT-1 ≤ 10 hrs
Donor lungs referred by 
Study Center to Sponsor 
for EVLP.
Standard lung recovery by 
Study Center surgeon.
Transport lungs to Sponsor 
facility. (Silver Spring, MD).
EVLP for at least 3 and no 
more than 6 hours with 
hourly and as requested lung 
data collection.
Lung data relayed to 
Study Center for 
transplant suitability 
evaluation
Lungs rejected Study 
Center. End evaluation. 
Lungs will not be 
transplanted and will be 
disposed of per OPO 
directions.
Lungs accepted by Study 
Center for transplant and 
repackaged according to 
OPTN policy for transport to 
Study Center.
1hr < CIT-2 ≤ 6 hrs

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The post-intervention phase of the study will then be split into two phases:  1) the Analysis 
Phase, which includes follow-up within one year post-intervention and 2) Long-term Follow-up, 
which will capture outcome data annually from 1-year post-intervention until 5-years 
post-intervention. Although the study will continue after one year, the database will be locked for 
analyses of endpoints after the last subject has his/her study visit at 1 Year.  The Long-term 
Follow-up data will be summarized when the study has completed in support of long-term 
evaluation.  
Analysis Phase 
Following transplantation, subjects will be admitted to the ICU, and the initial PaO2 and PGD 
Score will be recorded. The subject’s PGD Score will be recorded every 24 hrs for the next 
72 hrs. The ICU discharge date will be documented. Study visits will occur 30 days (±5), 90 days 
(±10), 6 months (±2 weeks), and 1 year (±4 weeks) post-transplant. Study assessments will be 
performed as outlined in the Schedule of Events (Appendix 1, Table 3). 
Long-term Follow-up 
Although the database will be locked and analyses of endpoints performed after the last subject 
has his/her study visit at 1 Year, the Sponsor will continue to collect specified outcome 
parameters that are required to be reported by transplant centers to OPTN/ United Network for 
Organ Sharing (UNOS). Collection will be annually for 5-years post-intervention; outcome 
collection is outlined in the Schedule of Events (Appendix 1, Table 4).  
3.1.1 
Lung Collection and EVLP Procedure 
3.1.1.1 
Lung Referral 
All donor lungs are allocated to transplant centers according to OPTN Policy 10.  Once an acute 
care hospital identifies a potential organ donor, at or near death, the regional OPO is contacted to 
coordinate the organ donation. The OPO enters specific donor demographics into a single 
national data base of all persons needing an organ transplant to generate a match run list of 
patients for each organ to be donated from deceased individuals.  In match run order, the OPO 
contacts a transplant center to offer the matched organ to a specific patient, and provides details 
of the donor’s medical history and other relevant information. The transplant center has one hour 
to accept the lung for the matched patient, otherwise the lung offer continues in match run 
sequence order for additional patients until a center accepts the lung(s), the match run list is 
exhausted or there are timing issues which may cause the OPO to suspend subsequent lung 
offers.  The lung acceptance by a center is based on a number of factors, but primarily depends 
on the transplant center’s staff decision that a specific donor lung is suitable for the intended 
recipient. If the transplant center accepts, the lung is shipped to the transplant center for a 
standard of care transplant. 
If the transplant center is also a Study Center in this trial, they then have the ability to enroll a 
consented patient into this study.  The lung(s) is sent to the Study Center as normal, and if the 
designated recipient is also consented for this study, they may be eligible for enrollment in the 
control group.  This eligibility is based on meeting the overall study inclusion criteria, not 

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meeting any exclusion criteria, and matching to an already enrolled EVLP recipient at that Study 
Center based on the criteria found in Section 5.3. 
If the referred organ is not suitable for standard of care transplantation, and meets the inclusion 
criteria for the EVLP group in this study, and does not meet any of the exclusion criteria, the 
Study Center may refer the lung(s) to the LB-1 facility for EVLP.  This decision is based on the 
protocol criteria as well as the medical expertise of the Study Center staff and the details of the 
particular case.  The Sponsor does not make recommendations for referring an organ to the LB-1 
facility for perfusion. The Sponsor will, however, verify that the inclusion/exclusion criteria for 
referred lungs are followed by the Study Center prior to accepting lungs for EVLP.  The 
verification process will happen when the OPO contacts the Sponsor facility to notify them that 
an organ has been referred for EVLP by a Study Center, and to discuss lung transportation 
logistics and other case details. If it is determined that an error has been made by the Study 
Center in determining study eligibility, the lung(s) will not be sent to the Sponsor for EVLP. 
3.1.1.2 
Lung Retrieval 
Upon retrieval, donor lungs will be packaged and transported to the Sponsor’s EVLP facility in 
Silver Spring, MD, according to standard procedures, following OPTN Policy 16. Upon arrival 
at the Sponsor’s facility, lungs will be placed onto the TES by a specifically-trained Ex Vivo 
Lung Specialist. Prior to starting perfusion, the duration of CIT-1 will be confirmed to be less 
than or equal to 10 hrs. 
The EVLP procedure will be performed by Ex Vivo Lung Specialists under remote video 
supervision by one of Sponsor’s Expert Medical Consultants:  Drs. Keshavjee, Cypel, or 
Waddell. The Sponsor will perfuse the lung using the TES for up to 6 hrs, collecting and relaying 
lung function assessment data hourly, or as requested by the Study Center transplant surgeon. 
Additionally, the Study Center surgeon will have access to remote monitoring capabilities at the 
Sponsor EVLP Center for evaluating lung function data and monitoring the procedure through a 
dedicated audio/video link. 
Perfusion Data Parameters 
EVLP begins once lung cannulation and extracorporeal perfusion circuit priming is complete. 
The EVLP procedure shall run for 3 to 6 hrs. At any time between 3 and 6 hrs of perfusion, the 
EVLP Specialist, in consultation with the Study Center transplant physician, and in collaboration 
with an Expert Medical Consultant, can stop the procedure, at which time the lung will be 
packaged for the Study Center or the procedure will be stopped without transplantation. The 
following perfusion parameters will be collected for internal monitoring every 10 min during the 
initial 1-hr warm-up phase, then hourly thereafter: 
• Pulmonary arterial flow (PAF), L/min 
• Pulmonary arterial pressure (PAP), mmHg 
• Left atrial pressure (LAP), mmHg 
 

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PVR will be calculated using the following formula, beginning at the first hour time point, then 
hourly for the duration of the EVLP: 
PVR (dynes x sec x cm-5) = [PAP-LAP] x 80 / PAF  
and measured with a LAP set to 5 and at end of ventilator expiration. 
Ventilation Data Parameters 
Ventilation shall begin when the lung temperature reaches 32°C measured from the temperature 
probe connected to the heat exchanger. Then, before each hourly oxygen challenge, the ventilator 
should be set at a tidal volume of 10 mL/kg (based on donor ideal body weight [IBW]) for 5 min 
at a fraction of inspired oxygen (FiO2) of 100% (1.0) prior to obtaining perfusate gas samples. 
After the perfusate gas sample has been collected, the ventilator tidal volume is set back to the 
maintenance settings of 7 mL/kg and FiO2 of 21% (0.21). 
The following ventilation parameters will be measured and recorded hourly at the end of each 
oxygen challenge: 
• Mean, peak and plateau airway pressure (mAwP, PAwP, platAwP), cm H2O 
• Static and dynamic compliance (mL/cm H2O) 
• Perfusate gas analysis at lung inflow and outflow:  PO2, partial pressure of carbon dioxide 
(PCO2), pH, glucose, and lactose. 
 
Other Data Parameters 
Bronchoscopy:  Bronchoscopy is performed with visual assessment observations recorded, 
including a description of secretions, at the one-, three-, and if necessary, five-hour marks of the 
EVLP procedure. A bronchoscopy may be performed following initial ventilation to clear the 
airways as indicated. Additional bronchoscopies can be performed upon request by the Study 
Center physician or the Expert Medical Consultant. All bronchoscopic evaluations will be 
recorded digitally and transmitted to the Study Center Investigator for review. 
X-ray:  A digital radiograph of the lung is taken after the first, third, and fifth (if necessary) hour 
marks to detect edema, consolidations, or other abnormalities; and the resulting image will be 
transmitted digitally to the Study Center Investigator and Expert Medical Consultant for review. 
3.1.1.3 
Transfer of EVLP Data to the Study Center 
All lungs referred to and accepted by the Sponsor for EVLP must have been previously allocated 
by an OPO to a Study Center recipient in compliance with OPTN Policy 10.   
Throughout the EVLP procedure, donor lung parameters are communicated by the EVLP 
Specialist for transplant suitability and evaluation by the Study Center Investigator, who will 
make the final determination of EVLP lung transplant suitability, based on the same set of donor 

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lung and recipient risk profiles used to evaluate and accept organs during in vivo donor 
assessment.  
3.1.1.4 
Acceptance of EVLP Lung for Transplant 
The EVLP procedure must run between 3 and 6 hrs to qualify the lungs for inclusion into the 
study. The Expert Medical Consultants, working with the Study Center surgeon/team will 
monitor and evaluate the quality of the perfusion procedure data remotely. Together, they will 
serve as a collaborative team regarding the EVLP procedure, including the timing of the EVLP 
termination. The Expert Medical Consultant(s) will answer questions, provide guidance, and as 
requested offer perspectives based upon their considerable experience with EVLP and lung 
transplantation.  However, final decisions reside with the Study Center surgeon/team.  The 
Expert Medical Consultants will not issue a recommendation regarding transplanting or not 
transplanting the lung(s). Specifically, if the donor lung meets EVLP study inclusion criteria 
(Section 5.2), the Study Center Investigator/team will make the final determination of transplant 
suitability per OPTN Policy 5.7. Study Center Investigators will provide feedback on the utility 
of the data parameters assessed for determining transplant suitability via CRF. These data will be 
used solely to inform future study design.  
Upon acceptance of an EVLP donor lung by the Study Center, the single lung or lung block is 
cooled according to TES methodology to 10°C. Thereafter, perfusion and ventilation are 
stopped.  
This point marks the start of CIT-2. The lung(s) is prepared for hypothermic storage by flushing 
with 500 mL cold (4°C) STEEN Solution, maintaining lung inflation (trachea is clamped). 
Accepted lung(s) will be repackaged by the Sponsor according to OPTN Policy 16, stored at 4°C 
in low potassium dextran cold storage solution and transported to the Study Center using 
methods to minimize CIT-2.  
Total preservation time (TPT) for the first lung transplanted from donor lung retrieval to end of 
CIT-2 must not be greater than a combined 22 hours and individual phase limits as follows:  
(≤ 10 hours CIT-1) + (3 - 6 hours EVLP) + (≤ 6 hours CIT-2) ≤ 22 hours 
Total preservation time (TPT) for the second lung transplanted in DLT procedures from donor 
lung retrieval to end of CIT-2 must not be greater than a combined 26 hours and individual phase 
limits as follows:  
(≤ 10 hours CIT-1) + (3 - 6 hours EVLP) + (≤ 10 hours CIT-2) ≤ 26 hours 
EVLP lungs that exceed 10 hrs of CIT-1, or are perfused for less than 3 hrs or more than 6 hrs 
will be discarded by the Sponsor according to the responsible OPO’s directions. 
First lung CIT-2 is the elapsed time between the end of the EVLP procedure and removal of the 
first lung from cold storage, marking the beginning of the implantation phase of the transplant 
procedure. This CIT-2 may not exceed 6 hrs. Prior to shipping EVLP lungs to the Study Center, 
an estimated time of arrival at the Study Center will be calculated by the EVLP Specialist in 

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consultation with the Study Center to ensure the criterion for CIT-2 will be met. Therefore, if the 
anticipated first lung CIT-2 will exceed 6 hrs due to logistical considerations (projected flight 
time and/or surgical staff schedule, etc.), the lungs shall not be transported to the Study Center. 
Similarly, if after leaving the EVLP facility, prolonged transport time or patient logistical or 
other issues compromise the ability to ensure actual first lung CIT-2 is less than 6 hours, the 
transplant shall not proceed.  
The implantation phase of the transplant procedure begins upon removal of the first lung from 
cold storage, marking the end of CIT-2. The warm ischemic time (WIT) period then begins, 
which lasts until the lung is reperfused in the recipient. This time period is expected to be no 
longer than the typical WIT at each Study Center for standard lung transplants.  
For DLT procedures, the second lung must remain in cold storage in low potassium dextran 
solution while the first lung implantation is being performed.  The time of removal of the second 
lung from cold storage after the first lung is implanted and the second lung WIT should be 
consistent with historical surgical experience for sequential DLT at each Study Center. However, 
if the time between the start of CIT-2 and removal of the second lung from cold storage exceeds 
10 hrs, a protocol deviation shall be documented on a CRF and shall be reported to the Sponsor. 
The reason for the delay and an assessment of the second lung’s condition prior to transplant 
shall be recorded in the CRF. These subjects will continue enrollment in the study and will be 
followed in the EVLP Group.   
3.1.1.5 
Request for Reallocation of Lungs After EVLP 
In the event the Study Center initially accepting, declines the lungs during or after completion of 
the EVLP assessment, where the lungs meet the inclusion criteria, the EVLP Specialist must 
contact the coordinating OPO (the “host” OPO) and provide the following information: 
• OPTN/UNOS donor identification number (ID#); 
• Name of the transplant Study Center and surgeon declining lungs after EVLP; 
• Reason the lungs were declined; 
• Names of all other Study Centers participating in the clinical trial; 
• Current status of the lung(s) (i.e., still on EVLP, packaged on ice, in transit); and 
• Contact information for the EVLP Specialist on call for the specific case. 
 
If the lungs meet the trial acceptance criteria (see Section 5.2.3), the Sponsor personnel will 
recommend the host OPO resume lung allocation according to their internal policies and 
procedures, reminding the OPO of the Study Centers participating in Study PXUS 14-001, and 
stressing that the EVLP procedure is investigational, and potential recipients must have signed 
the EVLP trial informed consent prior to participating in any study-related assessments or 
procedures.   
In the event the host OPO is able to reallocate the lungs to another participating Study Center, 
the host OPO will contact the EVLP Specialist, who will then contact the interested physician 
(Study Center Investigator) to facilitate Case Management Exchange (CMX) access and 

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information exchange about the case. The Investigator at the reallocated Study Center will 
assume the role of the transplant center for the EVLP case and will accept or decline the lungs 
upon review of the EVLP assessment data and in consultation with the Expert Medical 
Consultant on call.  
In the event the host OPO cannot reallocate the lungs to a participating Study Center, the EVLP 
Specialist will discuss with the host OPO the option of contacting TGH to determine if there is a 
need at that facility. The decision to reallocate to TGH will rest solely with the host OPO and 
will be in accordance with their internal policies and procedures. The reallocation will be 
documented in CMX and on the EVLP facility’s CRF. In the event the lungs cannot be 
reallocated, they will be discarded according to the Sponsor’s procedures for handling 
biomedical waste. 
3.2 
Rationale for Study Design and Control Group 
As described in Section 1, EVLP is a novel technology that allows extended assessment of lungs 
whose suitability for transplantation is initially uncertain. The extended donor lung preservation 
time may also enable better logistical coordination of the recipient and donor hospital transplant 
teams. 
This study is an unblinded, non-randomized, traditional feasibility multi-center study to evaluate 
the safety of subjects undergoing lung transplant after EVLP, as performed by the Sponsor using 
the TES. This study was built on the single-center experience including >100 EVLP-treated lung 
transplants at TGH, where similar survival to the contemporaneous (non-EVLP) lung transplant 
recipients was demonstrated.[ Cypel 2011a; Cypel 2011b; Cypel 2012; Tikkanen 2012; Munshi 
2013; Cypel 2013] Importantly, the contribution of EVLP was associated with a 36% increase in 
total lungs transplanted at TGH in 2013,[S Keshavjee, personal communication] without 
negatively impacting transplant volumes at surrounding hospitals [Tiwari 2014], supporting the 
notion that the adoption of EVLP technology resulted in transplantation of lungs that would have 
otherwise been discarded.[S Keshavjee, personal communication; Munshi 2013] 
This study proposal seeks to evaluate the feasibility of reproducing the TES at a central US 
facility where the donor lungs require an additional travel leg (after concluding the EVLP 
procedure) compared to standard lung transplantation. This second period of cold preservation 
will be evaluated by assessing safety measures of subjects with lungs transplanted following 
EVLP and comparing with subjects who have undergone a traditional lung transplant (i.e., 
contemporaneous control group). The primary safety endpoints of PGD3 at T72 and 30-day 
mortality have been selected. PGD3 has been shown to be a good predictor of transplanted organ 
function, as it has a significant impact on short- and long-term recipient survival in DLT [Suzuki 
2013], and 30-day mortality has been included as part of the primary endpoint, given the lesser 
degree of certainty of the prognostic significance of PGD3 in SLT (see also Section 6.16). 
Randomization is not possible in this study, as lung transplant is considered a life-saving 
procedure, and donors must match in size and blood type to potential recipients, so withholding a 
potentially-matched lung transplant is not ethical.  Patients not receiving an EVLP lung will be 

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considered for enrollment in a contemporaneous non-EVLP control group. The control group 
will be selected to best match the EVLP group with respect to the following criteria: 
• SLT versus DLT 
• LASDDG 
 
In order to be considered for eligibility, the control patient must “match” a priori to an EVLP 
subject who has already been enrolled. Because the ratio of standard lung transplant to EVLP 
transplant is expected to be approximately 4:1, it is feasible to obtain a control-EVLP match 
within the anticipated duration of the study.  
At the request of the Food and Drug Administration (FDA), long-term post-intervention 
follow-up has been included to assess outcome parameters within the 5 years after either 
standard or EVLP lung transplant. 
3.3 
Study Duration and Dates 
Data will be collected from the organ donor, EVLP procedure (if applicable), and each subject 
from the time of lung transplantation and up to one year post-transplant for the Analysis Phase. 
In addition, outcome data will be collected annually up to 5 years post-transplant.  
The study duration for the Analysis Phase (from first patient, first visit [FPFV] to last patient, 
last visit [LPLV] prior to database lock) is expected to be 3 years. The estimated time to 
complete enrollment is approximately 24 months. 

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4 
STUDY POPULATION SELECTION 
4.1 
Study Population 
The study will be open to all eligible male and female patients, aged 18 years or older, with 
end-stage lung disease listed for lung transplantation at a participating Study Center. These 
participants may not be receiving mechanical ventilation, ECMO or ECLS, at the time of initial 
lung offer prior to EVLP.  
Study Centers will offer the opportunity to participate in the study to its own listed recipients 
during time of listing for transplant or during periodically scheduled patient visits. It is expected 
that enrollment and recruitment activities between male and female recipients will approximate a 
similar gender mix compared to the Study Center’s general lung waitlist. 
A sample size of 132 subjects, receiving either SLT or DLT, is planned for this study, where 
66 subjects receive donor lung(s) after EVLP (EVLP Group) and 66 subjects are enrolled in a 
contemporaneous control group (Control Group). No more than two-thirds of the subjects 
enrolled (44 subjects per group) will have received a SLT or DLT. 
4.2 
Inclusion Criteria 
Each patient must meet the following criteria to be enrolled in this study: 
1. Male or female patients. 
2. All patients, 18 years of age or older. 
3. Patient already on or added to the active waiting list for a single or bilateral lung transplant. 
4. Patient or patient’s representative provides informed consent for participation in the study 
prior to participating in any study-related assessments or procedures. 
5. Patient or patient’s representative reconfirms informed consent for the study on the day of 
lung transplant if initial consent is > 24 hrs. 
6. Patient matches with and undergoes a transplant with a donor lung. 
 
4.3 
Exclusion Criteria 
Patients who meet any of the following criteria will be excluded from the study: 
1. Patients listed for same-side lung re-transplantation. 
2. Patients listed for multiple-organ transplantation including lung and any other organ. 
3. Patients listed for live donor lobar transplant. 
4. Patients positive for human immunodeficiency virus (HIV), active Hepatitis B or C, or 
Burkholderia cepacia infection.  

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5. Patients in the ICU at the time of the initial lung offer requiring ventilation, ECMO or ECLS. 
[Note: The decision to place the recipient on ECMO or other ECLS for post-transplant 
prophylaxis at time of or immediately prior to transplant is not considered an exclusion] 
6. Patient receives a conventional (non-EVLP) lung transplant but does not match to an EVLP 
subject based on the criteria for control matching outlined in Section 3.1. 
 
4.4 
Strategies for Recruitment and Retention 
This study will be offered to eligible end-stage lung recipients at Study Centers. Recipients will 
not be compensated for participation, but it is possible that a subject could receive an 
EVLP-treated lung transplant sooner than they would if they were waiting for a standard lung 
transplant. EVLP lungs have also been more extensively physiologically assessed than a 
conventionally procured lung. 
Following lung transplant, subjects require routine follow-up visits for immunosuppression 
monitoring and infection control regimens. For this reason, it is unlikely that subjects will be lost 
to follow-up unless he/she withdraws consent to participate in the study or changes the 
healthcare facility where he/she receives follow-up care. 
 

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5 
STUDY INTERVENTION 
5.1 
Description of Intervention 
The TES and has been used by the Toronto group for more than 225 clinical EVLP procedures 
(including at least 176 completed lung transplants). Nearly all of the hardware and disposables 
used in the TES are 510(k)-cleared by the Food and Drug Administration (FDA) for human 
clinical use, indicating appropriate and safe manufacturing procedures. The exception to this is 
the organ chamber and the lung cannulas, which are both made from medical-grade materials 
and are currently being used in clinical EVLP under the Humanitarian Device Exemption (HDE) 
#H120003. There are two classifications of system components:  Non-Fluid Path Hardware and 
Single-Use Fluid Path Disposables. A schematic that represents each classification component in 
relation to the other is shown in Figure 3. 
 
Figure 3.  
System Components of the Toronto EVLP System 
The Toronto Ex Vivo Lung Perfusion System (“Toronto EVLP System” or TES) comprises a 
combination of FDA-approved, off-the-shelf hospital equipment, including: a centrifugal bypass 
pump, heater/cooler, ICU ventilator, and a disposable bypass perfusion circuit. In addition, the 
following non-FDA-approved single-use disposables are necessary:  disposable organ chamber, 
disposable lung cannulas, and the perfusate STEEN Solution. 
The proposed TES indication is for extending preservation and assessment of donor lungs using 
normothermic lung perfusion and ventilation in a controlled environment outside the body (ex 
vivo). The device is intended to be used to perfuse lungs for male and female first-time, SLT or 
DLT recipients, aged 18 years or older with end-stage lung disease, not requiring ECMO, ECLS, 
or ventilation at the time of initial organ referral prior to EVLP. 

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The TES is intended to be used exclusively by the Sponsor in a Sponsor-controlled facility 
established exclusively for the purpose of perfusing and ventilating lungs ex vivo. The TES is 
NOT intended to be sold to any other entity nor used by an entity other than the Sponsor. 
Detailed descriptions of all system components currently in use can be found in Appendix 4. 
5.2 
Lung Transplantation 
Donor lungs are evaluated to assess if they meet the donor lung inclusion criteria (Pre-EVLP; 
Section 5.2.1). If the donor lungs meet criteria, they proceed through EVLP. After EVLP, the 
donor lungs are again evaluated for transplant suitability and must meet the donor lung inclusion 
criteria (Post-EVLP; Section 5.2.3.1) in order to be transplanted into a subject who meets the 
recipient eligibility criteria. 
5.2.1 
Donor Lung Inclusion Criteria (Pre-EVLP) 
Lungs are eligible for use in this study when an OPO documents that without EVLP, the lungs 
would not otherwise be used for transplantation. Data will be collected on the match run, 
including the recipients’ position on the list, the number of refusals prior to and after a study 
center’s acceptance, and the reason(s) for refusal. The OPO will also document the decision to 
either discontinue further standard allocation, or expedite allocation directly to a Study Center 
for EVLP if circumstances so dictate either approach to make the organ available for further 
evaluation and potential transplant via EVLP. 
Examples of such circumstances include: 
• Match run exhausted: Attempts to place the lungs via the match run sequence have yielded 
refusal responses to standard (non-EVLP) offers, and the OPO decides that the remaining 
allocation time supports the decision for EVLP;  
• Logistical challenges: The OPO does not have time to perform a lung-specific match run; for 
example, if the overall organ donation process is being accelerated due to donor 
deterioration, limited OR availability, donor family request, procurement teams for other 
organs with recipient urgency, other competing issues requiring donor surgery to be 
scheduled prior to lung placement, or allowing another procurement team to recover the 
lungs for an accepting center;  
• Donation after circulatory death (DCD): Refusal rates by transplant centers is high in these 
cases because evaluation of the donor lung function is limited, and donor expiry after 
withdrawal of care is unpredictable, often not occurring within the time limits established by 
the transplant centers or donor hospitals. Because of these factors, many transplant centers do 
not entertain DCD offers at all, meaning that they would not normally be used for transplant; 
• OR decline: An unexpected suitability issue is identified at time of procurement resulting in 
the decision that the previously designated recipient is no longer appropriate; frequently this 
severely limits the available time for the OPO to reallocate the lungs; or 

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1. Recipient availability: After procurement has started, the original intended recipient is 
unable to receive the transplant, again, creating a critical timing challenge for the OPO to 
allocate the lungs to another recipient. 
 
5.2.2 
Donor Lung Exclusion Criteria (Pre-EVLP) 
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 prior to donor lung excision.  
• Any purulent secretions not considered persistent identified in the donor lung prior to 
excision that do not clear by the hour 3 assessment of EVLP. 
• The donor lung has confirmed evidence of aspiration. 
• The donor lung has significant mechanical lung injury or trauma. 
• The donor has HIV or an active infectious disease such as Hepatitis B or C. 
• The CIT, 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 the Sponsor’s facility was 
> 10 hrs. 
 
5.2.3 
Donor Lung Criteria Post-EVLP Assessment 
Throughout each EVLP procedure, the donor lungs are evaluated for transplant suitability by the 
Study Center Investigator (i.e., transplant surgeon), in consultation with the Expert Medical 
Consultants. The Study Center Investigator will make the final determination of EVLP lung 
transplant suitability based on the same set of donor lung and recipient risk profiles used to 
evaluate and accept organs during standard in vivo donor assessment.  
In addition to the real-time review of the EVLP procedure by at least two lung transplant 
physicians, the Sponsor will conduct post-EVLP quality reviews of case data to ensure policies 
and procedures are adhered to. 
5.2.3.1 
Donor Lung Inclusion Criteria (Post-EVLP) 
The donor lung must meet each of the following conditions post-EVLP for transplant suitability 
consideration by the Study Center Investigator: 
• Partial pressure of oxygen in venous blood (PvO2)/FiO2 ≥350 mmHg at final EVLP 
evaluation time period 
•  < 15% increase from baseline value (defined as the first hour collection point) to final value 
of PVR, 
• < 15% increase from baseline value to final value of PAwP, 
• < 15% decrease from baseline value to final value of static lung compliance (Cstat), 
• TPT does not exceed the following: 

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- 
the CIT-1 time from cross clamp in the donor to the start of EVLP > 1 hr and ≤ 10 hrs, 
- 
the EVLP time > 3 hrs and ≤ 6 hrs, 
- 
the estimated CIT-2 from EVLP cool down to the start of the implantation phase of the 
transplant procedure (time of removal of first lung from cold storage) must be ≤ 6 hrs, 
- 
the estimated CIT-2 from EVLP cool down to the time of removal of the second lung 
from cold storage must be ≤ 10 hrs, 
• Study Center Investigator deems lung function suitable for intended subject. 
 
5.3 
Method of Assigning Patients to Intervention 
A patient who is a potential candidate for this study may be approached by his/her treating 
physician regarding the patient’s interest and desire for study information. This may take place 
during a Screening Visit up to one year prior to transplant, or during the Baseline visit on the day 
of transplant. Refer to Section 10.4 for informed consent procedures. 
All patients who have provided informed consent to participate in this study will be screened and 
eligibility will be assessed according to applicable Inclusion (Section 4.2) and Exclusion Criteria 
(Section 4.3). Each Study Center will maintain a Screening Log where the applicable patient 
information will be captured, including their LASDDG and whether he/she is listed for SLT or 
DLT. Screening logs will be provided to the Sponsor on a regular basis so that patient matching 
criteria can be tracked. This will allow identification of potential control subjects as EVLP 
subjects become active in the study upon transplantation. 
When lungs are matched from donor to recipient, the Study Center will make the determination 
if the lung qualifies for EVLP or not (Section 5.2). Based on the outcome of that decision and 
then review of criteria of that lung, either a standard transplant takes place or the lung undergoes 
EVLP for transplantation.  
After at least one EVLP subject has been enrolled at a Study Center, that site’s Investigators and 
their team will be notified that a Control Group slot is available for their Study Center based on 
the control matching criteria (SLT/ DLT and LASDDG). Study Centers will be notified again 
once that Control Group slot is filled at their site pending the next EVLP transplant. In this way, 
each Study Center will provide a matching Control Group subject for each EVLP Group subject 
enrolled at their site. 
Identification of potential control subjects will be done prospectively. Retrospective matching of 
control patients after standard lung transplantation is prohibited. Study enrollment commences 
upon lung transplantation, and enrollment will be tracked separately at each participating center 
by the clinical research organization (CRO), using site-specific identification and coding 
assigned per the CRF Instructions. Recipient data provided to the Sponsor or the CRO will 
include Subject ID#, but will not include patient-identifying information (name, social security #, 
etc.). 
Each participating lung transplant center will maintain a screening and study participant log, 
recording whether the subject received an EVLP-treated or non-EVLP-treated lung transplant, as 

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well as SLT or DLT and LASDDG, with subsequent screening identification numbers, dates of 
informed consent, and transplant dates. 
In order that no more than two-thirds of the subjects enrolled (44 subjects per group) will have 
received either a SLT or DLT, Study Centers will be kept informed regarding the numbers and 
types of transplants that have taken place and if any one type of transplant (single or double) will 
be limited to enrollment as the proportion reaches two-thirds in the overall study. 
Furthermore, to ensure the contemporaneous enrollment of Control Group subjects, Study 
Centers may not enroll more than three EVLP subjects prior to enrolling at least one matching 
control subject. In this way, at no time should a site have more than three enrolled EVLP 
subjects without matched control subjects. The Sponsor will notify any Study Center that reaches 
this three EVLP patient threshold to remind them that a control patient must be enrolled next. 
5.4 
Blinding 
This study cannot be blinded to the intervention (standard lung transplant vs. EVLP).  
5.5 
Restrictions 
There are no protocol-specific restrictions with respect to fluid, food, prior or concurrent 
medications, or subject activity during this study. 
5.6 
Intervention and Study Procedure Compliance 
Once a subject receives a lung transplant, he/she is subject to routine follow-up visits due to 
life-long requirements for immunosuppression monitoring and infection control regimens. For 
this reason, it is unlikely that subjects will be lost to follow-up unless he/she withdraws consent 
to participate in the study or changes the healthcare facility where he/she receives follow-up 
care. 
Refer to Section 10.9 regarding deviations from the study protocol. 
5.7 
Packaging and Labeling 
Investigational devices will contain the following label according to 21 Code of Federal 
Regulations (CFR) 812.5(a): 
“CAUTION-Investigational Device Limited by Federal (or US) Law to Investigational Use” 
5.8 
Storage and Accountability 
The TES is comprised of perfusion cart hardware (centrifugal pump, heater/cooler, pressure 
monitor, ICU ventilator), fluid path and non-fluid path disposables (see Appendix 4). 
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All EVLP-related investigational device hardware and disposables will be located and used 
exclusively at the Sponsor’s EVLP site in Silver Spring, MD. Devices from this study will never 
be sent to individual transplant study sites. A device disposition log shall be maintained by the 
Sponsor to track investigational product information including, but not limited to, product 
lot/serial/batch #, date of product expiration, manufacturer, date of use, date of disposal of 
unused product, and the staff initials. 
5.8.1 
STEEN Solution 
The Sponsor will maintain an inventory log listing the quantity received, lot/batch number, and 
expiration date. The STEEN Solution will be stored in a secure location at the recommended 
temperature between +4-8°C.   
Disposal of any opened STEEN Solution bottles from each procedure and any leftover solution 
will be performed according to the Sponsor’s standard operating procedures. The solution used 
during the EVLP procedure contains human serum albumin (HAS) and may contain some human 
red blood cells, so it will be disposed of accordingly. 
5.8.2 
EVLP Disposables 
The Sponsor will be responsible for the timely ordering and accurate dispensing of the TES 
disposables. The TES disposables will be shipped and stored at room temperature in a secure 
location at the Sponsor’s EVLP site. All disposables will be labeled with the lot number and 
expiration date and included in the inventory control log. Used disposables are to be discarded in 
accordance with the Sponsor’s policy. No TES disposables will be shipped from the Sponsor’s 
facility to a Study Center. 
5.9 
Investigational Product Retention at Study Center 
The Sponsor will be responsible for the accurate storage, inventory, and dispensing of the 
STEEN Solution and the TES disposables used exclusively at its own site. The TES disposables 
include (1) Sterile Organ Chamber, (2) Sterile Lung Cannulas, and (3) Sterile Disposable Lung 
Circuit. 
Required single-use device storage and stability conditions are shown in Table 1. 
Table 1.  
Single-use Device Storage and Stability Conditions 
Device 
Storage Condition 
Device Shelf Life 
XVIVO Organ Chamber 
Room temperature, store in dry location 
4 years 
XVIVO Lung Cannula Set 
Room temperature, store in dry location 
4 years 
STEEN Solution 
Store refrigerated between 4-8°C protected 
from light 
2 years 
Disposable perfusion circuit 
Room temperature, store in dry location 
2 years 
 
 
 

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6 
STUDY PROCEDURES 
All study procedures post-transplant for subjects enrolled in this study will follow the Study 
Center’s standard of care. 
6.1 
Donor and Donor Lung Information 
Data from the donor and donor lung that goes through EVLP will be captured by the EVLP 
Specialist on a donor/donor lung-specific CRF (termed the EVLP CRF). 
During the EVLP lung evaluation, perfusate blood gas will be collected by the EVLP Specialist 
hourly to assess PCO2, PO2 and pH both distally and proximally to the lung to assess the lung’s 
capacity to effectively exchange gas (see Section 5.2.3 and Section 6.12). 
The Sponsor will collect the following donor information once a donor lung becomes available 
for EVLP: 
- 
Date of Birth 
- 
Gender 
- 
Ethnicity 
- 
Race 
- 
Weight 
- 
Height 
- 
Blood group 
- 
Date and Time of Death  
- 
Cause of Death 
- 
Mechanism of Death 
- 
Circumstances of Death 
- 
Donor type (donation after brain death [DBD]/DCD) 
- 
Donor next of kin consent for research 
- 
Hospital information 
- 
PaO2:FiO2 
 
For Control Subjects, donor information will not be readily available to the Sponsor; therefore, 
the donor information listed above must be obtained by the Investigator (or designee) and 
forwarded to the Sponsor for data entry.  
6.2 
Informed Consent 
The informed consent process is described in Section 10.4. 
6.3 
Medical History 
Medical history should be obtained by the Study Center for all patients as standard of practice. 
Subject (recipient) medical history of diseases or conditions ongoing in the year prior to the 
Screening Visit will be recorded. Medical history will be reviewed with the subject at the 

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Baseline (Day 0) visit, within 24 hrs prior to transplant, to include any updates since the 
Screening Visit.  
6.4 
Concomitant Medications 
Concomitant medications will be reviewed with the subject at Baseline (Day 0; within 24 hrs of 
transplant), 30 days post-transplant, and 6 months post-transplant. Eligibility to participate in the 
study will not be prohibited based on medication alone. Concomitant medications will also be 
captured for the 2-week period prior to the onset of a serious adverse event (SAE).    
6.5 
Physical Examination 
Physical examination(s) should be performed by the Study Center for all patients as a standard of 
practice prior to listing patient for transplantation.  
A physical examination should be performed at the Baseline Visit. Symptom-directed physical 
examinations will be performed again at Day 30 and Month 6 post-transplant. Any values judged 
by the Investigator to be clinically significant abnormal changes from Baseline (before study 
intervention) should also be recorded on the Adverse Event CRF as an AE. 
Specific tests to assess lung capacity will also be obtained and recorded on the CRF. Upon 
admission to the ICU, the subject’s initial PaO2 is to be recorded.  
FEV1, measured as a percentage of predicted normal value, and oxygen required at rest are to be 
recorded at the time of hospital discharge (if prior to 30 days post-transplant), Day 30, Day 90, 
Month 6, and Year 1 post-transplant, and premature discontinuation (if applicable).  
In addition, after completion of the Analysis Phase, FEV1 and oxygen at rest will be collected 
annually by the Sponsor for the Long-term Follow-up Phase (Year 2, 3, 4, and 5). 
6.6 
Vital Signs 
Assessments of vital signs are to be collected at each scheduled study visit. The following vital 
sign parameters should be recorded:  height (baseline only), weight, heart rate, blood pressure, 
respiration rate, and oxygen saturation. 
Heart rate, blood pressure, respiration rate, and oxygen saturation will be measured after the 
subject has been seated at rest for at least 5 minutes. Systemic blood pressures may be obtained 
by cuff, and systemic arterial oxygen saturation may be obtained by pulse oximetry. 
6.7 
Primary Graft Dysfunction Score 
The subject’s PGD Score is to be determined by the Investigator at Baseline (Day 0) after 
transplantation and upon admission to the ICU, as well as 24, 48, and 72 hrs 
post-transplant.[Christie 2005]  
PGD Score will be as graded using the parameters in Table 2, where the P/F ratio is PaO2/FiO2. 

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Table 2.  
Primary Graft Dysfunction Grading 
Grade 
P/F Ratio 
Chest X-ray 
0 
>300 
Normal 
1 
>300 
Diffuse allograft infiltrates 
2 
200-300 
Diffuse allograft infiltrates 
3 
<200 
Diffuse allograft infiltrates 
 
If the subject is on ECMO at any time point, the PGD grade is automatically assessed as “3”. 
If the subject has been extubated prior to assessment, the presence or absence of radiographic 
infiltrates consistent with pulmonary edema will be reviewed and graded as follows for the PGD 
Grade:   
• If subject is extubated AND the chest x-ray is “Absent” of infiltrates, then the PGD Score is 
0. 
• If subject is extubated AND the chest x-ray is “Present” of infiltrates, then the PGD Score is 
1. 
 
Graft survival will be evaluated by the Investigator (or his/her designee) at Day 30, Day 90, 
Month 6, Year 1 post-transplant, and premature termination (if applicable). Graft survival will be 
measured as functioning or failed. If the graft fails within first year post-transplant, the date of 
graft failure will be collected. The primary cause of graft failure will also be captured as one of 
the following: 
- 
Primary Non-Function 
- 
Acute Rejection 
- 
Chronic Rejection  
- 
or Other: (if Other, Specify) 
After completion of the Analysis Phase, Graft Survival will be evaluated and collected annually 
by the Sponsor for the Long-term Follow-up Phase (Year 2, 3, 4, and 5). 
6.8 
Survival 
Subject survival, measured as living or dead, will be recorded Day 30, Day 90, Month 6, and 
Year 1 post-transplant. If the subject expires within first year post-transplant, the date of death 
and primary cause of death will be collected. 
After completion of the Analysis Phase, subject survival will be collected annually by the 
Sponsor for the Long-term Follow-up Phase (Year 2, 3, 4, and 5). 
6.9 
Bronchiolitis Obliterans Syndrome Grade 
During the Analysis Phase, evaluation of BOS will be conducted by the Investigator (or his/her 
designee) at Day 90, Month 6, Year 1 post-transplant, and premature termination (if applicable). 
Assessment will be noted as one of the following: 

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- 
NO BOS 
- 
Yes, Grade 0-p 
- 
Yes, Grade 1 
- 
Yes, Grade 2 
- 
Yes, Grade 3 
- 
Yes Grade Unknown (UNK) 
- 
Unknown 
 
After completion of the Analysis Phase, BOS Grade will be collected annually by the Sponsor 
for the Long-term Follow-up Phase (Year 2, 3, 4, and 5). 
6.10 Physical Capacity 
During the Analysis Phase, evaluation of physical capacity will be conducted by the Investigator 
(or his/her designee) at Day 90, Month 6, Year 1 post-transplant, and premature termination (if 
applicable). Assessment will be noted as one of the following: 
- 
No Limitations 
- 
Limited Mobility 
- 
Wheelchair bound or more limited 
- 
Hospitalized 
- 
UNK 
 
After completion of the Analysis Phase, Physical Capacity will be collected annually by the 
Sponsor for the Long-term Follow-up Phase (Year 2, 3, 4, and 5). 
6.11 Work Status 
During the Analysis Phase, evaluation of work status will be conducted by the Investigator (or 
his/her designee) at Day 90, Month 6, Year 1 post-transplant, and premature termination (if 
applicable). Assessment will be noted as one of the following: 
- 
Working Full-time 
- 
Working Part-time due to Demands of Treatment 
- 
Working Part-time due to Disability 
- 
Working Part-time due to Insurance Conflict 
- 
Working Part-time due to Inability to Find Full-time Work 
- 
Working Part-time due to Subject Choice 
- 
Working Part-time Reason UNK 
- 
Working Part-time vs. Full-time UNK 
 
After completion of the Analysis Phase, Work Status will be collected annually by the Sponsor 
for the Long-term Follow-up Phase (Year 2, 3, 4, and 5). 

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6.12 Clinical Laboratory Tests 
6.12.1 
Laboratory Parameters 
During the EVLP lung evaluation, perfusate blood gas will be collected by the EVLP Specialist 
hourly to assess PCO2, PO2 and pH both distally and proximally to the lung to assess the lung’s 
capacity to effectively exchange gas (see Appendix 4, ABG Analyzer). The Sponsor’s facility 
will test perfusate blood gas samples using a Siemens RapidPoint 500 ABG analyzer. 
Subject (recipient post-transplant) arterial blood gases (ABGs) must be determined by the 
Investigator, in order to calculate PGD grade (Section 6.7), at Baseline (Day 0, within 24 hrs of 
transplant), and 24, 48, and 72 hrs post-transplant. Laboratory results for tests performed as part 
of PGD scoring for this study and will be recorded on the Primary Graft Dysfunction CRF with 
the date and the time the assessment was performed.  
6.12.2 
Sample Collection, Storage, and Shipping 
The Sponsor will collect pre- and post-EVLP donor lung biopsies for future analysis or quality 
assurance (QA), and/or if requested/ required by transplanting center. Additionally, perfusate 
samples will be collected from the EVLP perfusion circuit for QA and future analysis. Samples 
will be identified by donor ID number. Consent for collecting and storing donor lung samples 
pre-transplantation for future research purposes will be obtained from the donor’s Legal Next of 
Kin (Section 10.4.1). 
6.13 Safety Reporting 
This study is designed to evaluate the safety of extending the preservation and assessment time 
of donor lungs using the TES as administered by the Sponsor in a dedicated and centralized 
facility. Subjects enrolled in this study suffer from end-stage lung failure where the only 
available treatment is lung transplantation. 
6.13.1 
Definitions 
Adverse Events 
An adverse event (AE) is any untoward medical occurrence, unintended disease or injury, or any 
untoward clinical signs (including abnormal laboratory findings) in a clinical investigation 
subject which does not necessarily have a causal relationship to the investigational medical 
device. All AEs are assessed by the Study Centers for severity, causality, outcome, seriousness, 
and if unanticipated, documented as such (see below). 
Serious Adverse Event (SAE) 
A serious adverse event (SAE) is defined by federal regulation as any AE that results in any of 
the following outcomes: death, life-threatening AE, hospitalization or prolongation of existing 
hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth 
defect. 

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Important medical events that may not result in death, be life threatening, or require 
hospitalization may be considered an SAE when, based upon appropriate medical judgment, they 
may jeopardize the subject and may require medical or surgical intervention to prevent one of the 
outcomes listed in this definition. Examples of such medical events include allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias 
or convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse. 
Unanticipated Adverse Device Effect (UADE) 
Any serious adverse device effect on health or safety or any life-threatening problem or death 
caused by or associated with a device, if that effect, problem, or death was not previously 
identified in nature, severity, or degree of incidence in the investigational plan or application 
(including a supplementary plan or application), or any other unanticipated serious problem 
associated with a device that relates to the rights, safety, or welfare of subjects. 
Anticipated Adverse Events not Related to EVLP 
Anticipated Adverse Events not related to EVLP are events inherent to the lung transplant 
surgical procedure and immunosuppressant medications that are expected to occur throughout 
the initial post-hospital stay in all subjects.[Lyu 2009] These events do not require reporting and 
are not considered AEs as defined or described elsewhere in this protocol. For the purposes of 
this protocol, Anticipated Adverse Events not related to EVLP are:  
• Surgical 
- 
Anesthesia related nausea/vomiting 
- 
Surgical incision, thoracotomy, incision-related pain and bleeding 
- 
Moderate bruising at surgical site 
- 
Chest tube placement, chest tube pain 
- 
Surgical lines, including arterial, Swan-Ganz catheter, triple lumen catheter 
- 
Ventilator use during and after surgery 
- 
Back pain related to operating room table or referred pain 
• Gastrointestinal  
- 
Nausea/vomiting  
- 
Constipation 
- 
Diarrhea 
- 
Gastroparesis 
- 
Hematemesis 
- 
Melena 
- 
C. difficile colitis 
- 
Gastritis 
- 
Esophagitis 
- 
Gastric/duodenal ulcer  
- 
Decreased appetite  
- 
Gastroesophageal reflux disease 
- 
Ileus 

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- 
Partial intestinal obstruction 
- 
Malnutrition/anorexia 
- 
Systemic fever/pain/malaise/weakness 
• Respiratory 
- 
Wheezing 
- 
Cough 
- 
Pleurisy 
- 
Pleural effusion 
- 
Pneumothorax 
- 
Bronchospasm 
- 
Diaphragmatic paralysis 
- 
Intra-pulmonary shunt 
- 
Cautery lesions 
- 
Bleeding secondary to biopsy 
• Cardiovascular observations 
- 
Phlebitis 
- 
Arrhythmias 
- 
Hypertension 
- 
Cold extremities 
- 
Pericarditis 
- 
Tamponade 
- 
Myocardial ischemia 
- 
Heart failure 
- 
Pericardial effusion 
- 
Peripheral edema 
- 
Hyper/hypotension 
- 
Hyperlipidemia 
- 
Deep vein thrombosis 
• Neurological 
- 
Hallucinations 
- 
Confusion 
- 
Headaches 
- 
Insomnia 
- 
Psychosis 
- 
Neuropathy 
- 
Anxiety 
- 
Depression 
- 
Tremor 
- 
Visual disturbances 
• Head/Eyes/Ears/Nose/Throat: 
- 
Sinusitis 
- 
Sore throat 
- 
Hoarseness 
- 
Paralyzed vocal cord 
- 
Cough 

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- 
Epistaxis 
- 
Thrush 
- 
Herpes 
• Renal/Genitourinary  
- 
Urinary tract infection 
- 
Urinary retention 
- 
Dysuria 
- 
Hematuria 
- 
Renal failure 
- 
Azotemia 
- 
Dehydration 
- 
Electrolyte imbalance 
• Hematological 
- 
Anemia 
- 
Leukopenia 
- 
Thrombocytopenia 
- 
Pancytopenia 
- 
Leukocytosis 
- 
Coagulopathy 
• Musculoskeletal 
- 
Myopathy 
- 
Tendonitis 
- 
Deconditioning 
- 
Weakness 
- 
Osteoporosis 
- 
Fracture 
- 
Pain 
- 
Osteonecrosis 
• Endocrinological 
- 
Osteopenia 
- 
Diabetes 
- 
Decreased testosterone 
- 
Vitamin D deficiency 
- 
Hyper/hypothyroidism 
- 
Adrenal insufficiency 
- 
Cushingoid changes 
 
Events Related to Study Endpoints 
Any adverse events that are also defined within the primary and secondary endpoints do not 
require reporting as AEs since these are reported within the CRF. For example, PGD within the 
first 72 hrs or subject death does not require separate AE reporting from the Study Center since 
these events are captured via CRF. However, if a subject death was the outcome of a fatal SAE, 
then that SAE should be captured on the CRF. Additionally, if an AE defined as a primary or 
secondary endpoint meets the UADE criteria, expedited reporting is required. 

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6.13.2 
Performing Adverse Events Assessments or Recording of Adverse Events 
The Study Center staff will record and monitor all AEs throughout the Analysis Phase of the 
study (1-year post-intervention), from the time of transplanted lung reperfusion until the end of 
the subject’s study participation. At all study visits, reports of AEs will be elicited by a verbal 
probe (“How are you feeling?”). Subjects will be encouraged to contact the Study Center to 
report an AE at any time. Appropriate measures, including medical intervention and/or 
procedures, will be instituted if clinically indicated at the discretion of the Investigator.  
All AEs occurring during the study must be documented, and any AEs occurring during the first 
90 days post-transplant must be reported in the CRFs for AEs. For each AE, the Investigator will 
evaluate the severity and seriousness, as well as the relationship of the AE to the device and 
procedure. Information relating to the AE, such as onset and cessation date and times, 
seriousness, severity, relationship to device/procedure, action taken, and outcome will also be 
documented in the subject’s source documentation for assessment. Where possible, AEs should 
be recorded using standard medical terminology. If several signs or symptoms are clearly related 
to a medically defined diagnosis or syndrome, the diagnosis or syndrome should be recorded, not 
the individual signs and symptoms. 
6.13.3 
Timing of Adverse Event Collection 
All AEs are collected from the time of transplanted lung reperfusion through subject 
participation duration (1 year post-operative). Reporting procedures are described in 
Section 6.13.7. 
Subjects with AEs that are ongoing at the subject’s last Study Center visit must be followed until 
resolution or for 30 days after the subject’s last Study Center visit, whichever comes first. 
Adverse events that are recorded during the 7 days following the subject’s last Study Center visit 
will be followed until resolution or for up to the 30 days after the subject’s last Study Center 
visit, whichever comes first. All AEs that are ongoing after follow-up for 30 days’ time will be 
recorded as ongoing. The Investigator is expected to provide or arrange appropriate supportive 
care for any subject with ongoing AE(s). 
Serious adverse events (SAEs) should be followed until they resolve or the event or their 
sequelae stabilize. Supplemental measurements and/or evaluations may be necessary to 
investigate fully the nature and/or causality of an AE or SAE. Such supplementary assessments 
may include additional laboratory tests, diagnostic procedures, or consultation with other 
healthcare professionals. The subject’s source documents and CRFs for AEs should be updated 
with any new or additional information as appropriate.  
If the subject reports or the Investigator learns of any new SAE that occurs up to 30 days after 
the subject’s last clinical site visit, the clinical site personnel will ensure that these data are 
reported on the AE CRF. 
6.13.4 
Severity 
The Investigator will use the following scale to grade the severity of any AEs: 

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• Mild:  no intervention required; no impact on activities of daily living (ADL) 
• Moderate:  minimal, local, or non-invasive intervention indicated; moderate impact on ADL 
• Severe:  significant symptoms requiring invasive intervention; subject seeks medical 
attention, needs major assistance with ADL 
 
6.13.5 
Relationship 
The relationship of an AE to EVLP procedure and lung transplant must be assessed by the 
Investigator using the following guidelines: 
• Related:  The event is associated with the use of the investigational device or with 
procedures beyond a reasonable doubt  
• Possibly Related:  The relationship with the use of the investigational device or procedure is 
weak but cannot be ruled out completely; alternative causes are also possible. 
• Unlikely:  The relationship with the use of the investigational device or procedure seems not 
relevant and/or the event can be reasonably explained by another cause, but additional 
information may be obtained. 
• Not related:  There is no temporal relationship between the investigational device or 
procedure and the event onset, an alternate etiology has been established. 
 
6.13.6 
Expectedness 
The Sponsor, Independent Medical Monitor, and the Study Principal Investigator will be 
responsible for determining whether an SAE is expected or unexpected. An AE will be 
considered unexpected if the nature, severity, or frequency of the event is not consistent with the 
risk information previously described for the intervention. Anticipated adverse events not related 
to EVLP as listed in Section 6.13.1 are for purposes of this study considered to be “expected” 
events and do not require AE reporting. 
6.13.7 
Reporting Procedures 
The Sponsor will report all AE’s occurring during the first 90 days post-transplant, and all SAEs 
occurring during the one-year Analysis Phase of the study to the FDA in the annual 
Investigational Device Exemption (IDE) report. Each reported AE will include date of onset, 
actions taken, severity, seriousness of the event, relationship of the event to the EVLP procedure 
or lung transplant, and the outcome of the event. 
6.13.7.1 
Reporting Serious Adverse Events 
All SAEs, including subject deaths, are reported to the CRO within one working day after 
awareness via the Adverse Event CRF. The Sponsor shall review all SAEs to assess if related or 
anticipated. Any event that meets the serious criteria, is unanticipated, and related to the device 
system is reviewed by the Sponsor Independent Medical Monitor and subject to expedited 
reporting to FDA and participating IRBs in accordance with the Unanticipated Adverse Device 
Effect requirements (21 CFR 812.150). The Sponsor or Sponsor’s representative will report any 

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results of an evaluation of UADE to the FDA, Institutional Review Board (IRB), and all 
Investigators within 10 business days following receipt of notice of the event(s). 
All other SAEs for the Analysis Phase of the study will be reported to FDA in the annual IDE 
report. 
In addition to the above, it is the responsibility of the Study Investigator to abide by the AE 
reporting requirements stipulated by the IRB.  
6.13.7.2 
Reporting Procedure for Serious Adverse Events 
Any AE meeting the specified SAE criteria will be submitted on an AE CRF to the CRO. This 
report may be sent by fax or email. Once submitted, the CRO will send a confirmation email to 
the Investigator within one business day. The Investigator should contact the CRO if this 
confirmation is not received. This process applies to both initial and follow-up SAE reports. 
SAE Reporting Contact Information:    
Safety Fax Line (US):   1-800-673-7523 
Product Safety Email:   ctisafety@ctifacts.com 
General questions about SAE reporting can be directed to the Safety Help Line (available 
8:00AM – 5:00PM Eastern Time):  1-800-755-0742 
The Study Investigator will complete an AE CRF with fax cover sheet found in the study manual 
and submit via fax or email within the following timelines:   
• All SAEs, including deaths, regardless of relationship, will be reported by fax or email within 
24 hrs of site awareness.  
• All SAEs will be followed until resolution or stabilization. 
 
6.13.8 
Initial Safety Review 
The Sponsor will temporarily pause the study after the twentieth (#20) subject has been enrolled 
to allow time for the FDA to review safety data on the first 10 EVLP subjects and any control 
subjects enrolled who have reached 90-days post-transplant.  
Data from the first 10 subjects through their 90-day visit will be submitted to FDA as an IDE 
Supplement for review. Submitted data will include graft survival, aggregate PGD scores, FEV1, 
oxygen required at rest, and BOS Grade. The study will be on hold during this review with the 
exception of Subjects 11 through 20 who are “ongoing”; these subjects will continue to come to 
the Study Center as specified in the protocol. Upon satisfactory review, the FDA will permit the 
continuation of the study to the full subject enrollment. If the FDA has concerns, the Sponsor 
will address these in a satisfactory manner.  

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6.13.9 
Halting Rules 
The Sponsor shall implement an immediate enrollment pause if there is any of the following:  
• a third subject death within the first 30 days post- transplant; 
• if the PGD3 rate at T72 ≥ 50% in the first 10 subjects; or  
• the Medical Monitor shall review all UADEs and deaths in the study and will make a 
determination if an unreasonable risk to subjects exist. If an unreasonable risk has been 
determined based on the opinion of the Medical Monitor, the trial, or the parts that cause the 
risk, shall be stopped until an alternate solution can be devised by the Sponsor and accepted 
by each IRB and FDA. 
 
6.14 Removal of Subjects from the Study 
Subjects may withdraw voluntarily from the study or the Investigator may terminate a subject's 
participation. Withdrawing from the study will not affect subject’s status/ability to receive a 
standard lung transplant. 
Subjects are free to withdraw from participation in the study at any time upon request. 
The Investigator may withdraw a subject from the study for any reason, including but not limited 
to, the following: 
• Any clinical AE, laboratory abnormality, or other medical condition or situation occurs such 
that continued participation in the study would not be in the best interest of the subject.  
• The subject meets an exclusion criterion (either newly-developed or not previously 
recognized) that precludes further study participation. 
• A protocol violation occurs. 
• The Sponsor or Investigator terminates the study. 
 
It is unlikely that a subject will discontinue study participation after receiving a lung transplant, 
as a lifetime of required follow-up, immunosuppression monitoring, and infection control is 
required after transplantation to minimize the chance of graft failure and/or death. Every effort 
will be made to undertake protocol-specified safety follow-up procedures to capture AEs, SAEs, 
and UADEs.   
6.15 Premature Termination or Suspension of the Study 
This study may be suspended or prematurely terminated if there is sufficient reasonable cause. 
Written notification, documenting the reason for study suspension or termination, will be 
provided by the suspending or terminating party to Study Investigators, the IDE Sponsor, and all 
regulatory authorities. If the study is prematurely terminated or suspended, the Principal 
Investigator will promptly inform the IRB and will provide the reason(s) for the termination or 
suspension.  

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Circumstances that may warrant termination include, but are not limited to: 
• Determination of unexpected, significant, or unacceptable risk to subjects. 
• Insufficient adherence to protocol requirements. 
• Data that are not sufficiently complete and/or evaluable.  
• Determination of futility. 
 
6.16 Appropriateness of Measurements 
PGD3 at T72 and 30-day mortality are the primary safety endpoints measured for subjects in this 
study (Section 2.1).  
PGD3 has been shown in the literature to be a very good predictor of transplanted organ function 
as it has a significant impact on short- and long-term recipient survival including: 
• PGD3 at T72 demonstrated a significantly higher risk of 30-day mortality, accounting for 
50% of all-cause deaths compared to PGD0 at T72.  
• PGD3 at T72 is associated with an increased 90-day mortality rate of 18% and an increased 
1-year mortality rate of 23%. 
• PGD3 at T72 has the strongest association with long-term mortality compared to PGD scores 
at other time points post-transplant even after 1 year.[Suzuki 2013] 
 
 Over 100 lung transplants using lungs after undergoing EVLP at TGH and showed similar 
30-day, 1-year, and 3-year survival outcomes compared to the contemporaneous (non-EVLP) 
recipient populations.[ Cypel 2011a; Cypel 2011b; Cypel 2012; Tikkanen 2012; Munshi 2013; 
Cypel 2013] Similarly, in this study, short-term and long-term survival will be documented for 
all subjects.  
While the prognostic value of PGD grading in DLT has gained clinical acceptance, the 
experience with PGD scores in SLT is more limited. In DLT, the measurement of oxygenation 
reflects the contribution of both transplanted lungs. In contrast, measured oxygenation reflects 
contributions from both a diseased, native lung and a transplanted graft when only a single lung 
is transplanted. The Lung Transplant Outcomes Group found the SLT itself was a risk factor for 
adverse PGD scores and was associated with worse long-term outcomes [Diamond 2013], 
although the reasons for this association are not understood. Thus, to address the lack of clinical 
clarity, the measurement of 30-day mortality is included as a co-primary endpoint, and is 
intended to account for the uncertainty provided by PGD scoring of SLT. Both co-primary 
endpoints will be considered to inform on prediction of long-term survival in SLT recipients. 
The contemporaneous control group will be used to provide context for interpreting these results. 
 
 

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7 
STUDY ACTIVITIES 
A review of the transplant candidate files, donor information, and lung evaluation is required to 
determine preliminary eligibility according to recipient and donor lung inclusion and exclusion 
criteria.  
The Study Schedule of Events is tabulated in Appendix 1 for both the Analysis Phase (Table 3) 
and the Long-term Follow-up Phase (Table 4).  
7.1 
Screening Visit (Days –365 to -1 [-24 hours]) 
A Screening Visit may occur any time from up to one year to the day of lung transplant. The 
following may be conducted during this visit: 
• Obtain informed consent per Section 10.4. 
• Determine patient eligibility according to applicable Inclusion (Section 4.2) and Exclusion 
Criteria (Section 4.3). 
 
7.2 
Intervention 
7.2.1 
Lung Assessment, Recipient Baseline, and Lung Transplant (Day 0) 
7.2.1.1 
Donor Lung Screening (Day 0, within 24 hours prior to transplant) 
For EVLP lung donors, the Sponsor will perform the following: 
• Collect donor information (see Section 6.1) 
• Confirm donor lung eligibility according to the donor Inclusion (Section 5.2.1) and Exclusion 
criteria (Section 5.2.2) for EVLP Assessment. 
 
For Control subjects, the Investigator will perform the following: 
• Collect donor information (see Section 6.1) 
• Forward donor information for entry into Sponsor CRF 
 
7.2.1.2 
Recipient Screening (Day 0, within 24 hours before transplant) 
For both EVLP and Control subjects, the Investigator will perform the following: 
• Consent or reconfirm consent in accordance with the IRB policy. 
• Collect the following recipient information: 
- 
Medical history of diseases or conditions ongoing in the past year. 
- 
Date of Birth 

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- 
Gender 
- 
Ethnicity 
- 
Race 
- 
Weight 
- 
Height 
- 
LASDDG 
- 
LAS 
- 
Oxygen requirement status (L/min) 
 
• Perform physical examination. 
• Confirm recipient eligibility in accordance with the recipient Inclusion (Section 4.2) and 
Exclusion Criteria (Section 4.3). 
 
7.2.1.3 
Donor Lung EVLP Evaluation (at completion) 
The Sponsor will perform the following: 
• Record preservation information (see Section 6.1):  cross clamp time/ start of first cold 
preservation (CIT-1), volume, type, macroscopic lung evaluation. 
• Confirm donor lung eligibility in accordance with the donor lung Inclusion (Section 5.2.3.1) 
for transplant suitability AFTER EVLP. 
• Clinical parameters will be collected and used as part of the EVLP suitability evaluation that 
is performed by the Investigator. 
 
7.2.1.4 
Lung Transplantation (Day 0) 
Provided all recipient and lung Inclusion and Exclusion Criteria have been met, the Investigator 
or his/her designee will record the following at the time of admission to the ICU after lung 
transplantation: 
• Hospital admission date 
• Transplant date and time, including removal from cold storage time for each lung 
• ICU admission time and date 
• Initial PaO2 and FiO2 upon ICU admission 
• PGD score (0 hrs) 
 
7.3 
Post-intervention Period; Analysis Phase (Day 1 to 1 Year Post-Transplant) 
7.3.1 
Visit 1 Procedures (24 Hours post-transplant) 
At 24-hrs post-transplant (± 4 hrs), the Investigator or his/her designee should perform the 
following: 
• Record PGD Score (Section 6.7) 

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• Assess any AEs 
 
7.3.2 
Visit 2 Procedures (48 Hours post-transplant) 
At 48-hrs post-transplant (± 8 hrs), the Investigator or his/her designee should perform the 
following: 
• Record PGD Score (Section 6.7) 
• Assess any AEs 
 
7.3.3 
Visit 3 Procedures (72 Hours post-transplant) 
At 72-hrs post-transplant (± 12 hrs), the Investigator or his/her designee should perform the 
following: 
• Record PGD Score (Section 6.7) 
• Record extubation date/time (if applicable) 
• Record ICU discharge time/date (if applicable) 
• Assess AEs 
 
7.3.4 
Visit 4 Procedures (Day 30 post-transplant) 
On Day 30 post-transplant (± 5 days), the Investigator or his/her designee should record the 
following: 
• Subject and graft survival and if failed, cause of failure 
• If extubated >72 hrs post-transplant, extubation time 
• FEV1 (Day 30 or upon hospital discharge, if before 30 days) 
• Oxygen required at rest (Day 30 or upon hospital discharge, if before 30 days) 
• Hospital discharge date and readmission date(s) (if applicable) 
• Assess AEs 
 
7.3.5 
Visit 5 Procedures (Day 90 post-transplant) 
On Day 90 post-transplant (± 10 days), the Investigator or his/her designee should record the 
following: 
• Subject and graft survival and if failed, cause of failure 
• FEV1 
• Oxygen required at rest 
• BOS Grade 
• Physical capacity 

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• Working for income status 
• Hospital readmission date(s) (if applicable) 
• Assess AEs 
 
7.3.6 
Visit 6 Procedures (Month 6 post-transplant) 
At Month 6 post-transplant (± 2 weeks), the Investigator or his/her designee should record the 
following: 
• Subject and graft survival and if failed, cause of failure 
• FEV1 
• Oxygen required at rest 
• BOS Grade 
• Physical capacity 
• Working for income status 
• Hospital readmission date(s) (if applicable) 
• Assess AEs 
 
7.3.7 
Visit 7 Procedures/ Final Visit (1 year post-transplant) 
The final study visit for the Analysis Phase will occur one year post-transplant At Year 1 post-
transplant (± 4 weeks), the Investigator or his/her designee should record the following: 
• Subject and graft survival and if failed, cause of failure 
• FEV1  
• Oxygen required at rest 
• BOS Grade 
• Physical capacity 
• Working for income status 
• Hospital readmission date/s (if applicable)  
• Assess AEs 
 
7.4 
Post-intervention Period; Long-term Follow-up Phase (1 to 5 Years Post-
Transplant) 
Outcome data will be collected annually for 5 years post-intervention. However, lung 
transplantation requires follow-up care for the life of the subject. The hospital where the 
transplant was performed, or another transplant hospital if the subject moves, will continue 
providing standard of care follow-up services to the subject for the rest of subject’s lifetime. 

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Visit 8 (Year 2), Visit 9 (Year 3), Visit 10 (Year 4), and Visit 11 (Year 5)  
The following data will be collected annually for Year 2 through Year 5 (±4 weeks) by the Study 
Center and reported to OPTN/UNOS database and retrieved by the Sponsor (see 
Section 10.11.2.3): 
• Subject and graft survival and if failed, cause of failure 
• FEV1  
• Oxygen required at rest 
• BOS Grade 
• Physical capacity 
• Working for income status 
• Hospital readmission date/s (if applicable) 
 
7.5 
Early Termination Procedures 
As lung transplant requires life-long follow-up care from the transplant center, it is unlikely a 
subject will withdraw from this study post-transplant. Subjects may withdraw consent to 
participate prior to receiving the intervention (lung transplant) within this study without 
consequence to the subject or study. In the event that a patient withdraws consent after lung 
transplant, the following data will be collected by the Study Center either through OPTN and/or 
SRTR reports or via an early termination visit: 
• Subject and graft survival and if failed, cause of failure  
• FEV1  
• Oxygen required at rest 
• BOS Grade 
• Physical capacity 
• Working for income status 
• Hospital readmission date/s (if applicable) 
• Assess AEs 
 
7.6 
Unscheduled Visits 
Upon receiving any lung transplant, a subject may require a number of unscheduled visits for a 
variety of reasons, including infection and rejection. If an unscheduled visit is performed due to a 
documentable AE, then it will be tracked as such. After 30 days post-transplant, all hospital 
readmissions and root cause will be documented and tracked in the standard OPTN/UNOS 
database and made available to the Sponsor. 

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8 
QUALITY CONTROL AND ASSURANCE 
Quality Management is the overall process of establishing and ensuring the quality of processes, 
data, and documentation associated with clinical research activities. It encompasses both quality 
control (QC), and QA activities. All sites conducting research under the sponsorship of the 
Sponsor are required to have a plan in place for assuring the quality of the research being 
conducted.  
Each site should have standard operating procedures (SOPs) and/or a quality management plan 
that describe:   
• How data will be evaluated for compliance with the protocol and for accuracy in relation to 
source documents.  
• The documents to be reviewed (e.g., CRFs, clinic notes), who is responsible, and the 
frequency for reviews.   
• Who will be responsible for addressing QA issues (correcting procedures that are not in 
compliance with protocol) and QC issues (correcting errors in data entry).  
• Staff training methods and how such training will be tracked. 
• If applicable, calibration exercises conducted prior to and during the study to train examiners 
and maintain acceptable intra- and inter-examiner agreement. 
 
8.1 
Sponsor’s Quality Process 
The Sponsor will conduct the EVLP lung assessment procedure exclusively at the Sponsor’s 
dedicated facility. All post-EVLP procedures will be reviewed by an in-house QA manager for 
compliance with the TES User Manual and clinical trial protocol, as well as for accuracy in 
relation to source documents. 
In addition, the Sponsor will use an independent CRO to oversee its activities. Finally, 
Independent Medical Monitors will review all UADE to verify if they are related to the EVLP 
procedure, the lung transplantation, or other controllable/ uncontrollable event (Section 10.8). 
8.2 
Training for Study Interventionalists 
Training will be completed prior to participation in the clinical trial as outlined in the following 
sections. 
8.2.1 
Transplant Center Research Personnel 
Study Center site personnel will be trained on study activities, provided a review of Good 
Clinical Practice (GCP), obtaining informed consent, and the study protocol.  

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8.2.2 
Lung Recovery Surgeons 
Surgeons recovering lungs for this study will be experienced lung recovery surgeons listed in the 
AOPO Credentials Information Network (ACIN). 
8.2.3 
Lung Transplant Surgeons 
All Study Center Investigators will be experienced practitioners of lung transplantation. Current 
licensure will be maintained in the study records for each participating surgeon. 
8.2.4 
EVLP Specialists 
Ex Vivo Lung Specialists, specifically trained to perform EVLP by University Health Network in 
Toronto, Canada, will perform all EVLP procedures exclusively at the Sponsor’s dedicated site 
in Silver Spring, MD. Each donor lung, meeting study Inclusion Criteria (Section 5.2) and 
offered to the Sponsor by a participating transplant center, will be perfused normothermically by 
the EVLS for up to 6 hours according to the procedures described in the TES User Manual. 
All EVLP Specialists performing procedures at the Sponsor’s site will have extensive training in 
the TES through a 6-month in-residence program at TGH, culminating in successful completion 
of the Ex Vivo Lung Specialist Certification and Privileging Exam administered through 
University Health Network, Toronto, Ontario. This training program is the first of its kind, and 
the most comprehensive for the newly emerging field of EVLP. 
The didactic portion of the EVLS training includes lectures and self-guided reading of applicable 
medical literature in the following areas: 
a. Lung transplantation- history and overview 
b. Lung allograft donation and procurement 
c. Legislative framework 
d. Lung anatomy and physiology 
e. Perfusion concepts 
f. Ventilation strategies 
g. TES 
 
The practical, hands-on experience includes observing a minimum of five research (animal) 
EVLP procedures and actively participating in at least 25 research EVLP procedures. 
Additionally, a minimum of five clinical (human) EVLP procedures will be observed and at least 
five more clinical cases will be performed with active participation, of which three must be 
transplanted at the end of the procedure.  
The final exam includes written, oral and practical assessments while independently performing 
a 12-hour long research procedure using the TES to perfuse bilateral swine lungs while being 
evaluated by a preceptor for the following skills: 
a. Cannulation of the pulmonary artery and left atrium without leaks. 

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b. Proper placement and securing of the endotracheal tube correctly in trachea. 
c. Able to discuss equipment used in the TES and rationale for why each piece was specifically 
chosen. 
d. Calibrate the ventilator, pump flow and pressure sensors independently. 
e. Effectively de-airs the perfusion circuit without difficulty. 
f. Place lungs on the EVLP circuit independently without kinks in the cannulas. 
g. Performs retrograde flushing of the lungs prior to perfusion. 
h. Calculates the correct lung flow and ventilation targets. 
i. Warms up lung in correct sequence. 
j. Turns on deoxygenation gas mixture at the correct time and begins ventilation in the correct 
sequence. 
k. Makes independent changes to the ventilator as required. 
l. Can operate and retrieve data from the Stöckert Centrifugal Pump Console (SCPC) pump, 
heater/cooler, pressure and temperature monitor, ventilator and ABG machine (see 
Appendix 4). 
m. Can perform x-ray and bronchoscopy of the lung independently. 
n. Can maintain a lung on the TES for a minimum of 12 hours without decrease in function. 
o. Can cool down lung in correct sequence. 
p. Can remove lung and repackage independently according to OPTN/UNOS policy. 
 
 

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9 
PLANNED STATISTICAL METHODS 
9.1 
General Considerations 
This section describes the planned statistical analyses in general terms. A complete description of 
the methodology will be specified in a statistical analysis plan (SAP), which will be finalized 
prior to database lock. Any changes in the statistical methods described in this protocol that 
occur prior to database lock will be documented in the statistical analysis plan and will not 
require a protocol amendment. 
Statistical analysis will be performed primarily on data collected during the Analysis Phase 
(1-year post-intervention). The database will be locked for analysis of endpoints after the last 
subject completes his/her study visit at Year 1, and all queries have been resolved. The 
Long-term Follow-up data will be summarized when the study has completed in support of long-
term evaluation.   
No statistical hypotheses will be tested in this study. For ease of presentation, contextual review 
and statistical programming, the descriptive statistics of the contemporaneous Control group will 
be presented with those of the EVLP group. Descriptive statistics will be presented as means, 
standard deviations (SD), medians, and ranges for the continuous variables and as frequencies 
and percentages for categorical variables. Tabulations will be used to summarize results from 
descriptive summaries and statistical analyses. A one-sided 95.0% CI will be provided, as 
appropriate, for the primary endpoints, and two sided 95.0% CI will be presented for all 
endpoints, as appropriate. 
9.2 
Determination of Sample Size 
In order to provide a sufficient number of subjects for reliable estimation of the primary 
endpoints, sample size was calculated based on a primary endpoint of PGD3 at T72. Estimates of 
PGD3 at T72 were based on historical data from EVLP transplant studies where EVLP subjects 
had rates of PGD3 at T72 ranging from 0% to 15% and conventional transplant subjects ranging 
from 16.8% to 30% [XVIXO Perfusion Inc. 2014; Cypel 2012; Cypel 2011a; Machuca 2014; 
Aigner 2012; Diamond 2013]. Assuming a PGD3 at T72 of 10% and a one-sided 95.0% 
confidence interval (CI) for a single proportion using the large sample normal approximation 
adjusted for a finite population of size 2057 (number of lung transplants performed in the US in 
2015 [OPTN 2015]), 66 subjects will be needed for the expected upper bound of the CI to not 
exceed a rate of 16% (nQuery Advisor 7.0, 2007). A total of 66 EVLP subjects and 66 Control 
subjects will be included in this study.  
Rates of 30-day mortality in the EVLP transplant studies have been low, ranging from 3% to 4%. 
For a sample size of 66, the probability of observing at least one event will be approximately 
87% to 93% if the true probability of 30-day mortality is 3% to 4% (nQuery Advisor 7.0, 2007). 
Subjects will be entered into the study as EVLP transplants occur; however, enrollment to either 
transplant subtype (single-lung, double-lung) will be limited to 44 subjects to provide a 
reasonable number of subjects of both subtypes for subgroup examinations. 

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A contemporaneous Control group will be entered into this study. This Control group will 
provide context of the EVLP results and estimation of Control group parameters for design of 
future studies. All analyses of the Control group will be descriptive and no formal statistical 
comparison will be made between the EVLP and Control groups. As such, the sample size for 
the Control group will be 66 subjects, and subjects will be matched to the EVLP Group for 
similarity. Because the ratio of standard lung transplant to EVLP transplant is estimated to be 
approximately 4:1, it is feasible to obtain a control-EVLP match within the anticipated duration 
of the study. 
9.3 
Analysis Populations  
All subject included in the analyses to the extent data are available. Planned exceptions will be 
noted in the SAP.  
Deviations from inclusion/exclusion criteria will be listed by subject. 
9.4 
Demographics and Baseline Characteristics 
Demographic data and baseline characteristics for all subjects collected prior to transplant will be 
listed and summarized overall, by Transplant Group (EVLP or Control), as well as by transplant 
subtype (SLT or DLT) using descriptive statistics.  
Medical history (medical conditions ending prior to EVLP transplant) will be coded using the 
WHO-drug dictionary, presented as a listing and summarized overall and by transplant subtype 
using the system organ class (SOC). 
9.5 
Primary Endpoint(s) 
9.5.1 
Primary Graft Dysfunction Grade 3 at 72 hours Post-transplant 
The PGD3 Score at 72 hrs post-transplant (T72), as defined in Section 6.7, will be used as the 
basis for the primary safety endpoint for analysis. The primary endpoint (PGD3 T72) will be 
calculated from PGD T72 as follows:  PGD T72 = {0, 1, & 2} will be coded to PGD3 T72 = 0 
and PGD T72 = {3} will be coded to PGD3 T72 = 1. 
If a subject dies prior to the T72 measurement, they will be coded to PGD3 T72 = 1. If the T72 
value is missing (not collected, not reported, not properly documented), then PGD3 will be 
coded to PGD3 T72 = 1 for the primary safety analysis.   
 
The primary analysis will be descriptive as the proportion of subjects with PGD3 T72 by 
Transplant Group (EVLP and Control). A one-sided 95% CI will be calculated around the 
proportion. A two-sided 95% CI will also be calculated. 
There will be no inferential testing conducted. 

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9.5.2 
30-Day Mortality 
Subject survival, measured as living or dead, will be recorded for Day 30, Month 6, and Year 1 
post-transplant (see Section 6.8). The primary endpoint of 30-Day mortality will be derived as 
follows:  Living at Day 30 will be coded to 0, and Dead before or on Day 30 will be coded to 1. 
If the vital status of the subject is missing (not collected, not reported, not properly documented), 
then 30-Day Mortality will remain missing for the primary analysis. 
The primary analysis will be descriptive as the proportion of subjects with 30-Day mortality, 
summarized by Transplant Group. A one-sided 95% CI will be calculated around the proportion. 
A two-sided 95% CI will also be calculated. 
Other supportive endpoints may be provided to supplement the primary analysis, including, but 
not limited to, median number of days to death and primary cause of death.  
Results may be displayed graphically. There will be no inferential testing conducted. 
9.6 
Secondary Endpoint(s) 
Secondary endpoints included the following: 
• PGD Score (Grades 0-3) measured at 0, 24, 48 and 72 hours post-transplant 
• Time to first extubation 
• ICU LOS, measured as total number of days post-transplant in the ICU until first hospital 
discharge, inclusive of ICU readmissions during that hospitalization  
• Hospital LOS, measured as total number of days in the hospital prior to discharge 
post-transplant 
• TPT defined as the elapsed time between first allograft lung removal from cold storage time 
prior to transplant in the recipient and the donor aortic cross clamp time at procurement 
• Assessment of the overall safety of TES lung transplants during subject's participation in the 
study, as reported through AEs (refer to Section 9.9.1 below). 
 
All secondary endpoints will be presented using descriptive statistics along with two sided 95% 
CIs by Transplant Group. Other supportive endpoints may be provided to supplement the 
secondary analyses.  
Results may be displayed graphically. There will be no inferential testing conducted. 
9.7 
Exploratory Endpoints 
Other safety endpoints that will be analyzed include: 
• Initial ICU PaO2: Evaluated as first PaO2 measured after ICU admission. 
• FEV1:  Evaluated at time of discharge, 30 days, 90 days, 6 months and 1 year post-transplant. 
FEV1 is measured as a percentage of predicted normal value. 

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• Oxygen Requirement at Rest:  Evaluated at time of discharge, 30 days, 90 days, 6 months 
and 1 year post-transplant.  
• Subject Survival:  Evaluated at 90 days, 6 months and 1 year post-transplant. Measured as 
living or dead. If the subject expires within first year post-transplant, the date of death and 
primary cause of death will be collected. 
• Graft Survival:  Evaluated at 30 days, 90 days, 6 months and 1 year post-transplant. 
Measured as functioning or failed. If the graft fails within first year post-transplant, the date 
of graft failure will be collected. 
• Primary Cause of Graft Failure:  Evaluated at 30 days, 90 days, 6 months and 1 year post-
transplant on all failed grafts.  
• Bronchiolitis Obliterans Syndrome (BOS) Grade:  Evaluated at 90 days 6 months and 1 year 
post-transplant.  
• Number of Re-hospitalizations after Transplant:  Evaluated at 6 months and 1 year 
post-transplant. Measured as total number of hospitalizations since initial discharge. 
• Physical Capacity:  Evaluated at 90 days, 6 months and 1 year post-transplant.  
• Working for Income after Transplant:  Evaluated at 90 days, 6 months and 1 year post-
transplant.   
 
All exploratory endpoints will be presented using descriptive statistics along with two sided 95% 
CIs by Transplant Group. Other supportive endpoints may be included as needed.  
Results may be displayed graphically. There will be no inferential testing conducted.  
In addition, supplemental analyses comparing the EVLP group and the Control Group may be 
performed to provide context of results observed in this study (details will be described in the 
SAP). 
9.8 
Missing Data 
The primary safety analysis is the proportion of subjects with a PDG3 at T72. PGD is measured 
in all lung transplant subjects at specific intervals following transplantation, including 24, 48, 
and 72 hrs. Protocol training will focus on the importance of obtaining PGD at T72 in every 
study subject.   
If a subject dies prior to the T72 measurement, they will be counted as a “failure” and classified 
as PGD3 for the primary safety analysis. If the T72 value is missing (not collected, not reported, 
not properly documented), then PGD3 will be assumed (“failure”), and they will be classified as 
such for the primary safety analysis.   

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9.9 
Other Safety Assessments 
9.9.1 
Adverse Events 
Adverse events will be recorded throughout the study, but only those occurring within the first 
90 days post-transplant will be reported to the Sponsor, unless they are considered SAEs. All 
SAEs will be recorded and reported to the Sponsor throughout the Analysis Phase. Adverse 
events and medical conditions will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA) coding dictionary. Intervention-emergent AEs will be defined as those 
events, which are newly occurring or worsening from Baseline (Day 0). In all cases only 
intervention-emergent AEs will be summarized.  
Intervention-emergent AEs will be summarized by Transplant Group as the number and 
percentage of subjects having any intervention-emergent AE, having an AE in each body system, 
and having each individual AE. Adverse events will further be categorized by severity, 
relationship to study intervention, and action taken. Other information collected will be listed, as 
appropriate.  
9.9.2 
Physical Examination and Vital Signs 
Physical examinations will be performed as described in Section 6.5, and vital signs will be 
recorded as described in Section 6.6. 
Vital sign data will be listed for each subject. Clinically significant values will be flagged. 
Any clinically significant abnormality prior to enrollment is to be recorded as medical history, 
and tabulation of those events will occur within medical history summaries. Any clinically 
significant abnormal change from baseline post-transplant is to be recorded as an AE and 
tabulation of those events will occur within AE summaries.  
9.9.3 
Laboratory Data 
Laboratory data will be collected as described in Section 6.12. 
Laboratory data will be listed for each subject. Laboratory data will be summarized for overall 
and Transplant Group by presenting the proportions of subjects with clinically significant 
abnormalities; shift tables, baseline to most extreme post-baseline value, using normal ranges; 
summary statistics of raw data and change from baseline values (means, medians, standard 
deviations, ranges), as appropriate. 
9.10 Interim Analysis 
There are no formal interim analyses planned for this study. However, as described in 
Section 6.13.8, the Sponsor will temporarily pause the study at EVLP subject #20 to allow time 
for the FDA to review safety data on the first 10 subjects enrolled who reach 90 days 
post-transplant.  

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Data from the first 10 subjects through their 90-day visit will be submitted to FDA as an IDE 
Supplement for review. Submitted data will include subject and graft survival, aggregate PGD 
scores, FEV1, oxygen required at rest, and BOS Grade. 
10 ADMINISTRATIVE CONSIDERATIONS 
10.1 Investigators and Study Administrative Structure 
The term “Investigator” as used in this protocol and in the CRFs refers to the Principal 
Investigator at each study site, or another staff member listed as a subinvestigator on the study 
site delegation log. The site Principal Investigator is ultimately responsible for the conduct of all 
aspects of the study at that site. The site Principal Investigator is also responsible for ensuring 
that all site staff working on the study are appropriately trained and supervised; staff training and 
delegation of responsibilities should be documented in the files.   
Prior to site activation, the Investigator must read, understand, and sign the Investigator 
Agreement in the protocol. The Investigator Agreement documents agreement to conduct the 
study according to the protocol, International Conference on Harmonization / Good Clinical 
Practice (ICH/GCP), and Code of Federal Regulations (CFR). Additional requirements must be 
met by the Investigator and institution, as described below. 
10.2 Institutional Review Board (IRB) or Independent Ethics Committee (IEC) 
Approval 
The protocol, informed consent form(s), recruitment materials, and all subject materials will be 
submitted to each participating study site’s local IRB for review and approval. In addition, the 
Sponsor will operate its EVLP site under the review of an independent third party IRB 
(Appendix 2).  
Approval of both the protocol and the ICF must be obtained before any subject is enrolled. Any 
amendment to the protocol will require review and approval by the IRB before the changes are 
implemented in the study.   
Each IRB must operate in compliance with 21 CFR 56, including being registered with the FDA. 
The IRB is to provide some form of documentation of compliance via a Statement of 
Compliance and/or a Federal Wide Assurance Number. If any member of the research team is a 
member of the IRB, written documentation is required that he/she did not vote or participate in 
the approval process 
10.3 Ethical Conduct of the Study 
The Investigator will ensure that this study is conducted in full conformity with the principles set 
forth in The Belmont Report:  Ethical Principles and Guidelines for the Protection of Human 
Subjects of Research, as drafted by the US National Commission for the Protection of Human 
Subjects of Biomedical and Behavioral Research (April 18, 1979) and codified in 
45 CFR Part 46 and/or the ICH E6; 62 Federal Regulations 25691 (1997). 

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10.4 Authorization and Consent 
10.4.1 
Donor Next of Kin Authorization 
Authorization for organ donation will be obtained by the federally-designated OPO in 
accordance with the requirements of the Uniform Anatomical Gift Act in the state of the donor 
hospital and in compliance with OPTN Policy 2. The OPO also must comply with its internal 
policy regarding donor (or donor family) authorization for additional lung assessment using 
EVLP. 
10.4.2 
Subject (Recipient) Consent 
Informed consent is a process that is initiated prior to the individual agreeing to participate in the 
study and continues throughout study participation. Subjects listed for single or bilateral lung 
transplantation with UNOS may be offered the option to participate in this study. A legal 
authorized representative may be used to consent for a subject that is unable to sign/ consent for 
themselves. The Study Center must adhere to IRB and State law requirements as to who is an 
acceptable Legal Authorized Representative. The Study Center will also obtain documentation 
that person signing consent is authorized to do so. 
Extensive discussion of risks and possible benefits of study participation will be provided to 
subjects and their families. A consent form describing in detail the study procedures and risks 
will be given to the subject. Each participating Study Center will be provided with a model 
informed consent form (ICF). Each institution may revise or add information to comply with 
institution consent templates, but may not remove procedural or risk content from the model 
form. Consent forms will be IRB-approved, and the subject is required to read and review the 
document or have the document read to him or her. The Investigator or designee will explain the 
research study to the subject and answer any questions that may arise.  
The subject will sign the ICF prior to any study-related assessments or procedures. Study-related 
assessments are defined as any study activities in which data are specifically collected from a 
potential subject that could later be used for analysis under this protocol. Pre-screening of 
potential subjects based on previously known medical histories or other information is not 
considered a study-related assessment. Study-related procedures are any medical procedures 
performed to screen or prepare a subject for lung transplantation under this protocol. Screening 
or other procedures performed for the purposes of general lung transplantation suitability or 
compatibility are not considered study-related procedures. 
If consent is obtained the same day that the subject begins study-related assessments or 
procedures, the subject’s medical record should document that consent was obtained prior to 
these activities. Subjects will be given the opportunity to discuss the study with their surrogates 
or think about it prior to agreeing to participate. The consent may be signed during an extended 
period of time prior to the transplant. This extended period timeframe shall be determined by the 
local IRB in reference to the timeframe before a subject is re-consenting versus reaffirming the 
original consent. The consent obtained prior to the day of transplant shall be reconfirmed at day 
of transplant by subject or subject’s legal representative. This shall be documented in the source 

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document by the site staff and will not involve the resigning of the consent unless requested by 
the IRB. A subject may withdraw consent at any time throughout the course of the study.  
A copy of the signed ICF will be given to subjects for their records. The rights and welfare of the 
subjects will be protected by emphasizing to them that the quality of their clinical care will not 
be adversely affected if they decline to participate in this study. 
The consent process will be documented in the clinical or research record. 
A subject is only considered enrolled in the study when he/she has signed the ICF and, at an 
approved Study Center, is transplanted with a donor lung. 
10.5 Subject Confidentiality 
Subject confidentiality is strictly held in trust by the Investigators, study staff, and the Sponsor 
and their agents. This confidentiality is extended to cover testing of biological samples and 
genetic tests in addition to any study information relating to subjects. 
The study protocol, documentation, data, and all other information generated will be held in 
strict confidence. No information concerning the study or the data will be released to any 
unauthorized third party without prior written approval of the Sponsor. 
The study monitor or other authorized representatives of the Sponsor may inspect all study 
documents and records required to be maintained by the Investigator, including but not limited 
to, medical records (office, clinic, or hospital) for the study subjects. The clinical study site will 
permit access to such records. 
Donor records will be redacted for any identifying donor information and instead will only use a 
pre-assigned UNOS Donor ID# to connect donor to recipient. The Sponsor will use the UNOS 
ID# to request baseline donor, 6- and 12-month recipient post-transplant reports from 
OPTN/SRTR to maintain recipient privacy. 
10.6 Study Monitoring 
The study will be monitored according to the guidelines summarized below. The Sponsor may 
choose to perform random inspections throughout the study as an element of quality assurance. 
Investigators shall allow auditing of their clinical investigation procedures and data. 
Data will be collected from EVLP lung transplant recipients and the non-EVLP lung transplant 
recipients included in the Control Cohort. These data will include basic lung transplant 
information along with primary and secondary endpoints as listed in this protocol. 
The monitor(s) will visit the site soon after the first subject is enrolled to assist in any questions 
the site might have concerning the study or CRF completion. Monitoring visits will occur based 
on number of subjects enrolled at a Study Center, duration of the study, level of compliance or a 
significant change in compliance, or a change in Study Center staff.   

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It is the responsibility of the study Sponsor to ensure that proper monitoring of this investigation 
is conducted. Appropriately trained personnel, appointed by the Sponsor, will complete any 
monitoring that is performed. The monitoring will be the responsibility of Sponsor study 
personnel or as designated. Monitors will ensure that the investigation is conducted in 
accordance with: 
• The signed Investigator’s Agreement 
• The study protocol 
• Appropriate laws and regulations 
• Any approval conditions imposed by reviewing IRB and/or regulatory agencies 
 
10.6.1 
Access to Centers 
The Investigator is required to permit monitoring and study record access in order for the 
monitors to perform their responsibility. The Investigator(s), co-investigator(s), and other study 
staff must be available during onsite visits by the study monitor. The Sponsor may choose to 
perform random inspections throughout the study as an element of QA. Investigators shall allow 
auditing of their clinical investigation procedures. 
10.6.2 
Summary of Monitoring Procedures & Responsibilities 
It is the responsibility of the study Sponsor to ensure that proper monitoring of the investigations 
is conducted and that IRB review and approval of the investigation is obtained. Monitoring visits 
will occur based on transplant volume at the center or at least annually. Trained personnel or 
delegates appointed by the study Sponsor will perform study monitoring in order to ensure that 
the investigation is conducted, recorded, and reported in accordance with: the aforementioned 
agreements, plans, and regulations. The Sponsor (or designee) must be allowed access to the 
subjects’ files as per the informed consent at the investigator’s site when so requested. 
10.6.3 
Routine Monitoring 
The following factors will be taken into account when determining the frequency of the 
monitoring visits: subject accrual rate at each center, total number of subjects enrolled at each 
center, protocol violations, risk-based assessments for the primary and secondary endpoints and 
study protocol compliance at each center. Monitors will require direct access to subject medical 
records pertinent to the study (and study inclusion criteria), study management documents, 
regulatory documents and Subject Informed Consent documents, as well as other potential 
applicable records not listed here. 
Monitors may ensure the Study Investigators maintain staff and facilities to conduct the clinical 
investigation safely and effectively. Monitors may conduct the following monitoring activities 
throughout the study: 
• Verification that the current IRB-approved informed consent was signed and dated by each 
subject. 

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• Verification of documentation in the subject’s record that informed consent was signed prior 
to participating in any study-related assessments or procedures and that a copy of the signed 
and dated consent form was provided to the subject. 
• Source documentation verification by reviewing the CRFs against source documentation for 
accuracy and completeness of information. 
• Verification that subjects and donor lung met study enrollment criteria. 
• Confirmation that the study is being conducted according to the study protocol and 
applicable regulations. 
• Verification that study deviations are documented and reported. 
• Verification that the procedures for recording and reporting adverse events to the Sponsor are 
followed. 
• Ensuring proper error correction. 
• Verification of training documentation of all study personnel participating in study related 
activities. 
• Reviewing all correspondence and regulatory documents, including confirmation of 
IRB-approved study protocol or amendments. 
• Resolution of outstanding issues and completion of assigned tasks will be documented by the 
monitors. 
 
10.7 Case Report Forms and Study Records 
Case report forms (CRFs) are used to transmit the information collected in the performance of 
this study to the Sponsor (or its designee) and to governmental agencies. CRFs must be 
completed for each subject enrolled. This study may use paper or electronic CRFs. All paper 
CRFs must be legible and completed in black ball point ink. Data entries for paper CRFs may be 
corrected only by drawing a single line through the incorrect entry and writing in the correct 
entry. Incorrect entries are not to be obliterated by blacking out or use of correction fluid or 
erasers. All corrections must be initialed and dated. Systems for electronic CRFs will be properly 
designed, validated, and implemented prior to use.  
A selected number of donor and subject variables are required data collected by the transplant 
center via the OPTN and UNOS. A data sharing agreement may be developed with the OPTN 
and/or UNOS for electronic transfer of those data elements directly to the Sponsor for each 
enrolled subject/donor. 
CRF general guidelines will be used to complete all CRFs. Subjects will be given identification 
numbers so that their identity cannot be determined by the Sponsor and donor data will be 
identified for use by their UNOS ID. The research coordinator will keep a Master Subject List 
that will equate the identifiers to the actual donors and subjects that are a part of this study. This 
list will be kept in a secure location and will not be part of the Sponsor’s regulatory documents. 
This information will only be made available to the Sponsor and/or their designee for routine 
verification of CRFs and also to the FDA if required for regulatory affairs. 

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The Investigator will review the CRFs for completeness and accuracy and sign and date the 
forms where indicated. Questions regarding missing or uninterpretable data will be 
communicated to the Principal Investigator/study coordinator for resolution and entered into a 
CRF correction form. The CRF correction form(s), after resolution of discrepancies, will be 
signed by the Principal Investigator and the revised data entered into a database. All records 
which support CRFs of this study or follow-up must be retained in the files of the Principal 
Investigator for a minimum of two years or until notification by the Sponsor, whichever is 
earlier. 
10.8 Independent Medical Monitor 
In addition to the Principal Investigator’s responsibility for oversight, study oversight will be 
under the direction of Independent Medical Monitors. The first Independent Medical Monitor is 
Dr. Martin Zamora, lung transplant pulmonologist at the University of Colorado, who has direct 
experience taking care of post-EVLP lung recipients. He is also the author of the medical journal 
article Medical Complications of Lung Transplantation.[Lyu 2009] Dr. Zamora is considered an 
expert in this area and well qualified to make a determination of unreasonable risk in relation to 
lung transplantation and EVLP.  
The second Independent Medical Monitor is Dr. Michael Mulligan, cardiothoracic surgeon at the 
University of Washington. Dr. Mulligan is clinically active with lung transplantation and lung 
volume reduction surgery. 
The Independent Medical Monitors are independent of the study and will be available in real 
time to review and recommend appropriate action regarding AEs and other safety issues. Their 
contact information is located in Appendix 2. 
10.9 Protocol Violations/Deviations 
A study deviation is defined as an event where the Study Investigator or site personnel did not 
conduct the study according to the study protocol, applicable laws or regulations or the 
Investigator agreement. 
Prior approval by the Sponsor is expected in those situations in which the Investigator 
anticipates, contemplates, or makes a conscious decision to depart from procedures specified in 
the study protocol, except when necessary to protect the life or physical well-being of a subject 
in an emergency. Prior approval is not expected in situations where unforeseen circumstances are 
beyond the Investigator’s control (e.g., inadvertent mistakes, equipment failure, subject unable to 
do required testing due to illness). 
All study deviations will be recorded on a Protocol Deviations form, including a description of 
the deviation, justification for the deviation, and corrective action for the deviation. Study 
deviations may be discovered through a variety of sources, such as during the CRF review, 
telephone conversations, and site monitoring. Study deviations should be reported to the 
applicable IRB in accordance with IRB policies and/or local laws. When relevant, ethics 
committees, competent authorities or the appropriate regulatory bodies should be informed. The 

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Sponsor will review all deviations from the study protocol. Corrective action and preventative 
action will be performed after protocol deviations are discovered during monitoring visits. 
Deviations will be reported to the CRO and the Sponsor regardless of whether medically 
justifiable, pre-approved by the Sponsor or taken to protect the subject in an emergency. Study 
deviations should be reported as soon as possible upon notification of the deviation. Investigators 
must notify the Sponsor and reviewing IRB within five working days. Examples of deviations 
from the study protocol may include: 
• No informed consent prior to transplant within a study subject. 
• Incorrect version of consent provided to subject. 
• Enrollment of subject prior to IRB approval. 
• Enrollment of subject during an IRB approval lapse. 
• Subject did not meet inclusion/exclusion criteria. 
• Required testing and/or measurements not performed. 
• Source data permanently missing. 
• Adverse event not reported by Investigator in the required regulatory time frame. 
• Unauthorized physician performed study procedures (e.g. implanting physician was not an 
Investigator). 
 
10.10 Access to Source Documentation 
Each participating site will maintain appropriate medical and research records for this study, in 
compliance with ICH E6, Section 4.9 and regulatory and institutional requirements for the 
protection of confidentiality of subjects. Each site will permit authorized representatives of the 
Sponsor and regulatory agencies to examine (and when required by applicable law, to copy) 
research records for the purposes of QA reviews, audits, and evaluation of the study safety, 
progress and data validity.   
Procedures and data collection will be documented utilizing site SOP or will be captured in site 
generated worksheets and data collection forms considered source documentation. Source 
documentation is defined as original documents, data, and records (e.g., hospital records, clinical 
and office charts, laboratory notes, memoranda, subjects' diaries or evaluation checklists, 
pharmacy dispensing records, recorded data from  automated instruments, copies or 
transcriptions certified after verification as being accurate copies, microfiches, photographic 
negatives, microfilm or magnetic media, x-rays, subject files, and records kept at the pharmacy, 
at the laboratories  and at medico-technical departments involved in the clinical trial). 
Source document worksheets may be used to facilitate data collection. The center may create 
source worksheets or use ones provided by the Sponsor or Sponsor’s representative. The 
worksheets may be used in conjunction with other center documentation. Source worksheets 
shall be provided for the EVLP data collection and post-EVLP assessments. During the study, it 
may be necessary to provide additional worksheets to the Study Center. This may occur without 
a formal process or written notification. 

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During the study, the use of the CRF as the original entry or source may occur if approved by the 
Sponsor. This agreement shall be documented in writing and filed with the protocol in the 
Investigator study file. The original data will be collected onto source documents (either the 
subject’s chart or a separate research subject chart that is kept in the research department) by the 
research site coordinator. This information will then be transcribed to the CRFs provided by the 
Sponsor for use in this study.  
10.11 Data Generation and Analysis 
The Investigators are responsible for ensuring the accuracy, completeness, legibility, and 
timeliness of the data reported. All source documents should be completed in a neat, legible 
manner to ensure accurate interpretation of data (Section 10.10). The Investigators will maintain 
adequate case histories of study subjects, including accurate CRFs, (Section 10.7) and source 
documentation. 
All donor identifying data will be redacted for the Sponsor and participating Investigators 
according to OPTN Policy 16 and only unique UNOS ID# shall be used to connect the donor to 
the recipient (subject). 
10.11.1 Data Management Responsibilities 
Data collection and accurate documentation are the responsibility of the study staff under the 
supervision of the Investigator. All source documents and laboratory reports must be reviewed 
by the study team and data entry staff who will ensure that they are accurate and complete. 
Unanticipated problems and AEs must be reviewed by the Investigator or designee. 
10.11.2 Data Capture Methods 
10.11.2.1 
Donor Data 
Donor lung data will be provided by the OPO and/or Study Centers through secure-access (read-
only) online database (‘DonorNet’) and/or through a paper-based medical record that 
accompanies the lung , or copies of donor information forwarded via electronic mail or facsimile. 
10.11.2.2 
EVLP Data 
EVLP procedure data will be recorded by the Sponsor during the clinical EVLP procedure. Data 
will be collected electronically in a secure online medical database (CMX). 
10.11.2.3 
Subject (Recipient Data) 
Subject data for the Analysis Phase, post-lung transplantation, will be collected by participating 
study site using the Sponsor’s CRF. Long-term follow-up data (Year 2 through Year 5) will be 
collected via the OPTN/UNOS database (TIEDI®) recipient follow-up forms. 

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10.12 Retention of Data 
10.12.1 Retention of Study Documents 
Study documents should be retained for a minimum of two years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region or until at least two years have elapsed since the formal 
discontinuation of clinical development of the investigational device. These documents should be 
retained for a longer period, however, if required by local regulations. No records will be 
destroyed without the written consent of the Sponsor, if applicable. It is the responsibility of the 
Sponsor to inform the Investigator when these documents no longer need to be retained. 
10.12.2 Future Use of Stored Specimens and Other Identifiable Data 
Donor lung biopsies and EVLP perfusate samples will be obtained and stored for potential future 
use. Donor lung biopsies and perfusate samples will be identified only by UNOS ID#. 
Donor next of kin will provide authorization for research use of the donor lung tissue and 
samples taken during the EVLP process. Additionally, subject consent includes a statement that 
pre-transplant donor lung “biopsies (about the size of your small finger) may be taken using a 
surgical stapler,” and that “Pieces of lungs may also be removed with staplers from standard 
organ donors as well.” 
10.13 Financial Disclosure 
Per 21 CFR 54, all Investigators are required to complete a Financial Disclosure form prior to 
site activation, attesting to the fact that they are unaware of any financial conflicts of interest, or 
disclosing potential conflicts, including payments, proprietary interests and/or equity interests. 
Completed forms will be maintained in the Trial Master File. 
10.14 Publication and Disclosure Policy 
The International Committee of Medical Journal Editors (ICMJE) member journals have adopted 
a clinical trials registration policy as a condition for publication. The ICMJE defines a clinical 
trial as any research project that prospectively assigns human subjects to intervention or 
concurrent comparison or control groups to study the cause-and-effect relationship between a 
medical intervention and a health outcome. Medical interventions include drugs, surgical 
procedures, devices, behavioral treatments, process-of-care changes, and the like. Health 
outcomes include any biomedical or health-related measures obtained in patients or participants, 
including pharmacokinetic measures and AEs. The ICMJE policy requires that all clinical trials 
be registered in a public trials registry such as ClinicalTrials.gov, which is sponsored by the 
National Library of Medicine. The Sponsor will register this study in ClinicalTrials.gov within 
30 days of study start, so the research results may be considered for publication in ICMJE 
member journals. The ICMJE does not review specific studies to determine whether registration 
is necessary; instead, the committee recommends that researchers who have questions about the 
need to register err on the side of registration or consult the editorial office of the journal in 
which they wish to publish. 

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U.S. Public Law 110-85 (Food and Drug Administration Amendments Act of 2007 or FDAAA), 
Title VIII, Section 801 mandates that a "responsible party" (i.e., the Sponsor or designated 
Principal Investigator) register and report results of certain "applicable clinical trials:"  
The Sponsor will develop subsequent publication policies prior to locking of the study data. 
10.15 Study Closure 
Study closure is defined as a specific date that is determined by study completion and/ or 
regulatory requirements have been satisfied per the study protocol and/or by decision of the 
Sponsor or FDA. Study closure visits will be conducted at all enrolling Study Centers in order to 
review record retention requirements with site personnel. A telephone contact may take the place 
of a study closure visit if appropriate (e.g., low subject enrollment, recent monitoring visit). 
Monitoring visits will be conducted by trained monitors and designees. A detailed Monitoring 
Plan will be developed identifying the frequency of monitoring and training requirements of the 
monitors. 

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11 REFERENCE LIST 
Aigner, C., et al. Clinical ex vivo lung perfusion – Pushing the limits. Am J Transplant 2012; 12: 
1839-1847. 
Avlonitis, VS, et al. Early Hemodynamic Injury During Donor Brain Death Determines the 
Severity of Primary Graft Dysfunction after Lung Transplantation. Am J Transplant 2007;7, 
83-90. 
Christie, J.D., et al. Report of the ISHLT Working Group on Primary Lung Graft Dysfunction 
part II: definition. A consensus statement of the International Society for Heart and Lung 
Transplantation. J Heart Lung Transplant 2005;24, 1454-1459. 
Chris Jaynes, CEO Perfusix Canada. 
Cypel M, Yeung J, Hirayama S, Keshavjee SK et al. Technique for Prolonged Normothermic Ex 
Vivo Lung Perfusion. J Heart Lung Transplant 2008a;27(12):1319-1325. 
Cypel M, Hirayama S, Rubacha M, Keshavjee SK et al. Ex-Vivo Normothermic Lung Perfusion 
(EVLP) Interrupts Ischemic Injury and Restores Cellular Metabolism. J Heart Lung Transplant 
2008b;27(2S):S199-200. 
Cypel M, Rubacha M, Yeung J, et. al.  Normothermic Ex Vivo Perfusion Prevents Lung Injury 
Compared to Extended Cold Preservation for Transplantation. Am J Transplantation 2009;9:1-8. 
Cypel M, Yeung J, Yeung JC, Keshavjee SK et al. Normothermic Ex Vivo Lung Perfusion in 
Clinical Lung Transplantation. N Engl J Med 2011a; 364:1431-40. 
Cypel M, Sato M, Yeung, JC, Keshavjee SK et al. One Year Survival and Functional Status of 
Patients from the human Ex Vivo Lung Perfusion (HELP) Trial.  J Heart Lung Transplant 
2011b;30(4S):S8. 
Cypel M, Yeung JC, Keshavjee SK et al. Experience with the first 50 ex vivo lung perfusions in 
clinical transplantation. J Thorac Cardiovasc Surg 2012; 144(5): 1200-07. 
Cypel M, Aigner C, Keshavjee SK et al. Three Center Experience with Clinical Normothermic 
Ex Vivo Lung Perfusion. J Heart Lung Transplant 2013; 32(4S):S16.  
Diamond JM, et al. Clinical risk factors for primary graft dysfunction after lung transplantation. 
Am J Respir Crit Care Med. 2013 Mar 1;187(5):527-34. 
Fisher, A.J, et al. Elevated levels of interleukin-8 in donor lungs is associated with early graft 
failure after lung transplantation. Am J Respir Crit Care Med 2001;163:259-265. 
Hayek D, Veremakis C, O'Brein JA. Time-dependent characteristics of hemodynamic instability 
in brain dead organ donors. Crit Care Med 1990;18:S204. 
Lyu DM, Zamora MR. Medical Complications of Lung Transplantation. Proc Am Thorac Soc 
2009;6:101-107. 
Machuca, TN and Cypel M. Ex vivo lung perfusion. J Thorac Dis 2014;6(8):1054–1062. 
Munshi L, Keshavjee SK, Cypel M. Donor management and lung preservation for lung 
transplantation.  Lancet (online) 2013; 1:318-328. 

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Organ Procurement & Transplantation Network. National Data 2015. US Department of Health 
and Human Services. https://optn.transplant.hrsa.gov/data/view-data-reports/national-data/# 
[Accessed 16Mar2016]. 
Power BM, Van Heerden PV. The physiological changes associated with brain death: current 
concepts and implications for the treatment of the brain dead organ donor. Anaesth Intens Care 
1995;23:26-36. 
Scientific Registry of Transplant Recipients (SRTR) Database. 2012 Annual Data Report. 
http://srtr.transplant.hrsa.gov/annual_reports/2012/ 
Shaf Keshavjee, MD, Surgeon in Chief at University Health Network in Toronto, Canada, 
personal communication. 
Steen S, et al. Transplantation of lungs from a non-heart-beating donor. Lancet 2001;357:825-
829. 
Suzuki Y, Cantu E, Christie JD.  Primary Graft Dysfunction Semin Respir Crit Care Med 
2013;34:305-19. 
Tikkanen JM, Cypel M, Keshavjee SK et al.  Long-Term Results of Transplantation of 
Normothermic Ex-Vivo Perfused Donor Lungs. J Heart Lung Transplant 2012; 32(4S):S146-7. 
Tiwari JL, et al. Ex-vivo lung perfusion does not have a negative effect on transplant rates at 
centers without this technology in a single organ procurement organization. J Heart Lung 
Transplant 2014;33(4S):S269. 
Tropmann C. Management of the organ donor. In Intensive Care Medicine, sixth edition Irwin 
RS and Rippe JM editors. Wolters Kluwer Health/Lippincott Williams & Wilkins. 2008:2091- 
2115. 
 Ware, L.B, et al. Assessment of lungs rejected for transplantation and implications for donor 
selection Lancet 2002;360:619-620. 
XVIVO Perfusion Inc. Sponsor Executive Summary 2014. 
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevi
ces/MedicalDevicesAdvisoryCommittee/Gastroenterology-
UrologyDevicesPanel/UCM389396.pdf Last accessed 03/05/16. 
 
 
 
 
 

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Appendix 1 Schedule of Events 
Table 3.  
Schedule of Events Within 1 Year Post-intervention 
Evaluation 
Screening 
Days -365 
to 0 
Baseline; 
Day 0 
Post-Intervention Period 
Follow-up 
Visit 1 
(ICU); 
24hr ± 4 
Visit 2 
(ICU); 
48hr ± 8 
Visit 3 
(ICU); 
72hr 
± 12 
Visit 4; 
Day 30 
± 5 
Visit 5; 
Day 90 
± 10 
Visit 6; 
6 mon  
± 2wks 
Visit 7; 
1 year 
 ± 4 wks 
Premature 
Discont’n 
Signed Informed Consentb 
X 
X 
- 
- 
- 
- 
- 
- 
- 
- 
I/E Criteria 
X 
Xa 
- 
- 
- 
- 
- 
- 
- 
- 
Print conmeds source 
 
Xa 
- 
- 
- 
X 
- 
- 
X 
- 
Donor data collectionc 
(Sponsor responsibility) 
- 
X 
- 
- 
- 
- 
- 
- 
- 
- 
EVLP data collectiond 
(Sponsor responsibility) 
- 
X 
- 
- 
- 
- 
- 
- 
- 
- 
Demographics and 
Baseline Disease 
Characteristics 
X 
Xa 
- 
- 
- 
- 
- 
- 
- 
- 
Medical History 
X 
Xa 
- 
- 
- 
- 
- 
- 
- 
- 
Study intervention 
(lung transplant) 
- 
X 
- 
- 
- 
- 
- 
- 
- 
- 
Post-transplant Assessments 
(Study Investigator) 
Vital sign assessments 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical Examination 
-  
Xa 
- 
- 
- 
X 
- 
X 
- 
- 
PGD Score (Section 6.7) 
- 
X 
X 
X 
X 
- 
- 
- 
- 
- 
PaO2 and FiO2 
- 
X 
- 
- 
- 
- 
- 
- 
- 
- 
Pulmonary function tests 
 
 
 
 
 
Xe 
X 
X 
X 
(X) 
FEV1 
- 
- 
- 
- 
- 
Xe 
X 
X 
X 
(X) 
Oxygen at rest 
- 
- 
- 
- 
- 
Xe 
X 
X 
X 
(X) 
BOS Grade 
- 
- 
- 
- 
- 
- 
X 
X 
X 
(X) 
ICU discharge 
- 
- 
- 
- 
(X) 
(X) 
- 
- 
- 
(X) 
Extubation date/time 
 
 
 
 
(X) 
(X) 
 
 
 
 
Hospital discharge 
- 
- 
- 
- 
- 
(X) 
- 
- 
- 
(X) 
Hospital redadmission 
- 
- 
- 
- 
- 
(X) 
(X) 
(X) 
(X) 
(X) 
Physical capacity 
- 
- 
- 
- 
- 
- 
X 
X 
X 
(X) 
Work status 
- 
- 
- 
- 
- 
- 
X 
X 
X 
(X) 
Adverse event assessment 
- 
X 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 

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Graft Survival Assessment 
- 
- 
- 
- 
- 
X 
X 
X 
X 
(X) 
Survival Assessment 
- 
- 
- 
- 
- 
X 
X 
X 
X 
(X) 
Abbreviations:  BOS=bronchiolitis obliterans syndrome; conmed=concomitant mediations; discont’n=discontinuation; FEV1=forced expiratory volume in 
one minute; hrs=hours; ICU=intensive care unit; I/E=inclusion/exclusion; mon=month; PaO2=partial pressure of oxygen in arterial blood; primary graft 
dysfunction; wks=weeks 
Note(s):  (x)=indicates “if applicable or as appropriate” 
a Data at Baseline are to be collected within 24 hrs prior to lung transplant. 
b Informed consent must be provided by the subject up to one year in advance and confirmed up to 24 hrs in advance of the lung transplant if required 
(Section 10.4.1). 
c Collection of donor demographics and suitability data. Confirm donor lung inclusion/exclusion criteria (Section 5.2.1 and Section 5.2.2). 
d Collect EVLP case data to determine transplant suitability and lung inclusion/exclusion criteria (Section 5.2.3 ). 
e At the time of discharge. 
 
 
Table 4.  
Schedule of Events:  Long-term Follow-up 
Evaluation 
Post-Intervention Period 
Follow-up 
Visit 8; 
2 year 
 ± 4 wks 
Visit 9; 
3 year 
 ± 4 wks 
Visit 10; 
4 year 
 ± 4 wks 
Visit 11; 
5 year 
 ± 4 wks 
Premature 
Discont’n 
FEV1 
X 
X 
X 
X 
(X) 
Oxygen at rest 
X 
X 
X 
X 
(X) 
BOS Grade 
X 
X 
X 
X 
(X) 
Physical capacity 
X 
X 
X 
X 
(X) 
Work status 
X 
X 
X 
X 
(X) 
Graft Survival Assessment 
X 
X 
X 
X 
(X) 
Survival Assessment 
X 
X 
X 
X 
(X) 
Abbreviations:  BOS=bronchiolitis obliterans syndrome; discont’n=discontinuation; FEV1=forced expiratory volume in one minute; PaO2=partial pressure 
of oxygen in arterial blood; primary graft dysfunction; wks=weeks 
Note(s):  (x)=indicates “if applicable or as appropriate” 

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Appendix 2 Key Study Personnel Contacts 
Expert Medical 
Consultants: 
Shaf Keshavjee, MD MSc FRCSC FACS 
Chief Scientific and Medical Officer, PERFUSIX, Inc. 
Surgeon in Chief, Sprott Department of Surgery  
Director, Toronto Lung Transplant Program 
Director, Latner Thoracic Research Laboratories 
190 Elizabeth St., RFE 1-408, Toronto, ON, M5G 2C4 
Phone:  416.340.3863 
Fax:      416.340.3185 
Email(s):   shaf.keshavjee@perfusix.com  
shaf.keshavjee@uhn.ca  
 
Marcelo Cypel MD, MSc 
Director of Clinical & Research Programs, PERFUSIX, Inc. 
Canada Research Chair in Lung Transplantation (Tier 2) 
Thoracic Surgeon, University Health Network 
Assistant Professor of Surgery, Division of Thoracic Surgery 
200 Elizabeth St. 9N969  
Toronto ON M5G2C4 Canada 
Phone:  416.340.4800 ext 5156  
Fax:      416.340.3478 
Email(s):   marcelo.cypel@perfusix.com  
marcelo.cypel@uhn.ca  
 
Thomas K Waddell, MD, MSc, PhD 
Director of Advanced Research, PERFUSIX, Inc. 
Chair, Division of Thoracic Surgery, University of Toronto 
Head, Division of Thoracic Surgery, University Health Network 
Senior Scientist, Toronto General Research Institute, UHN 
200 Elizabeth Street, 9N-949 
Toronto, ON   M5G 2C4 
Canada 
Phone:  416.340.3432 
Fax:      416.340.4556 
Email(s):   tom.waddell@perfusix.com 
Tom.waddell@uhn.ca 
 
Independent Medical 
Monitors:  
Martin Zamora, MD 
Transplant Pulmonologist  
Medical Director, Lung Transplant Program 
University of Colorado 
Anschutz Medical Campus 
Research Bldg 2, 9th Floor 
12700 E 19th Ave. 
Aurora, CO  80045 

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Phone:  303.724.6822 
Email:  marty.zamora@ucdenver.edu 
 
Michael S. Mulligan, MD 
Cardiothoracic Surgeon 
Director, Lung Transplant Program 
Director, Advanced Lung Disease Surgery Program 
University of Washington Medical Services 
1959 NE Pacific Street 
Seattle, WA 98195 
Phone:  206.598.4477 
Email:  msmmd@u.washington.edu 
 
Clinical Research 
Organization:  
CTI Clinical Trial and Consulting Services 
10123 Alliance Road 
Cincinnati, OH  45242 
Phone:  513.598.9290 
Sponsor IRB 
Sterling IRB 
6300 Powers Ferry Road 
Suite 600-351 
Atlanta, GA 30339 
Phone: 1.888.636.1062 
 

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Appendix 3 Risk and Risk Mitigation of EVLP 
Risk 
Risk Mitigation 
Document Reference 
Lung exposed to 
potential infectious 
material 
1) Add broad spectrum antibiotic to circulating perfusate 
(Imipenem, 500mg) 
2) Strict aseptic technique 
3) Pre-sterilized, single-use disposables wherever 
possible 
4) OR qualified procedure rooms with appropriate air 
handling and HEPA filtration 
1) TES Instruction for Use 
manual 
2) PX-1 Facility engineering 
drawings 
3) Specialist Training Core 
Curriculum 
4) Clinical Protocol 
Hardware generates 
bad/incorrect data 
1) Use calibrated equipment 
2) Toronto consulting surgeons and EVLP Specialists 
trained to identify incorrect data ranges for each 
parameter 
1) TES Instruction for Use 
manual 
2) Specialist Training Core 
Curriculum 
Multiple donor 
lungs become 
switched/ mixed up 
at facility 
1) Only 1 procedure per room is allowed 
2) Clearly identify all organ packaging and generated 
documentation using standard donor UNOS ID # 
3) Repackage lungs according to OPTN/UNOS 
guidelines 
1) OPTN Policy 16: Organ and 
Vessel Packaging, 
Labeling, Shipping, and 
Storage 
2) Clinical Protocol 
Over-ventilation of 
lung beyond safe 
volume 
1) Use a volume-controlled ventilator 
2) Use strict warming and protective ventilation volume 
strategies 
3) Monitor EVLP lung over time to observe function 
1) TES Instruction for Use 
manual 
2) Specialist Training Core 
Curriculum 
Donor lung 
procured incorrectly 
damaging its 
anatomy 
1) Study Site surgeon will retrieve lung(s) whenever 
possible. 
2) Lungs will be procured with the expectation that they 
will go back to the study site surgeon’s 
center/recipient. 
3) Toronto Procurement Protocol is available for review 
and implementation at donor sites.  
1) Clinical Protocol 
Donor lung lost 
during 
transportation/ 
logistical mishap, 
exceeding its safe 
CIT storage period 
1) This is a risk with or without EVLP.  We will 
mitigate this risk by using the same transportation 
methods (medical charter company/ medical courier) 
used by OPOs currently to transport organs to 
transplant centers 
1) Clinical Protocol 
Abbreviations:  CIT=cold ischemic time; HEPA= ; OPTN=Organ Procurement and Transplantation Network; 
UNOS ID=United Network for Organ Sharing Identification 
 

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Appendix 4 System Components of the Toronto EVLP System 
A schematic of the TES was shown in Figure 3. There are two classifications of system 
components:  Non-Fluid Path Hardware and Single-Use Fluid Path Disposables. 
Non-Fluid Path Hardware 
None of the following perfusion machine hardware used in the TES touches the fluid path. 
Therefore, each can be reused with minimal risk of contamination. 
1. Centrifugal Pump 
The benefit of using a centrifugal pump over a roller pump for ex vivo lung circulatory support is 
profound. Unlike a roller pump that pumps at a continuous pressure, a centrifugal pump will 
automatically back down its pressure when the internal resistance of the lungs increases. This is 
critical when warming up a hypothermically-preserved lung which is very cold (4°C) and thus, 
very stiff. A centrifugal pump will allow more flow and pressure to go through the lung only as 
its vascular resistance decreases during the warm-up phase. A roller pump cannot make these 
adaptations and can only pump a constant pressure through the lung, cold or warm, potentially 
over-pressurizing it and causing irreparable harm. The Stöckert Centrifugal Pump (“SCP”, 
FDA# K011838) and the Stöckert Centrifugal Pump Console (“SCPC”, FDA# K020571) are 
used by the Toronto Group for all EVLP procedures and will be the centrifugal pump used in the 
TES. The reason this pump was chosen over any other available pump is that the integrated flow 
sensor can be connected close to the pulmonary artery cannula, giving a much more accurate 
reading of flow rate at the point going into the lung. 
2. Extracorporeal Heater/Cooler 
The TES requires controlled, step-wise heating to warm up the lung to normothermic 
temperatures (37°C) from the wet ice storage and transportation temperatures. This allows the 
lung to be assessed at normal physiologic temperature and full metabolic activity. After the lung 
is determined to be transplantable, it is rapidly re-cooled down to 10°C, then placed back into a 
wet ice shipping container for delivery to the Study Center. Thus, the extracorporeal 
heater/cooler must be capable of delivering controlled liquid temperatures between 10 to 37°C. 
The Stöckert 3T (FDA# K052601) is a full-sized, compressor-cooled cardiac perfusion 
temperature-control device. It is capable of providing up to 23 L/min of flow into the heat 
exchanger and can deliver water temperatures from 0 to 50°C to maintain the temperature of an 
entire person during cardiac bypass. The 3T is used by the Toronto Group for all EVLP 
procedures and will be the heater/cooler used in the TES. The advantage that this device gives to 
the System is precise, digital control of temperatures and the ability to rapidly cool the assessed 
lung, minimizing warm ischemia. 
3. Volume-Controlled ICU Ventilator 
The TES requires an ICU-type ventilator to ventilate the lungs once they are at normal 
temperatures. The primary purpose of the ventilator is to allow physiologic respiration to occur 
within the lung tissue (O2 in, CO2 out) in order to measure the lung’s ability to exchange these 

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gasses. A volume-controlled ventilator is a critical component of the TES, because since there is 
no thoracic cavity to prevent excessive volumes from being applied to the lung, the ventilator 
itself must provide the protection. The Maquet Servo-i (FDA# K010925) is considered the 
gold-standard of volume-control ICU ventilators, allowing precise control of tidal volumes to 
minimize stretch injuries and pressures to protect against high airway pressures. The Servo-i is 
used by the Toronto Group for all EVLP procedures and will be the ventilator used in the TES. 
4. ABG Analyzer 
The ability of the lung to exchange CO2 with oxygen can be measured using a traditional blood 
gas analyzer (known as “ABG analyzer”). The Siemens RapidPoint 500 ABG Analyzer 
(FDA# K113216 and calibration cartridge K122398) measures PO2, PCO2, pH, glucose, and 
lactose, among other analytes (note:  this device is not directly connected to the TES, and 
therefore, is not shown in the above perfusion diagram). The Siemens RapidPoint 500 Analyzer 
analyzes samples of the STEEN Solution perfusate, measuring dissolved gas levels using a 
disposable sample cartridge that is replaced monthly according to manufacturer’s instructions. 
The Siemens RapidPoint is used by the Toronto Group for all EVLP procedures and will be the 
base analyzer for the TES. 
Single-Use Fluid Path Disposables 
All devices that come into direct contact with the fluid path will be single-use and pre-sterilized 
by the manufacturer. 
1. Organ Chamber 
The design of the organ container must ensure that the organ is protected in an aseptic 
environment and allowed to respire within the container, creating a slightly humid atmosphere to 
prevent the lung tissue from drying out. Additionally, there should be interfaces through the 
container to aseptically connect the lung to the perfusion circuit. Finally, as the lung starts to 
warm-up to normothermic temperatures, the bronchial arteries will start to perfuse and slowly 
trickle the perfusate out into the container, so it must be designed to collect the leaks aseptically 
and to connect back to the perfusion circuit to recirculate the captured perfusate. Currently, the 
XVIVO Organ Chamber™ is designed as a sterile, single-use container intended to be used as a 
temporary receptacle for isolated donor lungs in preparation for eventual transplantation into a 
recipient, and therefore, fits the requirement. If other Organ Chambers become available, they 
may be used if they meet these criteria. 
2. Lung Cannula Set 
There are two required cannulas to connect the lung to the perfusion circuit. The first attaches to 
the left atrial appendage (also called a ‘cuff’) at the point where the left atrium of the heart 
typically connects to the lung. The objective of this cannula is to connect the soft cuff of tissue to 
a device that tents (keeps open) the pulmonary veins, allowing the perfusate to flow out of the 
veins back into the perfusion circuit. In addition, there is a pressure cannula connected to the 
inside (lumen) of the cannula to collect accurate left atrial pressures to ensure a slight positive 
pressure (3-5 mmHg) in the atrium is maintained, preventing the veins from collapsing upon 

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themselves. The second required cannula is to connect the pulmonary artery to the perfusion 
circuit. In most cases, the pulmonary artery cannula can be a straight tube going into the 
pulmonary artery proximal to the point of bifurcation and therefore, perfuse both the left and 
right lungs simultaneously. However, in some cases when the heart is also procured for 
transplant, the pulmonary artery may not be long enough for a straight cannula and therefore, 
would need another flexible cannula (similar to the left atrium cannula) to be customized and 
anastomosed directly to the available pulmonary artery, ensuring a tight fit.   
Currently, the XVIVO Lung Cannula Pack™ fits this requirement as a sterile, single-use pack 
intended to be used to connect isolated donor lungs to the disposable perfusion circuit for ex-vivo 
assessment. There are three cannulas included in the Pack:  one cone-shaped left atrial cannula 
(green tape), one straight pulmonary artery cannula (yellow tape), and one cone-shaped cannula 
(white tape) to use either as a left atrial or as a pulmonary artery cannula back-up. If other Lung 
Cannula Sets become available, they may be used if they meet these criteria. 
3. Disposable Perfusion Circuit 
The Disposable Perfusion Circuit is a single-use, pre-sterilized, disposable extracorporeal 
perfusion circuit intended to connect to the perfusion hardware to facilitate perfusion of perfusate 
through isolated donor lungs during EVLP assessment. The components are provided by Maquet 
in a preassembled, sterilized surgical pack.  
Component Overview 
The Disposable Perfusion Circuit is made up of the fluid-path components. Any part that comes 
in direct contact with the fluid path is manufactured as single-use and packaged together as much 
as possible. In EVLP, the disposable circuit acts as the artificial circulatory system, interfacing 
with the centrifugal pump motor (via magnetic drive), a hollow-fiber oxygenation membrane that 
works in reverse to deoxygenate the perfusate by adding carbon dioxide and nitrogen and 
removing oxygen, a leukocyte filter to remove activated leukocytes, perfusion tubing, and a hard 
shell fluid reservoir to hold the excess perfusate. By running the oxygenator essentially in 
reverse, a mix of gases enters the lungs in a similar proportion as physiologic venous gas. This 
allows the lung itself to act as the ‘oxygenator’ in the circuit, and the resulting PO2 coming out of 
the lung can be measured and trended over time as part of the overall lung evaluation strategy. 
These components are used in an identical assembled combination every day in nearly every 
hospital in the world to support extracorporeal circulation during cardiac surgery and ECMO 
procedures. In fact, tens of thousands of these procedures using identical perfusion disposables 
occur each year in the US alone. 
Perfusion Circuit Function 
The perfusion circuit delivers the normothermic, deoxygenated perfusate to the lungs, then 
returns oxygenated perfusate to the reservoir for sampling and recirculation. The steps are 
summarized as follows: 
1. STEEN Solution perfusate is added into the disposable circuit through a standard aseptic 
interface on the hard shell reservoir. 

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2. The centrifugal pump head draws the Solution out through the reservoir and pumps it through 
the membrane oxygenator, which is connected to a venous gas mix (86% nitrogen, 8% 
carbon dioxide, 6% oxygen) where the dissolved oxygen in the circuit is displaced to a lower 
physiologic level prior to entering the lungs. This is also where perfusate is heated/cooled 
during the EVLP procedure via conduction by the extracorporeal heater/cooler. 
3. The Solution passes through a leukocyte reduction filter that traps activated leukocytes, 
preventing them from circulating back through the lung and from being transplanted into the 
recipient. 
4. The (non-disposable) flow sensor monitors flow rate (L/min) going into the lung via interface 
from the centrifugal pump control.  
5. The deoxygenated Solution enters into the lung through the pulmonary artery.  The 
pulmonary artery Lung Cannula records pressure at the point of interface between the 
cannula and lung. This is the pulmonary artery pressure (PAP). 
6. The oxygenated Solution exits the lung through the LA. The LA Lung Cannula records 
pressure at the point of interface between the cannula and left atrium. This is the left atrium 
pressure (LAP). 
7. The Solution drains back into the hard shell reservoir where it can be sampled for testing of 
pH, glucose, lactose, PO2 and PCO2 to assess lung function. 
8. Solution temperature is monitored exiting the lung at the reservoir and entering the lung at 
the oxygenator. 
9. The cycle repeats until the determination is made to either transplant or turn down the lung. 
 
A schematic of the perfusion circuit is shown in Figure 4. 
 
Figure 4.  
Schematic of Perfusion Circuit 

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Lung Perfusate 
STEEN Solution is a clear, sterile, non-pyrogenic, non-toxic physiological salt solution 
containing HSA and dextran 40. This solution is a low potassium (extracellular) electrolyte 
solution with physiological colloid-osmotic pressure (COP) designed for use as a temporary 
continuous normothermic machine perfusion solution for assessment and extended preservation 
of isolated donor lungs. 
The composition of STEEN Solution was designed to simulate the COP and crystalloid-osmotic 
properties of human plasma to permit safe, continuous ex-vivo lung perfusion at normothermia 
(37°C) for at least 12 hrs without the development of either tissue edema or dehydration. The 
COP and osmotic pressure of the solution were chosen to maintain optimal water balance 
between the cellular and the intra- and extra-vascular spaces. The optimal COP is provided by a 
proprietary combination of HSA (FDA-approved source) and dextran 40. The electrolyte 
composition is essentially extra-cellular (low potassium) with a phosphate buffer. The 
composition and physical properties of STEEN Solution are shown in Table 5. 
Table 5.  
Composition and Properties of STEEN Solution 
Composition 
calcium chloride, dextran 40, phosphate glucose, HSA, 
magnesium chloride, potassium chloride, sodium 
bicarbonate, sodium chloride, sodium dihydrogen, and 
water 
Solution Properties 
 
pH (20°C and ambient atmosphere) 
7.4 ± 0.3 
Osmolality (mOsm/kg) 
295 ± 20 
 
The primary mode of action for STEEN Solution is its ability to provide optimal COP, 
permitting stable fluid compartment homeostasis for sufficient time to allow meaningful 
functional evaluation of the lung at 37°C. STEEN Solution, therefore mimics the in vivo 
environment without the risk of edema formation in the absence of harmful pro-inflammatory 
cytokines and activated leucocytes associated with trauma, stress and brain death. This mode of 
action is primarily related to the water binding properties of albumin and its distributions across 
semi-permeable membranes between the intra- and extra-vascular spaces within the lung, and is 
not based on any metabolic or pharmacological action of either colloid. Additionally, it has been 
shown that red blood cells are not required for STEEN Solution to carry oxygen to the lung 
tissue as oxygen dissolves well in this Solution, and the lung is very efficient at removing 
oxygen from the Solution.[Cypel 2007] Acellular STEEN Solution has been used by the Toronto 
Group for all of their clinical EVLP procedures to date and will be the base perfusate used in the 
TES. 
The disposable EVLP perfusion circuit is primed with 1.5 L of STEEN Solution prior to use. 
STEEN Solution is allowed to warm-up to room temperature during the priming procedure 
pre-perfusion. The medications (and dosages) are added to the 1.5 L STEEN Solution prime are 
shown in Table 6. 

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Table 6.  
Medications Added to STEEN Solution during Prime 
Drug 
Dosage 
Reason added 
Heparin 
3000 IU 
Prevent residual blood from clotting 
Methylprednisolone  
(e.g., Solu-medrol) 
500 mg 
Steroid:  to decrease inflammation 
Imipenem 
(e.g., Primaxin) 
500 mg 
Broad-spectrum antibiotic to minimize bacterial 
infection risk 
 

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Appendix 5 Sponsor Signatures 
Study Title: 
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 
Study Number: 
PXUS 14-001, v6.0 
Final Date: 
03 November 2017 
 
This clinical study protocol was subject to critical review and has been approved by the Sponsor. 
The following personnel contributed to writing and/or approving this protocol: 
 
Signed: 
 
 
Date:  
 
Marc I. Lorber, MD 
Chief Medical Officer 
 
 
DD Mon YYYY 
 
 
 
 
 
 
 
Signed: 
 
 
Date:  
 
Jordan Shin, MD, PhD 
Medical Director 
 
 
DD Mon YYYY 
 
 
 
 
 
 
 
Signed: 
 
 
Date:  
 
Michael Roberts, MA, RAC 
Director, Regulatory Affairs 
 
 
DD Mon YYYY 
 
 
 
 
 
 

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Appendix 6 Investigator’s Signature 
Study Title: 
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 
Study Number: 
PXUS 14-001, v6.0 
Final Date: 
03 November 2017 
 
The signature below indicates the approval of this protocol and its appendices, and provides the 
necessary assurances that this trial will be conducted according to all stipulations of the protocol, 
including all statements regarding confidentiality, and according to local legal and regulatory 
requirements and applicable US federal regulations and ICH guidelines. 
Principal Investigator: 
Signed: 
 
Date: 
 
Printed 
Name:  
 
Title: 
 
Institution: