Lung Function Improvement After Bronchoscopic Lung Volume Reduction With Pulmonx Endobronchial Valves Used in Treatment of Emphysema
Phase: NA
Conditions: Emphysema
Sponsor: Pulmonx Corporation

Pulmonx LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Version:  June 23, 2017                                                CONFIDENTIAL 
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Lung Function Improvement after Bronchoscopic Lung Volume 
Reduction with Pulmonx Endobronchial Valves used in Treatment of 
Emphysema 
(LIBERATE STUDY) 
U.S. Investigational Device Exemption (IDE) Clinical Investigational Plan 
#630-0012_H 
ECO# 4000

Pulmonx LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
 
 
           
 
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Table of Contents 
CLINICAL INVESTIGATION PLAN AGREEMENT FORM .......................................................10 
1.0 
Background ......................................................................................................11 
1.1 
Pathophysiology of Emphysema ........................................................................11 
1.2 
Management of Emphysema:  Lung Volume Reduction Surgery (LVRS) ...........11 
1.3 
Bronchoscopic Lung Volume Reduction (BLVR) ................................................11 
1.4 
BLVR with the Pulmonx Endobronchial Valve (EBV) ..........................................12 
1.5 
Pivotal Investigation of the EBV:  The VENT Study (IDE#G020230) ..................12 
1.6 
Learnings from the VENT Study .........................................................................12 
1.7 
Collateral Ventilation Impacts Lung Volume Reduction ......................................12 
1.8 
Measurement of Collateral Ventilation ................................................................13 
1.9 
Conclusion from the Prior Studies ......................................................................14 
2.0 
Study device and intended use .......................................................................14 
3.0 
Study device / technology description ...........................................................14 
3.1 
Endobronchial Valve ..........................................................................................14 
3.2 
Delivery Catheter ...............................................................................................14 
4.0 
Study purpose ..................................................................................................14 
5.0 
Study Design ....................................................................................................15 
6.0 
Study population ..............................................................................................15 
6.1 
Optimal Medical Therapy ...................................................................................15 
7.0 
Study Objective ................................................................................................15 
7.1 
Primary Effectiveness Endpoint .........................................................................15 
7.2 
Safety Endpoint .................................................................................................16 
7.3 
Secondary Effectiveness Measures ...................................................................16 
7.4 
Additional Measures ..........................................................................................16 
7.5 
Crossover of Control Study Participants .............................................................17 
7.6 
Interim Analysis .................................................................................................17 
7.7 
Long-Term Follow-Up ........................................................................................18 
8.0 
Study participant management .......................................................................18 
8.1 
Clinical Site Study Team ....................................................................................18 
8.2 
Clinical Study Site Training ................................................................................18 
8.3 
Study Candidate Recruiting ...............................................................................18 
8.4 
Study Candidate Selection .................................................................................18 
8.5 
Screening Eligibility Criteria ...............................................................................19 
8.6 
Baseline Eligibility Criteria ..................................................................................22 
8.7 
Bronchoscopy Plan for CV Assessment and Determining Study Eligibility .........22 
8.8 
Study Procedure Eligibility Criteria .....................................................................22 
8.9 
Study Participant Enrollment ..............................................................................23 
8.10 
Follow-Up Visits .................................................................................................23 
8.11 
Retention of Study Participants ..........................................................................24 
9.0 
Pharmacologic treatments for study participants .........................................25 
9.1 
Optimization of Medications ...............................................................................25 
9.2 
Bronchodilators ..................................................................................................25 
9.3 
Corticosteroids ...................................................................................................25 
9.4 
Other Pharmacologic Agents .............................................................................25 
10.0 
Post-bronchoscopy PULMONARY REHABILITATION ...................................25 
10.1 
Pulmonary Rehabilitation Program .....................................................................26 

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11.0 
Bronchoscopy Procedure ...............................................................................26 
11.1 
Procedure Medications ......................................................................................27 
11.2 
Assessment of Study Procedure Eligibility Criteria .............................................28 
11.3 
Assignment to Control Arm ................................................................................28 
11.4 
Assignment to Study Treatment Arm..................................................................28 
11.5 
Execution of the Study Procedure ......................................................................29 
11.6 
Post-Bronchoscopy Recovery Period Procedures for Study Treatment Arm ......29 
11.7 
Procedures Prior to Discharge ...........................................................................31 
12.0 
Secondary Valve Procedures ..........................................................................32 
12.1 
Valve Removal ...................................................................................................32 
12.2 
Valve Replacement ............................................................................................32 
12.3 
Valve Adjustment ...............................................................................................32 
13.0 
Clinical Effectiveness Outcomes ....................................................................33 
13.1 
Spirometry .........................................................................................................33 
13.2 
Patient-Reported Health Status Measures .........................................................33 
13.3 
Body Plethysmography Testing ..........................................................................35 
13.4 
Diffusing Capacity Testing .................................................................................35 
13.5 
Medication Use ..................................................................................................36 
13.6 
Daily Diary .........................................................................................................36 
13.7 
Six-Minute Walk Distance (6MWD) Test ............................................................37 
13.8 
Blood Work ........................................................................................................37 
13.9 
Chest X-Ray ......................................................................................................38 
13.10 
Physical Exam ...................................................................................................38 
13.11 
High Resolution Computed Tomography ...........................................................38 
13.12 
BODE Index .......................................................................................................38 
14.0 
Sequence for Testing.......................................................................................39 
14.1 
Screening Assessment – within 6 months prior to randomization .......................39 
14.2 
Baseline Assessment - Conduct ≤ 120 days following screening eligibility .........40 
14.3 
Bronchoscopy Procedure – Should occur ≤ 60 days after baseline assessment 
visit ....................................................................................................................40 
14.4 
Post Procedure ..................................................................................................41 
14.5 
Prior to Discharge ..............................................................................................41 
14.6 
Daily Follow Up Phone Call for 10 Days after Discharge (up to 11:59 pm) .........42 
14.7 
Day 7 after Discharge Visit (+ 1 business day) ...................................................42 
14.8 
Day 30 Visit (+/- 5 days) .....................................................................................42 
14.9 
Day 45 Visit (+/- 5 days) .....................................................................................42 
14.10 
3 Month Visit (+/- 14 days) .................................................................................42 
14.11 
6 Month Visit (+/- 21 days) .................................................................................43 
14.12 
9 Month Visit (+/- 21 days) .................................................................................43 
14.13 
1 Year Visit (+/- 45 days) ...................................................................................43 
14.14 
Annual Visits (+/- 60) only for Study Participants treated with EBV ....................44 
15.0 
Safety Elements ...............................................................................................44 
15.1 
Adverse Events ..................................................................................................44 
15.2 
Serious Adverse Events .....................................................................................46 
15.3 
Management of Selected Anticipated Adverse Events .......................................46 
15.4 
Events Anticipated to Precipitate Valve Removal ...............................................47 
16.0 
Risk - benefit evalauation ................................................................................48 
16.1 
Potential Benefits ...............................................................................................48 
16.2 
Potential Risks ...................................................................................................48 

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16.3 
Risk Minimization ...............................................................................................48 
17.0 
Protection of Human Participants...................................................................48 
17.1 
Institutional Review Board (IRB) Approval .........................................................48 
17.2 
Confidentiality ....................................................................................................48 
17.3 
Ethical Considerations .......................................................................................49 
17.4 
Methods to Eliminate Bias ..................................................................................49 
17.5 
Early Termination of the Clinical Investigation ....................................................49 
18.0 
Clinical Site Training .......................................................................................49 
18.1 
Clinical Study Staff Training ...............................................................................49 
18.2 
Procedure and Training Videos ..........................................................................50 
18.3 
Physician Hands-on Training:  Endobronchial Valve ..........................................50 
18.4 
Physician Hands-on Training:  Chartis Assessment System ..............................50 
18.5 
Study Coordinator Training ................................................................................50 
18.6 
Protocol Training ................................................................................................51 
18.7 
Assistant Physicians, Scrub Nurses, and Technicians .......................................51 
18.8 
Valve Loader Training ........................................................................................51 
18.9 
Nursing Staff In-service ......................................................................................51 
19.0 
Study oversight ................................................................................................51 
19.1 
Data and Safety Monitoring Board (DSMB) ........................................................51 
19.2 
Clinical Events Committee .................................................................................52 
19.3 
Operations Committee .......................................................................................52 
19.4 
Core Radiology Laboratory ................................................................................52 
19.5 
Core Spirometry Laboratory ...............................................................................52 
19.6 
Daily Diary Data Acquisition ...............................................................................52 
20.0 
Data analysis overview ....................................................................................52 
20.1 
Populations for Effectiveness and Additional Measures .....................................52 
20.2 
Safety Analysis Population .................................................................................53 
20.3 
Primary Effectiveness Endpoint .........................................................................53 
20.4 
Safety Endpoint .................................................................................................54 
20.5 
Secondary Effectiveness Measures ...................................................................54 
20.6 
Additional Measures ..........................................................................................55 
20.7 
Interim Analysis .................................................................................................55 
20.8 
Long-Term Follow-up .........................................................................................55 
20.9 
Time Points for Data Analysis ............................................................................55 
20.10 
Statistical Analysis Plan .....................................................................................56 
21.0 
Regulatory and Reporting Requirements .......................................................56 
21.1 
Adverse Events and Reporting ...........................................................................56 
21.2 
Serious Adverse Events and Reporting ..............................................................56 
21.3 
Unanticipated Adverse Device Effects (UADE) and Reporting ...........................57 
21.4 
Informed Consent Violation Reporting ................................................................57 
21.5 
Protocol Deviation Reporting .............................................................................57 
21.6 
Investigator Reporting ........................................................................................57 
22.0 
Study Data Reporting and Processing ...........................................................58 
22.1 
Study Data Collection ........................................................................................58 
22.2 
Site Data Monitoring and Quality Control ...........................................................58 
22.3 
Communication ..................................................................................................58 
22.4 
Recruitment Tracking .........................................................................................58 
22.5 
Data Processing and Quality Control .................................................................58 
22.6 
Monitoring, Audits and Inspections ....................................................................59 

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Clinical Investigational Plan #630-0012-H 
 
 
           
 
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22.7 
Investigator Access to the Data and Publication Policies ...................................59 
23.0 
Additional Study and Administrative Elements .............................................59 
23.1 
Duration of Investigation ....................................................................................59 
23.2 
Participant Accountability ...................................................................................59 
23.3 
Documentation Requirements ............................................................................60 
23.4 
Study Monitoring ................................................................................................60 
23.5 
Data Management .............................................................................................60 
23.6 
Registration of the Clinical Trial ..........................................................................60 
23.7 
Amendments to the Clinical Investigational Plan ................................................60 
23.8 
Device Accountability .........................................................................................60 
23.9 
Deviations from the Clinical Investigation Plan ...................................................61 
24.0 
Investigator Responsibilities ..........................................................................61 
24.1 
Study Administration ..........................................................................................61 
24.2 
Institutional Review Board (IRB) Approval .........................................................61 
24.3 
Conduct the Informed Consent Process .............................................................62 
24.4 
Study Coordinator ..............................................................................................62 
24.5 
Investigator Records ..........................................................................................62 
25.0 
Sponsor Responsibilities ................................................................................63 
25.1 
Clinical Site Selection and Training ....................................................................63 
25.2 
Good Clinical Practice ........................................................................................64 
25.3 
Clinical Site Management ..................................................................................64 
25.4 
Study Sponsor Monitoring on Site ......................................................................64 
25.5 
Sponsor Records ...............................................................................................65 
25.6 
Sponsor Reports ................................................................................................65 
25.7 
Investigator List ..................................................................................................66 
25.8 
Progress Reports ...............................................................................................66 
25.9 
Recall and Device Disposition ............................................................................66 
25.10 
Final Reports .....................................................................................................66 
26.0 
Glossary of terms ............................................................................................66 
27.0 
References .......................................................................................................68 
 
Appendices 
Appendix 1 
Study Participant Flow 
Appendix 2 
Study Participant Screening and Enrollment Flowchart 
Appendix 3 
Example Informed Consent Form: Study Screening 
Appendix 4 
Screening Log 
Appendix 5 
Screening Eligibility Criteria 
Appendix 6 
HRCT Scan Acquisition Protocol 
Appendix 7 
Baseline Eligibility Criteria 
Appendix 8 
Example Informed Consent: Study Participation 
Appendix 9 
Bronchoscopy Procedure Planning: Radiologic Identification of Target Treatment 
Lobe (s) 
Appendix 10 Study Procedure Eligibility Criteria 
Appendix 11 Bronchoscopy Procedure Flow 
Appendix 12 Required Schedule for Tests and Procedures at Screening and Baseline 
Appendix 13 Pulmonary Rehabilitation Program MOP 
Appendix 13a Pulmonary Rehabilitation Facility Information Form 
Appendix 13b Post-bronchoscopy Pulmonary Rehabilitation In-Clinic Log 
Appendix 14 Procedure for Assessing Target Treatment Lobe CV using the Chartis System 

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Clinical Investigational Plan #630-0012-H 
 
 
           
 
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Appendix 15 Segmental Bronchial Targets for Lobar Occlusion 
Appendix 16 Example of a Medical Alert Card 
Appendix 17 Post- EBV Procedure Discharge Instructions for the Study Treatment Arm 
Appendix 18 Management of Pneumothorax 
Appendix 19 Statistical Analysis Plan 
Appendix 20 Example Informed Consent: Crossover Participant 
 

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Executive Summary 
 
Study Device and 
Intended Use 
 
The Pulmonx Zephyr Endobronchial Valve (EBV) is an implantable 
bronchial valve intended to decrease volume in targeted regions of 
the lung. It is indicated for the treatment of patients with 
hyperinflation associated with severe heterogeneous emphysema in 
regions of the lung that have little or no collateral ventilation as 
assessed by the Chartis System.  
  
Study Purpose 
 
The purpose of this study is to assess the safety and effectiveness 
of bronchoscopic lung volume reduction (BLVR) using the Pulmonx 
Endobronchial Valve (EBV) in treated study participants compared 
to control participants to support a premarket approval application to 
FDA.  
  
Study Design 
 
This will be a multi-center, prospective, randomized, controlled study 
with EBV treatment statistically evaluated using Intent-to-Treat (ITT) 
analyses. A maximum of 183 study participants, who meet study 
entry criteria, consisting of screening eligibility criteria, baseline 
eligibility criteria, and procedure eligibility criteria, will be enrolled.  
Safety and effectiveness of BLVR using the Pulmonx EBV will be 
evaluated at 1 year.  For study participants who have been treated 
with EBV, a secondary valve intervention such as valve removal, 
replacement, or adjustment may be considered during the study 
follow-up.  Long-term data will be collected annually for EBV-treated 
study participants through 5 years.  Per the regulatory plan agreed 
to with FDA, 1 year of follow-up is required pre-approval and the 
remaining 4 years of follow-up will be conducted post-approval.   
  
Study Population 
 
The study population will be comprised of 183 study participants with 
severe heterogeneous emphysema as defined by the study eligibility 
criteria. The study participants will be randomly assigned at a 2:1 
ratio to the study treatment along with optimal medical therapy or to 
optimal medical therapy alone. 
     
Study Objective 
 
The objective of the study will be to evaluate lung function changes 
and adverse events after BLVR using the Pulmonx EBV.  
     
Primary Effectiveness 
Endpoint 
 
The percentage of study participants in the EBV treatment arm 
meeting the clinically significant threshold of >15% improved forced 
expiratory volume in one second (FEV1), obtained immediately 
following bronchodilator therapy, as compared to the percentage in 
the control arm at 1 year post-procedure. 

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Safety Endpoint 
 
Evaluation of the short- and long-term adverse events profile of the 
EBV treatment arm during the treatment period, defined as the day 
of the study procedure until 45 days after the study procedure 
(short), and in the post-treatment period, defined as 46 days after 
the study procedure until the 1-year follow-up visit (long).  
   
Secondary Effectiveness 
Measures 
 
Treatment Lobe Volume Reduction (TLVR) for the Treatment Arm 
• 
TLVR, measured as the ‘absolute change from baseline’ 
for treated lobe volume as seen via HRCT (high 
resolution computed tomography), will be evaluated at 45 
days and 1 year.  
• 
TLVR, measured as the ‘percentage change from 
baseline’ for treated lobe volume as seen via HRCT, will 
be evaluated at 45 days and 1 year.  
  
St. George’s Respiratory Questionnaire (SGRQ) 
• 
Difference between study arms in ‘absolute change from 
baseline’ for SGRQ score at 1 year.   
 
FEV1  
• 
Persistence of treatment effect will be evaluated by 
determining the difference between study arms for 
‘absolute change from baseline’ for FEV1 at 45 days, 6 
months, and 1 year. 
• 
Persistence of treatment effect will be evaluated by 
determining the difference between study arms for 
‘percentage change from baseline’ for FEV1 at 45 days, 6 
months, and 1 year.   
 
6-Minute Walk Distance (6MWD) 
• 
Difference between study arms in ‘absolute change from 
baseline’ for 6MWD at 1 year.  
• 
Difference between study arms in ‘percentage change 
from baseline’ for 6MWD at 1 year.  
 
Additional Measures 
 
Mean changes and/or changes measured using responder analyses 
for:  
• 
Spirometry, including FEV1, forced vital capacity (FVC) and 
the ratio of FEV1/FVC 
• 
Body plethysmography, including residual volume (RV), 
inspiratory capacity (IC), functional residual capacity (FRC), 
total lung capacity (TLC), and the ratios of RV/TLC and 
IC/TLC 
• 
SGRQ global and domain (i.e. ‘symptoms’, ‘activity’, and 
‘impacts on daily life’) scores 

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• 
Modified Medical Research Council (mMRC) dyspnea scale 
score 
• 
BODE Index 
• 
Transitional Dyspnea Index (TDI) from Baseline Dyspnea 
Index (BDI) 
• 
COPD Assessment Test (CAT) 
• 
SF-36 Health Survey 
• 
EQ-5D Health Survey 
• 
Health Care Utilization Questionnaire 
• 
6 minute walk distance 
• 
Borg scale dyspnea scores before and after 6MWD test 
• 
Change in use of ‘maintenance’ medications, including 
bronchodilators, corticosteroids, antibiotics, and anti-
inflammatories 
• 
Daily diary (EXACT-PRO, pulmonary rehabilitation 
compliance, health status changes)  
• 
Carbon Monoxide Diffusing Capacity (DLCO) 
• 
Lung radiographic features 
• 
Blood chemistry measures 
 
Crossover of Control 
Study Participants 
 
 
After completing the 1 year visit, if a control study participant 
continues to qualify for the study treatment, (s)he will be permitted to 
crossover to the study treatment.   
 
Interim Data Analysis 
 
An interim data analysis designed to evaluate effectiveness for 
continuing crossover of control arm study participants after the 1- 
year follow-up visit to EBV treatment will be performed when 74 
study participants have completed the 1-year follow-up.  If crossover 
of control arm study participants is found to be justified by the interim 
analysis then crossover of control arm study participants after (s)he 
has reached the 1-year time point may be continued. The results of 
the interim analysis will be reviewed by the DSMB and FDA.  If the 
DSMB recommends not continuing  crossing control arm participants 
to EBV treatment then those control arm patients who have not 
crossed over will exit from the study per protocol after the 1-year 
visit.   
 
Long-Term Follow-Up 
 
Data will be collected annually through 5 years for study participants 
receiving the study treatment.  Per the regulatory plan agreed to with 
FDA, 1 year of follow-up is required pre-approval and the remaining 
4 years of follow-up will be conducted post-approval.  The annual 2-, 
3-, 4-, and 5-year data will consist of FEV1 and adverse events. 

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CLINICAL INVESTIGATION PLAN AGREEMENT FORM 
 
I agree to the terms of this clinical investigation plan. I will conduct the investigation according to 
the procedures specified herein.  
 
 
Site No.:  
Principal Clinical Investigator 
Name: 
 
Signature: _____________________ 
Date: ______________ 
 
 
 
 

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1.0    BACKGROUND 
1.1 Pathophysiology of Emphysema 
Emphysema is a debilitating and progressive disease that presents a major health 
problem globally.  It is characterized by gradual, irreversible destruction of lung tissue and 
loss of elastic recoil within the lungs, causing loss of ability to expel air and efficiently 
absorb oxygen.  Emphysema dramatically reduces a person’s expiratory function, leading 
to dyspnea (breathlessness), lessened capacity for performing daily living activities, and 
reduced quality of life.   
Breathlessness in emphysema is thought to result from three primary problems: 1) loss of 
parenchymal tissue for gas exchange, 2) gas trapping which limits expiration, and 3) 
altered breathing mechanics of the chest wall and diaphragm as a result of hyperinflation. 
Breathlessness during exercise worsens as patients must breathe at even higher lung 
volumes to exchange sufficient air (dynamic hyperinflation).  As emphysema progresses, 
the diseased, hyperinflated areas of the lung eventually fill the chest cavity, leaving less 
room for functioning lung tissue and preventing adequate diaphragmatic and chest wall 
function.   
1.2 Management of Emphysema:  Lung Volume Reduction Surgery (LVRS) 
The goals of therapy for emphysema are to slow the progressive decline in lung function, 
prevent and shorten exacerbations of the disease, improve exercise capacity and quality 
of life, and prolong survival [1].  Medical treatment for palliating symptoms associated with 
emphysema is well established and widely used but is of limited efficacy [2,3].  
Lung volume reduction surgery (LVRS) has been shown to offer relief to patients suffering 
from emphysema when other treatment options fail [4-10].  The physiologic basis of LVRS 
is directly tied to the pathophysiology of emphysema.  With LVRS, the physician aims to 
reduce hyperinflation by removing the most hyperinflated portions of the lung, leaving the 
remaining lung room to expand and therefore function more efficiently and allow improved 
breathing mechanics.  The National Emphysema Treatment Trial (NETT) compared LVRS 
to optimal medical management in 1,218 patients with advanced emphysema of various 
morphologies [10].  Clear clinical benefits were observed with LVRS over optimal medical 
management.   
After LVRS, improvement in dyspnea and increases in exercise tolerance correlate best 
with reduced hyperinflation and increased transdiaphragmatic pressure resulting from 
repositioning of the diaphragm and recruitment of inspiratory respiratory muscles [11,12].  
An additional mechanism is increased elastic recoil of the lung, probably because the most 
severely hyperinflated part of the lung is resected.  These changes often result in marked 
improvement of lung function, commonly reported using forced expiratory volume in one 
second (FEV1).  Moreover, LVRS has also been found to lengthen survival in patients with 
heterogeneous emphysema [13,14].  Nevertheless, the reported risks of procedure-related 
morbidity and mortality with LVRS are of substantial concern [15].   
1.3 Bronchoscopic Lung Volume Reduction (BLVR) 
A less invasive approach to LVRS using the bronchoscope has long been sought.  The 
goal of bronchoscopic lung volume reduction (BLVR) is to obtain similar physiologic 
benefits as LVRS, without the risk of chest surgery. The aim in BLVR procedures is to 

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reduce or eliminate the impact of hyperinflated lung tissue on adjoining higher functioning 
lung tissue.  
1.4 BLVR with the Pulmonx Endobronchial Valve (EBV) 
Pulmonx has developed a one-way valve that can be implanted during bronchoscopy, 
where the aim is to block inspiratory airflow into targeted, hyperinflated regions of the lung, 
while permitting exhaled gas to escape. When an endobronchial valve is placed in a 
bronchial lumen and is performing as intended, air is restricted from going through or 
around the valve during inspiration and gas is allowed to vent during expiration.  The 
Pulmonx Zephyr valve has been previously studied in a large multi-center, prospective, 
randomized trial [16,17]. At that time, the Zephyr valve was manufactured by Emphasys 
Medical Inc. (Redwood City, CA).  
1.5 Pivotal Investigation of the EBV:  The VENT Study (IDE#G020230) 
The Endobronchial Valve for Emphysema Palliation Trial (VENT study) was a prospective, 
randomized, controlled study conducted in the United States to evaluate the Zephyr EBV 
in comparison with optimal medical treatment in patients with heterogeneous emphysema.  
The Zephyr EBV is a silicone covered stent-like device with a built-in one-way valve that 
lets air out of, but not into, targeted regions of the lung.  The valve was placed 
bronchoscopically into the target lobar bronchus.   
The VENT study results were reviewed by FDA as part of PMA P070025 and were 
presented at a meeting of the Anesthesiology and Respiratory Therapy Devices Advisory 
Panel in December 2008.  While the effectiveness outcomes for the EBV-treated study 
group were significantly improved over the control group, and the results of the study 
successfully met the pre-determined primary endpoints, the Advisory Panel and FDA 
concluded that the mean results did not reach minimally important clinical difference.  
However, it was recognized that outcomes with EBV appeared to be clinically meaningful 
in a discrete subgroup of patients.   
1.6 Learnings from the VENT Study 
As presented to FDA during the PMA review of the Zephyr endobronchial valve, analyses 
of VENT study participant subgroups indicated that the Zephyr EBV had higher 
effectiveness in study participants who had certain lung radiographic features.  Key 
findings of the VENT study data indicated that EBV therapy was optimized in patients who 
had high resolution computed tomography (HRCT) findings suggestive of a complete 
fissure between the EBV-treated lobe and the adjacent lobe [16,17].   
Complete fissure, as determined via qualitative assessment of HRCT scans, is thought to 
correspond to lack of inter-lobar collateral ventilation (CV) [18].  Researchers in the clinical 
community have theorized that presence of lobar CV is likely to mitigate clinical response 
to EBV treatment [19,20].  
1.7 Collateral Ventilation Impacts Lung Volume Reduction 
During the 1930’s, Van Allen and Lindskog [21] were the first to demonstrate 
experimentally that presence of CV allows inter-lobar communication of air.  As the use of 
surgical treatments for emphysema grew and direct observation of the in vivo tissue 
condition was possible, collateral air flow was found to be linked to the regional over-
distention and air trapping known to exist with emphysema [22].  Collateral channels were 

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found to occur more frequently in emphysema patients than in normal subjects and the 
channels were wider and less resistant during exhalation [23].   
Understanding CV pathways in endobronchial lung volume reduction candidates and 
having the ability to selectively target treatment effectively has become an important 
clinical goal.  It has been hypothesized by researchers in the clinical community that CV 
was likely to be a primary reason for the infrequency of observing clinically significant lung 
volume reduction in patients participating in the VENT study. Assessment of inter-lobar 
CV, as described below, will be performed in the proposed trial as a means to select study 
participants who are likely to experience significant lung volume reduction with the 
Pulmonx Zephyr EBV.   
1.8 Measurement of Collateral Ventilation  
In 2005, Pulmonx, Inc. developed an integrated system for CV assessment now known as 
the Chartis® Catheter and Chartis® Console.  The Chartis System is a catheter-based 
device that allows sealing of a lung compartment and measurement of air pressure and 
flow from the sealed compartment (K111522 for Chartis Catheter and K111764 for Chartis 
Console1).  Based on these measurements, CV within a lobe targeted for endobronchial 
treatment can be identified.   
Safety and feasibility of obtaining measurements predictive of atelectasis after EBV 
treatment using the Chartis system has been previously reported [24] (NCT00684892).  
Gompelmann and colleagues observed that in 18/20 (90%) of the EBV treated cases, 
post-procedure atelectasis response, as visualized using chest X-ray, matched the Chartis 
system prediction of presence or absence of collateral ventilation.  No adverse events 
associated with use of the Chartis system were observed.   
In a later, larger, prospective multi-center study conducted in Germany, the Netherlands, 
and Sweden, the Chartis System was used successfully as a tool to identify emphysema 
patients who would achieve clinically significant lung volume reduction after EBV treatment 
[25] (NCT01101958).  Patients were prospectively classified using the Chartis System 
during the bronchoscopy procedure—prior to EBV placement—as having or not having CV 
in the targeted treatment lobe. The patients who were classified as having little or no lobar 
CV had significant target lobe volume reduction and significantly improved respiratory 
function, exercise performance, and quality of life measures after EBV treatment whereas 
those who were identified as having CV did not.   
The secondary objective of the Chartis multicenter study was to compare the accuracy of 
the Chartis System and visual assessment of HRCT fissure completeness for assessing 
CV status by evaluating their relationship with volumetric reduction of the treated lobe after 
EBV placement. Diagnostic accuracy of the Chartis System for prospectively classifying 
presence or absence of CV in a lobe targeted for EBV treatment, when compared to the 
observed response to the EBV procedure as measured using volumetric reduction seen 
with HRCT, was found to be similar to HRCT fissure analysis.   
                                                 
1 Cleared indications for use: The Chartis System is indicated for use by bronchoscopists during a diagnostic 
bronchoscopy in adult patients in a bronchoscopy suite. The system, composed of the Chartis Catheter and Chartis 
Console, is designed to measure pressure and flow in order to calculate resistance to airflow and quantify collateral 
ventilation in isolated lung compartments. The Chartis Catheter is used through the working channel of a 
bronchoscope and connects to the Chartis Console. The Chartis Console is a re-usable piece of capital equipment 
that displays the patient information. 

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1.9 Conclusion from the Prior Studies  
The evidence from the prior investigations suggest that BLVR performed using the 
Pulmonx Zephyr EBV may induce regional lung volume reduction associated with 
improved clinical condition in patients identified as having little or no CV.    
2.0    STUDY DEVICE AND INTENDED USE 
The Pulmonx Zephyr Endobronchial Valve (EBV) is an implantable bronchial valve 
intended to decrease volume in targeted regions of the lung.  It is indicated for the 
treatment of patients with hyperinflation associated with severe heterogeneous 
emphysema in regions of the lung that have little or no collateral ventilation as assessed 
by the Chartis System.     
 
3.0   STUDY DEVICE / TECHNOLOGY DESCRIPTION 
The Pulmonx Zephyr Endobronchial Valve (EBV) is a device that incorporates a one-way 
valve that is implanted in a bronchial lumen.  A stent-like self-expanding retainer that 
secures the implanted EBV in place supports the one-way valve.  The implanted EBV is 
designed to allow air to be vented from the isolated lung segment while preventing air 
from refilling the isolated lung during inhalation.  It is not anticipated that the study device 
will require modification during execution of the study.    
3.1 Endobronchial Valve  
The EBV is assembled from two distinct components:  a one-way valve and a retainer.   
3.1.1 
One-Way Valve 
A one-way polymer valve is mounted inside the retainer.  The valve vents during 
exhalation and closes when flow is reversed (inhalation).  
3.1.2 
Retainer 
The retainer is a self-expanding tubular mesh structure that is laser cut from 
Nitinol tubing.  The retainer is covered with silicone in order to create a seal 
between the implant and the bronchial wall.  When the EBV is delivered into the 
target lumen, the retainer expands to contact the walls of the bronchial lumen.   
3.2 Delivery Catheter  
The flexible delivery catheter facilitates placement of the EBV in a targeted bronchial 
lumen. The delivery catheter is very similar to currently marketed tracheobronchial stent 
delivery catheters and will be familiar to physicians trained in the placement of airway 
stents.  The EBV is compressed into the retractable distal housing.  The EBV is 
deployed by actuating the deployment handle, which retracts the distal housing and 
releases the EBV to expand inside the target lumen.  The delivery catheter can then be 
retracted from the EBV and removed from the patient.  
 
4.0    STUDY PURPOSE 
The purpose of this study is to assess the safety and effectiveness of BLVR using the 
Pulmonx Endobronchial Valve (EBV) in treated study participants compared to control 
participants to support a premarket approval application to FDA.   

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5.0    STUDY DESIGN 
This will be a multi-center prospective, randomized, controlled study with EBV treatment 
statistically evaluated using Intent-to-Treat (ITT) analyses. Random assignment will be 
conducted using an allocation ratio of 2:1; two study participants will be randomized to 
the EBV Treatment arm for every one participant randomized to the Control arm.  A 
maximum of 183 patients with severe heterogeneous emphysema, who meet study entry 
criteria, consisting of screening eligibility criteria, baseline eligibility criteria, and 
procedure eligibility criteria, will be enrolled.  Safety and effectiveness of BLVR using the 
Pulmonx EBV will be evaluated at 1 year.  For study participants who have been treated 
with EBV, a secondary intervention such as valve removal, replacement, or adjustment, 
as described in this protocol, may be considered during the study follow-up.  Long-term 
data will be collected annually through 5 years.  Per the regulatory plan agreed to with 
FDA, 1 year of follow-up is required pre-approval and the remaining 4 years of follow-up 
will be conducted post-approval.  The flow of study participants through the study 
protocol is shown in Appendix 1. 
 
6.0    STUDY POPULATION 
The study population will be comprised of 183 study participants with severe 
heterogeneous emphysema as defined by the study eligibility criteria.  The study 
participants will be randomly assigned to the study treatment along with optimal medical 
therapy or optimal medical therapy alone.   
6.1 Optimal Medical Therapy 
All study participants will receive optimal medical therapy, defined for the purposes of this 
protocol as maximal medical treatment for stable COPD as indicated by the 2011 
NIH/WHO GOLD guidelines [26].  The optimal medical therapy will be initiated, if not 
begun previously, upon a study candidate’s enrollment into the study.  The GOLD 
recommendations for optimal medical therapy consist of smoking cessation support, 
oxygen supplementation, pharmacological treatments, and pulmonary rehabilitation.  All 
enrolled study participants will be provided access to a smoking cessation support 
program and will receive oxygen supplementation as medically indicated during their 
participation in the study.  Pharmacological treatments and pulmonary rehabilitation 
therapy are described in detail in Section 9.0 and Section 10.0, respectively.  All study 
participants will meet the study eligibility criteria for having current Pneumococcus and 
Influenza vaccinations.   
      
7.0    STUDY OBJECTIVE 
The objective of the study will be to evaluate lung function changes and adverse events 
after BLVR using the Pulmonx EBV.     
7.1 Primary Effectiveness Endpoint 
The percentage of EBV Treatment arm study participants meeting the threshold of >15% 
improved forced expiratory volume in one second (FEV1), obtained immediately following 

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bronchodilator therapy, as compared to the percentage in the Control arm at 1 year post-
procedure.  
7.2 Safety Endpoint 
Evaluation of the short- and long-term adverse events profile of the EBV Treatment arm 
during the treatment period, defined as the day of the study procedure until 45 days after 
the study procedure (short), and in the post-treatment period, defined as 46 days after 
the study procedure until the 1-year follow-up visit (long).   
7.3 Secondary Effectiveness Measures 
Secondary effectiveness measures will consist of the following:    
 
1) Treatment Lobe Volume Reduction (TLVR) for the EBV Treatment Arm 
i. TLVR, measured as the ‘absolute change from baseline’ for treated 
lobe volume as seen via HRCT, will be evaluated at 45 days and 1 
year.   
ii. TLVR, measured as the ‘percentage change from baseline’ for treated 
lobe volume as seen via HRCT, will be evaluated at 45 days and 1 
year.   
 
2) St. George’s Respiratory Questionnaire (SGRQ)  
i. Difference between study arms in ‘absolute change from baseline’ for 
SGRQ score at 1 year.  
 
3) FEV1  
i. Persistence of treatment effect will be evaluated by determining the 
difference between study arms for ‘absolute change from baseline’ for 
FEV1 at 45 days, 6 months, and 1 year. 
ii. Persistence of treatment effect will be evaluated by determining the 
difference between study arms for ‘percentage change from baseline’ 
for FEV1 at 45 days, 6 months, and 1 year. 
 
4) 6-Minute Walk Distance 
i. Difference between study arms in ‘absolute change from baseline’ for 
6MWD at 1 year.   
ii. Difference between study arms in ‘percentage change from baseline’ 
for 6MWD at 1 year.   
7.4 Additional Measures 
Mean changes and/or changes measured using responder analyses for:   
• 
Spirometry, including FEV1, forced vital capacity (FVC) and the ratio of FEV1/FVC  
• 
Body plethysmography, including residual volume (RV), inspiratory capacity (IC), 
functional residual capacity (FRC), total lung capacity (TLC), and the ratios of 
RV/TLC and IC/TLC 
• 
SGRQ global and domain (i.e. ‘symptoms’, ‘activity’ and ‘impacts on daily life’) 
score 
• 
Modified Medical Research Council (mMRC) dyspnea scale score 
• 
BODE Index 
• 
Transitional Dyspnea Index (TDI) from Baseline Dyspnea Index (BDI) 

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• 
COPD Assessment Test (CAT) 
• 
SF-36 Health Survey 
• 
EQ-5D Health Survey 
• 
Health Care Utilization Questionnaire 
• 
6 minute walk distance 
• 
Borg scale dyspnea scores before and after 6MWD test 
• 
Change in use of ‘maintenance’ medications, including bronchodilators, 
corticosteroids, antibiotics, and anti-inflammatories 
• 
Daily diary (EXACT-PRO, pulmonary rehabilitation compliance, health status 
changes)  
• 
Carbon Monoxide Diffusing Capacity (DLCO) 
• 
Lung radiographic features 
• 
Blood chemistry measures 
   
7.5 Crossover of Control Study Participants 
After completing the 1-year visit, a control arm participant may be permitted to crossover 
to the study treatment if (s)he continues to qualify for the study treatment. In order to 
qualify for crossover, a control arm participant must have been followed up successfully 
through 1 year and demonstrate lack of a clinically important response.  The crossover 
procedure must be scheduled to occur within the 60 days after the 1 year visit.  After 
treatment, the follow-up visits and testing at each visit will be identical to the study 
schedule for treatment arm participants. 
 
Note: Per Revision H of this protocol, the requirement of a heterogeneity score of 15% 
between lobes is not applicable for any remaining crossover subjects. The most diseased 
target can be treated regardless of heterogeneity, provided that  the target lobe is  
collateral ventilation negative (CV-).  
 
Patients treated after approval of this Amendment will fall outside of the original 60 day 
window from the 1-year visit date. This delay will not be marked as a deviation from the 
protocol. 
7.6 Interim Analysis 
An interim data analysis designed to evaluate effectiveness for continuing crossover of 
Control arm study participants after the 1 year follow-up visit to EBV treatment will be 
performed when 74 (50% of the required minimum of 147) study participants have 
completed the 1 year follow-up.  If crossover of Control arm study participants is found to 
be justified by the interim analysis then crossover of Control arm study participants after 
(s)he has reached the 1-year time point may be continued. The results of the interim 
analysis will be reviewed by the DSMB and FDA.  If the DSMB recommends not 
continuing crossing control arm participants to EBV treatment, then those control arm 
participants who have not crossed over will exit from the study protocol after the 1-year 
visit.      
 

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7.7 Long-Term Follow-Up 
Data will be collected annually through 5 years for study participants receiving the study 
treatment.  Per the regulatory plan agreed to with FDA, 1 year of follow-up is required 
pre-approval and the remaining 4 years of follow-up will be conducted post-approval.  
The annual 2-, 3-, 4-, and 5-year follow-up data will consist of FEV1 and adverse events. 
 
8.0    STUDY PARTICIPANT MANAGEMENT  
8.1 Clinical Site Study Team 
The Principal Investigator at each clinical site will be responsible for identifying and 
providing oversight of the study team at the clinical site.  The clinical site study team will 
be responsible for executing all study-related activities.     
8.2 Clinical Study Site Training  
Prior to enrolling any study participants, the site Principal Investigator(s) and the Study 
Coordinator(s) will complete the Pulmonx Clinical Study Training Program.  An overview 
of the training program is provided in Section 18.0.      
8.3 Study Candidate Recruiting  
After obtaining approval from the Institutional Review Board (IRB) overseeing their site, 
patients at the site may be approached by clinical site staff as candidates for the study.  
Clinical sites will be encouraged to advertise for local recruitment and web-links to study 
information may be provided to relevant organizations.  Additionally, study investigators 
will be provided with written and electronic study-related materials that they may provide 
to referring care providers in their regions.   
8.4 Study Candidate Selection  
Any clinic patient may be considered for study candidacy while receiving routine care for 
emphysema.  The screening flow for study candidates, with timing of study participant 
enrollment, is shown in Appendix 2.   
 
Prior to initiating any study screening-related activities with individual patients, all study 
candidates will sign a Screening Informed Consent Form (Appendix 3), or similar, to 
acknowledge their willingness to participate in study screening activities.  A screening 
log that shows all screened patients who sign the Informed Consent will be maintained.  
The intent of the screening log (Appendix 4) is to capture the reasons that chronic 
obstructive pulmonary disease (COPD) patients who are interested in the study are not 
eligible to participate.     
8.4.1 
Informed Consent and HIPAA Authorization 
The informed consent process will be conducted in accordance with the 
Declaration of Helsinki, International Congress of Harmonization (ICH) Good 
Clinical Practice guidelines (to the extent that they are consistent with U.S. 
Federal regulations), and the U.S. Federal Code of Regulations, Section 21, Part 
50. The Principal Investigator or a member of his/her staff should approach study 
candidates who meet study eligibility criteria to obtain informed consent.  The 

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Investigator or his/her designee will explain the purpose of the study and the 
anticipated benefits and associated risks of study participation.  
 
The study candidate will be given an Informed Consent Form.  This form(s) (or 
modifications) must have prior approval of the study site’s Institutional Review 
Board (IRB) before use.  The study candidate will be given adequate time to 
review the Informed Consent Form.   Study candidates may not be consented 
after receiving any medication (e.g. sedatives, narcotics, etc.) that might alter 
their ability to comprehend the informed consent.  After the study candidate has 
had the opportunity to read the form and discuss the study information with study 
site personnel, they will be asked to make a decision regarding participation in 
the study.  
 
All study candidates who choose to participate in the study will sign the Informed 
Consent Form prior to commencement of any study-specific testing. Failure to 
provide informed consent renders the study candidate ineligible for the study.  
The signed Informed Consent Form will be retained at the investigational site, 
and copies will be provided to the study participant.  Study participants may 
voluntarily withdraw from the study at any time following enrollment into the 
study. 
 
The HIPAA Authorization (Health Insurance Portability and Accountability Act) 
adds to protections already provided by the informed consent.  These additions 
state that the study participant must be informed that they can withdraw 
authorization to use data or samples not already submitted to the study sponsor 
and that the request must be in writing.  If the study participant allows samples to 
be used after withdrawal from the study, this permission may be withdrawn at a 
later date.  The HIPAA authorization specifies who may review confidential 
medical information, to whom test results will be submitted, and that test results 
obtained solely for research will not be part of the study participant’s medical 
record.  A copy of the study participant’s information, including the signed 
consent form and HIPAA Authorization, must be provided to the study participant. 
8.5 Screening Eligibility Criteria 
All study candidates will have signed a study Screening or Study Procedure Informed 
Consent form prior to undergoing any testing to determine study eligibility.  The 
screening eligibility criteria are given in Appendix 5. It is recommended that screening 
eligibility criteria testing be conducted sequentially in the order shown here:  medical 
history collection and physical examination, an echocardiogram, volumetric high 
resolution computed tomography (CT) (see Section 8.5.1 below), electrocardiography 
(ECG), spirometry, body plethysmography, diffusing capacity (DLCO), 6MWD, arterial 
blood gases (ABGs), complete blood count (CBC), alpha 1-antitrypsin deficiency 
detection, plasma cotinine level (or arterial carboxyhemoglobin if using nicotine 
products) and serum fibrinogen.   
 
If the study candidate has had a CT within the last three months prior to signing the 
screening consent and the images were obtained in accordance with the CT scan 
protocol then a repeat CT scan will not be necessary. Of note, screening of CT scan 
records of clinic patients seen previously for medical care at the study site is permitted.  

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8.5.1 
CT Screening Eligibility Criteria  
Acquisition of CT scans will be standardized across clinical sites by training sites 
and using an imaging procedures core manual.  The protocol will include volume 
acquisition thin section obtained at suspended breath hold at full inspiration 
(TLC) and full expiration (RV).  Images will be reconstructed using a smooth or 
standard filter; the protocol is detailed in Appendix 6.  The radiology 
technologists at the clinical sites will be trained to the HRCT data collection 
protocol.   
 
The clinical site will evaluate HRCT images to determine screening eligibility of 
the study candidate.  The grading system used by the clinical sites to evaluate 
HRCT scans will be standardized and site personnel will be trained to use it.  The 
HRCT eligibility criteria will be assessed by determining parenchymal destruction 
and emphysema heterogeneity scores using the total lung capacity (TLC) scan 
and the definitions below (Sections 8.5.1.1 and 8.5.1.2). The site will use FDA 
cleared software, which may include VCAR (GE Medical Systems, Milwaukee, 
WI), Apollo (VIDA, Coralville, IA), syngo Lung Care CT (Siemens Healthcare 
Solutions, Deerfield, IL), MeVis Visia CT Lung System (MeVis Medical Solutions, 
Milwaukee, WI), Myrian (Intrasense, Montpellier, France), or other 510k cleared 
software to measure lung density to determine parenchymal destruction.   
 
The site reader will use the parenchymal destruction scores provided by the 
software to calculate emphysema heterogeneity using a provided worksheet.  
The CT study must exhibit sufficient landmarking to be evaluated using the 
software as it is intended for delineating lobar parenchymal destruction. 
8.5.1.1  Definition of Parenchymal Destruction Score 
Lobar parenchymal destruction scores will be determined, on thin section 
volumetric series, using specialized software to calculate the proportion of 
image voxels within a lobe that fall below a pre-defined Hounsfield unit 
threshold.  These scores will be reported as a parenchymal destruction 
score for each lung lobe.  For example, a parenchymal destruction score 
of 50% means that 50% of the volume of that lobe meeting the Hounsfield 
threshold and will be considered destroyed by emphysema. 
8.5.1.2  Definition of Emphysema Heterogeneity Score 
Emphysema heterogeneity score will be defined as the difference (in 
percent) between the parenchymal destruction scores of the target lobe 
and the ipsilateral non-target lobe(s).   
 
For the left lung, emphysema heterogeneity will be quantified by 
calculating the difference between the target treatment lobe (left upper 
lobe [LUL] or left lower lobe [LLL]) parenchymal destruction score and the 
ipsilateral non-target lobe parenchymal destruction score.  
 
 
 
 
 
 
 
 
Parenchymal 
Destruction 
Score for LUL 
Parenchymal 
Destruction 
Score for LLL 
 
compared to 

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For the right lung, emphysema heterogeneity will be quantified by 
calculating the difference between the parenchymal destruction scores for 
all three lobes separately (right upper lobe [RUL], right middle lobe [RML], 
and right lower lobe [RLL]).    
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The Study Bronchoscopy Plan described in Section 8.7 below will be utilized to determine if a 
study candidate meets the emphysema heterogeneity criterion and qualifies to proceed with 
study screening.     
8.5.2 
 Supervised Pulmonary Rehabilitation Program Required to Establish 
Baseline Eligibility  
A study candidate who has completed a supervised pulmonary rehabilitation 
program within the last six months prior to the baseline eligibility screening visit, 
or who is regularly performing maintenance respiratory rehabilitation if initial 
supervised therapy occurred more than six months prior, may proceed to 
baseline testing provided that the pulmonary rehabilitation program is 
documented and meets the criteria specified by this study protocol.  The 
pulmonary rehabilitation program will include at least two visits to the 
rehabilitation center per week.  Minimum attendance of eight visits will be 
required to fulfill the study enrollment pulmonary rehabilitation program 
requirement.  Any study candidate who has not completed at least eight visits will 
not be eligible to enter the study.   
 
 
Parenchymal 
Destruction 
Score for RUL  
Parenchymal 
Destruction 
Score for RLL 
compared to 
 
Parenchymal 
Destruction 
Score for RUL 
Parenchymal 
Destruction 
Score for RML 
compared to 
 
Parenchymal 
Destruction 
Score for RLL 
Parenchymal 
Destruction 
Score for RML 
compared to 

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8.6 Baseline Eligibility Criteria 
Any study candidate who meets the screening eligibility criteria and has successfully 
completed a supervised pulmonary rehabilitation program may have clinical testing to 
support assessment of the baseline eligibility criteria (Appendix 7). The baseline 
eligibility determination must be made < 120 days following the screening eligibility 
determination. It is recommended that baseline eligibility testing be conducted 
sequentially in the order listed in Section 14.0.  Study candidates who meet the 
screening and baseline eligibility criteria may be considered for study enrollment.   
 
Study candidates meeting the screening and baseline eligibility criteria will be required to 
have signed the Study Informed Consent Form (Appendix 8) or similar prior to 
undergoing the bronchoscopy procedure to assess study procedure eligibility.  Study 
candidates who have met the screening and baseline eligibility criteria but who are no 
longer interested in participating in the study or who do not sign the Study Informed 
Consent Form will be recorded on the screening log.  
 
Study-related testing should not be conducted if the study participant is having an active 
COPD exacerbation at the time of baseline testing. If a study participant has a COPD 
exacerbation, the baseline testing should be postponed until the exacerbation is 
resolved as determined by the site principal investigator. 
 
8.7 Bronchoscopy Plan for CV Assessment and Determining Study Eligibility 
A bronchoscopy procedure plan will be created by the Study Investigator for each study 
candidate. The goal of bronchoscopy planning is to determine whether the study 
candidate meets the emphysema heterogeneity eligibility criterion and to pre-identify the 
lobe(s) most appropriate for study treatment (EBV placement).  The bronchoscopy plan 
will be developed using the CT scan collected during the study participant’s eligibility 
screening (see Section 8.5.1).  The pre-identified lobe(s) will be assessed for CV using 
the Chartis System during the bronchoscopy procedure.  The bronchoscopy plan will be 
documented using the appropriate Case Report Form.   
8.7.1 
Algorithm for Radiologic Determination of Emphysema Heterogeneity and 
Identification of Target Treatment Lobe(s)   
The bronchoscopy plan will be completed using   the flowchart algorithm 
provided in Appendix 9.  Lobes in both lungs may be eligible to undergo 
treatment but only one lung will be treated.   
 
Note: Per Revision H of this protocol, the requirement of a heterogeneity score of 15% 
between lobes is not applicable for any remaining crossover subjects.  The most diseased 
target can be treated regardless of heterogeneity, provided that the target lobe is collateral 
ventilation negative (CV-). 
 
8.8 Study Procedure Eligibility Criteria    
The final study procedure eligibility criteria will be assessed during the bronchoscopy 
procedure (Appendix 10).  The bronchoscopy procedure should occur < 60 days after 
the baseline assessment visit.  Those study participants who are found to be eligible to 

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participate in the study will be enrolled into the study and randomly assigned to 
treatment (or control) at that time.  If randomly assigned to the study treatment arm, the 
study participant will undergo the study-directed treatment during the same session 
unless this is contraindicated by the length of time the study participant has been under 
anesthesia; if the time remaining for safe administration of anesthesia is considered to 
be insufficient for completing the study procedure, it will be deferred to another session.    
 
To meet the study procedure eligibility criteria, the study participant must have at least 
one pre-identified target lobe (upper or lower lobe), as delineated in the bronchoscopy 
procedure plan, which is found to have little or no CV as measured by the Chartis 
System (see Section 11.2).  A flow chart showing the key decision-points during the 
bronchoscopy procedure is provided in Appendix 11.  Every effort will be made to have 
Pulmonx technical staff at all bronchoscopy procedures to provide support.   
8.9 Study Participant Enrollment  
A study candidate will be enrolled into the study after meeting all screening and baseline 
eligibility criteria, providing informed consent for study participation, and meeting the 
study procedure eligibility criteria.  Enrollment of a study candidate as a study participant 
will be documented using the appropriate Case Report Form.   
 
8.9.1 
Randomization Assignment and Study Treatment 
A study participant will be randomly assigned to treatment or control after 
determining he/she meets the study procedure eligibility criteria during the 
bronchoscopy procedure (see Section 11.2).  If the study participant does not meet 
the study procedure eligibility criteria, he/she will not be randomly assigned to 
treatment nor receive any study-related treatment.  If the study candidate is found 
to meet the study procedure eligibility criteria, then (s)he will be randomly assigned 
to study treatment during the bronchoscopy procedure.  
 
Random assignment will be conducted using an allocation ratio of 2:1; two study 
participants will be randomized to the EBV Treatment arm for every one 
participant randomized to the Control arm.  Random assignment will be 
conducted using a stratified permuted block design generated separately for 
each clinical site, with assignment stratified by anatomical site of the planned 
treatment (e.g. right lung or left lung).  Mixed block sizes will be used.  The goal 
of stratification will be to ensure a 2:1 randomization mix within each stratum.  
8.10 Follow-Up Visits 
8.10.1 
Study Schedule 
The required study schedule for study participants is shown in Section 14.0 and 
Appendix 12.      
8.10.1.1 
Study Participants Treated with EBV   
Any study participant receiving EBV treatment will be followed-up 
annually through 5 years.   
8.10.2 
 Visit Windows  
The study follow-up visits required by the study protocol are shown in the Table 
below.  The study follow-up visits should be scheduled within the ranges 

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(windows) specified in the Table.  These windows have been established to allow 
for maximum data collection in a study population known to have a high risk of 
missing clinic visits due to confounding clinical circumstances.  It is 
recommended that all efforts be made to schedule follow-up visits as early as 
possible within the visit window in case the visit may need to be rescheduled.  
Utilization of these visit windows will aid in avoiding imputation of data during 
statistical analysis.   
Study-related testing should not be conducted if the study participant is having an 
active COPD exacerbation at the time of a study follow-up visit. If a study 
participant has a COPD exacerbation, the study visit should be cancelled and 
rescheduled to be conducted at 14 days, or as early as possible after 14 days, 
following the initiation of treatment for the exacerbation. The clinical study site will 
document in the study participant’s medical record all incidents in which a 
scheduled study visit is cancelled and rescheduled due to occurrence of a COPD 
exacerbation.   
When the study participant informs the site of the COPD exacerbation, the 
investigator may request the study participant to come in for evaluation.  This 
evaluation may include a physical examination and review of medications and 
will be classified as an interim visit.   
If the rescheduled study follow-up visit falls outside of the study follow-up visit 
window, it will be recorded as an out of window protocol deviation.  If the study 
participant fails to make the rescheduled study follow-up visit it will be captured 
as a missed visit and protocol deviation.        
Table.  Study Follow-Visits and Windows for Scheduling the Visits  
 
Visit 
Range 
1 
24-Hour‡ 
+/- 8 hours 
2 
 Daily phone call for 10 days following discharge‡ 
by 11:59 pm local time 
3 
7 days after discharge‡ (phone call not required on this day) 
+ 1 business day 
4 
30-day‡ 
+/-5 days 
5 
45-day 
+/- 10 days 
6 
3-Month 
+/- 14 days 
7 
6-Month 
+/- 21 days 
8 
9-Month 
+/- 21 days 
9 
1-Year 
+/- 45 days 
10-13 
2, 3, 4, 5 Years‡ 
+/- 60 days 
 ‡ EBV-treated study participants only; *Procedure day = Day 0 
8.11 Retention of Study Participants   
Every effort should be made by clinical site staff to retain study participants for the 
duration of the study.  Study participants failing to return for follow-up, or failing to return 
contact attempts by site staff for follow-up visits, shall be contacted a minimum of three 
times by the Study Coordinator or Investigator, with the last attempt by certified mail, 
before exiting the study participant as lost to follow-up. All contact attempts of study 
participants who do not return for follow-up should be documented in the study 
participant’s medical record.     

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8.11.1 
Participant Withdrawal 
Study participants may choose to withdraw from the study at any time without 
penalty or loss of benefits to which they are otherwise entitled.  If a study 
participant provides a reason(s) for early withdrawal, the reason(s) shall be 
documented on the appropriate Case Report Form and in the study participant’s 
medical record.  If possible, a final medical exam, along with spirometry 
assessment, shall be performed prior to their withdrawal.      
   
 
9.0 PHARMACOLOGIC TREATMENTS FOR STUDY PARTICIPANTS 
9.1 Optimization of Medications 
Study participants will be carefully monitored at each study visit to confirm that 
pharmacological treatment is optimized.  Optimization of pharmacological treatment will 
also be assessed immediately prior to the bronchoscopy procedure; if there is any 
reason to believe that the study participant is not receiving optimized medical therapy, 
the bronchoscopy procedure may be postponed.   
9.2 Bronchodilators 
Study participants may receive maintenance bronchodilator therapy, which may include 
an inhaled long acting beta-agonist, an inhaled anticholinergic, or both.  These may be 
administered by metered dose inhaler, dry powder inhaler or drug aerosol.  These agents 
may also be combined with theophylline at the discretion of the treating physician.  A 
standardized regimen of treatment will not be required since study participants may have 
variable responses to bronchodilator treatment or need individualized treatment 
depending on their condition. 
9.3 Corticosteroids  
Study participants may receive corticosteroid(s) for mitigation of COPD exacerbations.  
The treating physician will determine medication regimen and instruct study participants 
on appropriate use.  
9.4 Other Pharmacologic Agents 
Other pharmacologic treatments such as mycolytic agents, antibiotics, anti-
inflammatories, and other medications such as antioxidant agents, immunoregulators, 
antitussives, and vasodilators may be prescribed at any time they are medically 
indicated.   
 
10.0 POST-BRONCHOSCOPY PULMONARY REHABILITATION  
The pulmonary rehabilitation program should include the elements recommended by the 
American Thoracic Society and European Respiratory Society Statement on Pulmonary 
Rehabilitation [27].  In general, the post-bronchoscopy program should consist of a 
supervised ‘in clinic’ pulmonary rehabilitation component and a ‘home-based’ 

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maintenance pulmonary rehabilitation component.  The active ‘in clinic’ pulmonary 
rehabilitation program should be initiated for all study participants within the first 30 days 
following the bronchoscopy procedure. For study participants in the treatment arm, 
initiation of the program must be cleared by the investigator.  For the active ‘in clinic’ 
component of the program, the ATS/ERS practice guidelines recommend a minimum of 
20 sessions be given at least three times per week although twice-weekly supervised 
plus one unsupervised home session may also be acceptable. For the maintenance 
component, study participants will be advised to adhere to a program consisting of at 
least 3 home-based sessions per week.    
10.1 Pulmonary Rehabilitation Program 
A Pulmonary Rehabilitation Manual for the study, an example of which is provided in 
Appendix 13, will be provided to each study site.  This manual will contain details 
regarding administration of the pulmonary rehabilitation program including definitions of 
responsibilities and requirements for identification and qualification of the pulmonary 
rehabilitation facility.   
10.1.1 
Pulmonary Rehabilitation Program Elements 
The pulmonary rehabilitation program should consist of lower limb endurance 
training, upper limb endurance training, and lower and upper limb strength 
training.  A list of suggested exercises is provided in the Pulmonary 
Rehabilitation Manual.  If deemed necessary by the therapist, oxygen saturation 
may be monitored during exercise. The home rehabilitation program will be 
developed for individual patients by the pulmonary rehabilitation center at each 
clinical site.  The therapist will suggest appropriate exercises.    
• 
Lower limb endurance training 
Lower limb endurance training should consist of walking, either done on a 
treadmill, or ambulating freely indoors or outdoors, for >20 minutes in a 
session.       
• 
Upper limb endurance training 
Upper limb endurance training consists of a group of exercises involving 
some form and level of resistance for each hand (e.g. dumbbells or 
Therabands).      
• 
Lower and upper limb strength training 
Lower and upper limb strength training consists of a group of exercise 
involving some form and level of resistance (e.g. dumbbells or 
Therabands).       
 
11.0 BRONCHOSCOPY PROCEDURE 
Every effort will be made for a Pulmonx representative to be in attendance at a study 
participant’s bronchoscopy procedure.  The bronchoscopy procedure should be recorded on 
video, CD ROM, or DVD and a copy maintained in the study participant’s files.  Alternatively, 
photographs of valve placement may be obtained.  Prior to the procedure, identify and 
document site personnel responsible for managing any pneumothorax.  During the 
bronchoscopy procedure, all study candidates will undergo assessment of study eligibility using 

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the Chartis System.  All study candidates found to be eligible to undergo the study procedure 
will be enrolled into the study and will be randomly assigned at that time. All enrolled study 
participants will be treated as randomly assigned.  See Appendix 11 for an overview of the 
events occurring during bronchoscopy procedure. 
11.1 Procedure Medications 
In addition to the medications described in Pharmacologic Treatments (Section 9), the 
peri-procedural medication regimen shown in the Table below is recommended.   
 
Table. Summary of Procedure Medications (or equivalent) 
 
Medication 
Before 
Procedure 
During 
Procedure 
Post-
Procedure 
Cease use of anti-coagulants 5-7 days before 
X 
 
 
Cease use of aspirin at least 3 days before, if indicated per 
physician discretion 
X 
 
 
Inhaled bronchodilator 20 minutes before 
X 
 
 
Initiate prophylactic antibiotic (e.g. Cephalosporin or 
Quinolone) 
X 
 
 
Anesthetic 
 
X 
 
Oral course of prophylactic antibiotics (5-7 days) 
 
 
X 
Bronchodilator therapy 
 
 
X 
 
11.1.1 
Medications administered prior to the bronchoscopy 
Study candidates will be asked to cease using anti-coagulant medications (if 
applicable) 5-7 days before the procedure and to refrain from taking aspirin for at 
least three days before the procedure if indicated per physician discretion. At the 
preference of the treating physician, prophylactic antibiotics and/or 
corticosteroids may be administered one or two days prior to the procedure.  
Approximately 20 minutes before the procedure, study candidates may be 
treated using an inhaled bronchodilator.  Just prior to the procedure, intravenous 
first or second generation antibiotics such as cephalosporin or quinolone (e.g. 
Ancef, Kefzol, Cefaclor) should be administered.       
11.1.2 
Medications administered during the bronchoscopy 
The procedure anesthetic will be administered according to standard local 
protocols used for bronchoscopy. Assessment of collateral ventilation using the 
Chartis System will be performed under conscious sedation with unassisted 
breathing.  The study procedure (EBV placement) may be performed under 
conscious sedation with unassisted breathing or under general anesthesia with 
the patient on a ventilator.    
11.1.3 
Medications administered following the bronchoscopy 
For the 24 hours after the procedure, intravenous first or second generation 
cephalosporin or quinolone (e.g. Ancef, Kefzol, Cefaclor) should be administered.  
A standard-of-care corticosteroid regimen may also be initiated at this time.  

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Beginning at 24 hours after the procedure, study participants will receive, or 
continue to receive if initiated previously, a five to seven day prophylactic course 
of oral cephalosporin, quinolone, or macrolide antibiotics.   
11.2 Assessment of Study Procedure Eligibility Criteria  
Study procedure eligibility will be determined by assessing CV of the pre-identified target 
treatment lobe(s), as documented in the bronchoscopy plan (Section 8.8), using the 
Chartis System.  All potential target treatment lobes identified in the bronchoscopy plan 
will be assessed during the bronchoscopy session. The Chartis System will be used as 
described in the Instructions for Use.  The CV assessment(s) will be performed under 
conscious sedation with unassisted breathing.  The procedure for assessing CV, along 
with case examples, is provided in Appendix 14.  
11.2.1 
Study Participant Meets Study Procedure Eligibility Criteria 
If the study participant meets the study eligibility criteria, (s)he will be randomly 
assigned to study treatment or control.     
11.2.1.1 
 Randomization Assignment 
A study participant will be randomly assigned to treatment using 
the method required by the study sponsor.  Study staff will 
conduct random assignment of study participants by either 
telephoning or electronically accessing a centralized location from 
the bronchoscopy suite to learn the study participant’s random 
assignment. Random assignment will be documented using the 
appropriate Case Report Form.   
    
11.2.2 
Study Participant Does NOT Meet Study Procedure Eligibility Criteria 
If the study candidate does not meet the study procedure eligibility criteria, the 
bronchoscopy procedure will be terminated using the standard practice 
guidelines at the clinical site.  The study candidate will be permitted to recover 
from anesthesia by following the clinical site hospital’s standard protocol.     
11.3 Assignment to Control Arm  
If the study participant is randomly assigned to the Control arm, the 
bronchoscopy procedure will be terminated using the standard practice 
guidelines at the clinical site and the study participant will be followed up as 
described in Section 8.10 and Appendix 12.    
11.4 Assignment to Study Treatment Arm  
If the study participant is randomly assigned to the EBV treatment arm, (s)he 
should immediately undergo the study procedure (see Section 11.5). However, in 
any case in which there may be insufficient time to complete the study procedure 
because the time to safely administer the anesthesia is running out, the study 
procedure may be deferred. The study participant will be followed up as 
described in Section 8.10 and Appendix 12.  

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11.5 Execution of the Study Procedure  
The study treatment will be considered to be initiated immediately upon introduction of 
the EBV delivery catheter into the bronchoscope. The study procedure may be 
performed with the study participant under conscious sedation with unassisted breathing 
or under general anesthesia on a ventilator.  For study participants who are not on a 
ventilator, a bite block may be used to facilitate access.  For general anesthesia 
procedures, a rigid bronchoscope in conjunction with a flexible bronchoscope or a 
flexible bronchoscope alone through an endotracheal tube may be used for valve 
placement.  The study device will be placed in accordance with the study protocol 
requirements and the Instructions for Use.  The target treatment lobe(s) will consist of 
only one of the following:  LUL, LLL, RUL, RLL, or RUL+RML.   
11.5.1 
Lobar Occlusion with EBV 
The target lobe is intended to be completely occluded with EBV placement, 
meaning that all airways feeding the lobe are to be blocked with a valve.  Lobar 
occlusion is required as the segmental boundaries are often largely destroyed in 
cases of advanced emphysema.  If valves do not occlude the entire lobe, gas 
may freely travel from a non-valved segment to a valved segment, reducing the 
potential benefit.  Valves may be placed at the lobar, segmental, or sub-
segmental levels, in this order of preference, depending on the anatomy of the 
study participant.  Whenever possible, valves should be placed in an earlier 
generation bronchus (e.g. if a large valve will fit in the left upper lobe bronchus, 
that should be the target instead of a valve placed in each of the segmental 
bronchi).  Potential targets at the segmental bronchi level are shown in 
Appendix 15.   
Success for achieving lobar occlusion must be verified, via bronchoscopy, 
immediately following valve placement and recorded on the appropriate CRF.  If 
a valve appears to be misplaced or misaligned, it will be removed and replaced.  
If it is not possible to place or align the valve correctly then the valve will be 
removed and the reason for not placing the valve will be recorded on the 
appropriate CRF.   
11.6 Post-Bronchoscopy Recovery Period Procedures for Study Treatment Arm 
   
Study participants who receive the study treatment will be required to stay in the hospital 
for at least 5 nights.  During the hospital stay, chest X-rays will be obtained daily, 
including a chest X-ray at Day 0, Day 1, Day 2, Day 3, Day 4, and Day 5.  If a study 
participant is being treated for a pneumothorax during the study procedure hospital stay, 
collection of chest X-rays beyond Day 5 will be at the discretion of the study physician, 
with a protocol mandated chest X-ray on the day of discharge.  An overview of the post-
procedure hospital stay for study participants who receive the study treatment is shown 
below.    
 
Post-Study Procedure Checklist For Coordinators 
Day 0-Post-Study Procedure  
____ Ensure that patient is transferred to appropriate recovery area as per local  
 
hospital’s standard protocol. 

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____ Ensure that chest x-ray is obtained and reviewed by treating physician within 1 hour (± 
30 minutes) of procedure for assessment of volume reduction and pneumothorax. 
   
____ Ensure that patient receives antibiotics, corticosteroids, bronchodilators, or any other 
medications as needed. 
 
____ Ensure that vital signs and pulse oximetry are recorded and assessed during the 24 
hours following the procedure. 
 
____ Ensure that patient is assessed for any adverse events. 
 
 
Day 1-Hospital Stay 
____ Ensure that chest x-ray is obtained and reviewed by treating physician for assessment of 
volume reduction and pneumothorax. 
 
____ Ensure that ABG and serum fibrinogen samples have been collected. 
 
____ Ensure that patient completes Daily Diary. 
 
____ Ensure that patient is assessed for any adverse events. 
 
 
Day 2-Hospital Stay 
____ Ensure that chest x-ray is obtained and reviewed by treating physician for assessment of 
volume reduction and pneumothorax. 
 
____ Ensure that patient completes Daily Diary. 
 
____ Ensure that patient is assessed for any adverse events. 
 
 
Day 3-Hospital Stay 
____ Ensure that chest x-ray is obtained and reviewed by treating physician for assessment of 
volume reduction and pneumothorax. 
 
____ Ensure that patient completes Daily Diary. 
 
____ Ensure that patient is assessed for any adverse events. 
 
 
Day 4-Hospital Stay 
____ Ensure that chest x-ray is obtained and reviewed by treating physician for assessment of 
volume reduction and pneumothorax. 
 
____ Ensure that patient completes Daily Diary. 

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____ Ensure that patient is assessed for any adverse events. 
 
 
Day 5-Hospital Discharge 
 
____ Ensure that treating physician completes a physical examination. 
 
____ Ensure that chest x-ray is obtained and reviewed by treating physician for assessment of 
volume reduction and pneumothorax. 
 
____ Ensure that patient completes Daily Diary. 
 
____ Ensure that patient is assessed for any adverse events. 
 
____ Ensure that treating physician has cleared the patient for discharge. 
 
____ Ensure that patient receives antibiotics, corticosteroids, bronchodilators, or any other 
medications as needed. 
 
____ Ensure that patient receives Medical Alert Card, Treated Study Participant Bracelet, 
Transferring Instructions if Late Pneumothorax, and Post-Discharge Instructions.  
Ensure that you have discussed these items with the study participant and caregivers 
and that they have been given opportunity to ask/have answered any questions. 
 
____ Ensure that you have explained to the patient that he/she will be called every day for the 
next 10 days to follow up on how he/she is doing and whether he/she has experienced 
any adverse events.  If there is a specific time of day that works best for the patient, 
ensure that this is documented (Time of Call). 
 
 
11.7 Procedures Prior to Discharge  
The Study Coordinator should schedule the appropriate study follow-up visits with the 
study participant prior to their discharge from the hospital.  See Section 14.0 for the 
detailed procedures.  Prior to discharge, all study participants should receive post-
operative bronchodilator inhalers and be prescribed a prophylactic course of antibiotics 
if this was not previously done.  
 
For the study treatment arm, a Medical Alert Card containing emergency contact 
information, which will be completed by the research staff, and post-discharge 
instructions will be provided to study participants that received the study treatment.  An 
example of the Medical Alert Card and the Post-Discharge Instructions are provided as 
Appendix 16 and Appendix 17, respectively. The Treated Study Participant Bracelet 
and Transferring Instructions if Late Pneumothorax should also be given to the study 
participant.   
        

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12.0 SECONDARY VALVE PROCEDURES 
Any study participant who receives EBV treatment may undergo valve removal, 
replacement, or adjustment while participating in the study.  In the case of a secondary 
valve procedure(s), the follow-up schedule will be calculated from the date of the initial 
treatment.  These procedures and the conditions in which they may be considered are 
described below.    
12.1 Valve Removal 
Study investigators may consider removing valves due to occurrence of an adverse 
event (see Section 15.0).  Valves may be removed according to the Manufacturer’s 
Instructions for Use.    
12.2 Valve Replacement  
Study investigators may consider replacing valves for study participants who expectorate 
a valve(s) or in cases where the valve(s) was removed due to an adverse event (See 
Section 14.0) which has since been resolved.  Up through the 1-year follow-up time 
point, valves may be replaced up to a maximum of two times.  The treating physician will 
determine the timing of a valve replacement on a per-patient basis.    Valves may be 
replaced according to the Manufacturer’s Instructions for Use.   
12.3 Valve Adjustment 
It is anticipated that there may be a few cases in which a valve may not have been 
initially placed to occlude the treated lobe.  In any case where clinical evidence exists 
that a valve was not placed to block the airway leading into the target lobe, adjustment of 
the valve may be considered by the investigator.  Valve adjustment will be considered to 
be part of the study procedure since clinical effect with the Pulmonx EBV is thought to be 
associated with placing valves to achieve lobar occlusion.  
 
Valve adjustment may be performed only once for a study participant and should be 
performed within 75 days of the study procedure.  In any case in which it is necessary to 
re-schedule a valve adjustment due to a study participant’s illness (e.g. COPD 
exacerbation), the valve adjustment may be conducted up to 90 days post-procedure.        
 
The investigator may consider valve adjustment if both of the following are observed:  
 
1) The 45-day HRCT scan, as read by the core radiology reading laboratory and 
measured using FDA cleared software designed to evaluate HRCT changes, 
shows less than 50% volumetric reduction in the EBV-treated lobe. 
 
2) The 45-day HRCT scan, as read by the core radiology reading laboratory, 
demonstrates signs indicative of incomplete occlusion, including no valve in a 
segmental airway, anatomic variation resulting in the valve not occluding 
accessory branches, leakage around the valve, and incorrect placement. 
 
The post-procedure flow and follow-up testing schedule for study participants having 
valve adjustment is shown in Appendix 1 and Appendix 12.  The bronchoscopy 
procedure for the valve adjustment will be conducted as described in Section 11.      
 

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13.0   CLINICAL EFFECTIVENESS OUTCOMES 
13.1 Spirometry  
Spirometry testing will be performed using the guidelines outlined in the ATS/ERS Task 
Force ‘Standardisation of Lung Function Testing’ [28,29].  Spirometry testing will be 
conducted both before and after bronchodilator use.  For each of these conditions, 
the maneuver should be repeated until at least three good efforts are captured to ensure 
that spirometry results are acceptable and reproducible. All three good efforts will be 
recorded.  Spirometric reference values from the third National Health and Nutrition 
Examination Survey (NHANES III) [30] should be used for this study.    
13.2 Patient-Reported Health Status Measures 
The study participant should complete the health status questionnaires themselves but 
the Clinical Coordinator or designee should be available to give advice if it is required. 
The opinions of family, friends or members of staff should not influence the study 
participant’s responses. These questionnaires are designed to elicit the patient’s opinion 
of his/her health, not someone else’s opinion of it. If the spouse or partner has 
accompanied the patient, then they should be asked to wait in a separate area while the 
study participant completes the questionnaires. Similarly, the study participant should not 
be allowed to take the questionnaires home. 
 
The questionnaires should be completed in a quiet area free from distraction and, ideally, 
the study participant should be able to sit at a desk or table. The Study Coordinator or 
designee should explain to the study participant why they are completing these 
questionnaires, and how important it is for the researchers to understand how they feel 
about their illness and the effect it has on their daily life.  The study participant should be 
asked to complete the questionnaires as honestly as possible and it should be stressed 
that there are no right or wrong answers; the study participants should be instructed to 
provide the answer that the study participant feels best applies to them. It should be 
explained that they must answer every question and that study staff will be available to 
answer any questions. 
 
Once the study participant has finished completing the questionnaires, the study 
Coordinator or designee should review ALL questionnaires to confirm that a response 
has been given to every question.  If there are missed items, the affected 
questionnaire(s) should be returned to the study participant before they leave the clinic 
so that they can complete the missed items.  
13.2.1 
St. George’s Respiratory Questionnaire (SGRQ) 
The St. George’s Respiratory Questionnaire (SGRQ) is designed to measure and 
quantify disease-specific health status in patients with chronic airflow limitation.  
The SGRQ was developed in Britain and has been used extensively worldwide.  
It has been evaluated for reliability and validity in numerous studies of patients 
with COPD and has been validated for clinical use in the United States [31].   
The SGRQ instrument consists of three discrete component scales (symptoms, 
activity, and impacts on daily life).   The first part (“Symptoms”) evaluates 
symptomatology, including frequency of cough, sputum production, wheeze, and 
breathlessness. The second part includes questions to address two components:  
“Activity” and “Impacts”.  The “Activity” component includes questions that 

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address activities that cause breathlessness or are limited due to breathlessness.  
The “Impacts” section includes questions that explore the effects of the patient’s 
health status on factors such as employment, being in control of health, panic, 
stigmatization, the need for medication, side effects of prescribed therapies, 
health expectations, and disturbances of daily life.   A total score is calculated 
from all three components.  The scoring range for the components and total 
score is 0-100, with a lower score indicating relatively higher wellness and a 
higher score representing higher disability.   
13.2.2 
Modified Medical Research Council (mMRC) Dyspnea Scale 
The modified Medical Research Council Dyspnea Scale was developed and 
validated as a simple measure that could be used to quantify the effect of 
breathlessness on daily activities [32].  It consists of five statements designed to 
collect information about perceived breathlessness.  The statements are:  Grade 
1, “I only get breathless with strenuous exercise”; Grade 2, “ I get short of breath 
when hurrying on level or up a slight hill”; Grade 3, “I walk slower than people of 
the same age on the level because of breathlessness or have to stop for breath 
when walking at my own pace on the level”; Grade 4, “I stop for breath after 
walking 100 yards or after a few minutes on the level”; Grade 5, “I am too 
breathless to leave the house”.   
13.2.3 
Baseline/Transitional Dyspnea Index (BDI/TDI) 
The BDI/TDI is used to quantify dyspnea and its validity has been reported [33].  
The BDI will be collected at the baseline visit and the TDI should be collected at 
the 3-month, 6-month, 9-month, and 1-year follow-up visits.  The assessment 
measures three domains:  1) functional impairment, which determines the impact 
of breathlessness on the ability to carry out activities; 2) magnitude of task, which 
determines the type of task that causes breathlessness; and 3) magnitude of 
effort, which establishes the level of effort that results in breathlessness.  The 
score ranges from -3 (major deterioration) to +3 (major improvement) for each 
domain.  The sum of all domains is the total score.  A change of at least 1 unit is 
thought to represent a clinically meaningful effect.   
13.2.4 
COPD Assessment Test (CAT) 
The COPD Assessment Test consists of eight items, all of which are self-
assessed by patient to have a score ranging from 0 to 5 and it has been 
validated [34]. The eight items are designed to quantify magnitude of symptoms 
related to cough, phlegm, chest tightness, breathlessness, daily activities 
limitation, self-confidence, quality of sleep, and energy level.       
13.2.5 
Short Form (SF)-36 
The SF-36 is a validated, subject-based health status assessment survey 
designed to assess the impact of a disease state on an individual's general 
sense of wellbeing [35]. It has been used extensively across many medical 
specialties to assess general health-related status and is commonly used in 
health economic studies.   
13.2.6 
EuroQol (EQ-5D) 
The EQ-5D is a standardized instrument that is used as a measure of health 
outcome [36].  It is applicable to a wide range of health conditions and 
treatments.  The questionnaire is comprised of questions that provide a 
descriptive state of health in the areas of mobility, self-care, usual activity, 
pain/discomfort and anxiety/depression. Every question contains three response 

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categories: level 1 – ‘no problems’, level 2 – ‘some problems’ and level 3 – 
‘inability or extreme problems’.  
13.2.7 
Health Care Utilization Questionnaire 
The study participant will self-report health care utilization data such as physician 
office visits, emergency room visits, hospitalizations for respiratory symptoms, 
and use of home health care.     
13.3 Body Plethysmography Testing 
Body plethysmography will be used to determine the volume of thoracic gas (VTG) per 
the American Association of Respiratory Care (AARC) Clinical Practice Guideline “Body 
Plethysmography: 2001 Revision and Update” [37].  The reported VTG should be 
averaged from a minimum of 3-5 separate, acceptable panting maneuvers; should be 
calculated using values that agree within 5% of the mean (widely varying values should 
be averaged, and reported as variable); should indicate whether the thoracic volume 
was at functional residual capacity (FRC) or at some other level; should be compared 
with other lung volume determinations (He dilution, N2 washout) if such are being 
performed.    
Lung volumes including the slow vital capacity (VC) maneuver and its subdivisions 
inspiratory capacity (IC) and expiratory reserve volume (ERV) should be performed 
during the same testing session.  The ERV, IC, and VC should be measured in 
conjunction with each VTG trial before disconnecting from the measuring system.  
Tracing should be added to illustrate correct performance.  The largest volume of VC or 
forced vital capacity (FVC) obtained should be used for calculation of derived lung 
volumes.  The mean values should be reported for IC and ERV from acceptable VTG 
maneuvers.  Total lung capacity (TLC) = mean FRC + mean IC (mean IC should be 
close to the largest IC) and RV = TLC – largest VC.  
Airways resistance and specific airways conductance maneuvers should be conducted 
such that the open-shutter panting maneuver shows a relatively closed loop.  The 
panting frequency for within-testing session comparisons (i.e. pre- and post-
bronchodilator testing) and for serial testing in a given study participant should be kept 
constant to aid in interpretation.  Consensus of the group suggests a range of 60-90 
cycles per minute.   
A linked, rather than unlinked, maneuver should be performed; this means that 
following shutter closure at FRC, an expiratory maneuver to RV is performed, 
followed by an inspiratory VC maneuver to TLC. 
Body plethysmography values recorded on the CRF will be post-bronchodilator.  
Body plethysmography reference values from the ATS statement on ‘Lung 
Function Testing:  Selection of Reference Values and Interpretative Strategies’ 
[38] should be used for this study.  
13.4 Diffusing Capacity Testing 
Diffusing capacity will be corrected for hemoglobin. 
Diffusing capacity testing will be measured using the single-breath carbon monoxide 
methods.  The test will be conducted per the ATS document “Standardisation of the 
Single-Breath Determination of Carbon-Monoxide Uptake in the Lung” [39].  Acceptable 
test criteria include the use of proper quality controlled equipment, inspired volume of 
85% of vital capacity in less than 4 seconds, a stable breath-hold for 8 to 12 seconds, no 

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evidence of leaks or Valsalva or Muller maneuvers, expiration in less than 4 seconds 
with appropriate clearance of dead space and proper sampling/analysis of alveolar gas.   
If clinically acceptable, the study participant should not breathe supplemental oxygen for 
10 minutes prior to the test.  There should be at least two acceptable tests that meet the 
reproducibility requirement of being within +/- 10% or 3 ml CO of the average DLCO.  The 
average of at least two acceptable tests that meet this reproducibility requirement should 
be reported. 
13.5 Medication Use 
Medication use is expected to fall within the guidelines established for treating COPD 
[40].  Study participants will be asked to provide information regarding their use of four 
classes of medications, including bronchodilators (beta-agonists, anticholinergics, 
methylxanthines), corticosteroids, antibiotics, and anti-inflammatories (e.g. statins, 
roflumilast).  Addition of new medications in these classes or alterations in dose over the 
course of the study will be tracked.  Study participants will be requested to bring all 
medication containers with them to each follow-up visit.     
13.6 Daily Diary   
The daily diary (hard-copy form) will be given to the study candidate at the baseline visit 
and collected at the bronchoscopy procedure visit and then electronically at the 45-day, 
3-month, 6-month, 9-month, and 1-year follow-up visits.     
 
Study participants will be asked to maintain a daily diary in which they will note 
compliance to the pulmonary rehabilitation program, complete the EXACT-PRO 
questionnaire, and note health status changes. They will be asked to complete the diary 
immediately before going to bed at night.  Completion of the daily diary will begin on the 
first day after the bronchoscopy procedure and will be completed through the 1 year 
follow-up visit. Every effort will be made to ensure that study participants complete all 
diary entries, although failure to do so will not be considered a protocol deviation.      
13.6.1 
Pulmonary Rehabilitation Program Compliance 
Study participants will be asked to self-report the number of exercises performed 
that day and the amount of time (minutes) spent doing them.       
13.6.2 
EXACT-PRO Questionnaire 
The EXACT-PRO was developed to serve as a standardized outcome measure 
to evaluate COPD exacerbations [41].  Respondents are asked to self-report 
symptoms such as cough, mucous discharge, chest discomfort, and 
breathlessness.  The questionnaire consists of 14 items, in which the patient 
grades the symptom as experienced by selecting one of five different responses 
(e.g. ‘not at all’, ‘rarely’, ‘occasionally’, ‘frequently’, ‘almost constantly’).       
13.6.3 
Health Status Changes 
Health status changes data will consist of asking the study participant to self-
report changes in maintenance medications, presence of emphysema symptoms, 
and whether or not they may have been deterred from their normal daily activities 
due to their emphysema symptoms. 

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13.7 Six-Minute Walk Distance (6MWD) Test 
Six-minute walk distance testing will be performed according to the “ATS Statement” 
Guidelines for the Six-Minute Walk Test – March 2002” [42].  The test should be 
performed indoors, along a flat, straight, enclosed corridor with a hard surface that is 
seldom traveled.  The walking course must be 30 meters in length.  The length of the 
corridor should be marked every 3 meters.  The turnaround points should be marked 
with a cone.  A starting line, which marks the beginning and the end of each 60-meter 
lap, should be marked on the floor.  The study participant should rate their baseline 
dyspnea and overall fatigue before the test and rate their dyspnea and overall fatigue 
after the test using the Borg scale.  Required equipment, patient preparation, and 
measurements are specified in the ATS guidelines.  
13.7.1 
Dyspnea Assessment 
Dyspnea and overall fatigue will be measured in all study participants using the 
Borg Scale [43,44] immediately prior to and immediately after performing the 
6MWD test.   
13.8 Blood Work  
Blood chemistry variables collected during for the study will include arterial blood gases 
(ABGs), complete blood counts (CBCs), serum (or plasma) fibrinogen, plasma cotinine 
and/or arterial carboxyhemoglobin, and alpha-1 anti-trypsin deficiency.  
  
 
13.8.1 
 Arterial Blood Gases (ABGs)  
Blood gases should be collected with the study participant breathing room air.  If 
the study participant is receiving supplemental oxygen at the time arterial blood 
gases are intended to be sampled, the supplemental oxygen should be 
discontinued for 10 minutes prior to sampling.  If during this 10-minute period 
oxygen saturation falls below 80%, supplemental oxygen should be provided and 
increased in one liter/minute increments every three minutes until the minimum 
flow necessary to achieve 90% oxygen saturation is reached.  Blood gases 
should then be sampled at this point.  Subsequent blood gas samples should be 
taken under the same supplemental oxygen flow rate conditions.    
13.8.2 
 Complete Blood Counts (CBCs)   
Complete blood counts will be collected to characterize general health status.      
13.8.3 
 Serum Fibrinogen   
Blood fibrinogen is a measure of systemic inflammation.  Increased levels have 
been shown to be associated with increased risk of COPD exacerbations [45]. 
13.8.4 
 Plasma Cotinine and/or Arterial Carboxyhemoglobin    
Plasma cotinine and/or arterial carboxyhemoglobin counts will be collected to 
monitor nicotine use.    
13.8.5 
 Alpha-1 Antitrypsin Protease Inhibitor Counts  
Alpha-1 antitrypsin protease inhibitor counts will be used to assess screening 
eligibility criteria.  

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13.9 Chest X-Ray 
Chest X-ray will be collected as specified in Section 14.0 and at any other time in which it 
may be considered medically necessary following the bronchoscopy procedure to screen 
for signs of volume reduction and pneumothorax.    
 
13.10 
 Physical Exam 
A routine medical examination will be performed as specified in Section 14.0.     
13.11 
High Resolution Computed Tomography  
All attempts will be made to acquire volumetric high resolution computed tomography 
(HRCT) images using standardized methods across clinical sites at all times of 
acquisition.  The CT scans should be obtained using the study CT acquisition protocol 
(see Appendix 6).   
 
The screening CT study, collected for all study participants as part of the study 
screening process, will be considered the baseline CT for statistical analysis.  Study 
investigators, in conjunction with the site-based radiologist(s) if desired, will evaluate CT 
images collected for study candidates during screening using an FDA approved software 
package to determine whether study candidates meet study eligibility criteria.     
 
For study participants who receive the study treatment, post-bronchoscopy follow-up CT 
studies will be collected at the 45-day and 1-year visits.  For study participants who 
receive the study treatment and undergo valve adjustment, an additional HRCT scan will 
be collected at the 3-month visit.   
 
Clinical site personnel will transmit the CT studies in original DICOM format to a core 
reading laboratory who will assess the image quality of the studies and review and 
analyze the images. The CT images will be analyzed quantitatively using automated 
510k cleared software and qualitatively, depending on the variable of interest, by the 
core reading laboratory.   
 
The core reading laboratory will assess all HRCT scans to determine whether study 
participants who received the study treatment may be candidates for valve adjustment.  
This will be conducted by 1) determining volumetric change between the screening 
HRCT scan and post-procedure 45-day HRCT scans in the treated lobe and 2) 
evaluating valve placement in the target airways.  For study participants who undergo a 
valve adjustment procedure, the 3-month CT scan will be assessed for volumetric 
change in the treated lobe; valve placement will also be evaluated.  The 1-year HRCT 
scans will be assessed to determine target lobe volume reduction.  In addition, the 1-
year HRCT scans may be examined to assess valve placement for lobar occlusion and 
other radiographic features. 
13.12 
BODE Index  
The BODE index is a multidimensional measure that has been reported to be predictive 
of risk of death from any cause and from respiratory causes [46,47]. It combines four 
measures frequently used in COPD studies as a composite score: body-mass index 
(BMI), obstruction (FEV1 % predicted), dyspnea, usually characterized using the mMRC 

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survey score, and exercise capacity, as determined using the 6MWD test.  Each 
component is graded and a score of 0 to 10 is obtained as indicated in the table below. 
The BODE Index will be calculated and reported in the final study report.  
Table.  Determination of the BODE Index Score. 
 
Points for BODE Index Score 
 
0 
1 
2 
3 
BMI  (kg.m-2) 
>21 
<21 
 
FEV1 % predicted 
>65 
50-64 
36-49 
<35 
MMRC 
0-1 
2 
3 
4 
6MWD (m) 
>350 
250-349 
150-249 
<149 
  
 
 
14.0 SEQUENCE FOR TESTING   
14.1 Screening Assessment – within 6 months prior to randomization 
• 
Informed Consent  
• 
Inclusion and Exclusion Criteria 
• 
Medical History 
• 
Vital Signs/Physical Exam 
• 
Lung Function Testing (Study Protocol Section 13.0) 
o Spirometry (collected using your clinic’s normal care regime) 
o Body Plethysmography 
o Diffusing Capacity (DLco) 
• 
HRCT Scan (Study Protocol Section 8.5.1, Appendix 6 and core lab Protocol) 
o In order for the study candidate to be found to meet the HRCT emphysema lobar 
destruction score criterion and the emphysema heterogeneity score criterion, the 
CT scan must be collected using the HRCT scan acquisition protocol   
▪ 
Full inspiratory scan (TLC) 
▪ 
Full expiratory scan (RV) 
o Forward CT scans to core lab of all candidates meeting the HRCT scan 
screening eligibility criteria 
▪ 
Forward the first 5 Myrian analyses (both (in)eligible candidates) to core 
lab to confirm proficiency for using the CT scan screening software   
o NOTE:  A pre-existing CT scan that the study candidate provides to you or that is 
found during the chart screening may be “pre-screened” using the CT scan 
screening software. 
• 
ECG  
• 
6-Minute Walk Distance (Study Protocol Section 13.7) 
• 
Echocardiogram 
• 
Blood Work (Study Protocol Section 13.8) 
o Arterial Blood Gases (ABGs)  
o Complete Blood Counts (CBCs) 
o Alpha-1 Antitrypsin Deficiency Test 
o Plasma Cotinine  

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▪ 
use Arterial Carboxyhemoglobin if candidate uses nicotine products) 
o Serum Fibrinogen 
 
If the Study Screening Eligibility Criteria are met by the Candidate, ask the Candidate to 
begin the Study Eligibility Pulmonary Rehabilitation Program (if the Study Candidate has 
already met the Pulmonary Rehabilitation Criterion you may proceed with the Baseline 
Visit) 
 
14.2 Baseline Assessment - Conduct ≤ 120 days following screening eligibility 
• 
Sign Participation Informed Consent (if only Screening Informed Consent was collected 
previously) 
• 
Pulmonary Rehabilitation Eligibility Criterion Completed  
o At least 8 sessions (4 weeks with 2 sessions per week; Study Protocol Section 
10.1) 
• 
Spirometry  
• 
6-Minute Walk Distance (Study Protocol Section 13.7) 
 
After confirmation of Baseline Eligibility: 
• 
Vital Signs/Physical Exam 
• 
Medication Use 
• 
Vaccinations, if necessary (Pneumococcal, Influenza) 
• 
Self-Reported Health Status Measures  
o SGRQ  
o SF-36  
o EQ-5D  
o BDI  
o mMRC  
o CAT  
o Health Care Utilization  
• 
Daily Diary  
o Send paper diary home with study candidate to complete daily for 7 days prior to 
the scheduled bronchoscopy procedure 
• 
Create Bronchoscopy Procedure Plan 
• 
Contact Pulmonx and schedule Procedure date 
 
14.3 Bronchoscopy Procedure – Should occur ≤ 60 days after baseline 
assessment visit 
• Pre-Procedure Orders and Preparation 
o Female – pregnancy test, if applicable to informed consent 
o Ensure study personnel are identified for pneumothorax management 
 
Recommended: 
o Prophylactic antibiotic regimen may be initiated 2 days prior to procedure if 
desired by study investigator  
o Corticosteroids may be may be initiated 2 days prior to procedure if desired by 
investigator  

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o Inhaled bronchodilator may be given 20 min prior to procedure 
o Prior to the procedure, IV first or second generation antibiotics should be 
administered   
o Record or collect photos of EBV placement   
 
• Bronchoscopy  
o Anesthesia = conscious sedation with study candidate breathing spontaneously  
o Chartis System: assessment of target lobe collateral ventilation   
o After confirmation of study device eligibility criterion (finding of little or no 
collateral ventilation in targeted treatment lobe) proceed with randomization  
 
• Study Device Placement 
o May convert study participant to general anesthesia 
o Record device lot numbers and valve placement location on worksheet 
 
14.4 Post Procedure  
• 
Study Treatment Arm:  
o Perform chest x-ray within 1 hour (± 30 minutes) 
o Monitor vital signs and pulse oximetry for first 24 hours  
o Collect ABGs and serum fibrinogen at 24 hours 
o Antibiotics 
o Bronchodilator Therapy 
o Perform chest X-rays daily x 5 days during hospital stay 
 
• 
Control Arm:  
o Monitor vital signs and pulse oximetry until discharge 
o Collect ABGs and serum fibrinogen before discharge 
 
14.5 Prior to Discharge  
• 
Study Treatment Arm 
o Perform pre-discharge chest X-ray and physical examination 
o Schedule follow-up visits, including daily contact through 10 days 
o Bronchodilator inhaler, course of antibiotics, corticosteroids 
o Disburse Daily Diary  
o Provide Medical Alert Card, Treated Study Participant Bracelet, Transferring 
Instructions if Late Pneumothorax, and Post-Procedure Instructions 
o Adverse Event Assessment 
 
• 
Control Arm 
o Schedule follow-up visits 
o Bronchodilator inhaler, course of antibiotics, corticosteroids 
o Disburse Daily Diary  
 

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14.6 Daily Follow Up Phone Call for 10 Days after Discharge (up to 11:59 pm) 
• 
Study Treatment Arm 
o Symptom Checklist 
o Follow up may occur in hospital if subject is still hospitalized 
 
14.7 Day 7 after Discharge Visit (+ 1 business day) 
Study Treatment Arm Only 
• 
Vital Signs/Physical Exam  
• 
Chest X-ray 
• 
Symptom Checklist 
• 
Investigator to assess for return to regular activity and initiation of the protocol 
required pulmonary rehabilitation program 
o Assessment should show lack of evidence of pneumothorax, infection, or 
exacerbation, tolerance of light activities, and physical condition at least 
similar to or better than at the baseline visit 
• 
Adverse Events assessment 
• 
Symptom Checklist may be conducted during visit 
 
14.8 Day 30 Visit (+/- 5 days) 
Study Treatment Arm Only 
• 
Vital Signs/Physical Exam 
• 
Chest X-ray 
• 
Adverse Events assessment 
 
14.9 Day 45 Visit (+/- 5 days) 
• 
Vital Signs/Physical Exam 
• 
Medication Use 
• 
Daily Diary Collection  
• 
Spirometry  
• 
Body Plethysmography  
• 
DLco  
• 
Collect mMRC Survey  
• 
6-Minute Walk Distance 
• 
Adverse Event Assessment 
• 
Study Treatment Arm 
o Chest X-ray  
o HRCT Scan (may be completed in a separate visit) 
o Forward CT scan to core lab 
14.10 
3 Month Visit (+/- 14 days) 
• 
Vital Signs/Physical Exam 

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• 
Medication Use 
• 
Daily Diary Collection  
• 
Collect SGRQ Survey  
• 
Collect Health Care Utilization Survey 
• 
Collect TDI Survey  
• 
Collect CAT Survey 
• 
Study Treatment Arm 
o Only EBV treated participants who undergo valve adjustment -- may be 
completed in a separate visit 
▪ 
HRCT, forward CT scan to core lab 
▪ 
 Chest X-ray 
▪ 
Body Plethysmography 
 
14.11 
6 Month Visit (+/- 21 days) 
• 
Vital Signs/Physical Exam 
• 
Medication Use 
• 
Daily Diary Collection  
• 
Spirometry  
• 
Collect SGRQ Survey  
• 
Collect Health Care Utilization Survey 
• 
Collect mMRC Survey 
• 
Collect TDI Survey 
• 
Collect CAT Survey  
• 
6-Minute Walk Distance  
• 
Adverse Event Assessment 
 
14.12 
9 Month Visit (+/- 21 days) 
• 
Medication Use 
• 
Daily Diary Collection  
• 
Collect TDI Survey 
• 
Collect CAT Survey 
• 
Collect Health Care Utilization Survey 
 
14.13 
1 Year Visit (+/- 45 days)  
• 
Vital Signs/Physical Exam 
• 
Medication Use 
• 
Daily Diary Collection  
• 
Spirometry  
• 
Collect SGRQ Survey  
• 
Collect Health Care Utilization Survey  
• 
Collect SF-36 Survey  
• 
Collect EQ-5D Survey  
• 
Body Plethysmography 
• 
DLco 

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• 
Collect TDI Survey  
• 
Collect CAT Survey  
• 
Collect mMRC Survey  
• 
6-Minute Walk Distance  
 
The following may be completed in a separate visit or in order as scheduling permits after all 
other testing 
• 
ECG  
• 
Blood Work (ABGs, CBCs, plasma cotinine, serum fibrinogen) 
• 
Adverse Event Assessment  
• 
Study Treatment Arm  
o HRCT Scan for EBV treated participants 
o Forward CT scan to core lab 
• 
Control Arm 
o After completing the 1-year visit testing, assess suitability for crossing over to 
study treatment.   
o The study investigator must document the participant’s suitability for crossing 
over to study treatment; to qualify for crossover, a control arm participant must 
have been followed up successfully through 1 year and demonstrate lack of a 
clinically important response  
o The crossover procedure must be scheduled to occur within the next 60 days 
following the 1-year visit   
o After receiving the study treatment, the follow-up visits and testing at each visit 
will be identical to the schedule for treatment arm participants  
 
14.14 
Annual Visits (+/- 60) only for Study Participants treated with EBV 
• 
Spirometry  
• 
Adverse Event Assessment 
 
 
15.0  SAFETY ELEMENTS 
15.1 Adverse Events 
Previous studies of emphysema patients who were followed longitudinally and treated 
using medical management [10,16,17], diagnostic or interventional bronchoscopy 
[448,49], or endobronchial valves [16,17] indicate that a moderate risk of adverse events 
may be anticipated during this study.  Adverse events will be graded by defining their 
severity and relatedness to the study device.  
 
It is anticipated that the rates for adverse events will be higher for the study treatment 
arm than control arm during the treatment period (‘short’, or day of the study procedure 
to 45 days) but that the rates for these occurrences will be similar for both study arms 
during the post-treatment period (‘long’, or 46 days to 1 year). 
 
Adverse events that may be observed include:   
 

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❖ Cardiovascular events such as: 
o New onset cardiac arrhythmia  
o New diagnosis of congestive heart failure, which may be indicated by >1-point 
increase in NYHA functional classification score  
o Acute myocardial infarct requiring medical care 
o New diagnosis transient ischemia attack (TIA) or stroke 
o New diagnosis deep vein thrombosis 
o Pulmonary embolism, which may be indicated by direct clinical evidence or V/Q 
evidence of segmental or larger perfusion defects   
 
❖ COPD and Emphysema events such as:   
o COPD exacerbation requiring treatment with antibiotics and/or oral steroids 
▪ 
AECOPD requiring emergency room visit or hospitalization 
o Respiratory failure requiring re-intubation at any time during follow-up and/or 
invasive mechanical ventilation >24 hours after the bronchoscopy procedure 
o Pneumonia requiring treatment with antibiotics, indicated by consolidation on X-
ray or CT scan and clinical characteristics of active infection (fever, leukocytosis, 
hypotension)  
 
❖ Pulmonary / Thoracic events such as: 
o Hemoptysis requiring new evaluation or intervention 
o Pneumothorax indicated by clinical symptoms and/or X-ray 
▪ 
Pneumothorax requiring intervention 
o Empyema requiring new evaluation or intervention 
o Non-cardiac chest pain driving the study participant to seek medical care 
o Pleural effusion noted radiologically 
o Lung mass / cancer noted radiologically 
o Fractured rib noted radiologically 
o Laryngospasm driving the study participant to seek medical care 
o Dysphonia driving the study participant to seek medical care 
o Hypoxemia requiring increased or new oxygen use  
o Adverse tracheobronchial observations such as bronchial granulation tissue, 
bronchial ulceration, bronchial trauma 
 
❖ Other events such as: 
o Death, any cause 
o Septicemia as evidenced by constitutional signs and symptoms consistent with 
bloodstream infection (with at least two separate blood cultures positive for the 
same pathogen(s), requiring systemic antimicrobial therapy)   
o Non-pulmonary infection requiring medical care 
o Fever > 99.5 ⁰C for > 24 hours 
 
❖ Endobronchial Valve events such as:   
o Valve expectoration, as reported by the study participant 
o Valve migration, as indicated by clinical and/or radiological evidence that a valve 
has left the target airway 
o Pneumonia distal to implanted valves, indicated by consolidation on X-ray or CT 
scan and clinical characteristics of active infection (fever, leukocytosis, 
hypotension) 

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and commercial information that must not be disclosed to persons not directly involved with the study.  Duplication 
and distribution of this document require prior written approval from Pulmonx 
15.2 Serious Adverse Events   
An adverse event is considered serious if it meets the definition of a serious adverse 
event (SAE) as defined in Section 21.2.  Serious adverse events may occur at any time 
during the study and will be reported as serious regardless of when they occur, provided 
they meet the definition of a serious adverse event.  
15.3 Management of Selected Anticipated Adverse Events 
15.3.1 
Pneumothorax   
Pneumothorax is an expected and anticipated event in patients undergoing a 
lung volume reduction procedure.  With lung volume reduction surgery (LVRS), 
pneumothorax occurs in all (100%) cases and all patients leave the operating 
room with a chest tube(s) to manage air leaks.  After EBV treatment, it is 
anticipated that the collapsed lung in the target lobe or expanding lung in 
adjacent lobe(s) may develop an air leak(s).  With lung volume reduction 
procedures, achieving a higher success rate may be associated with having a 
higher risk of pneumothorax.   
 
In the VENT study, pneumothorax was seen in 15%-20% of EBV-treated study 
participants who were thought to have little or no lobar CV (i.e. had HRCT 
suggestive of complete fissure) along with HRCT evidence of lobar occlusion 
with valve treatment.  Therefore, it is anticipated in this study that approximately 
one in five of EBV-treated study participants may experience a post-procedure 
pneumothorax.   
 
Study participants who received the study treatment will be provided with a 
Medical Alert Card, Treated Study Participant Bracelet, Transferring Instructions 
if Late Pneumothorax, and Post-Procedure Instructions prior to hospital 
discharge.  Study participants who received the study treatment will be contacted 
during the 10 days after discharge and asked about increased chest pain, 
nausea, and new, worsening shortness of breath, which are all potential 
indicators of pneumothorax. 
 
A suggested treatment plan for managing any suspected pneumothorax is 
provided in Appendix 18.  Any study participant who has a persistent 
pneumothorax requiring care beyond a chest tube should be transferred to the 
treating hospital and attended to by the treating physician and his or her study 
team. 
 
15.3.2 
Pneumonia  
Pneumonia-like symptoms, including low-grade fever, increased sputum, and 
radiographic abnormalities, are anticipated consequences of bronchoscopy.  In 
this study, pneumonia will be defined as:  1) fever (> 99 ⁰F) persisting for >48 
hours and 2) white blood count >15,000 cells/mcL.  Any study participant having 
clinical and radiological signs of pneumonia or pneumonia-like symptoms will be 
medically treated.       
15.3.2.1 
Pneumonia Distal to Valve(s)  
Any study participant observed to have consolidation on X-ray or 
CT scan and clinical characteristics of active infection (fever, 

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leukocytosis, and hypotension) will be considered to have 
pneumonia distal to valve(s).       
15.3.3 
COPD Exacerbation 
Any study participant reporting or admitted to the hospital for suspected COPD 
exacerbation will undergo immediate clinical evaluation and a treatment plan will 
be formulated.  An exacerbation will be defined as a worsening of the study 
participant’s symptoms from his or her usual stable state that is beyond normal 
day-to-day variations, and is acute in onset, and requires modification of the 
study participant’s medication regimen.  Commonly reported symptoms are 
worsening breathlessness, cough, increased sputum production, and change in 
sputum color.     
15.3.4 
Hemoptysis  
Any study participant experiencing hemoptysis will be immediately evaluated and 
a treatment plan will be formulated.  Generally, only minimal hemoptysis after the 
procedure is observed.  Larger amounts of bleeding may require imaging or 
endoscopy as dictated clinically at the discretion of the study investigator. 
Massive hemoptysis is defined as > 200 ml blood loss in less than 24 hours.       
15.3.5 
Respiratory Failure  
Any study participant experiencing respiratory failure requiring re-intubation will 
undergo immediate clinical evaluation and management as dictated by the 
underlying etiology.       
15.4 Events Anticipated to Precipitate Valve Removal 
In the U.S. VENT study, 31 (14.5%) patients underwent valve removal after the 
procedure. Therefore, it is anticipated that valve removal attributed to the following 
conditions may occur.       
15.4.1 
Valve Migration  
In any case in which a valve migration, as defined in Section 15, is observed, 
removal of the valve is required.    
15.4.2 
Pneumonia and Pneumonia Distal to Valve(s) 
If the pneumonia does not resolve normally with medical therapy then valve 
removal may be considered. 
15.4.3 
Respiratory Failure  
Valve removal may be considered if the device placement itself is felt to be the 
causative factor.         
15.4.4 
Hemoptysis 
In cases where hemoptysis is observed, valve removal may be considered.   
15.4.5 
Granulation  
In cases where granulation is observed, valve removal may be considered.   
15.4.6 
Continuing COPD exacerbations 
In cases where a study participant has recurrent COPD exacerbations, valve 
removal may be considered.     
15.4.7 
Increased Dyspnea 
In cases where severely increased dyspnea is observed, valve removal may be 
considered.     

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15.4.8 
Request by Study Participant   
A study participant may request that the valves be removed for any reason.  
 
16.0   RISK - BENEFIT EVALAUATION 
16.1 Potential Benefits 
Potential benefits include improvement in the study participant’s lung function and other 
improvements that may be associated with improved lung function.    
16.2 Potential Risks 
The primary risks associated with use of the Pulmonx EBV, as proposed in this study 
protocol (see Adverse Events section), are similar to other bronchoscopic and surgical 
procedures used to treat emphysema.   
16.3 Risk Minimization 
Risk mitigation measures include the following:  
a) 
The use of standard medical grade materials that have been thoroughly 
characterized and tested to assure biocompatibility, 
b) 
Extensive pre-clinical evaluation including in vitro bench testing and animal study, 
c) 
Prior human clinical trial experience including four hundred ninety two (492) 
patients followed for one year.  
d) 
The well-established, standard nature of the bronchoscopic procedure and 
technique (i.e., used in placement of bronchial stents), 
e) 
The ability to abort the procedure at any time.  The physician may elect to 
discontinue the use of the Pulmonx Endobronchial Valve at any time in favor of 
alternative medical or surgical procedures, and   
f) 
Reversibility, as the Pulmonx Endobronchial Valves may be removed. 
 
17.0   PROTECTION OF HUMAN PARTICIPANTS 
17.1 Institutional Review Board (IRB) Approval  
The Investigator will obtain IRB approval prior to asking participants to sign the Informed 
Consent Form and complete any study-specific procedures.  The IRB approval must be 
maintained for the duration of the study.  If IRB approval is withdrawn, the Investigator 
must immediately discontinue any study related activities that will not adversely affect the 
health and welfare of the study participant. The investigator must notify the study 
Sponsor of such withdrawal in writing within 5 working days.  
17.2 Confidentiality 
All information and data concerning participants or their participation in this trial will be 
considered confidential, and handled in compliance with the Declaration of Helsinki, ICH 
guidelines (to the extent that they are consistent with U.S. federal regulations), CFR 
section 21, and HIPAA requirements. Only authorized personnel, the study Sponsor or 

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its designees, and FDA will have access to these confidential files. All data used in 
analysis, reporting, and publication of this clinical trial will be maintained without 
identifiable reference to the participant. 
17.3 Ethical Considerations 
This study will be performed in accordance with the principles in the Declaration of 
Helsinki.  These principles suggest that biomedical research involving human subjects 
should: 
• 
Conform to generally accepted scientific principles. 
• 
Be conducted only under the supervision and direction of scientifically or 
medically qualified persons. 
• 
Be preceded by careful assessment of risks in comparison with benefits to the 
participant or to others. 
• 
Be more concerned with the interest of the participant than those of science and 
society. 
• 
Respect the privacy of the participant. 
• 
Preserve the accuracy of the results in publication. 
• 
Inform each potential participant of the aims, methods, anticipated benefits and 
potential hazards of the study, the discomfort it may entail, and alternatives to 
study participation. 
• 
Never interfere with the physician-patient relationship. 
17.4 Methods to Eliminate Bias 
Steps will be taken to minimize the effects of any bias that might occur when conducting 
a clinical trial of this nature.  All candidates presenting to the clinic that meet the eligibility 
criteria will be invited to participate in the study.  No other criteria, apart from the 
eligibility criteria listed in this protocol, will be used to consider candidates for enrollment 
in the study.  Participant selection criteria will be closely followed and the demographics 
and the condition of each participant will be documented prior to treatment.  Additionally, 
a standardized arm-specific treatment protocol will be followed for each participant and it 
will be clearly documented.  Finally, both the investigative site staff and the study 
participants will be instructed to complete the data forms in a consistent manner.  Any 
significant deviations from the procedures described in this protocol will be documented. 
17.5 Early Termination of the Clinical Investigation 
If the investigation is terminated prematurely or suspended, the Sponsor will promptly 
inform the Clinical Investigators/investigation sites of the termination or suspension and 
the reason(s) for this. The Independent Ethics Committee (IEC) will also be informed 
promptly and provided with the reason(s) for the termination or suspension by the 
Sponsor or by the Clinical Investigator/investigation sites. 
 
18.0 CLINICAL SITE TRAINING 
18.1 Clinical Study Staff Training 
The site Principal Investigator will be responsible for the supervision of the trial and will 
provide direction to all other research staff as necessary.  The Study Sponsor will train 

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the Principal Investigator and clinical study staff through conference calls, face-to-face 
meetings, and site visits.   
18.2 Procedure and Training Videos 
All site Investigators participating in the study will attend a presentation designed to 
convey the technical aspects of the study device and procedure.   
18.3 Physician Hands-on Training:  Endobronchial Valve 
All site Investigators will be trained on an anatomical bronchial model that simulates the 
clinical experience of using the EBV.  After instruction from a qualified Pulmonx trainer 
and passing the training program evaluation, the physician will demonstrate successful 
placements as well as successful removals of valves using the bronchial model. 
 
18.3.1 
Valve Placement 
A minimum of four consecutive successful placements must be demonstrated in 
different anatomical locations to achieve lobar occlusion.  A successful 
placement has been achieved when the trainer verifies appropriate placement.  
• 
At least two large valves shall be successfully placed.  One (1) in the right 
upper and one (1) in the left upper bronchus.  
• 
At least two small valves shall be successfully placed.  One (1) in the right 
apical bronchus and one (1) in the left apicoposterior bronchus.   
18.3.2 
Valve Removal 
A minimum of two successful removals must be demonstrated.  A successful 
removal has been achieved when the trainer verifies that all elements of the 
device have been retrieved from the bronchial model.  
18.4 Physician Hands-on Training:  Chartis Assessment System 
All site Investigators will be trained on the Chartis Assessment System using an 
anatomical bronchial model that simulates the clinical experience of using the Chartis 
System.  After instruction from a qualified Pulmonx trainer, the physician will 
demonstrate successful catheter placements to simulate isolation of the discrete lung 
lobes.   
 
The Investigator will also be trained to determine CV status for a series of sample 
assessments to demonstrate accurate interpretation.  
18.5 Study Coordinator Training 
The Study Coordinator(s) with primary responsibility for managing the study at each site 
will be provided with comprehensive training on the study device, study procedure, post-
procedure study participant management, study protocol, and duties and responsibilities 
of the Study Coordinator.  They will be provided with detailed information on important 
logistical and administrative tasks with regards to reporting requirements, CRF 
management, and product tracking.  Each site coordinator will receive a study binder 
containing, at a minimum, the study protocol, case report forms (CRFs), sample 
informed consent document, and study contact information.  

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18.6 Protocol Training 
Prior to enrollment of study participants, the site Principal Investigator(s), Sub-
Investigators, and the Study Coordinator(s) will meet with Pulmonx personnel to discuss 
the protocol and to ensure that all study eligibility criteria and study protocol details are 
well understood.  Staff will be trained to encourage all study participants to continue full 
adherence to the study protocol activities and follow-up schedule.  A training record will 
be maintained for each site Investigator and Study Coordinator and shall be used to 
document completion of successful training.   
18.7 Assistant Physicians, Scrub Nurses, and Technicians 
The site Principal Investigator (or designee) will be responsible for providing oversight of 
all allied health personnel who will be assisting with execution of study-related activities 
in order to ensure compliance with clinical trial requirements.   
18.8 Valve Loader Training 
Each site will designate at least one person who will be trained in the loading of the 
valves into the delivery systems during the procedure.  These designees will undergo 
training in loading techniques by qualified Pulmonx personnel.  They will then 
demonstrate three successful valves loadings, as verified by the trainer.   
18.9 Nursing Staff In-service 
The Principal Investigator will provide oversight of all nursing staff responsible for post-
procedure care in order to ensure compliance with clinical trial requirements.     
 
19.0   STUDY OVERSIGHT  
19.1 Data and Safety Monitoring Board (DSMB) 
A data safety monitoring board (DSMB) will be utilized to review data to evaluate safety of 
study participants during their participation in the study and to review the interim data 
analysis.  The DSMB will consist of a statistician, a pulmonologist, and a thoracic surgeon 
with LVRS experience who have no scientific, financial, or other conflict of interest related 
to the investigation. Members will not have any direct affiliation with the study Sponsor or 
the Investigational Sites that would create a conflict of interest impacting their ability to 
serve objectively on the DSMB. 
The DSMB will be responsible for making recommendations to the Operations Committee 
regarding the primary endpoint at the interim analysis and monitoring for any potential 
problems at any time during the study. DSMB responsibilities, membership, meeting 
frequency and procedures will be documented in a committee charter but the DSMB may 
call a meeting at any time if there is reason to suspect that safety is an issue.  The DSMB 
will be provided access to all study safety data including all adverse event reports. 
Interaction on the part of DSMB members with clinicians, nurses, technicians and other 
protocol participants will be strongly discouraged in order to avoid any potential bias. The 
DSMB will function in accordance with applicable regulatory guidelines. 
 
The DSMB will be expected to review all adverse events and other safety outcomes for 
the duration of the study.  Meetings are anticipated to be conducted on a quarterly basis.  

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The DSMB will also have the responsibility to review the interim analysis.  During the 
course of the trial, the DSMB will review accumulating safety data to monitor for 
incidence of trends that would warrant modification or termination of the trial.  Any DSMB 
recommendations for study modification or termination because of concerns of subject 
safety or issues relating to data monitoring or quality control will be submitted in writing 
to Pulmonx for consideration.   
19.2  Clinical Events Committee 
The Clinical Events Committee (CEC) will consist of board-certified physicians who may 
be specialists in pulmonology, thoracic surgery, interventional pulmonology, or thoracic 
radiology who are not otherwise participating in the study (Note: The CEC members will be 
not be DSMB participants). The CEC will regularly review and adjudicate all serious and/or 
potentially device-related Adverse Events through at least the 1 year follow-up visit and 
may also conduct an annual review at 2, 3, 4, and 5 years.  
19.3 Operations Committee 
This committee will be responsible for the day-to-day administrative management of the 
trial. This committee will meet as needed by conference or teleconference to monitor study 
participant enrollment, clinical site progress, and protocol compliance. It will also be 
responsible for reviewing the final results, determining the methods of presentation and 
publication, and selection of secondary projects and publications. 
19.4 Core Radiology Laboratory 
The core radiology laboratory will be responsible for training clinical sites to the HRCT 
acquisition protocol, monitoring their adherence to the HRCT protocol, and assessing study 
participant HRCT scans.   
19.5 Core Spirometry Laboratory 
The core spirometry laboratory will be responsible for training and monitoring clinical 
sites for adherence to the spirometry acquisition protocol, and conducting quality 
assurance of spirometry collection during the study.  
19.6 Daily Diary Data Acquisition 
Core laboratory equipment and processes will direct the Daily Diary data acquisition.    
  
20.0    DATA ANALYSIS OVERVIEW 
20.1 Populations for Effectiveness and Additional Measures 
The primary analysis population will be made up of study participants enrolled as ITT 
study participants.  The ITT study population will consist of all study participants who 
have been randomly assigned to study treatment or control, regardless of whether or not 
they undergo the assigned treatment.  
 
Statistical analyses will also be performed on a Completed Cases (CC) basis and Per-
Protocol (PP) basis. The CC population is defined as all randomized and eligible patients 
who received study-directed treatment and had 1 year of follow-up. The PP population is 

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defined as all randomized study participants who meet study eligibility criteria, who were 
treated as randomly assigned, and had follow-up for the endpoints.  
 
If applicable, statistical analyses will also be conducted after sorting patients by the 
actual treatment received regardless of their randomization assignment.  
20.2 Safety Analysis Population 
Both the ITT analysis population and ‘As Treated’ (AT) analysis population will be used to 
assess the safety data.  For the AT analysis, study participants will be analyzed based on 
the treatment they actually received.            
20.3 Primary Effectiveness Endpoint 
Achievement of the primary effectiveness endpoint will be determined by assessing the 
percentage of study participants in the EBV Treatment arm who meet the threshold of 
>15% improved forced expiratory volume in one second (FEV1), collected post-
bronchodilator, as compared to the Control arm at 1 year post-procedure. 
 
FEV1 is the volume of air exhaled during the first second of a forced expiratory maneuver 
and is commonly used to measure airway obstruction.  It is a well-accepted parameter 
for both staging of COPD and assessment of lung function improvement after treatment.  
Increased expiratory flow resistance, manifested as a decreased FEV1, is one of the 
hallmarks of emphysema.  The Global Initiative for Chronic Obstructive Lung Disease 
(GOLD) reports that FEV1 is the gold standard for measuring airflow limitation in COPD 
(44).  In addition, FEV1 is used to classify COPD into severity stages.  One of the most 
important predictors of survival in COPD is the degree of airway obstruction as 
measured by post-bronchodilator FEV1 (45-47).  Decline of FEV1 is associated with 
adverse health consequences such as increased COPD exacerbations and reduced 
quality of life (48).     
20.3.1 
Sample Size Rationale  
The results of two prospective studies were used to inform the sample size 
estimation.  The Endobronchial Valve for Emphysema Palliation Trial (“VENT 
Pivotal Trial”, IDE#G020230, NCT00129584) was a multi-center, prospective, 
randomized, controlled study conducted at sites in both the United States and 
Europe to assess the safety and effectiveness of using the Zephyr EBV device for 
palliating symptoms associated with severe heterogeneous emphysema.  Four 
hundred ninety two (492) participants were enrolled into the study and randomized 
to Zephyr EBV Treatment or medical management (control) [16,17].  The Chartis 
Pulmonary Assessment System study is a recently completed prospective post-
market study that was conducted in Germany, The Netherlands, and Sweden.  The 
primary objective of the study was to quantify the accuracy of the Chartis System 
when used to identify targeted treatment lobes as having or not having inter-lobar 
CV in patients with emphysema who were to be treated using endobronchial valves 
(26).  The results of both the VENT Study and the Chartis System study showed 
that treatment effect with the endobronchial valve is correlated with lack of inter-
lobar CV [16,17,25].   
Patients in the VENT Study and in the Chartis Study who were considered to have 
little or no inter-lobar CV contributed the information used for the sample size 
estimate.  Patients who have little or no lobar CV in the targeted treatment lobe are 
expected to be good responders to endobronchial valve treatment.  For the sample 

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size estimate, a ‘responder’ was considered to be a study participant who had 
>15% improved FEV1 after EBV treatment.   
Based on the results of these studies, the responder rate in the EBV Study 
Treatment Group is expected to be approximately 35% at 1 year.  The responder 
rate for the control group is not expected to exceed 10% at 1 year.   Assuming a 
two-sided 0.05 alpha level, study power of 90%, and 2:1 allocation random 
assignment, a sample size of 147 will be adequate to test for superiority.   
The study sample size will be increased to 183 in order to allow for 20% lost to 
follow-up and incomplete data.  Each study site will be allowed to enroll a 
maximum of 25 study participants.  
20.4 Safety Endpoint  
Safety will be determined by evaluating the adverse events profile for the EBV 
Treatment Group for 1) the shorter-term treatment period, defined as the day of the 
study procedure until 45 days after the study procedure (‘short’) and 2) the longer-term 
post-treatment period, defined as 46 days after the study procedure until the 1 year 
follow-up visit (‘long’).   
20.5 Secondary Effectiveness Measures 
The following will be assessed for the EBV treatment arm:   
1) Treatment Lobe Volume Reduction (TLVR) for the EBV Treatment Arm 
a. TLVR, measured as the ‘absolute change from baseline’ for treated lobe 
volume as seen via HRCT (high resolution computed tomography), will be 
evaluated at 45 days and 1 year.  
b. TLVR, measured as the ‘percentage change from baseline’ for treated lobe 
volume as seen via HRCT will be evaluated at 45 days and 1 year.   
 
The study participants in the EBV treatment arm will be compared to the control arm at 1 
year to assess:  
 
2) St. George’s Respiratory Questionnaire  
a. Difference between study arms in ‘absolute change from baseline’ for SGRQ 
score at 1 year.   
 
3) FEV1  
a. Persistence of treatment effect will be evaluated by determining the difference 
between study arms for ‘absolute change from baseline’ for FEV1 at 45 days, 
6 months, and 1 year.  
b. Persistence of treatment effect will be evaluated by determining the difference 
between study arms for ‘percentage change from baseline’ for FEV1 at 45 
days, 6 months, and 1 year.  
 
 
4) 6-Minute Walk Distance  
a. Difference between study arms in ‘absolute change from baseline’ for 6-
minute walk distance at one year.   
b. Difference between study arms in ‘percentage change from baseline’ for 6-
minute walk distance at one year.   

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20.6 Additional Measures 
Mean changes and/or changes measured using responder analyses for:   
 
• 
Spirometry including FEV1, forced vital capacity (FVC and, the ratio of FEV1/FVC  
• 
Body plethysmography including residual volume (RV), inspiratory capacity (IC), functional 
residual capacity (FRC), total lung capacity (TLC), and the ratios of RV/TLC and IC/TLC  
• 
SGRQ global and domain (i.e. ‘symptoms’, ‘activity’ and ‘impacts on daily life’ scores  
• 
Modified Medical Research Council (mMRC) Dyspnea Scale Score  
• 
BODE Index  
• 
Transitional Dyspnea Index (TDI) from Baseline Dyspnea Index (BDI) 
• 
COPD Assessment Test (CAT) 
• 
SF-36 Health Survey score 
• 
EQ-5D Health Survey score 
• 
Health Care Utilization Questionnaire 
• 
6 minute walk distance 
• 
Borg scale dyspnea scores before and after 6MWD test  
• 
Change in use of ‘maintenance’ medications, including bronchodilators, 
corticosteroids, antibiotics, and anti-inflammatories  
• 
Daily diary (EXACT-PRO, pulmonary rehabilitation compliance, health status 
changes)  
• 
Carbon Monoxide Diffusing Capacity (DLCO) 
• 
Lung radiographic features 
• 
Blood chemistry measures 
20.7 Interim Analysis   
An interim analysis designed to evaluate effectiveness for continuing crossover of control 
arm study participants after the 1 year follow-up visit to EBV treatment will be performed 
when 74 (50% of the required minimum of 147) study participants have completed the 1 
year follow-up. If crossover of control arm study participants is found to be justified by the 
interim analysis then crossover of a control arm study participant after (s)/he has reached 
the 1 year follow-up time point may be continued.   The results of the interim analysis will 
be reviewed by the DSMB and FDA.  If the DSMB recommends  not continuing crossing 
control arm participants to EBV treatment then those control arm participants who have 
not crossed over will exit from the study per protocol after the 1-year visit.   
20.8 Long-Term Follow-up 
Data will be collected annually through 5 years for study participants receiving the study 
treatment.  Per the regulatory plan agreed to with FDA, 1 year of follow-up is required 
pre-approval and the remaining 4 years of follow-up will be conducted post-approval.  
The annual 2-, 3-, 4-, and 5-year data will consist of FEV1 scores and adverse events. 
20.9 Time Points for Data Analysis   
20.9.1 
Length of Follow-up for PMA Study Data Analysis   
Safety and effectiveness will be evaluated at the Interim Analysis and at 1 year.    
20.9.2 
 Length of Follow-up for Durability Data Analysis  
Long-term data will be collected annually through 5 years.  

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20.10 
Statistical Analysis Plan 
The details for the Statistical Analysis Plan are provided in Appendix 19. 
 
21.0    REGULATORY AND REPORTING REQUIREMENTS  
21.1 Adverse Events and Reporting 
An adverse event (AE) is an untoward medical occurrence in a patient or clinical 
investigation participant receiving a procedure using a medical device and that does not 
necessarily have a causal relationship with the treatment. An adverse event can 
therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of a medical device, 
whether or not related to the medical device.  Generally, a condition is an adverse event 
if it is undesirable and was not present before the participant underwent the procedure or 
is more severe than before the participant underwent the procedure, and/or is more 
frequent than before the participant underwent the procedure. 
Adverse event information will be collected over the entire duration of the study. 
Collection of adverse event data will commence upon random assignment of a study 
participant.  The following information will be recorded on the appropriate case report 
form: 
 
• 
Event diagnosis or syndrome 
• 
Date of onset 
• 
Duration 
• 
Severity (mild, moderate, or severe) 
• 
Relationship to the device (not related, possibly related, probably related, related, 
or unknown) 
• 
Relationship to the procedure (not related, possibly related, probably related, 
related, or unknown) 
• 
Action taken, and  
• 
Outcome (not resolved, resolved with sequelae, or resolved).  
 
If the diagnosis or syndrome is not known, the unfavorable or unintended sign or symptom 
experienced by the participant should be recorded on the CRF.  Adverse events will be 
determined by the study investigator treating the study subject.  Adverse events will be 
monitored and treated as appropriate until the event has subsided or, in case of 
permanent impairment, until the event stabilizes and the overall clinical outcome has been 
ascertained.  Adverse events will be followed until resolution or until the end of the study. 
In addition, all IRB and FDA reporting requirements will be followed.   
21.2 Serious Adverse Events and Reporting 
A serious adverse event (SAE) is any untoward medical occurrence that: 
• 
Results in death, 
• 
Is life-threatening,  
• 
Requires inpatient hospitalization or prolongation of existing 
hospitalization, or 
• 
Results in persistent or significant disability/incapacity, or congenital 

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anomaly/birth defect. 
All serious adverse events should be reported immediately (within 24 hours of 
knowledge of the event) to the study sponsor.  All IRB and FDA reporting requirements 
will be followed. 
21.3 Unanticipated Adverse Device Effects (UADE) and Reporting 
Unanticipated adverse device effects (UADE) are defined as:  Any serious adverse 
effect on health or safety or any life-threatening problem or death caused by, or 
associated with the study device, if that effect, problem, or death was not previously 
identified in nature, severity, or degree of incidence in the investigational plan, 
Investigator’s Brochure, or package insert, or any other unanticipated serious problem 
associated with a device that relates to the rights, safety, or welfare of subjects.  All 
unanticipated adverse device effects must be reported immediately (within 24 hours of 
knowledge of the event) to the study Sponsor.  The Investigator must submit to the 
sponsor and to the reviewing IRB a written report as soon as possible, but in no event 
later than 5 working days after the Investigator first learns of the event.  
A sponsor who conducts an evaluation of a UADE under CFR 812.46(b) shall report the 
results of such evaluation to FDA and to all reviewing IRBs and participating 
investigators within 10 working days after the sponsor first receives notice of the effect.  
Thereafter the sponsor shall submit such additional reports concerning the effect as FDA 
requests. 
A sponsor who determines that a UADE presents an unreasonable risk to subjects shall 
terminate all investigations or parts of investigations presenting that risk as soon as 
possible.  Termination shall occur not later than 5 working days after the sponsor makes 
this determination and not later than 15 working days after the sponsor first received 
notice of the effect.  
21.4 Informed Consent Violation Reporting 
If the Investigator uses an investigational device prior to obtaining informed consent from 
an intended study participant, the Investigator shall report such use to the sponsor and 
the reviewing IRB within 5 working days after the event occurs. 
21.5 Protocol Deviation Reporting 
The Investigator must notify the sponsor and the reviewing IRB of any deviation from the 
Investigational plan to protect the life or physical well-being of a study participant in an 
emergency.  Such notice shall be given as soon as possible, but in no event later than 5 
working days after the emergency occurred.  All other deviations from the protocol will 
be reported on the appropriate case report form and reported to the IRB, if required.  
21.6 Investigator Reporting 
The Investigator must, upon request by the reviewing IRB/EC, FDA, or study sponsor, 
provide accurate, complete, and current information, or a summary report, about any 
aspect of the investigation. 
 

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22.0   STUDY DATA REPORTING AND PROCESSING 
22.1 Study Data Collection 
The Case Report Form set is designed to accommodate the specific features of the trial 
design.  Modification of the CRFs may be done to ensure all required data is appropriately 
recorded.  Significant modifications will be reviewed and approved by the Operations 
Committee.       
22.2 Site Data Monitoring and Quality Control 
Study coordinators or investigators at each clinical site will perform primary data 
collection based on source-documented hospital chart reviews.  Case Report Forms will 
be submitted to data management in an expedited fashion.   
 
To ensure proper tracking of Case Report Forms and test reports obtained from the 
individual clinical sites, a master tracking system will be utilized.  Deficiencies identified 
by the master tracking system and any other specific clinical sites needs will be 
communicated regularly.  In addition, regularly scheduled teleconferences between the 
Study Coordinator(s) for each site and the sponsor may occur.   
 
All clinical sites will be monitored periodically by the sponsor’s personnel, or sponsor’s 
designee, for protocol adherence, accuracy of CRF completion, and compliance to 
applicable regulations.  Ongoing and/or serious non-compliance with respect to these 
standards will be evaluated and appropriate corrective/preventive actions required will 
be determined.  If corrective/preventive actions are not subsequently undertaken, the 
clinical sites will be asked withdraw from the study.   
22.3 Communication 
During execution of the study protocol, the sponsor will coordinate and host 
teleconference calls between the sponsor monitor, data management, and / or each 
clinical site, as necessary, to resolve any problems concerning the protocol and / or data 
collection.  Every effort will be made to ensure compliance with the protocol.  In addition, 
sponsor representative(s) will maintain personal contact with the Investigator and staff 
throughout the study by phone, mail, email and on-site visits.  If problems cannot be 
resolved immediately, an appropriate expert(s) will be consulted.     
22.4 Recruitment Tracking 
A weekly recruitment status report generated by the master tracking system will be used 
regularly to identify variations in recruitment frequency among sites.  For any well-
balanced trial, a normal distribution in recruitment is expected; however, outliers will be 
investigated for trial compliance.   
22.5 Data Processing and Quality Control 
Data gathered during the course of the study will be reported on the study CRFs via a 
secure web-based database.  The sponsor will evaluate all CRFs upon receipt.  Missing, 
incomplete, or inconsistent data will be requested form the Investigator and corrections 
will be made.  All efforts will be made to avoid loss of data.  All changes will be 
appropriately documented.  Passwords will be issued to appropriate personnel to ensure 

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confidentiality and protection of the data by allowing variable levels of access to the 
computer system.  
22.6 Monitoring, Audits and Inspections 
During the investigation, the monitor will have regular contacts with the investigative site. 
These contacts will include visits to confirm that the facilities remain adequate to 
specified standards and that the investigative team is carrying out the procedure stated 
in the investigational plan. All data must be accurately recorded in the Case Report 
Forms. Source data verification (a comparison of data in the CRF with the subject’s 
medical records and other records at the investigation site) with access to records will 
also be performed. The monitor or other sponsor personnel will be available between 
visits if the Investigator or other staff at the site needs information and/or advice.  
Authorized representatives of the study sponsor, and FDA, may visit the site to perform 
audits / inspections, including source data verification. 
22.7  Investigator Access to the Data and Publication Policies 
At the conclusion of the trial, a multi-center abstract reporting the primary results will be 
prepared and presented at a major medical meeting.  A multi-center publication will also 
be prepared for publication in a reputable medical journal.  The publication of results from 
any single center experience within the trial will not be allowed until the aggregate study 
results have been published, unless there is written consent from the study sponsor.  The 
analysis of other pre-specified and non-pre-specified endpoints will be performed by the 
sponsor.  Such analyses as well as other proposed investigations will require the approval 
of the Operations Committee.  It is anticipated that many secondary manuscripts with 
principal authorship drawn from members of the Steering Committee.  For purposes of 
timely abstract presentation and publication, such secondary publications will be delegated 
to the appropriate principal authors, and final analyses and manuscript review for all multi-
center data will require the approval of the Operations Committee.   
 
23.0   ADDITIONAL STUDY AND ADMINISTRATIVE ELEMENTS 
23.1 Duration of Investigation 
It is anticipated that some of the study participants will take part in this clinical study for 
up to 7 years. Given an accrual rate of approximately 15 patients per month, it is 
anticipated that time for recruitment will be 12 months for the enrollment of 183 study 
participants to yield an estimated final completed study group total of 147 study 
participants.  
23.2 Participant Accountability 
23.2.1 
Missed Follow-up Visits 
Study participants that miss a scheduled visit will be contacted to reschedule as 
soon as possible. Study participants failing to return for follow-up, or failing to 
return to contact attempts by site staff for follow-up visits, shall be contacted a 
minimum of three times by the Study Coordinator or Investigator, with the last 
attempt by certified mail, before exiting the study participant as lost to follow-up.   

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23.2.2 
Participant Withdrawal  
Study participants will be advised that they may voluntarily withdraw from the 
study at any time and they will be instructed to notify the Investigator 
immediately, should they choose to withdraw. Study participants may withdraw 
for any reason and are not obligated to reveal their reasons for withdrawal.  
23.3 Documentation Requirements 
All study information beginning at the screening assessment continuing through the final 
follow-up will be recorded on source documents such as initial history and physical 
noting eligibility, outside medical records, written records of all research procedures, 
including questionnaires, diaries, follow-up documentation, lab work, pathology reports, 
ECGs, X-ray reports, and any other diagnostic information, record of medications 
dispensed or devices used, clinic charts or hospital records. Data will be transcribed 
onto participant case report forms (CRFs) or recorded on eCRFs (electronic CRFs) in a 
database supplied by the sponsor.  
23.4 Study Monitoring  
Monitoring of the study will be conducted by the sponsor or its designee following 
21CFR 50, 54, 56, and 812 and the guidelines established by the Declaration of Helsinki 
and ICH GCP (to the extent that they are consistent with U.S. federal regulations). A site 
initiation meeting will be held and periodic site visits will be performed. The monitor will 
maintain oral and written communications with the Investigators and study personnel. 
Case report forms will be reviewed with source records and compliance with the protocol 
will be documented.  
23.5 Data Management  
Study data will be maintained in a password-protected electronic database created by 
the Sponsor specifically for this research study. Study participants will be identified only 
by an anonymous study identification number. 
23.6 Registration of the Clinical Trial 
The clinical trial will be registered and maintained on the publicly available clinical trials 
website (www.clinicaltrials.gov) by the study sponsor within 21 days of the first study 
enrollment.    
23.7 Amendments to the Clinical Investigational Plan 
Any change to the approved investigational plan must be documented in a written and 
numbered CIP amendment with a justification for the amendment. Changes to the 
investigational plan will only be effected following IRB and FDA approval as applicable. 
23.8 Device Accountability 
All of the valves and valve delivery catheters used in the study will be maintained in a 
secure location at the investigational site until used or returned to the sponsor.  Study 
devices will only be used under the Investigator’s supervision in study participants. The 
Investigator will not supply the study device to any person not authorized under this 
protocol to receive it. The Investigator shall maintain accurate device accounting records 
including quantity and date of receipt, person in receipt, lot number, use or disposition, 

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participant identification associated with device, date of expiration (if applicable) and 
quantity and date of any devices returned to the Sponsor.  
23.9 Deviations from the Clinical Investigation Plan 
Except in an emergency, prior approval by the study Sponsor is required for changes in 
or deviations from the investigational plan.  If the changes or deviations may affect the 
scientific soundness of the study or the rights, safety, or welfare of participants, FDA and 
IRB approval is required.  Every effort should be made to comply with the requirements 
of the protocol.   Deviations will be recorded with an explanation for the change. The 
study Sponsor is responsible for analyzing the deviations and assessing their 
significance.  Corrective action will be implemented to avoid repeat deviations.   
 
24.0 INVESTIGATOR RESPONSIBILITIES 
The Investigator is responsible for ensuring that this investigation is conducted according 
to all signed agreements, the study protocol, and the applicable code of Federal 
Regulations.  This section describes these responsibilities at his/her site.   
24.1 Study Administration    
The Investigator must read and acknowledge his/her understanding of the study protocol 
and ensure adequate training of staff for executing the study has occurred.  Specifically, 
he/she must:  Sign the Protocol Signature Page, Clinical Trial Agreement, Non-
Disclosure Agreement and Financial Disclosure and provide a copy of each to the 
Pulmonx Clinical Research Department or designee.   
• 
Provide current copies of each Investigator’s, Sub-Investigator’s, and Coordinator’s 
Curriculum Vitae (CV) to the Pulmonx Clinical Research Department. 
• 
Provide current copies of each Investigator’s, and Sub-Investigator’s Medical License as 
required throughout the course of the study.  
• 
Provide documentation of GCP training for all study staff.  
• 
Complete training using the Pulmonx Chartis Assessment System prior to treating 
enrolled subjects.  
• 
Complete training using the Pulmonx Endobronchial Valve System prior to treating 
enrolled subjects.  
• 
Delegate appropriate and qualified staff as indicated on the Site Delegation of Authority 
Log.  
• 
Complete all required study procedures and documentation at all visits. 
24.2 Institutional Review Board (IRB) Approval 
The Investigator must submit the study protocol to his/her IRB and obtain their written 
approval before being allowed to participate in the study.  Specific responsibilities 
include:   
• 
Submit proposed protocol amendments and informed consent revisions to the IRB/IEC 
and await approval. 

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• 
Inform sponsor and IRB of any unanticipated device-related events (UADEs) within 24 
hours of knowledge. 
• 
Submit all required reports to IRB/IEC and sponsor within specified timeframes. 
24.3 Conduct the Informed Consent Process 
Part of the IRB approval must include approval of an Informed Consent Form specific to 
the study.  The Investigator or his/her designee must administer these approved 
Informed Consent text to each prospective study candidate and obtain the study 
candidate’s signature on the text, prior to conducting any study-specific tests and 
enrollment into the study, respectively.  The study sponsor will provide Sample Informed 
Consent text for the Informed Consent forms to the Investigator.  This text may be 
modified to suit the requirements of the individual site.  A copy of the informed consent 
form that has been approved by the reviewing IRB will be provided to the study sponsor.  
Specifically, the Investigator must:   
• 
Explain all study procedures to the study candidates and obtain written informed 
consent.   
• 
Ensure HIPAA Authorization is obtained from each study participant and on file. 
24.4 Study Coordinator 
To assure proper execution of the study protocol, each investigator must identify a Study 
Coordinator for the site.  Working with and under the authority of the Investigator, the 
Study Coordinator assures that all study requirements are fulfilled, and is the contact 
person at the site for all aspects of study administration.   
24.5 Investigator Records 
Each Investigator must maintain the following accurate, complete, and current records 
relating to the conduct of the investigation.  The data for some of these reports may be 
available in computerized form from the sponsor but the final responsibility for 
maintenance remains with the Investigator.  Study-related documents must be retained 
for a minimum of two years after study completion and access must be permitted to the 
study sponsor monitor to inspect facilities and records.  Specific examples of records 
maintenance include:   
24.5.1 
Correspondence 
The study site will maintain records of all correspondence with another 
Investigator, an IRB, a Core Laboratory, the Study Sponsor, a monitor, or FDA, 
including required reports. 
24.5.2 
Study Devices 
Records of receipt, use, or disposition of the study device, including receipt 
dates, serial and lot numbers, names of all persons who received or used the 
device, why and how many devices were returned to the study Sponsor or 
otherwise disposed of.   
24.5.3 
Study Participant Records 
Records of each study participant’s case history, including study-required Case 
Report Forms, evidence of informed consent, all relevant observations of 
adverse device effects, the condition of each study participant upon entering and 

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during the course of the investigation, relevant medical history, the results of all 
diagnostic testing, and the date of each study treatment.    
24.5.4 
Protocol and Deviations 
The protocol, along with any documentation showing the dates and reasons for  
any protocol deviations, will be maintained by the study site.   
24.5.5 
Investigator Reports   
The reports for which the Investigator has responsibility to generate are shown in 
the table below.  The table also shows who should be the recipient of the report 
and timeframe for submitting it. While some of these reports will be developed by 
or with the assistance of Pulmonx, the final responsibility for them rest with the 
Investigator.   
Type of Report 
Prepared by Investigator 
For: 
Time Constraints of 
Notification 
Unanticipated Adverse Effect 
Sponsor  
As soon as possible but no 
later than 10 working days 
after knowledge of the event. 
Withdrawal of IRB Approval 
Sponsor 
Within 5 working days. 
Progress Report 
Sponsor / IRB  
Submitted at least annually. 
Protocol Deviations to protect the 
life or physical well-being of the 
subject in an emergency 
Sponsor / IRB 
Within 5 working days. 
Informed Consent Not Obtained 
prior to device use 
Sponsor / IRB  
Within 5 working days. 
Final Summary Report 
Sponsor / IRB  
Within 3 months of study 
completion/termination. 
  
25.0  SPONSOR RESPONSIBILITIES  
25.1 Clinical Site Selection and Training    
• 
Submit the IDE application to FDA and obtain approval from FDA to initiate the study. 
• 
Ensure that IRB approval and continuing review are obtained. 
• 
Select the clinical Investigators and study sites, and other consultants who participate in 
the study. 
• 
Ensure that the Investigator is an appropriately qualified practitioner legally entitled to 
practice. 
• 
Ensure that the Investigator is trained and experienced in the field of application of the 
device under consideration. 
• 
Ensure that the Investigator has sufficient background and meets the requirements for 
conducting a clinical investigation. 
• 
Ensure that the appropriate information and training are provided to the Investigator in 
the use of the device to be used in the study in accordance with the clinical investigation 
plan. 

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• 
Obtain from each participating Investigator a signed agreement which includes:  1) 
Investigator’s CV, statement of the investigator’s relevant experience and/or information 
regarding other research activities, including instances where the research activity was 
terminated. 
• 
Provide financial support to each study site and the core laboratories per individual 
contracts with each site.   
• 
Provide the study device to participating study sites, in quantities sufficient to support 
study activities, per agreements executed with the study sites.   
• 
Provide training to Principal Investigator(s) and Study Coordinator(s).   
25.2 Good Clinical Practice  
• 
Ensure that the study is conducted according to ICH Good Clinical Practice Guidelines 
(to the extent that they are consistent with U.S. federal regulations), and all applicable 
regulatory standards per federal regulations for clinical study sites, core laboratories, 
and other participants, and perform regular site monitoring to assure compliance with 
them.   
• 
Perform site monitoring of clinical data at clinical study sites. 
• 
Provide the Investigator with sufficient clinical study material and help the Investigator to 
carry out the clinical investigation in compliance with the approved protocol. 
• 
Evaluate (together with the Investigator) all serious adverse events (SAE) and 
unanticipated adverse device effects (UADE) without delay and take all necessary steps 
to protect the study participant. The appropriate authorities will be notified of all SAEs 
and UADEs in accordance with the legal requirements.  
• 
The Sponsor will inform the Investigator(s) when the prescribed period for retaining 
clinical study documents has elapsed. 
25.3 Clinical Site Management    
The sponsor reserves the right to: 
• 
Demand the exclusion of a study participant from the clinical investigation in the case of 
ineligibility. 
• 
Exclude/Terminate Investigator(s) from the clinical investigation because of severe 
protocol deviations or because of fraud and misconduct. 
• 
Terminate the study investigation prematurely. If this should become necessary, the 
Sponsor and the Investigator will conclude the proceedings after consideration and 
consultation, taking into account the protection of the study participants’ interests.  
25.4 Study Sponsor Monitoring on Site 
 
The study Sponsor personnel or their designee will perform study site monitoring.  Each 
site will be monitored according to 21 CFR 812 and Pulmonx Inc. (or designee’s) internal 
monitoring SOPs.  This will be done to ensure that the study is conducted in full 
compliance with all applicable regulations, and with the study protocol.  A pre-
investigation meeting will occur with each potential study site in order to orient the 
prospective Investigator and staff to the clinical trial protocol, applicable regulations and 
requirements, and expectations of the study, including the numbers and time frame for 

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study participant enrollment, study participant selection, informed consent, 
randomization, required clinical data and record keeping.  The prospective study site will 
be evaluated to ensure that it has an adequate patient base and can provide sufficient 
staff and documentation support to conduct the study properly.   
 
No study site may receive shipment of the study device components until Pulmonx 
receives the following documents:   
1. Written IRB approval for conduct of the study 
2. Review of the site’s approved written study-specific informed consent document. 
3. Executed Clinical Trial Agreement 
25.5 Sponsor Records    
25.5.1 
Correspondence 
Records of all correspondence with Investigators, IRB, Core Laboratories, 
Clinical Research Organizations (CRO), study monitors, or FDA, including 
required reports, will be maintained. 
25.5.2 
Study Devices 
Records of study device shipments and disposition shall be maintained.  Records 
of shipments shall include the name and address of the consignee, type and 
quantity of devices shipped.  Records of disposition shall describe the batch 
numbers of any devices returned to the Sponsor, repaired, or disposed of in 
other ways by the Investigator or another person, and the reasons for and 
method of disposal.   
25.5.3 
Research Agreements and Financial Disclosure 
The sponsor shall maintain signed copies of clinical site and investigator 
agreements, including the financial disclosure information. 
25.5.4 
Study Participant Records 
The sponsor shall maintain records concerning adverse device effects.   
25.6 Sponsor Reports 
25.6.1 
Unanticipated Adverse Device Effects 
The sponsor shall report the result of such evaluations to FDA and to all 
reviewing IRB’s and participating Investigators within 10 working days after the 
sponsor first receives notice of the effect.   
25.6.2 
Withdrawal of IRB Approval 
The sponsor shall notify FDA and all reviewing IRB’s and participating 
Investigators of any withdrawal of approval of an investigation or a part of an 
investigation by a reviewing IRB within 5 working days after receipt of the 
withdrawal of approval.   
25.6.3 
Withdrawal of FDA Approval 
The sponsor shall notify all reviewing IRB’s and participating Investigators of any 
withdrawal of approval of an investigation or a part of an investigation by FDA 
within 5 working days after receipt of the withdrawal of approval.   

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25.7 Investigator List 
The sponsor shall maintain and update as necessary a current of the names and 
addressed of all Investigators participating the investigation.   
25.8 Progress Reports 
The sponsor shall submit annual progress reports to all reviewing IRB’s and FDA.   
25.9 Recall and Device Disposition 
The sponsor shall notify FDA and all reviewing IRB’s of any request that an Investigator 
return, report, or otherwise dispose of any study devices.  
25.10 
Final Reports 
The sponsor shall submit to FDA and all reviewing IRB’s a final report upon completion 
or termination of the study.   
 
 
26.0 GLOSSARY OF TERMS 
6MWD Test – The six-minute walk distance test is a cardiopulmonary function test that measures 
a patient’s exercise capacity by the distance that he or she can walk in six minutes.  
AE – An Adverse Event is any pulmonary complication whether considered major or minor and 
whether or not associated directly with the Pulmonx Endobronchial Valve procedure. Anticipated 
AE’s are listed as endpoints, but unanticipated events are documented as well. 
Atelectasis – Lung collapse. 
Body Plethysmography – a box-like device in which the patient sits that measures pressure and 
volume changes in the lung to determine functional residual capacity and other lung volumes. 
COPD – Chronic obstructive pulmonary disease is a condition in which the lungs are limited by 
airway narrowing and air trapping. 
CRF – Case report forms are used to collect data for this study. 
CV – Collateral ventilation; inter-lobar communication of air 
HRCT Scan – a high-resolution computed tomography scan used to generate a cross-sectional 
image of the lungs and other thoracic organs and tissues. 
Diffusing Capacity – Measures the rate of carbon monoxide gas transfer across the alveolar-
capillary blood-gas membrane (DLCO).  
DLCO – a measure of diffusing capacity (see above) 
Dyspnea – Shortness of breath.  
EBV – Pulmonx Endobronchial Valve 

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ECG – Electrocardiogram; a recording of the heart’s electrical activity. 
EBV – Pulmonx Endobronchial Valve (EBV) Procedure – a bronchoscopic method of delivering 
and deploying a valve to prevent inspiratory airflow into a targeted lung segment while allowing for 
expiratory airflow. 
ERV – Expiratory reserve volume – the maximal amount of gas that can be exhaled from the 
resting end-expiratory level. 
FEV1 – Forced expiratory volume in one second is the minimum volume of gas that can be 
forcefully exhaled in one second after a maximal inspiration. 
FRC – Functional residual capacity:  the volume in the lungs at the end-expiratory position. 
FVC – Forced vital capacity is the total volume forcefully exhaled after a maximal inspiration. 
Heterogeneous – A term used to describe non-uniform distribution of diseased, emphysematous 
areas in the lung. 
Homogeneous – A term used to describe uniform distribution of diseased, emphysematous areas 
in the lung. 
IC – Inspiratory capacity is the volume of gas that can be inhaled during maximal forced inhalation 
after normal expiration. 
LVRS – acronym for lung volume reduction surgery. 
mmHg – Millimeters of mercury is a unit of measure for pressure. 
NETT – acronym for National Emphysema Treatment Trial 
PaCO2 – Partial pressure of carbon dioxide in arterial blood. 
PaO2 – Partial pressure of oxygen in arterial blood. 
RV – Residual volume:  the volume of air remaining in the lungs after a maximal exhalation. 
SAT – Blood saturation is the percentage of hemoglobin sites occupied by oxygen molecules.  
SGRQ – St. George’s Respiratory Questionnaire: a standardized quality of life measurement used 
to assess patients with obstructive pulmonary diseases. 
Spirometry – a method of measuring lung volumes and flows. 
TLC – Total lung capacity is the total volume of gas that is held within the lungs at maximal 
inspiration. 
VC – Vital capacity:  the volume equal to TLC – RV. 
VTG – Volume of thoracic gas: the absolute volume of gas in the thorax at any point in time and 
any level of alveolar pressure.  

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The contents of this document are propriety and confidential.  This protocol contains valuable engineering, clinical 
and commercial information that must not be disclosed to persons not directly involved with the study.  Duplication 
and distribution of this document require prior written approval from Pulmonx 
V/Q Scan – Ventilation/perfusion scan is used to assess regional lung function. Note: Xenon gas 
will be used at some centers to identify areas of poor ventilation in the lung.  
 
27.0  REFERENCES 
1.  The National Emphysema Treatment Trial Research Group.  Rationale and design of the 
national Emphysema Treatment Trial.  Chest 1999;116;1750-1761.   
2. Barr RG, Celli BR, Martinez FJ, Ries AL, Rennard SI, Reilly JJ Jr, Sciurba FC, Thomashow 
BM, Wise RA.  Physician and patient perceptions in COPD:  the COPD Resource Network 
Needs Assessment Survey. Am J Med 2005;118(12):1415.  
 
3.  Mannino DM, Homa DM, Akinbami LJ, Ford ES, Redd SC.  Chronic obstructive pulmonary 
disease surveillance—United States, 1971-2000. MMWR Surveill Summ 2002;51(6):1-16.   
 
4.  Sciurba FC, Rogers RM, Keenan RJ, et al.  Improvement in pulmonary function and elastic 
recoil after lung-reduction surgery for diffuse emphysema.  N Engl J Med 1996;334:1095-9. 
 
5.  Martinez FJ. Montes de Oca M, Whyte RI, et al.  Lung-volume reduction improves dyspnea, 
dynamic hyperinflation, and respiratory muscle function.  Am J Respir Crit Care Med 
1997;155:1984-90. 
 
6.  Sabanathan A, Sabanathan S, Shah R., Richardson J.  Lung volume reduction surgery for 
emphysema.  J Cardiovasc Surg 1998;39:237-43. 
 
7. Geddes D, Davies M, Koyama H.  Effect of lung-volume-reduction surgery in patients with 
severe emphysema.  N Engl J Med 2000;343:239-245. 
 
8.  Gelb AF, et al.  Lung function four years after lung volume reduction surgery for emphysema.  
Chest 1999;116,1608-1615. 
 
9.  Criner GJ, Cordova FC, Furukawa S, Kuzma AM, Travaline JM, Levenson V, O’Brien GM.    
Prospective randomized trial comparing bilateral lung volume reduction surgery to pulmonary 
rehabilitation in severe chronic obstructive pulmonary disease.  Am J Respir Crit Care Med 
1999;160(6):2018-27.   
 
10.  Fishman A, Martinez F, Naunheim K, Piantodosi S, Wise R, Ries A, Weinmann, Wood DE; 
National Emphysema Treatment Trial Research Group.  A randomized trial comparing lung-
volume-reduction surgery with medical therapy for severe emphysema. N Engl J Med 
2003;348(21):2059-73.   
 
11.  Gelb AF, McKenna RJ, Jr., Brenner M, Epstein JD, Zamel N. Lung function 5 yr after lung 
volume reduction surgery for emphysema. Am J Respir Crit Care Med 2001;163:1562-6. 
 
12.  Martinez FJ, de Oca MM, Whyte RI, Stetz J, Gay SE, Celli BR. Lung-volume reduction 
improves dyspnea, dynamic hyperinflation, and respiratory muscle function. Am J Respir Crit 
Care Med 1997;155:1984-93. 
 

Pulmonx LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
 
 
           
 
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              Page 69 of 71 
The contents of this document are propriety and confidential.  This protocol contains valuable engineering, clinical 
and commercial information that must not be disclosed to persons not directly involved with the study.  Duplication 
and distribution of this document require prior written approval from Pulmonx 
13.  Benzo R, Farrell MH, chang CC, Martinez JF, Kaplan R, Reilly J, Criner G, Wise R, Make 
B, Luketich J, Fishman AP, Sciurba FC; NETT Research Group.  Integrating health status and 
survival data:  the palliative effect of lung volume reduction surgery.  Am J Respir Crit Care Med 
2009;180(3):239-46.   
 
14.  Naunheim KS, Wood DE, Krasna MJ, DeCamp MM Jr, Ginsburg ME, McKenna RJ Jr, 
Criner GJ, Hoffman EA, Sternberg AL, Deschamps C.  National Emphysema Treatment Trial 
Research Group.  Predictors of operative mortality and cardiopulmonary morbidity in the 
National Emphysema Treatment Trial. J Thorac Cardiovasc Surg 2006;131(1):43-53.   
 
15.  Naunheim KS.  Lung-volume reduction surgery: a vanishing operation? J Thorac 
Cardiovasc Surg 2007;133(6):1412-13.   
 
16.  Sciurba F, Ernst A, Herth F, Strange C, Criner G, Marquette C, Kovitz K, Chiacchierini R, 
Goldin J, McLennan G.  A randomized study of endobronchical valves for advanced 
emphysema.  N Engl J Med 2010;363:1233-44.   
 
17.  Herth FJF, Noppen M, Valipour A, Leroy S, Vergnon JM, Ficker JH, Egan JJ, Gasparini S, 
Agusti C, Holmes-Higgin D, Ernst A, and the International VENT Study Group.  Efficacy 
predictors of lung volume reduction with Zephyr valves in a European cohort.  Eur Respir J, 
2012;Jan 26[epub ahead of print].   
 
18.  Hayhurst MD, MacNee W, Flenley DC, Wright D, McLean A, Lamb D, Wightman AJ, Best J.  
Diagnosis of pulmonary emphysema by computerized tomography.  Lancet 1984;2:320-2. 
 
19.  Fessler HE.  Collateral ventilation, the bane of bronchoscopic volume reduction.  Am J 
Respir Crit Care Med 2005;171:423-24.   
 
20.  Cetti EJ, Moore AJ, Geddes DM.  Understanging collateral ventilation is probably central to 
planning new bronchoscopic techniques for treating emphysema.  Thorax 2006;61:371-3. 
 
21. Van Allen CM, Lindskog GE, Richter DW.  Gaseous interchange between adjacent lung 
lobules.  The Yale journal of biology and medicine 1930;2:297. 
 
22.  Culiner MM.  Bronchial cysts and collateral ventilation.  Dis Chest 1964;45:627-38.   
 
23.  Hogg JC, Macklem PT, Thurlbeck WM.  The resistance of collateral channels in excised 
human lungs.  J Clin Invest 1969;48(3):421-31.   
 
24.  Gompelmann D, Eberhardt R, Michaud G, Ernst A, Herth FJF.  Predicting atelectasis by 
assessment of collateral ventilation prior to endobronchial lung volume reduction: A feasibility 
study.  Respiration 2010;80(5):419-25.   
 
25.  Herth FJF, Slebos DJ, Ficker JH, Ek L, Schmidt B, Reichenberger F.  A study of the use of 
Chartis system to optimize subject selection for endobronchial lung volume reduction (ELVR) in 
subjects with heterogeneous emphysema.  Accepted for publication; Eur Respir J April 2012.         
 
26.  Global Initiative for Chronic Obstructive Lung Disease (GOLD):  Global strategy for the 
diagnosis, management, and prevention of chronic obstructive pulmonary disease (Updated 
2010).   
   

Pulmonx LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
 
 
           
 
Version:  June 23, 2017                                                CONFIDENTIAL  
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The contents of this document are propriety and confidential.  This protocol contains valuable engineering, clinical 
and commercial information that must not be disclosed to persons not directly involved with the study.  Duplication 
and distribution of this document require prior written approval from Pulmonx 
27.  Nici L, Donner C, Wouters E, Zuwallack R, Ambrosino N, Bourbeau J, Carone M, Celli B, 
Engelen M, Fahy B, Garvey C, Roger Goldstein R, Gosselink R, Lareau S, MacIntyre N, Maltais 
F, Morgan M, O’Donnell D, Prefault C, Reardon J, Rochester C, Schols A, Singh S, Troosters T, 
on behalf of the ATS/ERS Pulmonary Rehabilitation Writing Committee.  American Thoracic 
Society/European Respiratory Society Statement on Pulmonary Rehabilitation.  Am J Respir 
Crit Care Med 2006;173:1390-1413.   
 
28.  Miller MR, Crapo R, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Enright P, 
van der Grinten CPM, Gustafsson P, Jensen R, Johnson DC, MacIntryre N, McKay R, Navajas 
D, Pedersen OF, Pellegrino R, Viegi G, Wanger J.  General considerations for lung function 
testing.  Eur Respir J 2005;26:153-61.   
 
29.  Miller, MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, 
vander Grinten CPM, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, 
Pedersen OF, Pellegrino R, Viegi G, Wanger J. Standardisation of spirometry.  Eur Respir J 
2005;26:319-38.  
 
30.  Hankinson JL, Odencrantz JR, Fedan KB.  Spirometric Reference Values from a Sample of 
the General U.S. Population.  Am J Respir Crit Care Med 1999; 159:179-187. 
31.  Barr JT, Schumacher GE, Freeman S, LeMoine M, Bakst AW, Jones PW.  American 
translation, modification, and validation of the St. George’s Respiratory Questionnaire.  Clin 
Ther 2000;22(9):1121-45. 
 
32.  Bestall JC, Paul EA, Garrod R, Garnham R, Jones PW, Wedzicha JA. Usefulness of the 
Medical Research Council (MRC) dyspnoea scale as a measure of disability in patients with 
chronic obstructive pulmonary disease.  Thorax 1999;54;581-6.   
 
33.  Witek TJ Jr and Mahler DA.  Minimal important difference of the transition dyspnea index in 
a multinational clinical trial.  Eur Respir J 2003;21:267-72.  
 
34.  Jones PW, Harding G, Berry P, Wiklund I, Chen WH, Leidy NK. Development and first 
validation of the COPD Assessment Test. Eur Respir J 2009;34: 648–654.   
 
35.  Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36).  
Conceptual framework and item selection. Med Care 1992;30:473-483. 
 
36.  The EuroQol Group. EuroQol-a new facility for the measurement of health-related quality of 
life. Health Policy 1990;16:199-208. 
 
37.  Wanger J, Clausen JL, Coates A, Pedersen OF, Brusasco V, Burgos F, Casaburi R, Crapo 
R, Enright P, van der Grinten CPM, Gustafsson P, Hankinson J, Jensen R, Johnson D, 
MacIntyre N, McKay R, Miller MR, Navajas D, Pellegrino R, Viegi G.  Standardisation of the 
measurement of lung volumes.  Eur Respir J 2005;26:511-22.   
 
38.  ATS Statement:  Lung Function Testing:  Selection of Reference Values and Interpretative 
Strategies, Official Statement of the American Thoracic Society, Approved March 1991.  Am 
Rev Respir Dis 1991; 144:1202-1218. 
 
39.  MacIntyre N, Crapo RO, Viegi G, Johnson DC, van der Grinten CPM, Brusasco V, Burgos 
R, Casaburi R, Coates A, Enright P, Gustafsson P, Hankinson J, Jensen R, McKay R, Miller 

Pulmonx LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
 
 
           
 
Version:  June 23, 2017                                                CONFIDENTIAL  
              Page 71 of 71 
The contents of this document are propriety and confidential.  This protocol contains valuable engineering, clinical 
and commercial information that must not be disclosed to persons not directly involved with the study.  Duplication 
and distribution of this document require prior written approval from Pulmonx 
MR, Navajas D, Pedersen OF, Pellegrino R, Wanger J.  Standardisation of the single-breath 
determination of carbon monoxide uptake in the lung.  Eur Respir J 2005;26:720-35.   
 
40.  Qaseem A, Wilt JT, Weinberger SE, Hanania NA, Criner G, van der Molen T, et al, for the 
American College of Physicians, the American College of Chest Physicians, the American 
Thoracic Society, and the European Respiratory Society.  Diagnosis and management of stable 
chronic obstructive pulmonary disease:  a clinical practice guideline update from the American 
College of Physicians, the American College of Chest Physicians, the American Thoracic 
Society, and the European Respiratory Society.  Ann Intern Med 2011;155(3):179-191. 
 
41.  Leidy NK, Wilcox TK, Jones PW, Roberts L, Powers JH, Sethi S; EXACT-PRO Study 
Group.  Standardizing measurement of chronic obstructive pulmonary disease exacerbations.  
Reliability and validity of a patient-reported diary.  Am J Respir Crit Care Med 2011;183(3):323-
9.   
 
42. ATS Statement: Guidelines for the Six-Minute Walk Test, Official Statement of the American 
Thoracic Society, Approved March 2002. Am J Crit Care Med 2002; 166:111-117. 
 
43.  Silverman M, Barry J, Hellerstein H, et al. Variability of the perceived sense of effort in 
breathing during exercise in patients with chronic obstructive pulmonary disease. Am Rev 
Respir Dis 1988;137 (1):206-9. 
 
44.  Dyspnea: Mechanisms, Assessment, and Management: A Consensus Statement, Official 
Statement of the American Thoracic Society, Adopted July 1998. Am J Crit Care Med 1999; 
159:321-340. 
 
45.  Groenewegen KH, Postma DS, Hop WCJ, Wielders PLML, Schlösser NJJ, Wouters EFM.  
Increased systemic inflammation is a risk factor for COPD exacerbations. Chest 2008;133:350-
57.  
   
46. Celli BR, Cote CG, Marin JM, Casanova C, Montes de Oca M, Mendez RA, Pinto Plata V, 
Cabral HJ.  The body-mass index, airflow obstruction, dyspnea, and exercise capcity index in 
chronic obstructive pulmonary disease.  N Engl J Med 2004;350:1005-12.   
  
47.  Martinez FJ, Foster G, Curtis JL, Criner G, Weinmann G, Fishman A, DeCamp MM, Benditt 
J, Sciurba F, Make B, Mohsenifar Z, Diaz P, Hoffman E, Wise R, for the NETT Research Group.  
Predictors of mortality in patients with emphysema and severe airflow obstruction.  Am J Respir 
Crit Care Med 2006;173:1326-34.   
 
48.  Faguang J, Deguang M, Dongling C, Enqing F, Yonghong X, Tonggang L.  Severe 
complications of bronchoscopy.  Respiration 2008;76:429-433. 
 
49.  Shah PL, Slebos DJ, Cardoso PFG, Cetti E, Voelker K, Levine B, Russell ME, Goldin J, 
Brown M, Cooper JD, Sybrecht GW, the EASE trial study group.  Bronchoscopic lung-volume 
reduction with Exhale airway stents for emphysema (EASE trial): randomized, sham-controlled, 
multicentre trial.  Lancet 2011;378:997-1005.   
 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 1.  Study Participant Flow 
 
 
  
 
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D 
 
 
Initial Eligibility Screen 
Found Eligible for Study Procedure:  Enrolled, Randomized, Treated as Assigned
Bronchoscopy with Study Procedure Eligibility Screen (CV Assessment) 
Control 
EBV Treatment 
45 Day Visit (+/‐ 10 days) Chest X‐ray, CT scan 
Baseline Eligibility Screen & Baseline Assessments
Year 2, Year 3, Year 4, Year 5 (+/‐ 60 days) 
Spirometry, Adverse Events  
3 Month Visit (+/‐ 14 days) 
Clinical Measures
6 Month Visit (+/‐ 21 days) 
Clinical Measures
1 Year Visit (+/‐ 45 days) 
Clinical Measures
Post‐Procedure 5 Night Hospital Stay 
Chest X‐ray (within 1 hour ± 30 min) & Daily Chest X‐ray until discharge
Daily Follow‐Up Telephone Contact for 10 Days (to 11:59 pm) 
EBV Treatment, 
if allowed  
Control Arm 
EBV Treated Arm 
Study Exit 
Valve Adjustment? 
(see Section12.3)
Yes
No
Valve Adjustment Procedure  
(within 75 days of study procedure unless COPD 
exacerbation occurs, then within 90 days) 
Daily Follow‐Up Telephone Contact 
for 10 Days after Discharge  
Adverse Events
Post‐Procedure 5 Night Hospital Stay 
Chest X‐ray (within 1 hour ± 30 min) & Daily 
Chest X‐ray until discharge 
9 Month Visit (+/‐ 21 days) 
Health Status Changes Only
45 Day Visit (+/‐ 10 days) 
 
1 Year Visit (+/‐ 45 days) 
CT, Clinical Measures
<120 Days 
<60 Days 
30 Day Visit (+/‐ 5 days) Chest X‐ray 
 Day 7 after Discharge Visit (+1 business day) Chest X‐ray 
Day 7 after Discharge Visit (+1 business day)
Chest X‐ray 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 2.  Study Participant Screening and Enrollment Flowchart 
 
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              Page 1 of 1 
 
 
 
 
 
 
Initial Eligibility Screening  
Signed Screening or Study Participation Informed Consent  
Physical Examination & Medical History  
CT Assessment by Clinical Site 
Electrocardiogram (ECG) 
Lung Function Testing (Spirometry, Body Plethysmography, DLCO) 
6-minute walk distance (6MWD) 
Blood Work (ABGs, CBCs, alpha-1 antitrypsin, plasma cotinine, serum fibrinogen) 
Meets Screening Eligibility Criteria  
No  
Yes 
Patient is not eligible for study.  Note 
reason onto screening log  
Baseline Eligibility Screening  
Pulmonary Rehabilitation Eligibility Criterion Completed  
Spirometry, 6MWD 
No  
Yes 
Patient is not eligible for study.   Note 
reason onto screening log  
Collect Other Baseline Measures 
Self-Reported Health Status Measures (HRQOL) 
Medication Use, Vaccinations if needed 
 Create Bronchoscopy Procedure Plan 
Bronchoscopy Procedure  
Meets Study Procedure Eligibility Criteria? 
Meets Baseline Eligibility Criteria  
Signed Study Informed Consent (if not done at screening) 
No  
Yes 
Enrolled, Randomized, Treated as Assigned 
Patient is not eligible for study.  Note 
reason onto screening log  
Enter Study Candidate onto Screening Log  

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 3.  Example Informed Consent Form:  Study Screening  
 
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             CONFIDENTIAL  
              Page 1 of 4 
 
 
 
Investigator Name: ________________  
Site ID#___________________ 
Institution: _______________________  
Participant ID: ______________ 
________________________________ 
________________________________  
Telephone: _________________ 
 
 
Dear Patient: 
 
You are being invited to be screened for a clinical study involving research.  This Informed Consent Letter 
describes the study and the screening tests that must be done to find out if you would be a candidate for the study.  
If you choose to be screened for the study you must read this form carefully. You are urged to discuss any 
questions you have with your physician and / or the hospital’s research staff.   
 
 
Purpose of the Research Study 
Since you are being asked to consider undergoing screening to find out if you may be a candidate for this study, 
you have probably suffered an impaired lifestyle as a result of emphysema.  Emphysema is a serious disease that 
afflicts more than four million people worldwide.  It is one form of Chronic Obstructive Pulmonary Disease, or 
COPD.  Emphysema causes the lungs to lose the ability to move air in and out normally and to efficiently absorb 
oxygen, making breathing more difficult.   
 
The purpose of this research is to study a medical device that is designed to be placed by a doctor in a diseased 
section of the lungs.  This device is called the Pulmonx Endobronchial Valve (EBV).  The EBV is a one-way 
valve that blocks off the diseased lung section to inhaled air but lets the trapped air already inside the area escape.   
With placement of the EBV, the diseased part of the lung collapses; this allows the healthier parts of the lung to 
expand.  The aim of the EBV treatment is to help someone with emphysema breathe more easily by allowing the 
healthier parts of the lung to work better.  This research study is designed to investigate the safety and 
effectiveness of the Pulmonx EBV for treating emphysema symptoms.  The EBV is considered experimental.  
This means that it has not yet been approved by the U.S. FDA (Food and Drug Administration) for commercial 
use in the United States. 
 
 
 
Number of Patients in the Study 
Approximately two hundred (200) patients will be enrolled into this study. In order to qualify for enrollment into 
this study, you must undergo a bronchoscopy procedure.  During the bronchoscopy procedure, your doctor will 
measure some of the airways in your lungs using a device that measures airflow to find out if you meet the study 
criteria for having the EBV treatment.  There is a chance that after measuring some of airways in your lungs you 
will not be eligible to take part in this study.   
 
During the bronchoscopy procedure, one hundred and eighty-three (183) patients will be found to qualify for the 
study.  The 183 patients who qualify for the study will be randomly assigned to the study treatment.  
Approximately two-thirds will be randomly assigned to the EBV treatment group and have EBV implanted in 
their lungs and approximately one-third will be randomly assigned to the control group and not have EBV 
implanted in their lungs.  This means that during the bronchoscopy procedure if you are found to be eligible to 
participate in the study, you will have a 2 in 3 chance of receiving EBV and a 1 in 3 chance of not receiving EBV. 
 
The results of the study will be evaluated after all of the study participants have made the 1-year visit.  For study 
participants who have EBV, they will be expected to continue coming to the research clinic once a year through 5 
years.   

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 3.  Example Informed Consent Form:  Study Screening  
 
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             CONFIDENTIAL  
              Page 2 of 4 
 
 
Tests and Evaluations 
If you agree to undergo the screening for this study, the following tests and assessments will be performed.  If you 
should feel dizzy, chest pain, palpitations, nausea, severe difficulty breathing or wheezing, during any of the 
testing, please let your healthcare professional know immediately.  
 
Chest X-ray 
During this test, a simple X-ray will be made of your chest.  
 
HRCT (High Resolution Computed Tomography) of Chest 
You will be asked to lie down on your back on an x-ray table that will slide into a large, tunnel-shaped 
machine.  You must not move during the test and will be asked to relax and breathe normally. The technician 
will also ask you to do some breathing maneuvers such as take a deep breath in or out.    
 
Echocardiogram 
An echocardiogram will be done to assess your heart’s function.  An echocardiogram is a test that uses sound 
waves to create a moving picture of the heart. The picture is much more detailed than a plain x-ray image and 
involves no radiation exposure.  
 
Electrocardiography (ECG) 
During this test, small electrodes will be attached to your skin in several places and measurements will be 
taken of your heart rhythm and blood flow in and out of your heart.   
 
Lung Function Tests  
Spirometry: During the test, you will be asked to breathe in and out of a mouthpiece while a machine 
measures the amount of air you are breathing into and out of your lungs.  These maneuvers may be somewhat 
difficult and you may become tired during the test but you will be allowed to rest periodically.   
 
Plethysmography: This test is used to determine how much air you can hold in your lungs.  You will sit in a 
small box, comparable to the size of a telephone booth, to undergo breathing tests similar to those described 
above. There is a chance that you may experience claustrophobia in addition to some fatigue.  
 
Diffusing Capacity:  This test is used to determine the overall ability of your lungs to transfer gas into and out 
of your blood.   
 
Six Minute Walk Test 
You will be asked to walk back and forth between a start and end point as many times as possible within 6 
minutes. You may stop and rest if needed.  Right before and right after the test you will be asked questions 
about how breathless you feel you are.  
 
Blood Gas (PaO2 and PaCO2) and Blood Chemistry Analysis 
A blood sample will be taken to measure the amount of oxygen and carbon dioxide in the sample. This blood 
sample will need to be taken from an artery (as opposed to a vein, which is done for the more routine blood 
tests), and therefore may be more painful than other blood tests that you may have had previously.  Standard 
compounds and the number of blood cells will also be measured.  You must have stopped smoking for at least 
4 months to participate in this study.  A blood test will be performed to confirm that you have stopped.  It is 
important that you do not smoke during the study.  In addition, the blood sample will be tested for alpha-1 
antitrypsin deficiency and a marker for systemic inflammation (serum fibrinogen).     
 
Pulmonary Rehabilitation Program 
In order to participate in this study, you will have:   
• 
Successfully completed a supervised pulmonary rehabilitation program within the past 6 months, 
or 
• 
Be regularly performing maintenance respiratory rehabilitation if you completed the pulmonary 
rehabilitation program more than 6 months ago.   

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 3.  Example Informed Consent Form:  Study Screening  
 
Version: June 23, 2017 
             CONFIDENTIAL  
              Page 3 of 4 
 
The supervised pulmonary rehabilitation program must have required you to attend at least 2 visits to the 
pulmonary rehabilitation center each week.  You will have to have documentation to show that you have attended 
at least 8 visits to the pulmonary rehabilitation center.  If you do not meet the criteria above, you will be offered 
an opportunity to complete a supervised pulmonary rehabilitation program as part of your participation in the 
study.  This supervised program will be paid for by the study sponsor and will be at no cost to you.  Your doctor 
may also make changes to your emphysema medications at this time.   
 
Financial Responsibility 
The costs of any routine medical care administered during the study will be the responsibility of you and/or your 
health insurer. For such routine costs, you will be responsible for any co-payments or deductibles required under 
your insurance. You are not, however, expected to pay for any medical care that is specifically required by the 
screening tests for this study.  
 
 
Questions 
If you have any questions about the screening for this study you should ask your doctor or one of his or her staff 
members.  
 
 
 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 3.  Example Informed Consent Form:  Study Screening  
 
Version: June 23, 2017 
             CONFIDENTIAL  
              Page 4 of 4 
 
Informed Consent 
I, ___________________________________, the undersigned hereby consent to be screened to find out if I may 
be a candidate for a research project titled: Lung Function Improvement after Bronchoscopic Lung Volume 
Reduction with Pulmonx Endobronchial Valves used to Treat Emphysema. 
 
If I agree to be screened for the research study and if my questions are answered, I should sign this form.  If I 
wish to refuse to be screened for the study, I may do so without any loss of medical care or benefits.  Once I have 
consented, I still have the right to withdraw from being screened at any time.  To withdraw, all I have to do is 
simply tell Dr. ________________________ or complete the Revocation of Consent at the bottom of this form. 
 
I will be given a copy of this form to keep and to refer to as needed. 
 
Printed Name of Participant (or legal representative):  
 
 
 
 
 
 
 
 
Signature: 
 
 
 
 
 
 
Date: 
 
 
 
 
 
 
 
I declare that I have been present when the research study was explained to the above participant and I believe 
that the participant has an application and understanding of the explanation given. 
 
Witness: 
 
 
 
 
 
 
Date: 
 
 
 
 
 
 
 
 
REVOCATION OF CONSENT 
I hereby wish to WITHDRAW my consent to be screened for the research study described above.  Withdrawal 
WILL NOT jeopardize any treatment or my relationship with _________________ Hospital. 
 
Printed Name of Participant (or legal representative):  
 
 
 
 
 
 
 
Signature: 
 
 
 
 
 
 
Date: 
 
 
 
 
 
 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 4. Screening Log 
 
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             CONFIDENTIAL  
              Page 1 of 3 
 
#  
Screen ID 
Met All Screening Eligibility Criteria 
If no, list number for criterion not 
met 
1 
 
 Yes 
 No 
 
2 
 
 Yes 
 No 
 
3 
 
 Yes 
 No 
 
4 
 
 Yes 
 No 
 
5 
 
 Yes 
 No 
 
6 
 
 Yes 
 No 
 
7 
 
 Yes 
 No 
 
8 
 
 Yes 
 No 
 
9 
 
 Yes 
 No 
 
10 
 
 Yes 
 No 
 
11 
 
 Yes 
 No 
 
12 
 
 Yes 
 No 
 
13 
 
 Yes 
 No 
 
14 
 
 Yes 
 No 
 
15 
 
 Yes 
 No 
 
16 
 
 Yes 
 No 
 
17 
 
 Yes 
 No 
 
18 
 
 Yes 
 No 
 
19 
 
 Yes 
 No 
 
20 
 
 Yes 
 No 
 
21 
 
 Yes 
 No 
 
22 
 
 Yes 
 No 
 
23 
 
 Yes 
 No 
 
24 
 
 Yes 
 No 
 
25 
 
 Yes 
 No 
 
26 
 
 Yes 
 No 
 
27 
 
 Yes 
 No 
 
28 
 
 Yes 
 No 
 
29 
 
 Yes 
 No 
 
30 
 
 Yes 
 No 
 
 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 4. Screening Log 
 
Version:  June 23, 2017 
             CONFIDENTIAL  
              Page 2 of 3 
 
#  
Screen ID 
Met All Baseline Eligibility Criteria 
If no, list number for criterion not 
met 
1 
 
 Yes 
 No 
 
2 
 
 Yes 
 No 
 
3 
 
 Yes 
 No 
 
4 
 
 Yes 
 No 
 
5 
 
 Yes 
 No 
 
6 
 
 Yes 
 No 
 
7 
 
 Yes 
 No 
 
8 
 
 Yes 
 No 
 
9 
 
 Yes 
 No 
 
10 
 
 Yes 
 No 
 
11 
 
 Yes 
 No 
 
12 
 
 Yes 
 No 
 
13 
 
 Yes 
 No 
 
14 
 
 Yes 
 No 
 
15 
 
 Yes 
 No 
 
16 
 
 Yes 
 No 
 
17 
 
 Yes 
 No 
 
18 
 
 Yes 
 No 
 
19 
 
 Yes 
 No 
 
20 
 
 Yes 
 No 
 
21 
 
 Yes 
 No 
 
22 
 
 Yes 
 No 
 
23 
 
 Yes 
 No 
 
24 
 
 Yes 
 No 
 
25 
 
 Yes 
 No 
 
26 
 
 Yes 
 No 
 
27 
 
 Yes 
 No 
 
28 
 
 Yes 
 No 
 
29 
 
 Yes 
 No 
 
30 
 
 Yes 
 No 
 
 
 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 4. Screening Log 
 
Version:  June 23, 2017 
             CONFIDENTIAL  
              Page 3 of 3 
 
#  
Screen ID 
Met All Study Procedure Eligibility Criteria 
If no, list number for criterion not 
met 
1 
 
 Yes 
 No 
 
2 
 
 Yes 
 No 
 
3 
 
 Yes 
 No 
 
4 
 
 Yes 
 No 
 
5 
 
 Yes 
 No 
 
6 
 
 Yes 
 No 
 
7 
 
 Yes 
 No 
 
8 
 
 Yes 
 No 
 
9 
 
 Yes 
 No 
 
10 
 
 Yes 
 No 
 
11 
 
 Yes 
 No 
 
12 
 
 Yes 
 No 
 
13 
 
 Yes 
 No 
 
14 
 
 Yes 
 No 
 
15 
 
 Yes 
 No 
 
16 
 
 Yes 
 No 
 
17 
 
 Yes 
 No 
 
18 
 
 Yes 
 No 
 
19 
 
 Yes 
 No 
 
20 
 
 Yes 
 No 
 
21 
 
 Yes 
 No 
 
22 
 
 Yes 
 No 
 
23 
 
 Yes 
 No 
 
24 
 
 Yes 
 No 
 
25 
 
 Yes 
 No 
 
26 
 
 Yes 
 No 
 
27 
 
 Yes 
 No 
 
28 
 
 Yes 
 No 
 
29 
 
 Yes 
 No 
 
30 
 
 Yes 
 No 
 
 
 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 5. Screening Eligibility Criteria 
Version:  June 23, 2017 
 CONFIDENTIAL 
 Page 1 of 1 
Screening Inclusion Criteria 
1 
Signed Screening or Study Procedure Informed Consent using a form that was reviewed and approved by the IRB 
2 
Age 40 to 75 years 
3 
BMI less than 35 kg/m2 
4 
Stable with  less than 20 mg prednisone (or equivalent) qd 
5 
Nonsmoking for 4 months prior to screening interview 
Screening Exclusion Criteria 
6 
Currently enrolled in another clinical trial studying an experimental treatment 
7 
Previously enrolled in this study for which protocol required follow up is not complete 
8 
Clinically significant (greater than 4 Tablespoons per day) sputum production 
9 
Two or more COPD exacerbation episodes requiring hospitalization in the last year at screening 
10 
Two or more instances of pneumonia episodes in the last year at screening 
11 
Unplanned weight loss >10% usual weight <90 days prior to enrollment 
12 
History of exercise-related syncope 
13 
Myocardial Infarction or congestive heart failure within 6 months of screening 
14 
Prior lung transplant, LVRS, bullectomy or lobectomy 
15 
Clinically significant bronchiectasis 
16 
Unable to safely discontinue anti-coagulants or platelet activity inhibitors for 7 days 
17 
Uncontrolled  pulmonary hypertension (systolic pulmonary arterial pressure > 45 mm Hg) or evidence or history of 
CorPulmonale as determined by recent echocardiogram (completed within the last 3 months prior to screening visit) 
18 
Pulmonary nodule requiring surgery as noted by chest X-ray or CT scan 
19 
HRCT collected per CT scanning protocol within the last 3 months of screening date and evaluated by clinical site personnel 
using 510k cleared CT software shows: 
a 
Parenchymal destruction score of greater than 75% in all three right lobes or both left lobes 
b 
Emphysema heterogeneity score less than 15% (Not Applicable for Crossover subjects as of Revision H of 
protocol) 
c 
Large bullae encompassing greater than 30% of either lung 
d 
Insufficient landmarks to evaluate the CT study using the software as it is intended 
20 
Left ventricular ejection fraction (LVEF) less than 45% as determined by recent echocardiogram (completed within the last 3 
months prior to screening visit) 
21 
Resting bradycardia (<50 beats/min), frequent multifocal PVCs, complex ventricular arrhythmia, sustained SVT 
22 
Dysrhythmia that might pose a risk during exercise or training 
23 
Post-bronchodilator FEV1 less than 15% or greater than 45% of predicted value at screening 
24 
TLC less than 100% predicted (determined by body plethysmography) at screening 
25 
RV less than 175% predicted (determined by body plethysmography) at screening 
26 
DLCO less than 20% predicted value at screening 
27 
6-minute walk distance less than 100 meters or  greater than 450 meters at screening 
28 
PaCO2 greater than 50mm Hg (Denver greater than 55 mm Hg) on room air at screening 
29 
PaO2 less than 45 mm Hg (Denver less than 30 mm Hg) on room air at screening 
30 
Elevated white cell count (>10,000 cells/mcL) at screening 
31 
Presence of alpha-1 anti-trypsin deficiency as determined by local laboratory ranges 
32 
Plasma cotinine level greater than 13.7 ng/ml (or arterial carboxyhemoglobin > 2.5% if using nicotine products) at screening 
33 
Any disease or condition that interferes with completion of initial or follow-up assessments 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 6.  HRCT Scan Acquisition Protocol 
Version:  June 23, 2017       
  CONFIDENTIAL 
 Page 1 of 6 
Overview of HRCT Data Collection 
 
HRCT acquired using Scan Acquisition Protocol 
Upon determining that the study candidate meets all screening and baseline eligibility criteria, 
site personnel will:  
a)
Complete the bronchoscopy plan
b)
Transmit screening HRCT scan data to the core reading laboratory
45-day and 1-year follow-ups* for Study Treatment Arm ONLY: 
a)
Acquire HRCT and transmit scan data to core reading lab
b)
Determine lobar volume change from baseline
c)
Evaluate EBV placement
d)
Apprise clinical site and sponsor of findings within 5 working days after the site transmits
the HRCT to the core reading lab
*Also 3-month follow-up for subjects with valve adjustment
Site personnel reviews TLC scan using sponsor-provided 510k cleared CT software to 
determine screening eligibility of the study candidate.  The study candidate is INELIGIBLE IF 
(s)he has: 
a)
Parenchymal destruction score >75% in all three right lobes or both left lobes;
b)
Emphysema heterogeneity score <15% (see Note for cross over subjects)
c)
Large bullae encompassing >30% of either lung
d)
Insufficient landmarks to evaluate the CT study using the software as it is intended
Site personnel will develop the bronchoscopy plan to: 
a)
Pre-identify target treatment lobes for assessing collateral ventilation
b)
Plan the EBV placement strategy (only to be performed during the
bronchoscopy if candidate meets study procedure eligibility and is randomly
assigned to study treatment)
NOTE:  HRCT scans should be submitted to the core reading lab as soon as possible 
after their acquisition 
For the first 5 candidates per site with conclusive (in)eligibility: export the 
CT analysis to CD and send to core reading laboratory for review 
CROSSOVER NOTE: Per Revision H of this protocol, the requirement of a heterogeneity score of 15% 
between lobes is not applicable for any remaining crossover subjects. The most diseased target can 
be treated regardless of heterogeneity, provided that the target lobe is collateral ventilation negative 
(CV-). 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 6.  HRCT Scan Acquisition Protocol 
 
Version:  June 23, 2017                         CONFIDENTIAL               Page 2 of 6 
 
Protocol for Acquiring HRCT Scans 
The scanning procedure described below will require approximately 15 minutes of 
the scanner time. Minimal respiratory motion and maximum accuracy and 
reproducibility are required for the duration of the scan.  In unusual cases, this may 
require more time. However, in many cases the procedure will be completed in 10 
minutes or less. 
Preparation of the Patient (3 minutes) 
Patients weighing more than 300 pounds (150 Kg) will not be scanned due to 
technical difficulties.  The technologist will ask women if they might be pregnant 
and will not scan them if they answer affirmatively.  The patient will lie in the supine 
position going head first into the CT gantry. 
Breath-Holding Instruction (3 minutes). 
The technologist will instruct the patient on the importance of breath-holding and 
immobility during scanning.  An interpreter will assist in the instruction of patients 
not fluent in English. Technologists will be trained to coach patients to attain 
reproducible maximum inspiratory breath-hold. To ensure that the breath-hold 
maneuver is performed as close to pulmonary function laboratory standards. The 
CT programmed auto-voice is never used; instead patients are coached prior to 
scanning as follows: 
For the TLC series: 
“Take your biggest breath in until you feel your lungs are completely full, in 
the same way you do in the lung function laboratory, and hold the breath.” 
For the RV series:  
 
For the RV Scan (Sequence #2), the patient should be coached with 
emphasis on instruction to blow all their air out.  The participant should be 
told “to take another big breath in to fill up their lungs and then to blow all 
the air out as hard and fast as possible without moving their body and then 
to squeeze all their air out until they feel that their lungs are completely 
empty and then they should signal that they are empty and hold their 
breath”.  This can be done by asking the patient to keep their toes apart at 
the beginning of the maneuver and to bring their toes together when they 
feel they are completely empty.  At this stage, the technologist should 
remind the subjects to hold their breath for the entire scan and start the 
scan. 
Only after the technologist is satisfied that the patient understands the importance 
of breath-holding should s/he proceed. 
 
 

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Clinical Investigational Plan #630-0012-H 
Appendix 6.  HRCT Scan Acquisition Protocol 
 
Version:  June 23, 2017                         CONFIDENTIAL               Page 3 of 6 
 
Checking the Scout Image (1 minute). 
The technologist will instruct the patient to take a deep breath in, and then to hold 
his/her breath (at end-inspiration) while acquiring anterior-posterior (A/P) and 
lateral scout image, beginning 10 mm above the sternal notch and ending 10 mm 
below the posterior costophrenic angle.  This will provide an A/P and lateral view 
of the chest on the image monitor at the operator console.  From this, the 
technologist will check patient centering and choose the position for the full chest 
scan. The table will be automatically moved to the start position.  The technologist 
will check patient and phantom positioning in the scout image. 
Imaging (6 minutes).   
Total imaging time will be approximately 6-19 seconds (depending on scanner 
generation and configuration). The technologist will instruct the patient to relax on 
the table while s/he reconstructs the images and assesses the adequacy of 
positioning, and lack of respiratory motion. 
Remember to keep consistent the selected FOV and table height for a patient 
at all study points.   
The imaging procedure involves the following mandatory sequence for all 
study patients:  
Supine, Full Chest at TLC 
In this sequence, thoracic CT will be performed with the patient in the supine 
position with arms above the head if possible. Image data will be acquired during 
suspended end inspiration (TLC). Images are non-gated and no intravenous 
contrast will be used.  Technical guidelines for thoracic CT image data 
acquisition will include: 
(a) TLC Scout: This series is to be acquired for planning the full chest CT and is to 
be acquired at TLC. 
(b) TLC Full Chest: Volumetric spiral studies will be performed through the entire 
chest at full inspiration.  
1. Breathing Instructions: Patient will be instructed to, “take a deep breath in 
until you feel your lungs are completely full, in the same way you do in the 
lung function laboratory.” 
2. Scanner Acquisition:  See Table 1.  Sample provided for each site; a 
protocol specific for chart will be provided.    
3. Anatomic Coverage:  Entire thorax (full chest).  Typically a ≤10 sec. 
acquisition on MDCT scanners. 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 6.  HRCT Scan Acquisition Protocol 
 
Version:  June 23, 2017                         CONFIDENTIAL               Page 4 of 6 
 
4. Dose Consideration: For the above scan the estimated dose is 2-3msv 
compared with conventional CT Chest of 5-7 msv.  
 
Supine, Full Chest at RV 
In this sequence, thoracic CT will be performed with the patient in the supine 
position with arms above the head if possible.  Image data will be acquired at 
residual volume (RV).  Images are non-gated and no intravenous contrast 
will be used.  Technical guidelines for thoracic CT image data acquisition will 
include: 
(a) RV scout – this series is to be acquired for planning the full chest CT and is 
to be acquired at RV. 
(b) RV Full Chest: Volumetric spiral studies will be performed through the entire 
chest using the same techniques as in Sequence 1 – except at residual 
volume: 10 mm collimation, pitch ≤ 1.5 reconstructed contiguously (i.e., every 
10 mm) using a standard reconstruction algorithm.   
1. Breathing Instructions:  The participant should be told “to take another big 
breath in to fill up their lungs and then to blow all the air out as hard and 
fast as possible without moving their body and then to squeeze all their air 
out until they feel that their lungs are completely empty and then they 
should signal that they are empty and hold their breath”.  This can be done 
by asking the patient to keep their toes apart at the beginning of the 
maneuver and to bring their toes together when they feel they are 
completely empty.  At this stage, the technologist should remind the 
subjects to hold their breath for the entire scan and start the san. 
2. Sample Acquisition (This will be tailored for each site based on available 
CT technology): Siemens Sensation 16 scanner, 120 kVp, 80 “effective” 
mAs, 0.5 sec rotation time, 16 x 0.75 mm collimation, 18 mm/rotation table 
feed (pitch 1.5); This will be specified for your site. 
3. Anatomic coverage:  Entire thorax (full chest).  Typically a ≤10 sec. 
Acquisition on MDCT scanners. 
4. Sample reconstructions  
i. Contiguous thick section – 10 mm thickness, 10 mm spacing, B30F 
reconstruction filter, Display Field of View of 35 cm (Typically 35 
images)  
ii. Overlapped thin section – 1.5mm thickness, 1 mm spacing, B50f 
reconstruction filter and DFOV = 35 cm (Typically 350 images). 
 
 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 6.  HRCT Scan Acquisition Protocol 
 
Version:  June 23, 2017                         CONFIDENTIAL               Page 5 of 6 
 
Table 1.   
Shaded fields are user input fields on the scanner console.  Other values are either calculated or 
derived from user inputs. 
Techniques for Siemens Sensation 16 
16-slice/0.5 sec  
Helical – Full Chest at TLC 
REQUIRED 
2.1.1.1 kV 
120 
2.1.1.2 Gantry Rotation Time 
0.5 sec 
2.1.1.3 mAs1 
(Regular 
patient-
Large patient values) 
80 – 100 
2.1.1.4 Collimation (mm)   
0.75 mm collimation 
2.1.1.5 Table 
incrementation 
(mm/rotation) – I 
18 mm 
2.1.1.6 Detector Collimation (mm) 
– T 
0.75 mm 
2.1.1.7 Number of active channels 
– N 
16 
2.1.1.8 Detector Configuration – N 
x T 
16 x 0.75 mm 
2.1.1.9 Pitch ([mm/rotation] /beam 
collimation) – I/NT 
1.5 
2.1.1.10 
Table 
Speed 
(mm/sec) 
36 mm/sec 
2.1.1.11 
Scan Time (40 cm 
thorax) 
12 sec 
2.1.1.12 
REQUIRED 
Reconstructed Thin Slice Width 
1.5 mm 
2.1.1.13 
REQUIRED 
Thin 
Slice Reconstruction Interval 
0.8 mm 
2.1.1.14 
REQUIRED Thick 
Slice Reconstruction Interval 
5.0mm 
2.1.1.15 
REQUIRED 
Thin 
and Thick Slice Reconstruction 
Algorithm 
B45f 
2.1.1.16 
REQUIRED 
# 
Images/Data set (40 cm) thin/thick 
500/60  
1 – Siemens Scanners use the term “effective mAs”  which is really [(mA*time)/Pitch].  Sites should enter the value in the 
mAs row at their scanner. 
Definitions 
T = Z axis collimation, or width of one data channel.  In multi-detector CT scanners, several 
detector elements maybe grouped together to form one data channel. 
N = # data channels, or the actual number of data channels used during an acquisition. 
I = Increment, or the table increment per rotation of the x-ray tube in a helical scan. 
Table 2.   

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 6.  HRCT Scan Acquisition Protocol 
 
Version:  June 23, 2017                         CONFIDENTIAL               Page 6 of 6 
 
Shaded fields are user input fields on the scanner console.  Other values are either calculated or 
derived from user inputs. 
Techniques for Siemens Sensation 16 
16-slice/0.5 sec  
Helical – Full Chest at RV 
REQUIRED 
2.1.1.1 kV 
120 
2.1.1.2 Gantry Rotation Time 
0.5 sec 
2.1.1.3 mAs1 
(Regular 
patient-
Large patient values) 
80 – 100 
2.1.1.4 Collimation (mm)   
0.75 mm collimation 
2.1.1.5 Table 
incrementation 
(mm/rotation) – I 
18 mm 
2.1.1.6 Detector Collimation (mm) 
– T 
0.75 mm 
2.1.1.7 Number of active channels 
– N 
16 
2.1.1.8 Detector Configuration – N 
x T 
16 x 0.75 mm 
2.1.1.9 Pitch ([mm/rotation] /beam 
collimation) – I/NT 
1.5 
2.1.1.10 
Table 
Speed 
(mm/sec) 
36 mm/sec 
2.1.1.11 
Scan Time (40 cm 
thorax) 
12 sec 
2.1.1.12 
REQUIRED 
Reconstructed Thin Slice Width 
1.5 mm 
2.1.1.13 
REQUIRED 
Thin 
Slice Reconstruction Interval 
0.8 mm 
2.1.1.14 
REQUIRED Thick 
Slice Reconstruction Interval 
5.0mm 
2.1.1.15 
REQUIRED 
Thin 
and Thick Slice Reconstruction 
Algorithm 
B45f 
2.1.1.16 
REQUIRED 
# 
Images/Data set (40 cm) thin/thick 
500/60  
1 – Siemens Scanners use the term “effective mAs”  which is really [(mA*time)/Pitch].  Sites should enter the value in the 
mAs row at their scanner. 
Definitions 
T = Z axis collimation, or width of one data channel.  In multi-detector CT scanners, several 
detector elements maybe grouped together to form one data channel. 
N = # data channels, or the actual number of data channels used during an acquisition. 
I = Increment, or the table increment per rotation of the x-ray tube in a helical scan. 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 7.  Baseline Eligibility Criteria 
Version:  June 23, 2017                         CONFIDENTIAL               Page 1 of 1 
 
 
Study Candidate Selection – Baseline Eligibility Criteria 
Baseline Inclusion Criteria 
1 
Completed a supervised pulmonary rehabilitation program less than equal to 6 months prior to the baseline exam or 
is regularly performing maintenance respiratory rehabilitation if initial supervised therapy occurred greater than 6 
months prior 
2 
Baseline evaluation occurred ≤ 120 days after screening exam 
3 
Signed written informed consent to participate in study using a form that was reviewed and approved by the IRB 
4 
Continued nonsmoking between initial screening and baseline exams 
5 
Willing and able to complete protocol required study follow-up assessments and procedures 
6 
FEV1 between 15% and 45% of predicted value at baseline exam 
7 
Post-rehabilitation 6-minute walk distance between 100 meters  and 500 meters at baseline exam 
8 
Current Pneumococcus vaccination 
9 
Current Influenza vaccination 
Baseline Exclusion Criteria 
10 
Myocardial infarction or diagnosis of congestive heart failure between screening and baseline exams 
11 
Fever or other clinical evidence of active infection at baseline exam 
12 
Two or more COPD exacerbation episodes between screening and baseline exams 
13 
Two or more pneumonia episodes between screening and baseline exams 
 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 8.  Example Informed Consent:  Study Participation 
 
Version:  June 23, 2017 
             CONFIDENTIAL  
              Page 1 of 17 
 
 
 
Investigator Name: ________________ 
 
Site ID#___________________ 
Institution: _______________________ 
 
Participant ID: ______________ 
________________________________ 
________________________________ 
 
Telephone: _________________ 
 
Dear Patient: 
 
You are being invited to participate in a clinical study involving research.  This Informed Consent Letter 
describes the study and your role as a participant.  If you choose to consider taking part in the study you 
must read this form carefully. You are urged to discuss any questions you have about the study with 
your physician and/or the hospital’s research staff.   
 
Persons who participate in a research study are entitled to certain rights.  These rights include, but are 
not limited to, your right to: 
 
• Be informed of the nature and purpose of the medical experiment (ie. study); 
• Be given an explanation of the procedures to be followed in the study, and information about the 
drugs or devices to be used; 
• Be given a description of any discomforts and risks that are reasonable to expect; 
• Be given an explanation of any benefits that are reasonable to expect; 
• Be given information about other appropriate treatments that might be given to you and information 
about their risks and benefits; 
• Be informed of the medical treatments, if any, that are available to you if complications should arise 
after the investigational (ie. study) procedure;  
• Be given an opportunity to ask questions concerning the study or the procedures involved in the 
study; 
• Be informed that you may withdraw your consent to participate in the study at any time; 
• Be given a copy of the consent form you signed;  
• Be given the opportunity to decide for yourself whether or not you should consent to take part in the 
study. 
 
 
Purpose of the Study 
Since you are being asked to participate in this study, you have probably suffered an impaired lifestyle 
as a result of emphysema.  Emphysema is a serious disease afflicting more than four million people 
worldwide.  It is one form of Chronic Obstructive Pulmonary Disease, or COPD.  Emphysema causes 
the lungs to lose the ability to move air in and out normally and to efficiently absorb oxygen. Eventually, 
breathing becomes more difficult as damaged parts of the lungs trap air. As the disease advances, the 
damaged, inelastic areas of the lung progressively expand within the chest cavity, leaving one constantly 
feeling out of breath. 
 
Lung volume reduction surgery (LVRS) has been shown to offer relief to patients suffering from 
emphysema.  With LVRS, some of the diseased portions of the lungs are removed.  This allows the 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 8.  Example Informed Consent:  Study Participation 
 
Version:  June 23, 2017 
             CONFIDENTIAL  
              Page 2 of 17 
 
remaining lung tissue to function better.  Other surgical procedures like plication (folding) and stapling 
of lung tissue, which are done without surgically removing parts of the lung, have been seen to have 
results similar to LVRS.  These results suggest that removal of damaged lung tissue is not necessary and 
that a process that gets rid of the trapped air in the damaged regions of the lungs should work in the 
same way.   
 
The purpose of this research is to study a medical device that is designed to produce lung volume 
reduction.  This device is called the Pulmonx Endobronchial Valve (EBV).  The EBV is a one-way 
valve that blocks off the diseased lung section to inhaled air but lets the trapped air already inside the 
area escape.  With placement of the EBV, the diseased part of the lung collapses; this allows the 
healthier parts of the lung to expand.  The EBV is considered experimental.  This means that it has not 
yet been approved by the U.S. FDA (Food and Drug Administration) for commercial use in the United 
States. 
 
The EBV can be placed by a doctor in a diseased section of the lungs using bronchoscopy.  
Bronchoscopy is a way to access your lungs using a small tube with a camera on the end.  With 
bronchoscopy, your physician can reach the airways in your lung by passing the tube through either your 
mouth or nose.  Use of bronchoscopy for performing lung volume reduction may have fewer risks than 
surgery and have reduced recovery time.  This study is designed to investigate the safety and 
effectiveness of the Pulmonx EBV for treating your emphysema symptoms as compared to a standard 
medical therapy program alone.   
 
 
Number of Patients in the Study 
Approximately two hundred (200) patients will be enrolled into this study. In order to qualify for 
enrollment into this study, you must undergo a bronchoscopy procedure.  During the bronchoscopy 
procedure, your doctor will measure some of the airways in your lungs using a device that measures 
airflow to find out if you meet the study criteria for having the EBV treatment.  There is a chance that 
after measuring some of airways in your lungs you will not be eligible to take part in this study.   
 
During the bronchoscopy procedure, one hundred and eighty-three (183) patients will be found to 
qualify for the study.  The 183 patients who qualify for the study will be randomly assigned to the study 
treatment.  Approximately two-thirds will be randomly assigned to the EBV treatment group and have 
EBV implanted in their lungs and approximately one-third will be randomly assigned to the control 
group and not have EBV implanted in their lungs.  This means that during the bronchoscopy procedure 
if you are found to be eligible to participate in the study, you will have a 2 in 3 chance of receiving EBV 
and a 1 in 3 chance of not receiving EBV.   
 
 
Tests and Evaluations 
If you agree to participate in the study, the following tests and assessments will be performed.  Most or 
all of these are routine medical assessments.  If you should feel dizzy, or have chest pain, palpitations, 
nausea, severe difficulty breathing or wheezing, during any of the following testing, please tell your 
healthcare professional immediately.  
 
Blood Gas (PaO2 and PaCO2) and Blood Chemistry Analysis 
A blood sample will be taken to measure the amount of oxygen and carbon dioxide in the sample.  
This blood sample will need to be taken from an artery (as opposed to a vein).  An arterial blood 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 8.  Example Informed Consent:  Study Participation 
 
Version:  June 23, 2017 
             CONFIDENTIAL  
              Page 3 of 17 
 
sample may be more painful than a venous blood sample, which is usually done for more routine 
blood samples.  Standard compounds and the number of blood cells will also be measured from the 
blood sample.  You must have stopped smoking for at least 4 months to participate in this study.  A 
blood test will be performed to confirm that you have stopped.  It is important that you do not smoke 
during this study.  
 
Chest X-ray 
During this test, a simple X-ray will be made of your chest.  
 
Echocardiogram 
An echocardiogram will be done to assess your heart’s function.  An echocardiogram is a test that 
uses sound waves to create a moving picture of the heart. The picture is much more detailed than a 
plain x-ray image and involves no radiation exposure. 
 
Fluoroscopy 
Fluoroscopy is used to make a moving picture of your chest.  In rare instances, fluoroscopy may be 
used by your study doctor if it is difficult for him/her to see your lung structures and anatomy using 
the bronchoscope alone.   
 
Electrocardiography (ECG) 
During this test, small electrodes will be attached to your skin in several places and measurements 
will be taken of your heart rhythm and blood flow in and out of your heart.   
 
Lung Function Tests  
Spirometry: During the test, you will be asked to breathe in and out of a mouthpiece while a machine 
measures the amount of air you are breathing into and out of your lungs.  These breathing maneuvers 
may be somewhat difficult and you may become tired during the test but you will be allowed to rest 
periodically.   
 
Plethysmography: This test is used to determine how much air you can hold in your lungs.  You will 
sit in a small box, comparable to the size of a telephone booth, to undergo breathing tests similar to 
those described above. There is a chance that you may experience claustrophobia in addition to 
fatigue.  
 
Diffusing Capacity:  This test is used to measure the ability of your lungs to transfer carbon  
monoxide.  You will be asked to breathe a mixture of helium, oxygen, nitrogen and carbon 
monoxide and hold your breath for 10 seconds. All together these lung function tests will take about 
90 minutes.   
 
HRCT (High Resolution Computed Tomography) of Chest 
You will be asked to lie down on your back on an x-ray table that will slide into a large, tunnel-
shaped machine.  You must not move during the test and will be asked to relax and breathe 
normally. The technician will also ask you to do some breathing maneuvers such as take a deep 
breath in or out.   
 
Pregnancy Test 
If you are a woman of child-bearing potential, a urine or blood pregnancy test may be performed.  

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 8.  Example Informed Consent:  Study Participation 
 
Version:  June 23, 2017 
             CONFIDENTIAL  
              Page 4 of 17 
 
 
Six Minute Walk Test 
You will be asked to walk back and forth between a start and end point as many times as possible 
within 6 minutes. You may stop and rest if needed.  Right before and right after the test you will be 
asked questions about how breathless you feel you are.  
 
Questionnaires 
During the study, you will be asked to complete a few simple questionnaires. These questionnaires 
will ask you about your daily activities and your opinion about your general health status and quality 
of life. You will also be asked about frequency of visits to health care providers, such as your regular 
physician, emergent care facilities, and the hospital. 
 
Pulmonary Rehabilitation Program—to be Eligible for the Study 
In order to participate in this study, you will have:   
• Successfully completed a supervised pulmonary rehabilitation program within the past 6 
months, or 
• Be regularly performing maintenance respiratory rehabilitation if you completed the 
pulmonary rehabilitation program more than 6 months ago.   
The supervised pulmonary rehabilitation program must have required you to attend at least 2 visits to 
the pulmonary rehabilitation center each week.  You will have to have documentation to show that 
you have attended at least 8 visits to the pulmonary rehabilitation center.  If you do not meet the 
criteria above, you will be offered an opportunity to complete a supervised pulmonary rehabilitation 
program as part of your participation in the study.  This supervised program will be paid for by the 
study sponsor and will be at no cost to you.   
 
 
 
Daily Diary 
At the baseline visit you will be given a paper based diary to answer some questions about your health 
and your pulmonary rehabilitation exercises.  You will be asked to complete the diary immediately 
before going to bed every night and it is expected to take you approximately 15 minutes each time.  The 
information that is recorded in the diary will be collected when you return for the bronchoscopy 
procedure.   
• Pulmonary rehabilitation program 
o You will be asked about how long you spent doing pulmonary rehabilitation exercises 
that day and how many exercises you did. 
• EXACT-PRO Questionnaire 
o You will be asked 14 questions about your COPD symptoms. 
• Health status changes 
o You will be asked if you’ve had any change to your medications, any emphysema 
symptoms, and whether or not your activities or lifestyle has changed from normal due to 
your emphysema symptoms.   
 
Description of the Study Treatment Groups 
 
Control Group 
All participants in this study will receive optimal medical therapy.  Optimal medical therapy consists of 
smoking cessation support, selected medications, pulmonary rehabilitation therapy, and oxygen 

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supplementation as medically necessary.  After their 1-year follow-up visit, control group participants 
may be eligible to receive the EBV treatment if they continue to meet study criteria.  If they receive 
EBV treatment, these participants will be followed up according to the same visit schedule as the initial 
EBV treatment group.     
 
EBV Treatment Group 
In addition to optimal medical therapy, the EBV treatment group will undergo bronchoscopic lung 
volume reduction using the Pulmonx EBV.   
 
 
Description of the Bronchoscopy Procedure 
During the bronchoscopy procedure, your physician will measure some of the airways in your lungs 
using a device called the Chartis® Pulmonary Assessment System.  This system is designed to measure 
air pressure and flow in lung airways.  The air pressure and flow measurements that are collected using 
the Chartis System will help the physician decide if you are eligible to potentially have the EBV 
treatment. Your physician will plan the areas that will be measured before the day of the bronchoscopy 
procedure using the results of your CT scan.      
 
If you are found to have air pressure and flow measurements that show you are NOT eligible to receive 
the EBV treatment, your physician and his or her team will stop the bronchoscopy procedure and you 
will not receive any further treatment during the bronchoscopy procedure.  
 
If you are found to have air pressure and flow measurements that show you are eligible to receive the 
EBV treatment, you will be randomly assigned to either the EBV treatment group or the control group.  
If you are randomly assigned to the EBV treatment group, you will have the EBV treatment.  If you are 
randomly assigned to the control group, you will not receive any further treatment during the 
bronchoscopy procedure.        
 
Personnel from the study sponsor (Pulmonx) will attend your bronchoscopy procedure.  The doctor’s 
view of the procedure (the inside of your lung) may also be videotaped or photographed.    
 
 
Description of the Study Procedure  
 
The EBV Procedure 
A bronchoscope (a tube with a camera at the tip, connected to a monitor) will be guided down an access 
tube all the way to the point where the EBV will be placed.  Once your physician can clearly see the area 
where the EBV will be placed, he or she will guide a catheter (flexible tube), with the EBV attached, to 
the targeted treatment area.  Once the catheter is in the proper position, he or she will implant the EBV 
in the lung. This may be done several times depending upon how many EBV are to be placed in your 
lungs.   
 
If there is a problem with the EBV at any time during or after the procedure that makes it difficult or 
inappropriate to continue with the study, your physician may remove the EBV.  In some cases, if the 
EBV is removed, it can be replaced.  In rare cases, the EBV may not have been placed in the original 
procedure as it was intended to be (to completely stop the airflow from the damaged part of the lung).  
This may initiate a discussion between you and your physician about having another procedure to adjust 
the placement of the EBV.    

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After the Bronchoscopy Procedure 
After the procedure, you will be taken to a recovery area of the hospital.  If you are in the control group 
(did not receive the EBV) or were found to not be eligible for the study, you will be allowed to go home 
a few hours after the bronchoscopy procedure.  If you had EBV placed (are in the study treatment 
group), you will be required to remain in the hospital for 5 nights.  Before you are discharged your study 
physician will examine you first and review your chest x-ray to confirm you are not experiencing any 
complications.  Your study physician may keep you in the hospital longer if he/she feels your health 
needs further monitoring.  
 
If you received the EBV, a chest x-ray will be taken at 1 hour and once each day during your 
hospitalization including the day you are discharged.  You may need to have additional x-rays at any 
time your study physician thinks it is medically necessary.  The nurses in this area are trained to closely 
watch your recovery and assist you in awakening from the anesthesia.  Your vital signs will be 
monitored, blood samples will be collected and any adverse events will be reviewed during your 
hospitalization.  The medical team will often encourage you to cough in order to help expel the 
anesthesia and any accumulation of mucus.  You may also experience the urge to cough.  This coughing 
sensation is normal and typically goes away.   
 
Before discharge from the hospital, you will be given a study bracelet to wear and a medical alert card to 
give to any physician that may need to treat you informing him/her of the pneumothorax risk.  
Additionally, you will be given post-discharge instructions by the study physician that you will be 
expected to follow.  
 
After Discharge (For the EBV Treatment Group) 
 
You will return to your study physician’s office 7 days after discharge for an examination, chest X-ray, 
and to answer questions about your health status.  At the 7 Day after Discharge visit, your study 
physician will examine you and ask you about potential symptoms of pneumothorax and about your use 
of medications.  A chest x-ray will be taken of your lungs at this time.  At this visit, the study doctor will 
assess you to determine if you may resume your regular activities and start the pulmonary rehabilitation 
program.   
 
After you are discharged from the hospital, you will be contacted once daily for 10 days to answer 
questions about your health status.  
 
 
After Discharge (For the EBV Treatment and Control Groups) 
 
Pulmonary Rehabilitation after the Bronchoscopy Procedure 
Within 30 days after the bronchoscopy procedure, you will be asked to begin a supervised pulmonary 
rehabilitation program.  It will consist of 20 sessions, to be done 2-3 times a week for 7-10 weeks.  Each 
pulmonary rehabilitation session will consist of endurance training and strength training for your upper 
and lower limbs.   
 
After you have completed the supervised pulmonary rehabilitation program you will be expected to do a 
home-based maintenance program which will be described to you by your pulmonary rehabilitation 

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specialist.  As soon as you are done with the supervised program you will be encouraged to follow this 
home-based program at least three times a week.  For the study, you should continue this program until 
at least your 1 year follow-up visit.   
 
Daily Electronic Diary 
From the first day after the bronchoscopy procedure until your 1 year follow-up visit, you will be 
expected to complete an electronic diary to answer some questions about your health and your 
pulmonary rehabilitation exercises.  You will be asked to complete the diary immediately before going 
to bed every night and it is expected to take you approximately 15 minutes each time.  The information 
that is recorded in the electronic diary will be collected at each of your study visits (up to your 1 year 
follow-up).  The study staff will remind you to bring your electronic diary to your visits.   
• Pulmonary rehabilitation program 
o You will be asked about how long you spent doing pulmonary rehabilitation exercises 
that day and how many exercises you did. 
• EXACT-PRO Questionnaire 
o You will be asked 14 questions about your COPD symptoms. 
• Health status changes 
o You will be asked if you’ve had any change to your medications, any emphysema 
symptoms, and whether or not your activities or lifestyle has changed from normal due to 
your emphysema symptoms.   
 
Length of the Study and Patient Evaluations 
The results of the study will be evaluated after all of the study participants have made the 1-year visit.  
For study participants who have EBV, they will be expected to continue coming to the research clinic 
once a year up through 5 years.  In this study, you will be evaluated several different times.  The 
following table outlines the tests and assessments, starting at the bronchoscopy procedure visit, that will 
be performed and when they will be performed.  Depending on the hospital where you have the 
procedure, some of these tests are standard for emphysema treatment and some are not.   
 
Table 1.  Follow-up Tests and Assessments 
Test or Assessment 
7 days 
after 
dis-
charge 
Daily 
phone 
contact 
over 
10 
days* 
30 
days 
45 
days 
3 
months 
6 
months 
9 
months 
1 
year 
Annual 
visits  
(2-5 
years) 
Early 
Termination 
Visit  
Physical Exam 
X^ 
 
X^ 
X 
X 
X 
 
X 
 
X 
Medications & Events 
Review 
 
 
 
X 
X 
X 
X 
X 
 
 
X-ray 
X^ 
 
X^ 
X^ 
 
 
 
 
 
 
Blood Work 
 
 
 
 
 
 
 
X 
 
 
Lung function  
 
 
 
X 
 
X 
 
X 
X 
X 
6 minute walk distance test 
 
 
 
X 
 
X 
 
X 
 
 
Quality of life surveys 
 
 
 
X 
X 
X 
X 
X 
 
 
Health Care Utilization 
 
 
 
 
X 
X 
X 
X 
 
 
CT scan‡ 
 
 
 
X^ 
‡ 
 
 
X^ 
 
 
 
 
 
 
 
 
 
 
 
 
 
Daily Diary 
Complete the daily diary every day before going to bed at night starting on the first day after the 
bronchoscopy procedure until the 1 year follow-up visit.  Bring the diary to every follow-up visit. 

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*You will be contacted at this interval by phone unless you are already being seen by your physician or you are still in the 
hospital.   
‡Study participants who undergo the study treatment will have a CT scan at 45 days and 1 year. For study participants who have 
a study procedure (valve) adjustment, a CT scan will be collected at 3 months too.   
†It is expected that study participants will complete the daily diary at home every day before bedtime starting right after 
discharge from the hospital after the bronchoscopy procedure through the 1 year follow-up (approximately 365 days).   
^EBV treated study participants only.   
   
 
Random Assignment to the Control Group 
If you are randomly assigned to the control group you potentially have the opportunity to receive the 
study treatment after you complete the 1-year follow up visit for the study. 
 
Summary of Knowledge about Lung Volume Reduction using the EBV 
The Pulmonx EBV device and procedure was tested extensively in laboratories and animals prior to 
clinical testing.  The EBV device and procedure are currently used outside of the United States, in some 
countries in Europe and Asia, as a standard treatment for emphysema patients.  The EBV was previously 
tested in the United States with a large study that included four hundred ninety-two (492) patients from 
both the United States and Europe.  The results of this large (VENT) study are discussed below. 
The Endobronchial Valve for Emphysema Palliation Trial (VENT study) was a multi-center, prospective, 
randomized, controlled study conducted in the United States and Europe to evaluate safety and 
effectiveness of endobronchial valve treatment (along with optimal medical management) compared to 
optimal medical management alone (control group).  In the U.S. study, the endobronchial valve treatment 
was found to improve forced expiratory volume in one second (FEV1) by an average value of 6.8% and 
the 6 minute walk distance test results by an average value of 5.8%.  These results were significantly better 
than the results seen with medical management alone.   The European patients had similar results.   
After the VENT study was finished, the data was further analyzed.  We found that patients who showed 
signs that the airflow in some parts of their lungs could be blocked off, had the best results with the EBV 
and procedure.  For the study you are considering taking part in, we are planning to select patients who 
show these same signs BEFORE they have the study treatment.  This will be done using the Chartis System 
during the bronchoscopy procedure.  At the end of the study, we will then compare the results of the EBV 
treatment to the control treatment.   
 
In the VENT study, some adverse events were seen. The type of major adverse events and the 
percentage of patients who had them are shown below:   
 
Table 2.  Adverse events that were seen through 90 days in the EBV Treatment Group in VENT Study  
 
Event 
% of 
Patients  
COPD exacerbation (without hospitalization) 
7.9% 
   COPD exacerbation (with hospitalization) 
1.4% 
Hemoptysis (coughing up any amount of blood)   
5.6% 
   Massive Hemoptysis (coughing up a large amount of blood) 
0.5% 
Valve expectoration, aspiration, migration (valve moved from the place it was put by 
the physician) 
4.7% 

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Event 
% of 
Patients  
Pneumonia  
2.3% 
   Pneumonia (distal, or behind, the valve) 
0.9% 
Formation of bronchial granulation (scab-like) tissue with valve  
2.3% 
Pulmonary infection (infection in the lung) 
1.9% 
Respiratory failure (poor lung function--too much carbon dioxide or too little oxygen in 
your blood--where you need to have assistance with breathing using a mechanical 
ventilator) 
1.4% 
Pneumothorax (air leak in the lung)  that required treatment for more than 7 days 
1.4% 
Pneumothorax (air leak in the lung) that expanded, or got larger 
1.4% 
Pneumothorax (air leak in the lung) that was stable, or stayed the same size 
1.4% 
Hypoxemia (decreased oxygen in the blood) 
1.4% 
Hypercapnia (excess carbon dioxide in the blood) 
0.9% 
Death 
0.9% 
Noncardiac chest pain 
0.5% 
Bronchial (airway) trauma 
0.5% 
 
 
Removal of the EBV in the VENT Study 
In some instances, patients enrolled in the valve treatment study group who experienced an adverse 
event required that the valves be removed.  In the U.S. VENT study, 31 (14.5%) patients had valve(s) 
removed after the procedure. The reasons for removal included:  valve migration, pneumonia, bleeding 
(hemoptysis), granulation, increased dyspnea (breathlessness), continuing COPD exacerbations, and 
patient request.      
 
Alternative Treatments for Emphysema 
Oxygen, drug therapy, nutrition and lifestyle changes are the standard therapies for patients with 
emphysema.   An additional alternative treatment may be Lung Volume Reduction Surgery (LVRS).   
 
Summary of Benefits and Risks of Participation in the LIBERATE Study 
As the EBV is still an investigational device in the United States, the actual benefits and risks are 
unknown at this time.  The investigators may learn from this study whether the EBV treatment and 
procedure is safe and effective.  There may or may not be direct benefit from your participation in this 
study.  
 
Potential Benefits 
Potential benefits you may experience as a participant in the study include having improved lung 
function and other improvements that may be associated with improved lung function, such as improved 
quality of life.  If it is determined that control group participants still meet study eligibility criteria and it 
seems clinically appropriate for them after their 1-year follow-up visit, the study sponsor will pay for 
these participants to undergo the EBV and bronchoscopy procedure.      

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Potential Risks 
The primary risks associated with use of the Pulmonx EBV are similar to other bronchoscopic and 
surgical procedures used to treat emphysema.  These are listed below.  While this list is comprehensive, 
there may be other risks that are still unknown.  The close monitoring that you will receive, as part of the 
study, should allow for detection of symptoms, should they be present.  This, in turn, should allow for 
early intervention by your physician if that is necessary.  Your physician will review all of the risks 
below with you so that you understand them.   
 
Previous clinical trial experience and experience from other countries around the world, where the EBV 
device is commercially available, has shown that in some people EBV treatment is associated with 
having a pneumothorax as a potential complication. A pneumothorax is a condition in which air leaks 
from the lung into the space between the lung and chest wall. This prevents the healthy lung from 
working well and can cause chest pain and shortness of breath.  As many as 1 in 5 patients may 
experience a pneumothorax after the study procedure. Most of these tend to occur in the early period 
following the valve placement and usually resolve after staying in hospital for a few days. Most 
frequently, a treatment using a small tube to drain out the air is required.  In rare cases, a pneumothorax 
may require a surgical intervention.  In addition, there is a chance that it can be a serious and life-
threatening complication.  
 
 
Potential Risks (Adverse Events)  
Acute bronchitis (inflammation or infection of the airways) 
Acute bronchospasm (spasm of the airway; may result in wheezing or increased shortness of breath) 
Acute respiratory distress syndrome (sudden, severe injury to lungs) 
Airway blockage due to implant migration 
Airway perforation (hole in the airway wall) 
Airway stenosis (narrowing) 
Anxiety 
Aphonia (difficulty talking) 
Aspiration (inhalation of vomit) 
Bowel function impairment 
Bronchial (airway) trauma or ulceration 
Chest pain 
COPD exacerbation (acute worsening of COPD symptoms) 
Death 
Depression 
Deep Vein Thromboembolism (DVT, blood clot) 
Dysphonia (hoarse or rough sounding voice) 
Empyema (presence of pus) 
Fever 
Formation of bronchial granulation (scab-like) tissue near the valve(s) 
Fractured Rib 
Headache 
Heart arrhythmias (irregular heartbeats) 
Heart Attack 
Heart failure (heart function is impaired; could result in increased breathlessness or fluid retention) 

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Hemoptysis (coughing up blood) 
Hemothorax (accumulation of blood between the lungs and the chest wall 
Iatrogenic injuries (injury caused by medical procedure) 
Impaired lung function 
Increased cough 
Increased dyspnea (shortness of breath) 
Increased hypercapnea (excess carbon dioxide in the blood) 
Increased hypoxemia (decreased oxygen in the blood) 
Infection  
Laryngospasm (throat spasm) 
Lethargy and disorientation 
Lung cancer or lung mass 
Nausea 
Pleural effusion (collection of fluid around the lungs) 
Pleuritis (inflammation of chest lining) 
Pneumonia 
Pneumothorax (air leak in the lung) 
Pulmonary shunting (uneven blood flow through the lung) 
Pulmonary embolism (a blood clot in the lung which can lead to chest pain and shortness of breath) 
Respiratory failure (poor lung function; could require you to have assistance with breathing using a 
mechanical ventilator) 
Septicemia (severe infection) 
Stroke or Transient Ischemic Attack (sudden temporary loss of neurological function) 
Valve expectoration, aspiration, or migration (valve moves from the place it was put by your 
physician) 
Vomiting 
Wheeze or whistling of valve 
 

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Other Potential Risks of Procedures that are Required by this Study 
 
Lung function and exercise tests.  You will be exerting yourself to your limits in these tests.  
Lightheadedness, dizziness, fainting, chest pain, irregular heartbeats, and rarely death have been seen 
during exercise tests.  You should inform the technicians or physicians if performing these tests makes 
you feel abnormal.  
 
Vein or artery blood tests.  The risks of drawing blood include temporary pain and discomfort and/or 
tenderness form the needle stick, redness, or bruising at the site, bleeding, fainting, and lightheadedness.  
While rare, there is a possibility of infection or a local blood clot with any procedure in which the skin is 
pierced by a needle.  
 
Radiation.  This study involves a radiation exposure from the CT scans and chest x-rays that is typical of 
other diagnostic tests using ionizing radiation.  There is a small chance that the study doctor may choose 
to use fluoroscopy during the bronchoscopy procedure to be able to see the EBV better than he/she can 
using the bronchoscope and this may expose you to some additional minimal radiation. The amount of 
radiation exposure received in this study is below the levels that are thought to result in a significant risk 
of harmful effects.  If you are especially concerned with radiation exposure, you should discuss this with 
your study doctor.   
 
Antibiotics.  Antibiotics will be provided to you around the time of the procedure and afterwards to 
minimize possible side effects.  All pharmaceutical drugs have side effects.  Antibiotics may also have 
side effects, including diarrhea, allergic reactions, and overgrowth of dangerous bacteria such as C. 
difficile which can result in a serious infection.  However, antibiotics are used routinely to treat COPD 
exacerbations.   
 
Anesthesia.  The side effects of moderate procedural sedation or general anesthesia medications and 
other medications required to perform bronchoscopy include, but are not limited to, allergic reaction, 
drowsiness, slurred speech, tremor, fatigue, low blood pressure, slowing of the heart rate, anxiety, 
confusion, dizziness, temporary loss of consciousness, and respiratory depression.  Trained medical 
professionals with extensive experience and expertise will administer the medications and will be 
responsible for your care during the course of the procedure.   
 
Echocardiogram.  If you have a transesophageal echocardiogram (TEE, as opposed to a transthoracic 
echocardiogram or TTE), some risks are associated with the medicine given to help you relax. For 
example, you may have a bad reaction to the medicine, problems breathing, and nausea (feeling sick to 
your stomach).  Your throat also might be sore for a few hours after the test. Rarely, the tube used 
during TEE causes minor throat injuries. 
 
Voluntary Participation and Study Withdrawal 
Decisions regarding whether or not you should participate in this study are entirely voluntary.  If you 
decide not to participate, you will not lose any benefits to which you are entitled, nor will you be denied 
access to other available treatments for emphysema.  You will receive the standard treatment and care 
normally provided by your physician. 
 
Information obtained in the operating room after anesthesia is given to you will affect whether or not 
you are eligible to receive treatment during the bronchoscopy procedure.  This will happen, for instance, 
if it is determined that the air pressure and flow measured in the airways in your lungs make you 

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ineligible to meet the study entry criteria or that the anatomy of your lung passageways does not allow 
the physician to place the EBV Implant.  In such an event, and if you are randomly assigned to the 
control group, will be sent to the recovery room without the valve treatment.   
 
Significant new findings discovered during the course of this study, which may affect your willingness 
to continue participating in the study, will be provided to you in writing.  You may withdraw your 
consent to participate in this study at any time without penalty or loss of benefits.  Also, your 
physician may terminate your participation if continuing participation does not appear to be in your best 
medical interest, or if Pulmonx, the study Sponsor, terminates the study. 
 
Precautions 
Within 30 days before and 30 days after participating in this study, you should not take part in any other 
research project.  This is to protect you from possible injury arising from excessive blood drawing, 
excess x-rays, and interactions with other research devices or drugs, or similar hazards. 
 
Pregnancy and Contraception (Birth Control) 
Pregnant women may not participate in this research study as the risk of the procedure on an embryo or 
unborn fetus is unknown.  Women of childbearing potential must actively utilize appropriate means of 
birth control to avoid becoming pregnant throughout the course of the study.  
 
Confidentiality 
Information derived from this study and from your medical record may be reviewed and photocopied by 
the Food and Drug Administration (FDA) and/or state and federal regulatory agencies and by the device 
manufacturer, Pulmonx Inc., with protection of confidentiality so far as permitted by applicable law.  
Information resulting from this study and from your medical record may be used for research purposes 
and may be published; however, you will not be identified by name in such publications.    
 
Financial Responsibility 
The costs of any routine medical care administered during the study will be the responsibility of you 
and/or your health insurer. For such routine costs, you will be responsible for any co-payments or 
deductibles required under your insurance. You are not, however, expected to absorb the cost of any 
medical care specifically required by participation in this study. The study Sponsor (Pulmonx) will pay 
for tests and procedures performed solely for the purpose of this study.   
 
Research Related Injury 
In the event that you believe participation in this research study has led to injury, contact your physician 
and he will review the matter with you. You should understand that neither _____________________ 
(hospital) nor the Federal Government has any programs to provide compensation for persons 
participating in research projects who may experience injury. However, necessary facilities, emergency 
treatment and professional services will be available to you. You should not expect anyone to pay you 
for pain, worry, lost income, or non-medical care costs that occur from taking part in this research study. 
No funds have been set aside by _________________ (hospital) to pay you in case of injury, nor will 
the study Sponsor provide direct compensation to patients in the event of an injury.  
 
Study Information at www.clinicaltrials.gov 
A description of this clinical trial will be available on the http:www.clinicaltrials.gov, as required by 
U.S. Law.  This web site will not include information that can identify you.  At most, the web site will 
include a summary of the results.  You can search this web site at any time.   

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Add Financial Compensation Section as Applicable 
This section is site specific – include financial compensation information as needed. 
 
Questions 
If you have any questions about the study, its procedures, risks or benefits, your alternatives or your 
rights, or if you experience a potentially research related injury you should contact your doctor. If you 
cannot reach your doctor, contact the alternate individual listed below. 
 
Physician Contact Information (24 hour): 
 
Name:  
______________________ 
 
Phone Number:______________________ 
Alternate Contact Information (24 hour): 
 
Name:  
______________________ 
 
Phone Number:______________________ 
 
 

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Authorization to Use and Disclose Health Information 
I agree to permit ____________________ (physician) and his/her staff (“Researchers”) to use and disclose 
health information that identifies me for the purposes described below.  I also agree to permit 
________________________ (hospital), my doctors, and my other health care providers to disclose health 
information in my medical records to the Researchers for the purposes described below.   
 
1. The health information that may be used and disclosed includes all information collected during 
the research described in this document and health information in my medical records that is 
relevant to the research described. 
2. The researchers and Pulmonx may use and share my health information to conduct research; 
disclose my health information to Pulmonx to confirm the research results; disclose my health 
information as required by law to representatives of government agencies and other persons who 
are required to watch over the safety, effectiveness and the conduct of the research; and remove 
from my health information my name and other information that could be used to identify me. 
3. Once information that could be used to identify me has been removed, the information that remains 
is no longer subject to this authorization and may be used and disclosed by the researchers and 
Pulmonx as permitted by law including for other research purposes. 
4. Once my health information has been disclosed to a third party, federal privacy laws may no longer 
protect it from further disclosure.  However, the researchers and Pulmonx agree to protect my 
health information by using and disclosing it only as permitted by me in this Authorization.  Also, 
no publication about the research will reveal my identity without my specific written permission.  
These limitations continue even if I revoke this Authorization.   
5. Please note that you do not have to sign this authorization, but if you do not, you may not be 
allowed to participate in this research study.  You may change your mind and revoke this 
authorization at any time.  However, if you revoke this authorization, you may no longer be 
allowed to participate in this research study.  Also, even if you revoke this authorization, the 
information already obtained may remain part of the research.  To revoke this authorization, you 
must write to: 
 
 
 
 
While the research is in progress, you will not be allowed to see your health information that is 
created or collected in the course of the research.  After the research is finished, however, you 
may see this information as described in (hospital) Notice of Information practices.     
 
6. This authorization does not have an expiration date. 
 
 
 
 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 8.  Example Informed Consent:  Study Participation 
 
Version:  June 23, 2017 
             CONFIDENTIAL  
              Page 16 of 17 
 
Informed Consent 
I, ___________________________________, the undersigned hereby consent to my involvement in the 
research project titled: Lung Function Improvement after Bronchoscopic Lung Volume Reduction 
with Pulmonx Endobronchial Valves used in Emphysema. 
1) The nature, purpose, and contemplated effects of the project, so far as it affects me, have been fully 
explained to my satisfaction by the research worker.  My consent is informed and given voluntarily. 
2) The details of the procedure proposed have also been explained to me. 
3) It has been explained to me that the purpose of this research project is to improve the quality of 
medical care, and that my involvement may not be of any benefit to me. 
4) I have been given the opportunity to have a member of my family or a friend present while the 
project is explained to me. 
5) I am informed that no information regarding my medical history will be divulged, other than that 
described in the consent form, and that my identity will be kept confidential in all published results 
of the study. 
6) I have been informed that my involvement in the project will not affect my relationship with my 
medical advisors in their management of my health.  I have also been told that I am free to withdraw 
from the project at any stage without prejudice for future treatment at this hospital, and if I so 
choose, I can ask for any information collected up to that point to be withheld from use in the 
research. 
7) I declare that all of my questions have been answered to my satisfaction. 
 
If I agree to participate in the research study and if my questions are answered, I should sign this form.  
If I wish to refuse to participate in the study, I may do so without any loss of medical care or benefits.  
Once I have consented, I still have the right to withdraw at any time.  To withdraw, all I have to do is 
complete the Revocation of Consent portion of the form below and provide to or simply tell Dr. 
________________________. 
 
I will be given a copy of this form to keep and to refer to as needed. 
 
Printed Name of Participant (or legal representative):  
 
 
 
 
 
 
 
 
Signature: 
 
 
 
 
 
 
Date:  
 
 
 
 
 
I declare that I have been present when the research study was explained to the above participant and I 
believe that the participant has an application and understanding of the explanation given. 
 
Witness: 
 
 
 
 
 
 
Date:  
 
 
 
 
 
 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 8.  Example Informed Consent:  Study Participation 
 
Version:  June 23, 2017 
             CONFIDENTIAL  
              Page 17 of 17 
 
 
 
 
REVOCATION OF CONSENT 
I hereby wish to WITHDRAW my consent to participate in the research proposal described above.  
Withdrawal WILL NOT jeopardize any treatment or my relationship with _________________ 
Hospital. 
 
Printed Name of Participant (or legal representative):  
 
 
 
 
 
 
 
Signature: 
 
 
 
 
 
 
Date:  
 
 
 
 
 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 9.  Bronchoscopy Procedure Planning:  Radiologic Identification of Target Treatment 
Lobe(s) 
Version:  June 23, 2017 
                         CONFIDENTIAL  
              Page 1 of 1 
 
 
 
Instructions:  Follow the procedure shown in the chart below to identify appropriate 
target lobes for study treatment.  Targeted lobes will be assessed for collateral 
ventilation during the bronchoscopy procedure using the Chartis System to determine 
whether the study participant meets the study procedure eligibility criteria.   
 
 
KEY 
DS = emphysema destruction score 
HS = emphysema heterogeneity score 
RUL = right upper lobe 
RML = right middle lobe 
RLL = right lower lobe 
LUL = left upper lobe 
LLL = left lower lobe 
Determine 
Emphysema Score of 
each Lobe using the    
-910 HU threshold
Left Lung
Target Lobe = LUL or LLL. All target 
lobes >50% emphysema score
Left Lung 
Heterogeneity
Right Lung
Target Lobe = RUL or (RUL + RML) or 
RLL. All target lobes >50% emphysema 
score
Right Lung 
Heterogeneity 
RUL – RML ≥ 15%
AND
RUL – RLL ≥ 15%
RUL =  Target
RLL – RML ≥ 15%
AND
RLL – RUL ≥ 15%
RLL =  Target
LUL – LLL ≥ 15%
LUL =  Target
LLL =  Target
LLL – LUL ≥ 15%
RUL – RLL ≥ 15% 
AND 
RML – RLL ≥ 15%
(RUL + RML) =  
Target
Is RML 
>50%?
(RUL + RML) =  
Secondary 
Target
Is RML 
>50%?
Note: Per Revision H of this protocol, the requirement of a 
heterogeneity score of 15% between lobes is not applicable 
for any remaining crossover subjects. The most diseased 
target can be treated regardless of heterogeneity, provided 
that the target lobe is collateral ventilation negative (CV-). 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 10.  Study Procedure Eligibility Criteria 
Version: June 23, 2017 
             CONFIDENTIAL  
              Page 1 of 1 
 
 
 
Study Candidate Selection – Study Procedure Eligibility Criteria 
Study Procedure Inclusion Criteria 
1 
Procedure occurs < 60 days following baseline exam 
2 
Continues to meet all screening and baseline eligibility criteria 
3 
Little or no collateral ventilation (CV-) as determined using the Chartis System 
Study Procedure Exclusion Criteria 
3 
Evidence of collateral ventilation (CV+) as determined using the Chartis System 
4 
Collateral ventilation could not be determined using the Chartis System   
5 
Collateral ventilation assessment was not conducted using the Chartis System 
 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 11.  Bronchoscopy Procedure Flow 
 
Version:  June 23, 2017 
             CONFIDENTIAL  
              Page 1 of 1 
 
 
 
 
 
 
Medications Management Prior to Bronchoscopy Procedure 
 See Clinical Investigation Plan, Section 11.1.1 
Assess CV of pre-identified target lobes using Chartis System to determine 
Study Procedure Eligibility  
Eligible for Study 
Control 
Proceed to post-procedure care and 
protocol-specified study follow-up visits 
Treatment 
Any of the pre-identified 
target lobe(s) identified as 
CV- 
All of the pre-identified 
target lobe(s) identified as 
CV+ 
CV assessment not 
conducted or CV could not 
be determined 
Not Eligible for Study 
Enrolled; Random Assignment 
OR 
OR 
Perform EBV (Study) 
Treatment 
OR 
Identify and document site personnel 
responsible for management of potential 
pneumothorax 

LIBERATE Study Clinical Investigation Plan #630-0012-H
Appendix 12.  Required Schedule for Tests and Procedures at Screening and Baseline
TESTING
Screen Eligibility Pre-Baseline 
Baseline Eligibility & 
Assessment
IMAGING
   Chest X-ray
   High Resolution CT Scan 
X
LUNG FUNCTION TESTING
   Spirometry
X
X
   Body Plethysmography
X
   Diffusing Capacity
X
EXERCISE TOLERANCE
   Six-Minute Walk Test
X
X
BASIC MEDICAL
   Medical History
X
   Vital Signs / Physical Exam 
X
X
   ECG
X
   Echocardiogram
X
   Review of Medications
X
X
BLOOD WORK
   Arterial Blood Gases (ABGs)
X
   Complete Blood Counts (CBCs)
X
   Alpha-1 Antitrypsin
X
   Plasma Cotinine or Arterial Carboxyhemoglobin
X
   Serum Fibrinogen
X
MEDICAL MANAGEMENT
   Pulmonary Rehabilitation
X
   Pneumococcal Vaccine
X
   Influenza Vaccine
X
HEALTH SURVEYS
   SGRQ
X
   MMRC
X
   BDI/TDI
X
   CAT
X
   SF-36
X
   EQ-5D
X
   Health Care Utilization
X
DAILY DIARY*
   PR Program Compliance
X
   Exact-PRO
X
   Health Status Change
X
*paper diary 
Version: June 23, 2017
Confidential
Page 1 of 4 

LIBERATE Study Clinical Investigation Plan #630-0012-H
Appendix 12.  Required Schedule for Follow Up Tests and Procedures CONTROL Subjects
TESTING
Day 0 - Bronchoscopy
45 Days
3 Months
6 Months
9 Months
1 Year
ET/EWD
LUNG FUNCTION TESTING
   Spirometry
X
X
X
X
   Body Plethysmography
X
X
   Diffusing Capacity
X
X
EXERCISE TOLERANCE
   Six-Minute Walk Test
X
X
X
BASIC MEDICAL
   Vital Signs / Physical Exam 
X
X
X
X
X
X
   Review of Medications
X
X
X
X
X
X
   Electrocardiography
X
   Pulse Oximetry
X
BLOOD WORK
   Arterial Blood Gases (ABGs)
X
X
   Complete Blood Counts (CBCs)
X
   Plasma Cotinine or Arterial Carboxyhemoglobin
X
   Serum Fibrinogen
X
X
MEDICAL MANAGEMENT
   Pulmonary Rehabilitation*
X
HEALTH SURVEYS
   SGRQ
X
X
X
   MMRC
X
X
X
   BDI/TDI
X
X
X
X
   CAT
X
X
X
X
   SF-36
X
   EQ-5D
X
   Health Care Utilization
X
X
X
X
DAILY DIARY**
   PR Program Compliance
X
X
X
X
X
   Exact-PRO
X
X
X
X
X
   Health Status Change
X
X
X
X
X
SAFETY
   Adverse Events
X
X
X
X
X
X
X
*starts within 30 days after bronchoscopy procedure; **daily diary recording to begin Day 1 after Bronchoscopy through 1 year follow up visit
Version: June 23, 2017
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LIBERATE Study Clinical Investigation Plan #630-0012-H
Appendix 12.  Required Schedule for Follow Up Tests and Procedures TREATED Subjects
TESTING
Day 0 - 
Index 
Procedure
Day 1 Day 2 Day 3 Day 4 Day 5 (or 
day of 
discharge)
Daily Phone 
Call (for 10 
days after 
discharge)*
Day 7 
After 
Discharge
30 
Days
45   
Days
3 
Months
6 
Months
9 
Months
1    
Year
2 
Years
3 
Years
4 
Years
5 
Years
ET/EWD
IMAGING
   Chest X-ray
X*
X
X
X
X
X
X
X
X
   Electrocardiography
X
   High Resolution CT Scan
X
X
LUNG FUNCTION TESTING
   Spirometry
X
X
X
X
X
X
X
X
   Body Plethysmography
X
X
   Diffusing Capacity
X
X
EXERCISE TOLERANCE
   Six-Minute Walk Test
X
X
X
BASIC MEDICAL
   Pulse Oximetry (first 24 hours after procedure)
X
   Vital Signs / Physical Exam 
X
X
X
X
X
X
X
X
X
   Symptom Checklist
X
X
   Review of Medications
X
X
X
X
X
X
X
BLOOD WORK
   Arterial Blood Gases (ABGs)
X
X
   Complete Blood Counts (CBCs)
X
   Plasma Cotinine or Arterial Carboxyhemoglobin
X
   Serum Fibrinogen
X
X
MEDICAL MANAGEMENT
   Pulmonary Rehabilitation**
X
HEALTH SURVEYS
   SGRQ
X
X
X
   MMRC
X
X
X
   BDI/TDI
X
X
X
X
   CAT
X
X
X
X
   SF-36
X
   EQ-5D
X
   Health Care Utilization
X
X
X
X
DAILY DIARY***
   PR Compliance
X
X
X
X
X
   Exact-PRO
X
X
X
X
X
X
X
X
X
X
X
X
X
   Health Status Change
X
X
X
X
X
X
X
X
X
X
X
X
X
SAFETY
   Adverse Events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
*chest x-ray within one hour (± 30 minutes)
**must receive PI approval to resume normal activities and the post-bronschoscopy pulmonary rehabilitation program; Pulmonary rehabilitation must be initiated within the first 30 days following the bronchoscopy procedure
***daily diary recording to begin Day 1 after Index Procedure through 1 year follow up visit
Version:  June 23, 2017
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LIBERATE Study Clinical Investigation Plan #630-0012-H
Appendix 12.  Required Schedule for Follow Up Tests and Procedures ADJUSTMENT
TESTING
Adjustment 
Procedure 
Visit
Day 1 
Day 2
Day 3
Day 4 
Day 5 (or 
day of 
discharge)
Daily Phone 
Call (for 10 
days after 
discharge)
Day 7 After 
Discharge
3 Months**
IMAGING
   Chest X-ray
X*
X
X
X
X
X
X
X
   High Resolution CT Scan
X
LUNG FUNCTION TESTING
   Body Plethysmography
X
BASIC MEDICAL
   Pulse Oximetry (first 24 hours after procedure)
X
   Vital Signs/Physical Exam
X
X
X
   Symptom Checklist
X
X
BLOOD WORK
   Arterial Blood Gases (ABGs)
X
   Serum Fibrinogen
X
SAFETY
   Adverse Events 
X
X
X
X
X
X
X
*Chest X-ray within one hour (± 30 minutes)**Study participants who undergo a valve adjustment procedure will resume the study mandated follow-up schedule after the 7-
Day Post-Discharge Visit following the the valve adjustment procedure, with the next planned clinic visit occuring at the 3 Month Visit after the initial study procedure. Study 
participants having a valve adjustment will undergo the testing required for all study treatment participants at the 3 Month Visit but will have additional testing consisting of CT 
scan, X-ray, and body plethysmography.
Version:  June 23, 2017
Confidential
Page 4 of 4

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 13.  Pulmonary Rehabilitation Program MOP 
Version:  June 23, 2017 
CONFIDENTIAL 
Page 1 of 8 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Post-Bronchoscopy  
Pulmonary Rehabilitation 
Manual of Operations 
 
 
 
 
 
 
 
 
 
 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 13.  Pulmonary Rehabilitation Program MOP 
Version:  June 23, 2017 
CONFIDENTIAL 
Page 2 of 8 
 
 
 
 
 
 
1.0 Background  
 
It is not the intent of the LIBERATE study sponsor to constrain study participants from 
taking part in a multidisciplinary PR program consisting of elements other than those 
delineated herein but rather to allow a uniform set of recommendations relative to a PR 
exercise program. The LIBERATE study PR program itself includes both an in-clinic 
element and a home-based maintenance element.   
 
 
2.0 Administrative Responsibilities 
 
Investigative Study Center Representative   
Each investigative study site will have a designated study representative(s) who is 
responsible for coordinating the care of study participants with the Pulmonary 
Rehabilitation (PR) centers.  For most study centers, this responsibility will reside with the 
study coordinator; however, the responsibility may be delegated to other qualified 
personnel at the study site. 
 
Pulmonary Rehabilitation Center Representative 
Each Pulmonary Rehabilitation center will have a designated representative(s) 
responsible for communicating with the investigative study center representative.  The 
designated PR representative will be responsible for ongoing coordination and 
communication with the designated Investigative Study Site Representative.   
 
 
  
3.0 Pulmonary Rehabilitation Center Qualifications 
 
The supervised PR program may be conducted at the investigative study site PR facility 
or at an off-site facility. The PR facilities utilized in the study should meet the qualifications 
outlined in this section.  
 
Personnel 
Each PR facility should have adequate staff. Staff members should include at a minimum: 
• A Licensed Physician and/or Registered Nurse  
• A Physical Therapist, Exercise Physiologist and/or Respiratory Therapist. 
 
Equipment 
The PR facility should have the following equipment in good working condition and readily 
available: 
 
 Supplemental Oxygen Source 
 Pulse Oximeter 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 13.  Pulmonary Rehabilitation Program MOP 
Version:  June 23, 2017 
CONFIDENTIAL 
Page 3 of 8 
 
 
 
 
 
 Heart Rate Monitor 
 Treadmill 
 Arm Ergometer 
 Free Weights, Therabands or other suitable forms of variable resistance. 
 
Training 
Training of each PR facility should consist of providing the facility with a copy of the 
LIBERATE Study protocol, including this Manual of Operations.   
 
Documentation 
Pulmonary Rehabilitation Facility Information Form 
This form is to be completed for each study participant and maintained in the study 
participant’s binder.  A copy of the form is attached to this manual as Appendix 13a. 
 
 
4.0 Pulmonary Rehabilitation Agreement 
 
It is anticipated that a Services Agreement will be executed between the investigative 
study site and the PR facility or the PR facility and the study sponsor.    
 
 
5.0 
Supervised In-Clinic Program 
 
The study participant’s initial visit to the PR facility should include the following elements: 
 
 A review of the Pulmonary Rehabilitation Patient Information sheet and any other 
educational materials relevant to PR education.  
 
 An assessment of the study participant’s need to take part in a smoking cessation 
program. If determined necessary, the PR facility is expected to aid and encourage 
the study participant’s attendance in such a program. 
 
 An initial assessment of the study participant’s physical condition including, at a 
minimum, the evaluation of: 
 
 Any physical limitations that may affect the selection of exercises to be 
performed. 
 Baseline characterization of strength and exercise tolerance. 
 Requirements for supplemental oxygen. 
 Establishment of specific PR exercise program and training for proper 
execution of each exercise maneuver. 
 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 13.  Pulmonary Rehabilitation Program MOP 
Version:  June 23, 2017 
CONFIDENTIAL 
Page 4 of 8 
 
 
 
 
 
Unless there are physical limitations, and in light of any limitations that exist, the PR 
exercise program is to consist of lower limb endurance training, upper limb endurance 
training, and lower and upper limb strength training.   
 
 
Sample Program 
 
Lower Limb Endurance Training 
Lower limb endurance training is recommended to be done on a treadmill or freely 
ambulating indoors or outdoors. The goal of the training is to exercise for at least 20 
minutes. Study participants may start at a lower duration and intensity and attempt to 
work up to this goal, with the starting level and progression guided by the therapist. If 
considered necessary by the therapist, oxygen saturation will be monitored during 
exercise. 
 
Upper Limb Endurance Training 
Upper limb endurance training consists of a group of exercises involving some form and 
level of resistance for each hand (e.g. dumbbells or Therabands).  Appropriate exercises 
will be selected by the therapist. The exercises should remain constant during the course 
of the program and should include a minimum of eight (8) individual exercises. A list of 
some examples of these exercises is provided below.  
 
Upper Limb Endurance Training Suggestions 
 
1. Punching bag 
2. Overhead scissors 
3. Pump the tire 
4. Windshield wipers 
5. Crawl stroke 
6. Backstroke 
7. Breaststroke 
8. Climb the mountain 
9. Arm jog 
10. Disco criss-cross 
 
The group of exercises should be performed as a set, one right after the other, with each 
exercise performed for the same length of time. The goal of this training is to gradually 
and continually increase tolerance to both duration of the exercise and resistance level 
over the course of the program.  The following general progression should apply: 
 
a. Select a resistance that can be tolerated while performing a complete set of 
exercises with a time of 20 seconds for each separate exercise.  
b. As the patient gets stronger, gradually increase the time for each exercise to a 
maximum of 90 seconds. 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 13.  Pulmonary Rehabilitation Program MOP 
Version:  June 23, 2017 
CONFIDENTIAL 
Page 5 of 8 
 
 
 
 
 
c. When a time of 90 seconds for each exercise is achieved, increase the level of 
resistance and restart with a time of 20 seconds for each exercise. 
 
Note: If the study participant is unable to perform unsupported arm exercises, an arm 
crank ergometer may be substituted at the therapist’s discretion. 
 
Lower and Upper Limb Strength Training 
Lower and upper limb strength training consists of a group of exercises involving some 
form and level of resistance (e.g. dumbbells or Therabands).  Appropriate exercises will 
be selected by the therapist. The exercises should remain constant during the course of 
the program and should include a minimum of eight (8) individual exercises. A list of 
suggested exercises is provided below.  
 
Lower and Upper Limb Strength Training Suggestions 
 
1. Chest butterfly (chest) 
2. Sit to stand from chair (legs) 
3. Side forward arm raise (shoulders) 
4. Seated knee extension (quadriceps) 
5. Sideward arm raise (shoulders) 
6. Seated march (hip flexors & abdominals) 
7. Shoulder shrugging (shoulders) 
8. Standing hamstring curl (hamstrings) 
9. T-tube pull-down (shoulders & back) 
10. Standing toe raise (calves) 
 
The group of exercises should be performed as a set with an appropriate amount of rest 
time between exercises. The goal of this training is to gradually and continually increase 
the patients’ tolerance to both the number of repetitions and resistance level over the 
course of the program.  The following general progression should apply for each exercise: 
 
a. Select a resistance that can be tolerated for 10 repetitions. 
b. As the study participant gets stronger, they should progress to 20 repetitions. 
c. When 20 repetitions are achieved on any given exercise increase the level of 
resistance and restart using 10 repetitions. 
 
Documentation 
Supervised In Clinic Pulmonary Rehabilitation Log 
This log is to be filled out by the PR therapist after every session and is to be maintained 
at the PR facility. A copy of the log should be provided to the investigative study site 
representative on a weekly basis to enable monitoring of the study participant’s progress 
and compliance with the PR program. A copy of the log is attached to this manual as 
Appendix 13b.   
 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 13.  Pulmonary Rehabilitation Program MOP 
Version:  June 23, 2017 
CONFIDENTIAL 
Page 6 of 8 
 
 
 
 
 
6.0 Home-Based Maintenance Pulmonary Rehabilitation Exercise Program 
 
At the completion of the Supervised in clinic PR program the study participant will be 
provided with a written prescription for a home-based PR maintenance program.  A copy 
of the written prescription should be provided to the Investigative Study Center 
Representative.   
 
Study participants will be encouraged to follow this program at least three times a week 
beginning immediately and for the duration of their involvement in the study unless 
prevented from doing so by a medical condition.  
 
The home-based maintenance PR program is recommended to consist of the following 
general components:  
Lower Limb Endurance Training: 
Walking for 20-30 minutes substituted for treadmill  
 
Upper Limb Endurance Training: 
As recommended by PR therapist, intended to be similar to in-clinic program. 
 
Lower and Upper Limb Strength Training: 
As recommended by PR therapist, intended to be similar to in-clinic program. 
 
 
7.0 Patient Information 
 
Scientific clinical studies have clearly demonstrated that those who comply with a regimen 
of pulmonary rehabilitation (PR) exercises and who remain physically active are in better 
overall health and function more effectively that their sedentary counterparts. The 
purpose of the Patient Information sheet is to provide study participants with the theory 
behind why this is the case, which may aid in their understanding of the importance of 
complying with the PR program for this study.   
 
The Patient Information Sheet (see the following section) has been provided to use as an 
educational tool to be reviewed with each patient.   
 
 
 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 13.  Pulmonary Rehabilitation Program MOP 
Version:  June 23, 2017 
CONFIDENTIAL 
Page 7 of 8 
 
 
 
 
 
Patient Information Sheet 
 
The nature of emphysema and its impact on your ability to function can contribute to a 
downward cycle of physical de-conditioning. This cycle has been described in several 
publications and is referred to as the “dyspnea cycle” or “downward spiral”.  An illustration 
of this cycle is shown below1. 
 
 
 
The cycle starts as a result of respiratory impairment (reduced pulmonary function) 
brought on by emphysema. As this impairment progresses you may have begun to 
experience discomfort and breathing difficulty, or dyspnea, during physical activity or 
exertion. In order to avoid this discomfort you may understandably start to refrain from or 
limit this activity. As for everyone, even highly trained athletes, a withdrawal from exertion 
(exercise) can lead to general physical de-conditioning.  
 
                                                 
1 Figure taken from “The Chronic Bronchitis and Emphysema Handbook”, Haas F, Hass SS, John Wiley & 
Sons, Inc., 2000. 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 13.  Pulmonary Rehabilitation Program MOP 
Version:  June 23, 2017 
CONFIDENTIAL 
Page 8 of 8 
 
 
 
 
 
Physical de-conditioning affects all of the systems in your body including the 
cardiovascular system and the musculoskeletal system.  As you know, the health and 
strength of these systems are crucial to maintaining a lifestyle that is as active as possible. 
 
Physical de-conditioning by itself (in the absence of a disease such as emphysema) is 
enough to contribute to discomfort during exercise for anyone.  This problem of discomfort 
is likely to be increased in patients suffering from emphysema.  The result of this 
discomfort during activity may cause you to further limit your physical exertion. This is the 
beginning of the “dyspnea cycle” or “downward spiral”.  
 
It is possible that some amount of your dyspnea is due to physical de-conditioning which 
is compounded by your reduced pulmonary function. Although pulmonary rehabilitation 
has not been demonstrated to improve pulmonary function, it has been demonstrated to 
improve exercise tolerance2. The reason for this is likely associated with some degree of 
“re-conditioning” of the bodies systems.  It is reasonable to expect that improved exercise 
tolerance will result in your ability to perform daily tasks with less discomfort. 
 
Conditioning as a result of exercise is a physiologically complex matter. It includes factors 
that are both easily comprehended and visually identifiable, such as improved muscle 
tone, as well as factors that are much more difficult to appreciate, such as improvements 
in blood flow due to a stronger heart muscle or improvements in the ability of the lungs to 
transfer oxygen to the blood and the ability of the recipient muscle cells to extract that 
oxygen.  Although some of these things may happen on a cellular level and may not be 
evident to you as a patient, they are significant in their role in promoting the health and 
strength of your body. 
 
The goal of your pulmonary rehabilitation program is to interrupt this “dyspnea cycle” in 
an effort to ensure that your physical limitations are as minimal as possible.  For this 
reason it is important for all patients to be committed to their Pulmonary Rehabilitation 
program. 
                                                 
2Pulmonary Rehabilitation: Joint AACP/AACVPR Evidence-Based Guidelines.  Chest 1997;112:1363-96 

   
  
     
 
Clinical Investigational Plan #630-0012-H 
Appendix 13a.  PR Facility Information Form 
Confidential 
Page 1 of 2 
June 23, 2017 
 
Pulmonary Rehabilitation Facility Information Form 
 
This form is to be completed by a representative from the Pulmonary Rehabilitation Facility to be 
involved in the LIBERATE Study. 
Referring LIBERATE  Study Site: 
 _______________________________________________________ 
PR Facility Name:   
 _______________________________________________________  
Address:   
 _______________________________________________________  
 
 _______________________________________________________  
Telephone: 
 _______________________________________________________  
Facsimile: 
 _______________________________________________________  
Email: 
 _______________________________________________________  
Director of PR Program: 
 _______________________________________________________  
 
Pulmonary Rehabilitation Personnel: 
Designated Study Representative(s):    _____________________________________________________  
 _____________________________________________________ 
Address:   
 _____________________________________________________  
(If different than above) 
 _____________________________________________________  
Telephone: 
 _____________________________________________________  
Facsimile: 
 _____________________________________________________  
Email: 
 _____________________________________________________  
Licensed Physician(s): 
 _____________________________________________________  
Licensed Nurse(s): 
 _____________________________________________________  
Physical Therapist(s): 
 _____________________________________________________  
Exercise Physiologist(s): 
 _____________________________________________________  
Other (specify): 
 _____________________________________________________  
Other (specify): 
 _____________________________________________________  
 
 

   
  
     
 
Clinical Investigational Plan #630-0012-H 
Appendix 13a.  PR Facility Information Form 
Confidential 
Page 2 of 2 
June 23, 2017 
Pulmonary Rehabilitation Facility Information Form 
 
Facility Equipment: 
a. Number of treadmills?   ___________  
b. Number of cycle ergometers?   ____________________________ 
c. Number of arm ergometers?    ____________________________ 
d. Are there free weights, Therabands, or other suitable forms of variable resistance equipment?   ____  
Sources of supplemental oxygen for exercise training? 
 _____________________________________________________________________________________  
 _____________________________________________________________________________________  
Pulse Oximeter available? ..................................................................................................... 
 Yes  
 No 
Heart Monitors available? .................................................................................................... 
 Yes  
 No 
Designated and secure storage area for LIBERATE Study documentation? ......................... 
 Yes  
 No 
 
 
 
Signature: 
I hereby certify that the information above is true and correct to the best of my knowledge: 
 
Signature:   ___________________________________   Date:   __________________________  
 
Name (please print):   ___________________________________  
 
Name of Pulmonary Rehabilitation Facility (please print):   _ _____ ________________________  
______________________________________________________________________________ 
 

 
 
 
 
 
         
In-clinic Pulmonary Rehabilitation Log – POST-Bronchoscopy PR 
 
Clinical Investigational Plan #630-0012-H 
Appendix 13b.  Post-bronchoscopy PR In-Clinic Log                                       Confidential                                     Page 1 of 2 
June 23, 2017 
 
Patient ID:  __________________ 
Facility Name:  ____________________________________________ 
 
Referring LIBERATE Study Site:  ____________________________________ 
 
All LIBERATE study participants should participate in a supervised pulmonary rehabilitation program that is 
initiated within 30 days following the bronchoscopy procedure.  The pulmonary rehabilitation program 
should include the elements recommended by the American Thoracic Society and European Respiratory 
Society Statement on Pulmonary Rehabilitation.  In general, the post-bronchoscopy program should consist 
of an active ‘in clinic’ pulmonary rehabilitation component and a ‘home-based’ maintenance pulmonary 
rehabilitation component.  The active ‘in clinic’ pulmonary rehabilitation program should be initiated for all 
study participants within the first 30 days following the bronchoscopy procedure. For the active ‘in clinic’ 
component of the program, the ATS/ERS practice guidelines recommend a minimum of 20 sessions be given 
at least three times per week although twice-weekly supervised plus one unsupervised home session may 
also be acceptable. For the maintenance component, study participants will be advised to adhere to a 
program consisting of at least 3 home-based sessions per week.  
 
 
AT THE END OF EACH WEEK OF THE ACTIVE ‘IN CLINIC’ PROGRAM, A COPY OF THE COMPLETED LOG 
SHOULD BE SENT TO THE INVESTIGATIVE SITE, WHICH WILL BE MAINTAINED IN THE STUDY PARTICIPANT’S 
STUDY BINDER. 
 
 
 
 
Session 1 
Session 2 
Session 3 
Date 
 
 
 
Duration of Entire Session (minutes) 
 
 
 
Therapist Initials 
 
 
 
 
Session 4 
Session 5 
Session 6 
Date 
 
 
 
Duration of Entire Session (minutes) 
 
 
 
Therapist Initials 
 
 
 
 
Session 7 
Session 8 
Session 9 
Date 
 
 
 
Duration of Entire Session (minutes) 
 
 
 
Therapist Initials 
 
 
 
 
 
 
 

 
 
 
 
 
         
In-clinic Pulmonary Rehabilitation Log – POST-Bronchoscopy PR 
 
Clinical Investigational Plan #630-0012-H 
Appendix 13b.  Post-bronchoscopy PR In-Clinic Log                                       Confidential                                     Page 2 of 2 
June 23, 2017 
 
 
 
Session 10 
Session 11 
Session 12 
Date 
 
 
 
Duration of Entire Session (minutes) 
 
 
 
Therapist Initials 
 
 
 
 
Session 13 
Session 14 
Session 15 
Date 
 
 
 
Duration of Entire Session (minutes) 
 
 
 
Therapist Initials 
 
 
 
 
Session 16 
Session 17 
Session 18 
Date 
 
 
 
Duration of Entire Session (minutes) 
 
 
 
Therapist Initials 
 
 
 
 
Session 19 
Session 20 
------------------------ 
Date 
 
 
 
Duration of Entire Session (minutes) 
 
 
 
Therapist Initials 
 
 
 
 
 
PLEASE ATTACH A COPY OF THE HOME-BASED PROGRAM SUGGESTED TO THE STUDY PARTICIPANT TO 
THIS FORM AT THE COMPLETION OF SESSION 20 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 14.  Procedure for Assessing Target Treatment Lobe CV using the Chartis System 
 
Version:  June 23, 2017 
             CONFIDENTIAL  
              Page 1 of 8 
 
 
Collateral ventilation (CV) status of the targeted treatment lobe will be assessed by following the 
steps shown below:   
1.  Place the Chartis catheter balloon.  The balloon should be placed to occlude all segments of the 
target treatment lobe.  
2.  The tip of the catheter should be placed in a manner that allows airflow from all segments of the 
target treatment lobe to reach the catheter tip. 
3.  Complete sealing of the target lobe by the balloon should be maintained throughout the entire 
duration of the assessment (including the 10-second pre-assessment and 10-second post-assessment 
periods). 
4.  NOTE:   
a. If difficulties are encountered with occluding the target lobe, measurement of the 
adjacent lobe/lobes may be used as a proxy measure of the collateral ventilation status 
of the target lobe. 
1. Example:  If the patient’s anatomy does not allow placement of the balloon in 
the LLL, the collateral ventilation of the LUL can be assessed and used in the 
treatment decision since the lobes share a common interlobar fissure and hence 
their collateral ventilation status.  
5.  After completing the assessment of the target treatment lobe, remove the Chartis catheter. 
 
 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 14.  Procedure for Assessing Target Treatment Lobe CV using the Chartis System 
 
Version:  June 23, 2017 
             CONFIDENTIAL  
              Page 2 of 8 
 
An example output for an acceptable Chartis System assessment is shown in Figure 1 below.   
While assessing CV status of a targeted treatment lobe, there are several important items to note 
during the assessment, including:   
1) The patient should demonstrate consistent tidal breathing prior to start of assessment.  This 
indicates that the patient has been adequately sedated.  Ensuring  adequate sedation will aid in 
achieving complete sealing of the targeted segment with the Chartis catheter balloon. 
2) Duration of the assessment should be 2 minutes or longer.   
3) Throughout the assessment, consistent deeper negative pressure should be observed.  This 
indicates that proper catheter balloon positioning and sealing has been achieved. 
4) At the end of the assessment, the total volume of air exhaled by the patient during the 
assessment should have been greater than 50 ml.   
5) During the post-assessment period, ensure that tidal breathing pattern has returned.  The 
balloon seal should be maintained until the review screen appears. 
6) During the assessment, if the patient coughs, the catheter tip clogs, or loss of the balloon seal is 
noted, the duration of the assessment should be extended.  If any of these issues are significant, 
the assessment should be abandoned and a new one should be re-initiated. 
7) During the assessment, if there is an instantaneous loss or drop in flow within the first 30 
seconds and flow does not resume, the assessment should be abandoned and a new one should 
be re-initiated. 
 
Deeper negative 
pressure 
Tidal breathing  
pre-assessment 
Tidal breathing  
post-assessment 
Assessment longer than 2 minutes 
Exhaled volume greater than 50mL 
Figure 1 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 14.  Procedure for Assessing Target Treatment Lobe CV using the Chartis System 
 
Version:  June 23, 2017 
             CONFIDENTIAL  
              Page 3 of 8 
 
Assessment of a Lobe that has Little or No Collateral Ventilation (CV- Lobe) 
1.  When high resistance to collateral ventilation or high collateral resistance is noted, the Chartis 
assessment indicates that the target treatment lobe has little or no collateral ventilation (is CV 
negative or CV-). 
2.  An example of a CV- assessment is shown in Figure 2 below.   
3.  The key features of a CV- assessment include:   
a. The peaks of the flow indicator waveforms (orange) show a steady downward trend. 
b. The Collateral Resistance index (Rndx) and / or Collateral Resistance realtime (Rrt) 
profile lines climb in a stepwise and steady fashion. 
c. Potential artifacts to avoid include:   
i. Instantaneous climbing of the Rndx and Rrt lines should not be considered a CV- 
assessment.  This observation could be an artifact of an underlying issue such as 
clogging of the catheter tip.   
ii. An instantaneous drop in flow seen within the first 30 seconds of the 
assessment should not be considered a CV- assessment.  This observation could 
be an artifact of distal airway collapse. 
 
 
 
 
Downward trend 
of flow 
Climb in Rndx 
Climb in Rrt 
Figure 2 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 14.  Procedure for Assessing Target Treatment Lobe CV using the Chartis System 
 
Version:  June 23, 2017 
             CONFIDENTIAL  
              Page 4 of 8 
 
Assessment of a Lobe that has Collateral Ventilation (CV+ Lobe) 
1.  When low resistance to collateral ventilation or low collateral resistance is noted, the Chartis 
assessment indicates that the target treatment lobe has high collateral ventilation (CV positive or 
CV+).   
2.  An example of a CV+ assessment is shown in Figure 3 below.   
3.  The key features of a CV+ assessment include:   
a. The peaks of the flow indicator waveforms (orange) remain flat and do not show a 
downward trend. 
b. The Collateral Resistance index (Rndx) and / or Collateral Resistance realtime (Rrt) 
profile lines have little or no change and do not steadily increase. 
 
 
 
 
 
 
 
Flow remains flat.   
No downward trend. 
No climb in  
Rndx or Rrt 
Figure 3 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 14.  Procedure for Assessing Target Treatment Lobe CV using the Chartis System 
 
Version:  June 23, 2017 
             CONFIDENTIAL  
              Page 5 of 8 
 
Other measurement anomalies which might affect the outcome of the collateral ventilation assessment 
include clogged catheter tip, instantaneous drop in flow, loss of balloon seal, and patient coughing.  It 
should be noted that these anomalies can occur together or independently during the course of an 
assessment.   
 
Assessment of a Lobe that has mucous clogging 
An example of a case with clogging at the catheter tip is shown in Figure 4.   
 
 
 
Clog 
Clog causes instantaneous climbing of 
the Rndx and Rrt lines and should not 
be considered a CV-
Figure 4 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 14.  Procedure for Assessing Target Treatment Lobe CV using the Chartis System 
 
Version:  June 23, 2017 
             CONFIDENTIAL  
              Page 6 of 8 
 
Assessment of a Patient with instantaneous drop in flow 
An example of a case with an instantaneous drop in flow is shown in Figure 5.   
 
 
 
 
 
 
Figure 5 
Instantaneous drop in flow. 
Instant drop in flow causes instantaneous 
climbing of the Rndx and Rrt lines and 
should not be considered a CV- 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 14.  Procedure for Assessing Target Treatment Lobe CV using the Chartis System 
 
Version:  June 23, 2017 
             CONFIDENTIAL  
              Page 7 of 8 
 
Assessment of a Patient with Loss of Balloon Seal 
An example of a case in which the balloon seal has been compromised is shown in Figure 6.   
 
 
 
 
 
 
 
 
Loss of Balloon Seal.  Reduced negative 
pressure indicates balloon lost its seal. 
Figure 6 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 14.  Procedure for Assessing Target Treatment Lobe CV using the Chartis System 
 
Version:  June 23, 2017 
             CONFIDENTIAL  
              Page 8 of 8 
 
Inadequate Balloon Seal and Coughing 
An example of a case having inadequate balloon seal at the beginning of the assessment and a cough at 
the end of the assessment is shown in Figure 7.   
 
 
 
 
 
 
Cough 
Inadequate balloon seal 
at beginning of 
assessment. 
Figure 7 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 15.  Segmental Bronchial Targets for Lobar Occlusion 
 
Version:  June 23, 2017 
             CONFIDENTIAL  
              Page 1 of 1 
 
 
The information shown in the table below may be used as a guide for EBV placement in 
bronchial targets to achieve lobar occlusion.   
 
 
Bronchial Segment Number 
Bronchi 
Right Upper Lobe 
B1 
B2 
B3 
Apical 
Posterior 
Anterior 
Right Middle Lobe 
B4 
B5 
Lateral 
Medial 
Right Lower Lobe 
B6 
B7 
B8 
B9 
B10 
Superior, lower lobe 
Medial basal 
Anterior basal 
Lateral basal 
Posterior basal 
Left Upper Lobe 
B1+2 
B3 
B4 
B5 
Apicoposterior 
Anterior 
Superior lingular 
Inferior lingular 
Left Lower Lobe 
B6 
B7+8 
B9 
B10 
Superior, lower lobe 
Anteromedial basal 
Lateral basal 
Posterior basal 
 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 16.  Example of a Medical Alert Card 
 
Version:  June 23, 2017 
             CONFIDENTIAL  
              Page 1 of 1 
 
 
 
Medical Alert Card - Example 
 
 
 
 
Medical Alert 
 
I, ____NAME OF PATIENT____ am enrolled in a clinical study for 
the treatment of emphysema being conducted at the NAME OF 
HOSPITAL, in NAME OF CITY AND STATE.  As part of this 
study, one or more implants have been placed within my airways. 
If I am involved in an accident or require other medical care, 
please first consult one of the contacts on the reverse side, unless 
the situation requires immediate emergent care.  If symptoms of 
pneumothorax are evident (chest pain, nausea, shortness of 
breath), please treat me as appropriate for pneumothorax.  If 
pneumothorax persists, please transfer me to the hospital 
specified above and on the back of this card. 
 
(FRONT) 
 
 
 
 
 
(BACK) 
 
Medical Alert – Contact Information 
 
Physician:  NAME OF PHYSICIAN  
24 hour contact number:  (xxx) xxx - xxxx 
 
Physician: NAME OF PHYSICIAN 
Phone: (xxx) xxx - xxxx 
 
Hospital Name:   
 
 
 
 
Address:   
 
 
 
 
 
 
 
 
 
 
 
 
Phone: (xxx) xxx - xxxx 
 
Treated Lung:  ________ (Lobe:  LUL, LLL, RUL, RLL) 
 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 17.  Post-EBV Procedure Discharge Instructions for the Study Treatment Arm 
 
Version: June 23, 2017 
             CONFIDENTIAL  
              Page 1 of 5 
 
 
Post-EBV Procedure Discharge Instructions for the Study Treatment Arm 
 
Key Points 
 
• Please contact the study doctor if you should experience more shortness of 
breath than usual, severe chest pain and/or tightness, nausea and/or dizziness, 
or any other symptoms or changes in your health that you are worrisome to you 
 
• Please wear your study bracelet and put your Medical Alert Card in your wallet in 
case of an emergency 
 
• Do not drive yourself home from the hospital or drive for at least 7 days after your 
procedure 
 
• Plan on having someone stay with you for the first few days and nights after you 
are discharged 
 
• Only engage in light physical activities for at least 7 days after you are 
discharged and don’t start pulmonary rehabilitation until the study doctor meets 
with you at your 7-day post-discharge visit 
 
 
Discharge Day Schedule 
 
Prior to your discharge, your study doctor will complete a physical examination and a 
chest x-ray to determine how you are doing and whether it is safe for you to leave the 
hospital.  If the study doctor decides that it is safe for you to go home, he/she and 
his/her staff will ensure that you have appropriate transportation from the hospital to 
your home.  You should not drive yourself home so you should plan on having a friend, 
relative, or colleague be available to drive you home.  Also, you should plan on having 
someone stay with you for several days after you are discharged to help support your 
transition home and your recovery from this procedure.  The study doctor and his/her 
team will provide you with a Medical Alert Card as well as the following set of discharge 
instructions.  
 
Recovery & Symptoms 
 
The time that it takes for you to recover from the Endobronchial Valve (EBV) procedure 
may vary depending on your age, physical well-being, and mental health.  It is important 
that you allow yourself the time to recover at your own pace.  Your regular doctor and 
the study doctor (as appropriate) can help manage any symptoms and problems that 
you may experience following the procedure.  Such symptoms may include: 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 17.  Post-EBV Procedure Discharge Instructions for the Study Treatment Arm 
 
Version: June 23, 2017 
             CONFIDENTIAL  
              Page 2 of 5 
 
 
 
1) Fatigue/Lack of Energy 
 
You have just undergone a fairly significant procedure so you may feel tired and 
have a lack of energy in the days and weeks following the procedure as your body 
heals, your general health status returns to normal, and you regain your strength.  
You should take it slow and easy and listen to your own body during this time so that 
you appropriately pace yourself and avoid overdoing it. 
 
2) Decrease in Appetite 
 
You may experience a temporary decrease in your appetite as the medicines from 
your procedure and post-procedure care wear off and your mouth and airways begin 
to recover from the bronchoscopy.  Your appetite should return to normal within 1-2 
weeks following the procedure.  If your appetite is poor, attempt to eat smaller, 
nutrient-rich (high protein and high calorie), and frequent meals and ensure that you 
are drinking a lot of fluids throughout the day (6-8 cups/day unless instructed 
otherwise by your doctor).  Sometimes, a decrease in appetite can be accompanied 
by feelings of nausea and/or dizziness.  If you should experience either of these 
symptoms, please contact your study doctor immediately. 
 
3) Pain/Discomfort 
 
You may experience some pain and discomfort in your nose, throat, airways, and 
chest in the days and weeks following the procedure as your body recovers from the 
bronchoscopy.  Normally, this pain and discomfort is only temporary and resolves 
within several days after the procedure.  It is important that you take any pain 
medications that have been prescribed for these symptoms as you may need them.  
If you should experience any sudden feelings of chest pain and/or tightness that are 
sharper and more severe than normal, please contact your study doctor 
immediately. 
 
4) Breathing Changes 
 
As a result of this procedure, your breathing function may decrease, stay the same, 
or improve.  It is important that you realize that you may not notice dramatic changes 
in your breathing function immediately following the procedure and it is possible that 
it may even decrease a little as your body heals and you regain your strength after 
the procedure.  Hopefully, you will experience less shortness of breath in the weeks 
and months following the procedure but this cannot be guaranteed.  If you should 
experience significantly more shortness of breath than usual, please contact your 
study doctor immediately.   
 
 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 17.  Post-EBV Procedure Discharge Instructions for the Study Treatment Arm 
 
Version: June 23, 2017 
             CONFIDENTIAL  
              Page 3 of 5 
 
 
 
5) Other Symptoms/Health Changes 
 
You may also experience increased shortness of breath that is accompanied by 
increased cough and/or wheezing, increased sputum production, changes in sputum 
color, and fever, which may suggest that you are having a COPD exacerbation or an 
episode of pneumonia.  Additionally, you may cough up a lot of blood or one of the 
valves or experience an increased or irregular heartbeat following the procedure, 
which may suggest some changes in your heart function.  It is important that you call 
your family doctor and/or the study doctor (as appropriate) as soon as you begin 
experiencing any of the symptoms above.  You should also call your family doctor 
and/or the study doctor (as appropriate) if you experience any other symptoms or 
changes in your health that seem out of the ordinary or worrisome to you. 
 
General Instructions 
 
It is important that you follow these general instructions as you continue your recovery 
from the EBV placement procedure at home in the days and weeks after this procedure.  
If you have any questions or concerns regarding these instructions, please discuss 
them with the study doctor and his/her study team. 
 
Activity 
 
In the days and week after discharge from the hospital, you should only engage in light 
physical activity as you are able and comfortable.  This means that you can participate 
in such activities as self-care, light household chores like cooking and laundry, 
socializing with friends and family, and light exercise like walking on a straight and level 
track.  For 7-10 days after discharge, you should avoid any activities that require heavy 
lifting, carrying, pushing, or pulling or put significant strain on your body, particularly 
your chest and arm muscles.  This includes activities like vacuuming, carrying groceries, 
shoveling snow, lifting weights, jogging/running, swimming, playing tennis, or doing 
aerobics.  Additionally, you will not be able to start your post-procedure pulmonary 
rehabilitation program until your study doctor has completed a physical examination, 
performed a chest x-ray, and authorized you to resume your normal daily activities 
during your visit with him or her 1 week following your discharge from the hospital. 
 
Driving/Traveling 
 
You should not drive for the first few days after discharge.  This is the amount of time 
that is usually required for you to regain the necessary mobility and strength to safely 
navigate and steer a car.  Additionally, you should avoid travelling out of state and 
particularly by air for at least 1 week after discharge.  If you have any problems or 
complications, this will help ensure that you are within close proximity and will have 
easy access to the treating hospital for evaluation and treatment.  

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 17.  Post-EBV Procedure Discharge Instructions for the Study Treatment Arm 
 
Version: June 23, 2017 
             CONFIDENTIAL  
              Page 4 of 5 
 
 
 
Returning to Work 
 
You should not return to work full-time until you feel physically and mentally strong 
enough to resume your normal work activities.  Depending on your job and required 
activity level, you may not be able to return to your full set of work responsibilities for 1-2 
weeks after the procedure.  If you have any questions or concerns or need special 
assistance regarding this instruction, please check with your study doctor. 
 
Medications 
 
After your procedure and prior to your discharge, your medications may change.  It is 
important that you take any new prescriptions and follow any new medication 
instructions provided to you by your study doctor and his/her team.  It is possible that 
you may need additional medications after you are discharged.  You should contact 
your family doctor and the study doctor (as appropriate) if you have any questions or 
concerns or have additional medication requirements. 
 
Problems after the Study Procedure 
 
You should ensure that your family doctor has been informed of your EBV placement 
procedure as he/she will continue to provide your ongoing regular medical care and 
management once you are discharged.  If you have any questions, concerns, or needs 
regarding your regular medical care after you are discharged, you should contact your 
family doctor.  If you have questions, concerns, or needs as they relate to this 
procedure or study, please contact your study doctor and his/her study team.   
 
Please keep your study doctor and his/her study team informed of any changes in your 
health or medications regardless of their relationship to this procedure or study.  
Additionally, please ensure that you wear your study bracelet and place your Medical 
Alert Card for this study in your wallet so that it is readily accessible to a health care 
professional(s) in the event that you experience a medical emergency. 
 
Calling the Study Doctor 
 
Please contact the study doctor for any of the following reasons: 
 
• increased shortness of breath 
• nausea and/or dizziness 
• sudden onset of sharp and severe chest pain/tightness 
• fever 
• increased cough and/or wheeze with or without increased sputum production and 
changes in color/thickness of sputum 
• coughing up significant amounts of blood 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 17.  Post-EBV Procedure Discharge Instructions for the Study Treatment Arm 
 
Version: June 23, 2017 
             CONFIDENTIAL  
              Page 5 of 5 
 
• coughing up valve(s) 
• irregular or increased heartbeat 
• any other worrisome problem or symptom 
 
 
 
 
If you have any questions or concerns after you leave the hospital, please contact your 
study doctor’s office or 24-hour number as follows: 
 
Dr.___[PI Name]____ 
Office:__[PI Office #]__ 
24-hour:___[PI Office #]___ 
 
Dr.__[Co-PI Name]__ 
Office:_[Co-PI Office #]_ 
24-hour:__[Co-PI Office #]__ 
 
Dr.__[Sub-I Name]__ 
Office:_[Sub-I Office #]_ 
24-hour:__[Sub-I Office #]__ 
 
  ___[SC Name]__   _ 
Office:_  [SC Office #]  _ 
 
   
 
 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 18.  Management of Pneumothorax  
 
 
Version:  June 23, 2017                                                                            CONFIDENTIAL  
                
 
Page 1 of 2 
 
 
Pneumothorax 
 
Large 
 
Symptomatic 
 
Small 
 
Asymptomatic 
Place Chest Drain 
• 
prefer small size 
• 
place with up to 20 cm of H2O suction 
Stable with airleak 
continuing > 7 days 
Unstable  
Remove all valves  
Remove one valve 
(preferably most proximal)  
ITT Study Participant 
with no valves 2º to 
complications  
Airleak stops  
Discontinue drain  
Airleak continues > 48 hours 
Consider valve 
replacement in 6 weeks 
Remove all valves  
Airleak continues > 48 hours 
Consider pleurodesis or 
surgical intervention  
ITT Study Participant 
with no valves 2º to 
complications  
Observe –  
repeat X-ray 2-4 
hours
Symptomatic or 
enlarging  
Stable with 
resolution  
Trapped lung collapse 
without airleak > 96 hrs 
Remove one valve 
(preferably most proximal)  
Re-expansion  
Discontinue drain  
Consider valve 
replacement in 6 weeks 
Lack of re-expansion 
within 48 hrs  
Remove all valves  
Discontinue drain 
ITT Study Participant 
with no valves 2º to 
complications  
Airleak stops  
Discontinue drain  
Consider valve 
replacement in 6 weeks 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 18.  Management of Pneumothorax  
Version:  June 23, 2017 
       CONFIDENTIAL  
              Page 2 of 2 
 
Management Considerations for EBV Patients at Potentially Increased Risk 
for Pneumothorax in the Immediate Post-EBV Procedure Period 
Case-related experience suggests that the development of substantial atelectasis in the 
immediate post-EBV procedure period may be associated with a higher risk of 
pneumothorax-related complications. A higher risk patient is defined as any patient that 
experiences acute, significant volume reduction immediately post-EBV treatment, usually 
determined by volume reduction visible on the 1-hour post-treatment chest x-ray. Out of an 
abundance of caution in this situation, the clinician should consider the following: 
• 
Performing a CT scan of the chest without contrast to evaluate for pneumothorax 
that may not be visible on plain x-ray imaging 
• 
Keep chest drainage set easily accessible and consider placement of a small bore 
catheter if any size pneumothorax is identified 
• 
Application of oxygen (FiO2 of 100%) 
• 
Consider reducing patient’s exertion for 48 hours 
Consider the methods suggested in a recent publication (Herzog 2015) where patients 
following a modified post-EBV care that included 48 hours of strict bed rest and, if needed, 
16 mg codeine up for cough to three times a day (TID), experienced statistically significant 
fewer pneumothoraces. 
Also, in the event of acute clinical deterioration, usual management protocols need to be 
followed. Placement of a chest tube should be considered if even a small pneumothorax is 
found on chest CT scanning following substantial atelectasis in the immediate post EBV 
procedure period. Additionally if clinical deterioration occurs that requires endotracheal 
intubation and positive pressure ventilation, bilateral chest drains should be placed if there 
is any suspicion of bilateral pneumothoraces. 
References 
1. 
Cormier Y, Laviolette M, Tardif A Prevention of pneumothorax in needle lung biopsy by 
breathing 100% oxygen. Thorax. 1980 Jan;35(1):37-41. 
 
2. 
Herzog D, Poellinger A, Doellinger F, Schuermann D, Temmesfeld-Wollbrueck B, Froeling 
V, Schreiter NF, Neumann K, Hippenstiel S, Suttorp N, Hubner RH. Modifying Post-
Operative Medical Care after EBV Implant May Reduce Pneumothorax Incidence. PLoS 
One.2015 May 26;10(5):e0128097. 
 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 19.  Statistical Analysis Plan   
 
Version:  June 23, 2017  
 
Page 1 of 14 
 
Analysis Summary 
 
 
Study Title: Lung Function Improvement after Bronchoscopic Lung Volume Reduction with 
Pulmonx Endobronchial Valves used in Treatment of Emphysema (Clinical Protocol 630-0012). 
 
 
Patient Population:  Male and female patients with severe heterogeneous emphysema meeting 
the study eligibility criteria. 
 
 
Study Design: This will be a multi-center, prospective, randomized, controlled study with EBV 
treatment statistically evaluated using Intent-to-Treat (ITT) analyses.  A maximum of 183 ITT 
study participants, who meet study entry criteria, consisting of screening eligibility criteria, 
baseline eligibility criteria, and procedure eligibility criteria, will be enrolled.  Safety and 
effectiveness of bronchoscopic lung volume reduction (BLVR) using the Pulmonx EBV will be 
evaluated at 1 year.  An interim analysis designed to evaluate effectiveness for continuing 
crossover of control participants at 1 year to EBV treatment will be performed when 74 study 
participants have completed the 1-year follow-up.  For study participants who have been treated 
with EBV, a secondary valve intervention such as valve removal, replacement, or adjustment 
may be considered during the study follow-up.  Long-term data will be collected annually for 
EBV-treated study participants through 5 years. Per the regulatory plan agreed to with FDA, 1 
year of follow-up is required pre-approval and the remaining 4 years of follow-up will be 
conducted post-approval.  
 
 
Primary Effectiveness Endpoint  
The percentage of study participants in the Endobronchial Valve (EBV) treatment arm who meet 
the threshold of >15% improved forced expiratory volume in one second (FEV1) as compared to 
the control arm at 1 year. Improved FEV1 will be calculated by determining the percentage 
change for FEV1 from baseline to 1 year post-procedure for individual study participants.    
 
 
Secondary Effectiveness Endpoints   
 
1) Treatment Lobe Volume Reduction (TLVR) for the Treatment Arm 
a. TLVR, measured as the ‘absolute change from baseline’ for treated lobe volume as 
seen via HRCT (high resolution computed tomography), will be evaluated at 45 days 
and 1 year.   
b. TLVR, measured as the ‘percentage change from baseline’ for treated lobe volume 
as seen via HRCT, will be evaluated at 45 days and 1 year.   
 
2) St. George’s Respiratory Questionnaire  
a. Difference between study arms in ‘absolute change from baseline’ for SGRQ score 
at 1 year.   
 
 
 
 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 19.  Statistical Analysis Plan   
 
Version:  June 23, 2017  
 
Page 2 of 14 
3) FEV1  
a. Persistence of treatment effect will be evaluated by determining the difference 
between study arms for ‘absolute change from baseline’ for FEV1 at 45 days, 6 
months, and 1 year.  
b. Persistence of treatment effect will be evaluated by determining the difference 
between study arms for ‘percentage change from baseline’ for FEV1 at 45 days, 6 
months, and 1 year.   
 
4) 6-Minute Walk Distance (6MWD) 
a. Difference between study arms in ‘absolute change from baseline’ for 6MWD at 1 
year.    
b. Difference between study arms in ‘percentage change from baseline’ for 6MWD at 1 
year.   
 
 
Safety Endpoint   
Evaluation of the short- and long-term adverse events profile of the EBV treatment arm during 
the treatment period, defined as the day of the study procedure until 45 days after the study 
procedure (short), and in the post-treatment period, defined as 46 days after the study 
procedure until the 1-year follow-up visit (long). 
 
 
Additional Measures 
• 
Spirometry, including FEV1, forced vital capacity (FVC) and the ratio of FEV1/FVC  
• 
Body plethysmography, including residual volume (RV), inspiratory capacity (IC), functional residual 
capacity (FRC),TLC, and the ratios of RV/TLC and IC/TLC  
• 
SGRQ global and domain (ie. ‘symptoms’, ‘activity’ and ‘impacts on daily life’) scores 
• 
Modified Medical Research Council (mMRC) Dyspnea Scale Score  
• 
BODE Index 
• 
Transitional Dyspnea Index (TDI) from Baseline Dyspnea Index (BDI) 
• 
COPD Assessment Test (CAT) 
• 
SF-36 Health Survey score 
• 
EQ-5D Health Survey score 
• 
Health Care Utilization Questionnaire 
• 
6MWD test 
• 
Borg scale dyspnea scores before and after 6MWD test  
• 
Change in use of ‘maintenance’ medications, including bronchodilators, corticosteroids, 
antibiotics, and anti-inflammatories  
• 
Pulmonary rehabilitation compliance diary responses 
• 
EXACT-PRO diary responses 
• 
Health  status change responses 
• 
Carbon Monoxide Diffusing Capacity (DLCO) 
• 
Lung radiographic features 
 
 
Interim Analysis 
An interim data analysis designed to evaluate effectiveness for continuing crossover of control 
arm study participants at 1 year to EBV treatment will be performed when 74 (50% of the total 
147) study participants have completed the 1 year follow-up.  The interim analysis will be 

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reviewed by the DSMB and FDA.  If crossover of control arm study participants is found to be 
justified by the interim analysis, then crossover of control arm study participants may be 
continued.  If the DSMB recommends not continuing crossing control arm participants to EBV 
treatment, then those control arm patients who have not yet crossed over will exit from the study 
per protocol after the 1-year visit.   
 
 
Long-Term Follow-up 
Data will be collected annually through 5 years. Per the regulatory plan agreed to with FDA, 1 
year of follow-up is required pre-approval and the remaining 4 years will be conducted post-
approval.  The 2-, 3-, 4-, and 5-year data will consist of FEV1 and adverse events. 
 
 
Definition of Study Success:  The study will be a success if the difference between the EBV 
Treatment arm and Control arm for the percentage of study participants meeting the threshold 
of >15% improved in FEV1 differs significantly (two-sided test at p<0.05) in favor of the 
treatment group at 1 year. This evaluation will be conducted at 1-year post-randomization.  
 
 
Number of Study Participants: 183   

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Statistical Methods 
 
I. 
Descriptive Statistics   
Means, standard deviations, medians, and confidence intervals will be reported for all 
continuous variables. Dichotomous variables will be reported as percentages and the 
numerator and denominator will be reported and defined. The frequency of adverse events 
will be reported as percentage rates with computed 95% two-sided exact confidence 
intervals (upper and lower). 
 
II.  Analyses of the Patient Populations  
These analyses are intended to determine the similarity of two treatment groups and 
similarity of patients from different study sites with respect to important demographic or other 
variables, either known or suspected to have an influence on the outcome variables.  The 
absence of similarity for any variable will identify that variable as a potential covariate in 
subsequent analyses.  
 
A. Comparability of Treatment Groups – To assess the success of the randomization 
process, the demographic and prognostic variables measured at study entry will be 
compared between the Treatment and Control arms.  Continuous variables will be 
compared with the two-sample t-test or the Wilcoxon two-sample rank test, and 
categorical variables will be compared with the Fisher’s exact test or a Chi-square 
test.  Comparability analyses will be done with two-sided tests with significance level 
of 0.05. 
 
B. Study Site Comparability –The appropriateness of pooling the data across study 
sites will be determined on a clinical basis, i.e., to ascertain if the sites used a 
common protocol, the sponsor adequately monitored the study to assure protocol 
compliance, and the data gathering and validation mechanisms were the same 
across all study sites (Meinert, 1986). 
 
An analysis will be done to determine if the magnitude of the clinical effect of the 
primary outcome is maintained if sites and/or site by treatment interactions are 
included in an analysis of covariance model.  We expect the majority of sites will 
show the treatment to be beneficial but statistically one would not expect all sites to 
show the treatment to be beneficial.  For those sites with contrary results, an analysis 
will be attempted to determine what factors at those sites led to the result (See 
expert statistical testimony from Dispute Resolution Panel transcript September 6, 
2001).   
 
C. In study sites with small numbers of patients, it will not be possible to evaluate site or 
site by treatment interaction.  The reason is that what may appear to be a site by 
treatment interaction may be a small numbers phenomenon.  For example, if there 
were only three patients from a given study site with one in the control group and two 
in the treated group, one success in each arm will appear to be a site by treatment 
interaction (100% success in the controls but 50% success in the treated arm).  
Hence, study sites with fewer than three patients in either treatment arm will be 
combined into one or more pseudo-sites to allow the comparison to be done.  The 
size of any pseudo-site created in this way will not exceed the size of the study site 
with the largest enrollment.   

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III.       Analyses Populations 
A. Geographic Cohort:  This study will be conducted at clinical sites inside and outside 
the U.S.   
B. Endpoint Analyses:  Primary and secondary study endpoints will be analyzed utilizing 
an intent-to-treat (ITT) population defined as all randomized patients analyzed by the 
groups to which they were randomly assigned (EBV treatment or control).  
Consenting patients who qualify for the study and are randomized into the study will 
be included in the ITT population, regardless of the actual treatment received. 
Consented patients who are found not to meet the study eligibility criteria prior to 
randomization will not be included in the intent-to-treat group.  
C. Secondary Analyses: Secondary analyses will also be performed on the study 
primary and secondary endpoints on a Completed Cases (CC) basis and Per-
Protocol (PP) basis. The CC population is defined as all randomized and eligible 
patients who received study-directed treatment and had 1 year of follow-up. The PP 
population is defined as all randomized patients who meet study eligibility criteria, 
who were treated as randomly assigned, and had follow-up for the endpoints.  Any 
visits where protocol violations occurred will be reviewed for possible exclusion from 
impacted analyses.  
D. Safety Analysis Population:  Both the ITT analysis population and ‘As Treated’ (AT) 
analysis population will be used to assess the safety data.  For the AT analysis, 
study participants will be analyzed based on the treatment they actually received.       
E. Secondary Valve Procedures:  If applicable, statistical analyses will also be 
conducted after sorting patients by the actual treatment received, specifically valve 
removal, valve replacement, and valve adjustment.     
 
IV. Effectiveness Analyses  
There is one primary effectiveness variable, four secondary effectiveness variables, and 
several additional effectiveness variables.  
 
A. Analysis of the Primary Effectiveness Endpoint  
Both an interim and an end of study analysis for the primary effectiveness endpoint are 
planned.  The primary effectiveness endpoint is the difference between the EBV 
treatment arm and control arm in percentage of study participants who reach a threshold 
of >15% improved FEV1, collected post-bronchodilator, at 1 year (see Table 1).  The 
FEV1 value will be calculated by determining the percentage change for FEV1 from 
baseline to 1-year post-procedure using:  ((FEV1 at 1 year follow-up subtracted from 
FEV1 at baseline) / FEV1 at baseline)) for individual study participants.  The two arms will 
be compared using the standard normal Z-statistic.     
 
 
Table 1.  Primary Effectiveness Endpoint 
Variable 
Unit 
Values Statistically Evaluated 
Forced Expiratory Volume (FEV1) 
>15% improved 
percentage of participants 
 
An interim data analysis designed to evaluate effectiveness for continuing crossover of 
control arm study participants at the 1 year follow-up to EBV treatment will be performed 

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when 74 (50% of the total 147) study participants have completed the 1 year follow-up.  
The interim analysis will be reviewed by the DSMB.   
 
To account for the interim analysis, the power spending function, defined as:  
φ
α
α
t
t =
)
(
 
will be used to preserve an overall type I error rate of 0.05 for the study.  Using the 
nTerim program (Statistical Solutions) to calculate the power spending function with:    
α =.05, φ=2.3 and t=.5, 
)
(t
α
=.01, 
the value of the Z-statistic must exceed 2.571 (nominal alpha <0.01) for the null 
hypothesis to be rejected at this interim look (see Table 2).   
 
Table 2.  Power Spending Function for Interim Analysis 
Looks 
1 
2 
Time 
0.5 
1 
Lower Bound 
-2.57057 
-2.00360 
Upper Bound 
2.57057 
2.00360 
Nominal Alpha 
0.01015 
0.04511 
Incremental Alpha 
0.01015 
0.03985 
Cumulative Alpha 
0.01015 
0.0500 
Exit Probability 
38.75 
50.52 
Cumulative Exit Probability 
38.75 
89.28 
 
If Z>2.571 then continuing crossover of control arm study participants will be strongly 
justified since the p-value will be <0.01.  This observation may provide evidence to stop 
the trial early.   
 
The study hypothesis will be tested again at the end of the study.  The Z-statistic will be 
calculated again, and by taking into account the interim analysis, will have a final critical 
boundary value of 2.004, per the nTerim program.  If the trial is not stopped as a result of 
the interim analysis, then the final Z-statistic must be greater than or equal to 2.004 in 
order to reject the null hypothesis at the final analysis (at the overall 2-sided 5% 
significance level).  Test statistic is “Z” as defined as:   
Z = 






+
−
−
C
T
C
T
n
n
p
p
p
p
1
1
)
1(
 
 
Where,  
T
p and 
C
p are the proportions of success for the primary endpoint in the treatment and 
control groups, respectively, p is the pooled estimate of the success rate, and  
T
n and 
C
n  are the sample sizes obtained in the treatment and control groups, 
respectively.  Two sets of (p,
T
p ,
C
p , 
T
n ,
C
n ) will be obtained:  one at the interim 
analysis and one at end of the study.   
 
 

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B.  Analysis of the Secondary Effectiveness Endpoints 
 
a. Treatment Lobe Volume Reduction for the Study Treatment Arm   
i. TLVR measured as the ‘absolute change from baseline’ in treated lobe 
volume as seen via HRCT (high resolution computed tomography), will be 
evaluated at 45 days. TLVR will be calculated for each study participant 
using: (treatment lobe volume at 45 days follow-up subtracted from the 
treatment lobe volume at baseline).  Descriptive statistics will be 
calculated for the study treatment arm and will include the mean, 
standard deviation and 95% confidence interval.  A one-sample t-statistic 
will be used to quantify the magnitude of the difference. 
ii. TLVR measured as the ‘percentage change from baseline’ in treated lobe 
volume as seen via HRCT, will be evaluated at 45 days.  TLVR will be 
calculated for each study participant using: (treatment lobe volume at 45 
days follow-up subtracted from the treatment lobe volume at baseline 
divided by treatment lobe volume at baseline).  Descriptive statistics will 
be calculated for the study treatment arm and will include the mean, 
standard deviation and 95% confidence interval.  A one-sample t-statistic 
will be used to quantify the magnitude of the difference. 
iii. TLVR measured as the ‘absolute change from baseline’ in treated lobe 
volume as seen via HRCT (high resolution computed tomography), will be 
evaluated at 1 year. TLVR will be calculated for each study participant 
using: (treatment lobe volume at 1 year follow-up subtracted from the 
treatment lobe volume at baseline).  Descriptive statistics will be 
calculated for the study treatment arm and will include the mean, 
standard deviation and 95% confidence interval.  A one-sample t-statistic 
will be used to quantify the magnitude of the difference. 
iv. TLVR measured as the ‘percentage change from baseline’ in treated lobe 
volume as seen via HRCT, will be evaluated at 1 year.  TLVR will be 
calculated for each study participant using: (treatment lobe volume at 1 
year follow-up subtracted from the treatment lobe volume at baseline 
divided by treatment lobe volume at baseline).  Descriptive statistics will 
be calculated for the study treatment arm and will include the mean, 
standard deviation and 95% confidence interval.  A one-sample t-statistic 
will be used to quantify the magnitude of the difference. 
 
 
b. St. George’s Respiratory Questionnaire (SGRQ)   
i. Difference between study arms in ‘absolute change from baseline’ for 
SGRQ score at 1 year. Descriptive statistics will include means, standard 
deviations and 95% confidence intervals. A two sample t-statistic will be 
used to quantify the magnitude of the difference between study groups. 
ii. Difference between study arms in ‘percentage change from baseline’ for 
SGRQ score at 1 year. Descriptive statistics will include means, standard 
deviations and 95% confidence intervals. A two sample t-statistic will be 
used to quantify the magnitude of the difference between study groups. 
 
 
 

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c. FEV1   
i. Persistence of the treatment effect will be evaluated by determining the 
difference between study arms for ‘absolute change from baseline’ for 
FEV1 at 45 days, 6 months, and 1 year. The FEV1 value will be calculated 
using: ((FEV1 at each of the follow-up time points) subtracted from (FEV1 
at baseline)) for individual study participants to determine the mean 
absolute change for each study arm.  At each of the three time points, 
descriptive statistics will include means, standard deviations and 95% 
confidence intervals.  A two-sample t-statistic will be used to quantify the 
magnitude of the difference between study groups. A repeated-measures 
model (GEE with an identity link function and exchangeable correlation 
structure) will be used to model the entire time course of outcomes as a 
function of baseline value and a main effect indicating treatment group 
membership.  
ii. Persistence of the treatment effect will be evaluated by determining the 
difference between study arms for ‘percentage change from baseline’ for 
FEV1 at 45 days, 6 months, and 1 year. The FEV1 values will be 
calculated using: ((FEV1 at each of the follow-up times) subtracted from 
(FEV1 at baseline divided by FEV1 at baseline)) for individual study 
participants to determine the mean absolute change for each study arm.  
At each of the three time points, descriptive statistics will include means, 
standard deviations and 95% confidence intervals.  A two-sample t-
statistic will be used to quantify the magnitude of the difference between 
study groups. A repeated-measures model (GEE with an identity link 
function and exchangeable correlation structure) will be used to model the 
entire time course of outcomes as a function of baseline value and a main 
effect indicating treatment group membership. 
 
d. 6-Minute Walk Distance (6MWD) 
i. Difference between study arms in ‘absolute change from baseline’ for 
6MWD at 1 year. Descriptive statistics will include means, standard 
deviations and 95% confidence intervals. A two sample t-statistic will be 
used to quantify the magnitude of the difference between study groups. 
ii. Difference between study arms in ‘percentage change from baseline’ for 
6MWD at 1 year. Descriptive statistics will include means, standard 
deviations and 95% confidence intervals. A two sample t-statistic will be 
used to quantify the magnitude of the difference between study groups. 
 
e. The secondary effectiveness endpoints are summarized in Table 3.   
 
Table 3. Secondary Effectiveness Endpoints 
Variable 
Unit 
Values Statistically Assessed 
Target Lobe Volume Reduction 
(TLVR) 
milliliters 
mean absolute change 
TLVR 
percent 
mean percent change 
SGRQ Global Score 
Points 
mean absolute change 
SGRQ 
percent 
mean percent change 
FEV1 
Liters 
mean absolute change 
FEV1 
percent 
mean percent change 
6-Minute Walk Distance 
Meters 
mean absolute change 

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6MWD 
percent  
mean percent change 
  
C. Analysis of Additional Effectiveness Endpoints   
 
a. Supporting Evidence for Effectiveness 
 
The following additional effectiveness endpoints will be measured for both study 
arms.  These are expected to provide supporting evidence of the effectiveness of 
EBV treatment. Results will be described with summary statistics. These 
endpoints will be described for each study arm separately and comparatively 
between arms by calculating mean change or difference in proportions, 
whichever is appropriate for the variable being analyzed.  The definitions for 
these additional effectiveness endpoints are shown in Table 4.   
 
Table 4.  Additional Effectiveness Endpoints 
Spirometry Measures 
FEV1 
>12% 
improved 
Percentage of participants 
Forced Vital Capacity (FVC) 
liters 
mean absolute and percent change 
FEV1/FVC 
ratio 
mean absolute change 
DLCO 
percentage 
mean absolute and percent change 
 
Body Plesthysmography Measures 
Residual Volume (RV) 
liters 
mean absolute and percent change 
Inspiratory Capacity (IC) 
liters 
mean absolute and percent change 
Functional Residual Capacity 
(FRC) 
 
mean absolute and percent change 
Total Lung Capacity (TLC) 
liters 
mean absolute and percent change 
RV/TLC 
ratio 
mean absolute change 
IC/TLC 
ratio 
mean absolute change 
 
Patient-Reported Health Status Measures 
SGRQ Global Score  
>4 points improved 
percentage of 
participants 
 
>8 points improved 
percentage of 
participants 
SGRQ Domain Scores 
 
 
   ‘Symptoms’ 
points 
mean absolute change 
   ‘Activity’ 
points 
mean absolute change 
   ‘Impacts Daily Life’ 
points 
mean absolute change 
mMRC Score 
semi-quantitative 
scale score 
mean absolute change 
COPD Assessment Test (CAT) 
points 
mean absolute change 
Transitional Dyspnea Index (TDI) 
points 
mean absolute change 
 
<1 point improved 
percent of participants 
Short Form (SF)-36 Health 
Survey 
points 
mean absolute change 
EQ-5D Health Survey 
points  
mean absolute change 
 
Other Measures 
BODE Index  
semi-quantitative scale 
score 
mean absolute change 

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<1, 0, >1 change 
percentage of 
participants 
6MWD – subjects stratified by 
distance walked at baseline 
meters 
mean absolute change 
 
>25 meters improved 
percentage of 
participants 
 
>54 meters improved 
percentage of 
participants 
Borg Scale Dyspnea Score:  
Before 6MWD test 
semi-quantitative scale 
score 
mean absolute change 
Borg Scale Dyspnea Score:   
After 6MWD test 
semi-quantitative scale 
score 
mean absolute change 
 
 
b. Informational Purposes:  
The following additional effectiveness endpoints will be measured in both 
treatment groups for informational purposes. Results will be described with 
summary statistics (see Table 5). These endpoints will be described for each 
treatment group separately and comparatively between groups by calculating 
mean change or difference in proportions, whichever is appropriate for the 
variable being analyzed. 
   
 
Table 5.  Informational Variables 
Variable 
Unit 
Values Statistically 
Assessed 
Maintenance Medications 
 
 
   Bronchodilators 
change in medication regimen 
percentage of participants 
   Corticosteroids 
change in medication regimen 
percentage of participants 
   Antibiotics 
change in medication regimen 
percentage of participants 
   Anti-Inflammatories 
change in medication regimen 
percentage of participants 
Pulmonary Rehabilitation 
Compliance Diary 
reported adherence to 
program 
percentage of participants 
   Adherence to program 
number of sessions / week 
mean absolute number 
   Intensity of program 
length of reported sessions 
mean absolute number 
EXACT-PRO Diary Entries 
points 
mean absolute number 
Health Utilization 
Measures 
frequency of use 
percentage of participants 
Lung Radiographic 
Features 
 
 
   TLVR 
volumetric change  
mean percentage change 
   valve occlusion   
qualitative assessment 
percentage of participants 
   inter-lobar fissures 
percent complete 
percentage of participants 
 
 
V. Adjustment for Potential Confounders 
The covariates shown in Table 6 may be potentially influential with respect to the 
effectiveness endpoints.  If any of these covariates are found to be out of balance between 
the groups (at the two-sided 0.10 level), they will be included in a multivariate analysis, 
along with an indicator of treatment group, to evaluate their potential effect on the study 
conclusions.  A multivariate logistic regression model will be used. 
 

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Table 6.  Covariates 
 
Baseline  
Procedure 
Follow-Up 
Gender 
X 
 
 
Age 
X 
 
 
Clinical Site 
X 
 
 
6MWD  
X 
 
 
Patient-reported health status measures (e.g. SGRQ) 
X 
 
 
Body Mass Index 
X 
 
 
BODE Index 
X 
 
 
Medication Use 
X 
 
 
Residual Volume (RV) 
X 
 
 
RV % Predicted 
X 
 
 
Total Lung Capacity (TLC) 
X 
 
 
TLC % Predicted 
X 
 
 
RV/TLC 
X 
 
 
IC/TLC 
X 
 
 
Vital Capacity 
X 
 
 
Forced Vital Capacity (FVC) 
X 
 
 
FVC % Predicted 
X 
 
 
FEV1 
X 
 
 
FEV1 % Predicted 
X 
 
 
FEV1 / FVC 
X 
 
 
Lobar Volume  
X 
 
 
Lobar Destruction Scores 
X 
 
 
Ipsilateral DS Heterogeneity 
X 
 
 
Severity of emphysema (GOLD classification) 
X 
 
 
Co-Morbidities 
X 
 
 
Target Treatment Lobe 
 
X 
 
Treatment Group 
 
X 
 
Target Lobe Volume Reduction 
 
 
X 
Lobar Occlusion  
 
 
X 
 
     
VI. Secondary Valve Procedures 
Secondary valve procedures will be evaluated by examining the proportion of patients who 
undergo valve removal, valve replacement, or valve adjustment, and describing the reasons 
they occurred.  Data for these study participants will be contrasted to data for study 
participants who did not receive a secondary valve procedure.  
  
VII. Safety Analyses  
Evaluation of the short- and long-term adverse events profile of the EBV treatment arm 
during the treatment period, defined as the day of the study procedure until 45 days after the 
study procedure (short), and in the post-treatment period, defined as 46 days after the study 
procedure until the 1-year follow-up visit (long).  Safety analyses will be performed by 
examining the proportion of patients in the EBV study arm that experiences adverse events.  
The rates and 95% exact confidence intervals will be presented on an event and on a per-
patient basis.   
 

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Adverse events will be categorized into clinically relevant groups (e.g.:  stable 
pneumothorax with no intervention, pneumothorax resolved with chest tube insertion in less 
than 7 days, prolonged air leak, etc.).  Adverse events occurring in the treatment arm will be 
further categorized by severity and as device-related, procedure-related, or neither, and by 
those occurring during procedure hospitalization and those occurring post-discharge.  
Rehospitalization rates will be reported by study arm on a Per-Patient (PPt) basis and on a 
Per-Event (PE) basis.  In study participants who receive EBV treatment, adverse events will 
be evaluated by stratifying participants by use of conscious sedation and general anesthesia 
during the bronchoscopy procedure as well as evaluating number of valves received and 
sites EBV were placed.   
 
VIII. 
Mortality 
A Kaplan-Meier survival curve for each study arm will graphically display the time to 
death from the time of randomization and a log rank test will be used to compare 
Kaplan-Meier curves between study arms.  A Cox proportional hazards model will be 
used to control for study site along with other significant co-variates as applicable. 
 
IX.      Patient Accountability and Missing Data 
Every effort will be made to collect all data points in the study. The sponsor plans to 
minimize the amount of missing data by appropriate management of the prospective 
clinical trial, proper screening of study subjects, and training of participating 
investigators, monitors and study coordinators.   
 
The analysis for the primary endpoint will be performed by imputing missing data. For 
study participant FEV1 data that is ‘intermittent’, missing outcomes will be imputed by 
linear interpolation using the FEV1 value from the latest non-missing data point before 
the missed data point and the earliest non-missed data point after the missed data point. 
For study participants with truncated data (e.g. participants who drop out or are lost to 
follow-up), a multiple imputation strategy will be performed using the propensity score 
method. In brief, for a particular outcome, the propensities for study participants to have 
missing data (for each treatment group separately), modeled by logistic regression, are 
grouped into strata based on percentiles of the logistic propensity score model. Within a 
stratum, a study participant with a missing observation has an imputed value assigned 
by randomly choosing a value from among the study participants in the same stratum 
with non-missing observations. This procedure will be repeated 20 times on the entire 
dataset, resulting in 20 different ‘complete’ datasets allowing for estimation of the effect 
on the outcome of interest, accounting for missing data.  
 
An additional analysis for the primary endpoint will be performed based on not imputing 
data.  All partial data that is available on subjects who drop out during the course of the 
study will be included.  In addition, sensitivity analyses such as worse-case or best-case 
imputation will be performed although it is recognized that they are biased.   
 
X.      Comparison of Crossed-Over Control versus Study Treatment Outcomes 
a. Effectiveness Outcomes 
 

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Table 7.  Effectiveness Endpoints for Control Arm Crossovers  
(comparison based on paired Control versus EBV Treatment differences)   
Variable 
Unit 
Values Statistically Evaluated 
Forced Expiratory Volume (FEV1) 
>15% improved 
percentage of participants 
     FEV1 
Liters 
mean absolute change 
     FEV1 
percent 
mean percent change 
SGRQ Global Score 
Points 
mean absolute change 
mMRC Score 
semi-quantitative 
scale score 
mean absolute change 
6-Minute Walk Distance 
Meters 
mean absolute change 
     6MWD – subjects stratified by 
distance walked at baseline 
meters 
mean absolute change 
     6MWD 
>25 meters 
improved 
percentage of participants 
DLCO 
percentage 
mean absolute and percent change 
Residual Volume (RV) 
liters 
mean absolute and percent change 
Inspiratory Capacity (IC) 
liters 
mean absolute and percent change 
Total Lung Capacity (TLC) 
liters 
mean absolute and percent change 
RV/TLC 
ratio 
mean absolute change 
IC/TLC 
ratio 
mean absolute change 
 
 
 
 
 
 
 
The time-course of outcomes will be described. A paired t-test statistic will be used to 
quantify the magnitude of the difference between treatment modalities for the 
quantitative outcomes. For binary outcomes, a McNemar test-statistic will be used to 
quantify the magnitude of the difference between the two treatment modalities. 
 
b.  Safety Outcomes 
Evaluation of the short- and long-term adverse events profile of crossed-over 
participants during the second year of follow-up, when they have the EBV treatment, will 
be assessed as in Section VII above. Additionally, the time-course of occurrence of 
Serious Adverse Events (SAEs) will be contrasted and compared for the first year 
(Control Treatment) versus second year (EBV Treatment) periods. For those SAEs that 
could occur with either Control or EBV Treatment, a McNemar test-statistic will be used 
to quantify the magnitude of the difference between the two treatment modalities. 
 
XI. Randomization  Assignment Method 
Study participants who are determined to meet screening, baseline, and procedure 
eligibility criteria will be randomly assigned to Study Treatment (EBV or Control).  Random 
assignment will be performed using a stratified permuted block design, generated 
separately for each clinical site, with assignment stratified by anatomical site of the 
planned treatment (e.g. right lung or left lung).  Mixed block sizes will be used. 
 
XII. Device Malfunction Analyses 
Results of any device malfunctions and their sequelae are to be presented descriptively.  
The rate and exact 95% confidence intervals will be computed.  
 

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XIII. 
Statistical Software 
The parametric and non-parametric analysis of variance and other primary analyses will 
be done using SAS, Version 9.2 or later or StatXact.    
  
 
References 
 
1. Meinert, C. (1986). Clinical Trials: Design, Conduct, and Analysis.  Oxford University Press, 
New York. 
 
2. Medical Devices Dispute Resolution Panel Meeting of September 6, 2001 (Panel 
Transcript) 
 

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Clinical Investigational Plan #630-0012-H 
Appendix 20.  Example Crossover Informed Consent 
 
 
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Investigator Name: ________________ 
 
Site ID#___________________ 
Institution: _______________________ 
 
Participant ID: ______________ 
________________________________ 
________________________________ 
 
Telephone: _________________ 
 
Dear Patient: 
 
You are being asked to participate in the treatment portion of the LIBERATE study because you have 
an impaired lifestyle as a result of emphysema, have successfully completed one year of participation 
in the control arm of the study and still meet the eligibility requirements.  Emphysema is a serious 
disease that afflicts more than four million people worldwide.  It is one form of Chronic Obstructive 
Pulmonary Disease, or COPD.  Emphysema causes the lungs to lose the ability to move air in and 
out normally and to efficiently absorb oxygen, making breathing more 
difficult. What you should know about a research study: 
• Someone will explain this research study to you. 
• You volunteer to be in a research study. 
• Whether you take part is up to you. 
• You can choose not to take part in the research study. 
• You can agree to take part now and later change your mind. 
• Whatever you decide, it will not affect your care. 
• Feel free to ask all the questions you want before and after you decide. 
 
Purpose of the Study 
The purpose of this research is to study a medical device that is designed to be placed by a doctor in a 
diseased section of the lungs.  This device is called the Pulmonx Endobronchial Valve (EBV).  The 
EBV is a one-way valve that blocks off the diseased lung section to inhaled air but lets the trapped air 
already inside the area escape.   With placement of the EBV, the diseased part of the lung collapses; 
this allows the healthier parts of the lung to expand.   The aim of the EBV treatment is to help 
someone with emphysema breathe more easily by allowing the healthier parts of the lung to work 
better.  This research study is designed to investigate the safety and effectiveness of the Pulmonx 
EBV for treating emphysema symptoms. 
The EBV is considered experimental.  This means that it has not yet been approved by the U.S. FDA 
(Food and Drug Administration) for commercial use in the United States. 
Since you have successfully completed the 1-year visit, you may consider crossover to the study 
treatment. In order to qualify for crossover, you must have been followed up successfully through 1 year 
and demonstrate lack of a clinically important response. 
The crossover procedure must be scheduled to occur within the 60 days after the 1 year visit. After 
treatment, the follow-up visits and testing at each visit will be identical to the study schedule for 
treatment arm participants. 
 

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Number of Patients in the Cross-over Portion of the Study 
About 60 patients are expected to be enrolled in the cross-over portion of the study at all research 
sites across the country.  In order to qualify for enrollment into the cross-over portion of the study, 
you must undergo a bronchoscopy procedure.  During the bronchoscopy procedure, your doctor will 
use a device that measures airflow in your lungs to find out if you meet the study criteria for having 
the EBV treatment.  There is a chance that after measuring some of airways in your lungs you will 
not be eligible to take part in this study.  During the bronchoscopy procedure, you may be found 
NOT to qualify for the cross-over portion of the study.   
 
Tests and Evaluations 
A number of tests and assessments will be performed. All of these tests will be the same as you had 
when you initially started participating in the study.  The results of the tests and assessments you 
completed at your 1-year follow-up visit will be used to decide if you qualify for the cross-over 
portion of the study. In addition, you will have a high resolution CT scan, similar to the one you 
had when you first decided to join the study.  All of the tests are described in detail below. If you 
qualify, you will have EBV implanted in your lungs. The study doctor will make the final 
determination of your eligibility during the bronchoscopy procedure.  If you are found to be eligible to 
participate in the cross-over portion of the study, you will receive EBV. 
 
Blood Gas (PaO2 and PaCO2) and Blood Chemistry Analysis 
A blood sample will be taken to measure the amount of oxygen and carbon dioxide in the sample.  
This blood sample will need to be taken from an artery (as opposed to a vein).  An arterial blood 
sample may be more painful than a venous blood sample, which is usually done for more routine 
blood samples.  Standard compounds and the number of blood cells will also be measured from the 
blood sample.  You must have stopped smoking for at least 4 months to participate in this study.  A 
blood test will be performed to confirm that you have stopped.  It is important that you do not smoke 
during this study.  
 
Chest X-ray 
During this test, a simple X-ray will be made of your chest.  
 
Lung Function Tests  
Spirometry: During the test, you will be asked to breathe in and out of a mouthpiece while a machine 
measures the amount of air you are breathing into and out of your lungs.  These breathing maneuvers 
may be somewhat difficult and you may become tired during the test but you will be allowed to rest 
periodically.   
 
Plethysmography: This test is used to determine how much air you can hold in your lungs.  You will 
sit in a small box, comparable to the size of a telephone booth, to undergo breathing tests similar to 
those described above. There is a chance that you may experience claustrophobia in addition to 
fatigue.  
 
Diffusing Capacity:  This test is used to measure the ability of your lungs to transfer carbon 
monoxide.  You will be asked to breathe a mixture of helium, oxygen, nitrogen and carbon 
monoxide and hold your breath for 10 seconds.  

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All together these lung function tests will take about 90 minutes.   
HRCT (High Resolution Computed Tomography) of Chest 
You will be asked to lie down on your back on an x-ray table that will slide into a large, tunnel-
shaped machine.  You must not move during the test and will be asked to relax and breathe 
normally. The technician will also ask you to do some breathing maneuvers such as take a deep 
breath in or out.   
 
Pregnancy Test 
If you are a woman of child-bearing potential, a urine or blood pregnancy test may be performed.  
Six Minute Walk Test 
You will be asked to walk back and forth between a start and end point as many times as possible 
within 6 minutes. You may stop and rest if needed.  Right before and right after the test you will be 
asked questions about how breathless you feel you are.  
 
Questionnaires 
During the study, you will be asked to complete a few simple questionnaires. These questionnaires 
will ask you about your daily activities and your opinion about your general health status and quality 
of life. You will also be asked about frequency of visits to health care providers, such as your regular 
physician, emergent care facilities, and the hospital. 
 
Pulmonary Rehabilitation Program—to be Eligible for the Study 
In order to participate in the cross-over portion of the study, you will have to:   
• Be regularly performing maintenance respiratory rehabilitation.   
 
Description of the Bronchoscopy Procedure 
During the bronchoscopy procedure, your physician will measure some of the airways in your lungs 
using a device called the Chartis® Pulmonary Assessment System.  This system is designed to measure 
air pressure and flow in lung airways.  The air pressure and flow measurements that are collected using 
the Chartis System will help the physician decide if you are eligible to potentially have the EBV 
treatment. Your physician will plan the areas that will be measured before the day of the bronchoscopy 
procedure using the results of your CT scan.      
 
If you are found to have air pressure and flow measurements that show you are NOT eligible to receive 
the EBV treatment, your physician and his or her team will stop the bronchoscopy procedure and you 
will not receive any further treatment during the bronchoscopy procedure.  
 
If you are found to have air pressure and flow measurements that show you are eligible to receive the 
EBV treatment, you will have the EBV treatment.   
 
In rare instances, fluoroscopy may be used by your study doctor if it is difficult for him/her to see your 
lung structures and anatomy using the bronchoscope alone. Fluoroscopy is making a moving picture of 
your lungs with x-rays. 
 
Personnel from the study sponsor (Pulmonx) will attend your bronchoscopy procedure.  The doctor’s 
view of the procedure (the inside of your lung) may also be videotaped or photographed.    

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Description of the Study Procedure  
 
The EBV Procedure 
A bronchoscope (a tube with a camera at the tip, connected to a monitor) will be guided down an access 
tube all the way to the point where the EBV will be placed.  Once your physician can clearly see the area 
where the EBV will be placed, he or she will guide a catheter (flexible tube), with the EBV attached, to 
the targeted treatment area.  Once the catheter is in the proper position, he or she will implant the EBV 
in the lung. This may be done several times depending upon how many EBV are to be placed in your 
lungs.   
 
If there is a problem with the EBV at any time during or after the procedure that makes it difficult or 
inappropriate to continue with the study, your physician may remove the EBV.  In some cases, if the 
EBV is removed, it can be replaced.  In rare cases, the EBV may not have been placed in the original 
procedure as it was intended to be (to completely stop the airflow from the damaged part of the lung).  
This may initiate a discussion between you and your physician about having another procedure to adjust 
the placement of the EBV.    
 
After the Bronchoscopy Procedure 
After the procedure, you will be taken to a recovery area of the hospital.  If you are found to not be 
eligible for the study, you will be allowed to go home a few hours after the bronchoscopy procedure.  If 
you had EBV placed, it is anticipated that you will remain in the hospital for 5 nights.  Before you are 
discharged your study physician will examine you first and review your chest x-ray to confirm you are 
not experiencing any complications.  Your study physician may keep you in the hospital longer if he/she 
feels your health needs further monitoring.  
 
If you received the EBV, a chest x-ray will be taken at 1 hour and once each day during your 
hospitalization including the day you are discharged.  You may need to have additional x-rays at any 
time your study physician thinks it is medically necessary if you are in the hospital longer than 5 days 
after the study procedure.  The nurses in this area are trained to closely watch your recovery and assist 
you in awakening from the anesthesia.  Your vital signs will be monitored, blood samples will be 
collected and any adverse events will be reviewed during your hospitalization.  The medical team will 
often encourage you to cough in order to help expel the anesthesia and any accumulation of mucus.  You 
may also experience the urge to cough.  This coughing sensation is normal and typically goes away.   
 
Before discharge from the hospital, you will be given a study bracelet to wear and a medical alert card to 
give to any physician that may need to treat you informing him/her of the pneumothorax risk.  
Additionally, you will be given post-discharge instructions by the study physician that you will be 
expected to follow.  
 
After Discharge 
 
You will return to your study physician’s office 7 days after discharge for an examination, chest X-ray, 
and to answer questions about your health status.  At the 7 Day after Discharge visit, your study 
physician will examine you and ask you about potential symptoms of pneumothorax and about your use 
of medications.  A chest x-ray will be taken of your lungs at this time.  At this visit, the study doctor will 

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assess you to determine if you may resume your regular activities and start the pulmonary rehabilitation 
program.   
 
After you are discharged from the hospital, you will be contacted once daily for 10 days to answer 
questions about your health status.  
 
After Discharge 
 
Pulmonary Rehabilitation after the Bronchoscopy Procedure 
Within 30 days after the bronchoscopy procedure, you will be asked to begin a supervised pulmonary 
rehabilitation program.  It will consist of 20 sessions, to be done 2-3 times a week for 7-10 weeks.  Each 
pulmonary rehabilitation session will consist of endurance training and strength training for your upper 
and lower limbs.   
 
After you have completed the supervised pulmonary rehabilitation program you will be expected to do a 
home-based maintenance program which will be described to you by your pulmonary rehabilitation 
specialist.  As soon as you are done with the supervised program you will be encouraged to follow this 
home-based program at least three times a week.  For the study, you should continue this program until 
at least your 1 year post-EBV placement follow-up visit.   
 
Length of the Study and Patient Evaluations 
The results of the study will be evaluated after all of the study participants have made the 1-year post-
bronchoscopy follow-up visit.  You will be expected to continue coming to the research clinic once a 
year up through 5 years.  In this study, you will be evaluated several different times.  The following 
table outlines the tests and assessments, starting at the baseline visit, that will be performed and when 
they will be performed.  Depending on the hospital where you have the procedure, some of these tests 
are standard for emphysema treatment and some are not.   
 
 
 
 
 
 
 
 
 
 
 
 
 

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Table 1:  List of Tests/Assessments 
 
+ Pulmonary rehabilitation starts within 30 days after bronchoscopy procedure - must receive PI approval to resume normal activities and the post-bronchoscopy pulmonary 
rehabilitation program; *all of this testing but the CT scan were obtained at your 1-year follow-up visit as a control; + X• serum fibrinogen and ABG only at day 1 hospital stay, ‡for 
study participants who have a study procedure (valve) adjustment, a CT scan, chest x-ray, and body plethysmography will be collected at 3 months post-new procedure. 
 
 
 
Test or Assessment 
Baseline 
Eligibility & 
Assessment* 
Day 0 
Index- 
procedure 
Days 1-4 
Hospital  
Stay 
Day 5 (or 
day of 
Discharge ) 
Daily phone 
contact over 
10 days* 
7 Days after 
Discharge 
30 Days 
45 days 
3 months 
6 months 
9 months 
1 year 
Annual 
visits 
(2-5 years) 
Early 
Termination 
Visit 
Vital Signs / Physical Exam 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Medications & Events Review 
X 
X 
X 
X 
X 
X 
X 
X 
Blood Work 
X 
X• 
X 
Arterial blood gases 
X 
X• 
X 
Pulse oximetry 24 hours after 
procedure 
X 
Spirometry 
X 
X 
 
X 
X 
X 
X 
Body Plethysmography 
X 
X 
X‡ 
X 
Diffusing Capacity 
X 
X 
X 
Symptom checklist 
X 
X 
6 minute walk distance test 
X 
X 
X 
X 
Quality of life surveys and 
questionnaires 
X 
X 
X 
X 
X 
X 
Health Care Utilization 
X 
X 
X 
X 
X 
CT scan 
X 
X 
X‡ 
X 
Chest x-ray 
 
X 
X 
X 
X 
X 
X 
X‡ 
Electrocardiography 
X 
 
 
 
 
 
 
 
X 
Pulmonary rehab compliance 
X 
X 
X 
X 
X 
X 
Pulmonary rehabilitation 
X+ 
Health status change 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Summary of Knowledge about Lung Volume Reduction using the EBV 
The Pulmonx EBV device and procedure was tested extensively in laboratories and animals prior to 
clinical testing.  The EBV device and procedure are currently used outside of the United States, in some 
countries in Europe and Asia, as a standard treatment for emphysema patients.  The EBV was previously 
tested in the United States with a large study that included four hundred ninety-two (492) patients from 
both the United States and Europe.  The results of this large (VENT) study are discussed below. 
The Endobronchial Valve for Emphysema Palliation Trial (VENT study) was a multi-center, prospective, 
randomized, controlled study conducted in the United States and Europe to evaluate safety and 
effectiveness of endobronchial valve treatment (along with optimal medical management) compared to 
optimal medical management alone (control group).  In the U.S. study, the endobronchial valve treatment 
was found to improve forced expiratory volume in one second (FEV1) by an average value of 6.8% and 
the 6 minute walk distance test results by an average value of 5.8%.  These results were significantly better 
than the results seen with medical management alone.   The European patients had similar results.   
After the VENT study was finished, the data was further analyzed.  We found that patients who showed 
signs that the airflow in some parts of their lungs could be blocked off, had the best results with the EBV 
and procedure.  For the study you are considering taking part in, we are planning to select patients who 
show these same signs BEFORE they have the study treatment.  This will be done using the Chartis System 
during the bronchoscopy procedure.  At the end of the study, we will then compare the results of the EBV 
treatment to the control treatment.   
 
In the VENT study, some adverse events were seen. The type of major adverse events and the 
percentage of patients who had them are shown below:   
 
Table 2.  Adverse events that were seen through 90 days in the EBV Treatment Group in VENT Study  
 
Event 
% of 
Patients  
COPD exacerbation (without hospitalization) 
7.9% 
   COPD exacerbation (with hospitalization) 
1.4% 
Hemoptysis (coughing up any amount of blood)   
5.6% 
   Massive Hemoptysis (coughing up a large amount of blood) 
0.5% 
Valve expectoration, aspiration, migration (valve moved from the place it was put by 
the physician) 
4.7% 
Pneumonia  
2.3% 
   Pneumonia (distal, or behind, the valve) 
0.9% 
Formation of bronchial granulation (scab-like) tissue with valve  
2.3% 
Pulmonary infection (infection in the lung) 
1.9% 
Respiratory failure (poor lung function--too much carbon dioxide or too little oxygen in 
your blood--where you need to have assistance with breathing using a mechanical 
ventilator) 
1.4% 
Pneumothorax (air leak in the lung)  that required treatment for more than 7 days 
1.4% 

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Pneumothorax (air leak in the lung) that expanded, or got larger 
1.4% 
Pneumothorax (air leak in the lung) that was stable, or stayed the same size 
1.4% 
Hypoxemia (decreased oxygen in the blood) 
1.4% 
Hypercapnia (excess carbon dioxide in the blood) 
0.9% 
Death 
0.9% 
Noncardiac chest pain 
0.5% 
Bronchial (airway) trauma 
0.5% 
 
Removal of the EBV in the VENT Study 
In some instances, patients enrolled in the valve treatment study group who experienced an adverse 
event required that the valves be removed.  In the U.S. VENT study, 31 (14.5%) patients had valve(s) 
removed after the procedure. The reasons for removal included:  valve migration, pneumonia, bleeding 
(hemoptysis), granulation, increased dyspnea (breathlessness), continuing COPD exacerbations, and 
patient request.      
 
Alternative Treatments for Emphysema 
Oxygen, drug therapy, nutrition and lifestyle changes are the standard therapies for patients with 
emphysema.   An additional alternative treatment may be Lung Volume Reduction Surgery (LVRS).   
 
Summary of Benefits and Risks of Participation in the LIBERATE Study 
As the EBV is still an investigational device in the United States, the actual benefits and risks are 
unknown at this time.  The investigators may learn from this study whether the EBV treatment and 
procedure is safe and effective.  There may or may not be direct benefit from your participation in this 
study.  
 
Potential Benefits 
Potential benefits you may experience as a participant in the cross-over portion of the study include 
having improved lung function and other improvements that may be associated with improved lung 
function, such as improved quality of life.   
 
Potential Risks 
The primary risks associated with use of the Pulmonx EBV are similar to other bronchoscopic and 
surgical procedures used to treat emphysema.  These are listed below.  While this list is comprehensive, 
there may be other risks that are still unknown.  The close monitoring that you will receive, as part of the 
study, should allow for detection of symptoms, should they be present.  This, in turn, should allow for 
early intervention by your physician if that is necessary.  Your physician will review all of the risks 
below with you so that you understand them.   
 
Previous clinical trial experience and experience from other countries around the world, where the EBV 
device is commercially available, has shown that in some people EBV treatment is associated with 
having a pneumothorax as a potential complication. A pneumothorax is a condition in which air leaks 
from the lung into the space between the lung and chest wall. This prevents the healthy lung from 
working well and can cause chest pain and shortness of breath.  As many as 1 in 3 patients may 

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experience a pneumothorax after the study procedure. Most of these tend to occur in the early period 
following the valve placement and usually resolve after staying in hospital for a few days. Most 
frequently, a treatment using a small tube to drain out the air is required.  In rare cases, a pneumothorax 
may require a surgical intervention.  In addition, there is a chance that it can be a serious and life-
threatening complication.   
 
Specifically in this study, the observed rate of pneumothorax events for patients treated with valves to 
date (16 June 2017) is 58 events out of 159 patients (36%).  Forty-six (46) of the 58 pneumothorax 
events (79%) occurred during the first 5 days following the procedure while the patient was still under 
supervision within the hospital.  
 
In addition, the observed rate of death in the first year for patients treated with valves in the LIBERATE 
Study is 5 events out of 128 patients (3.9%). In 2 cases, the patient had a “Do Not Resuscitate” (DNR) 
directive in place that prevented potential life-saving interventions by the physicians. 
 
Based on new information gained from this study so far, if the valve is not placed in the most diseased 
area of your lung, there is a higher risk that you could experience a pneumothorax that may require 
surgical intervention or that could be serious and life threatening. Your physician will discuss with you 
the area of the lung that will be treated so that you can understand whether you are at a higher risk of 
experiencing such an event. 
 
Potential Risks (Adverse Events)  
Acute bronchitis (inflammation or infection of the airways) 
Acute bronchospasm (spasm of the airway; may result in wheezing or increased shortness of breath) 
Acute respiratory distress syndrome (sudden, severe injury to lungs) 
Airway blockage due to implant migration 
Airway perforation (hole in the airway wall) 
Airway stenosis (narrowing) 
Anxiety 
Aphonia (difficulty talking) 
Aspiration (inhalation of vomit) 
Bowel function impairment 
Bronchial (airway) trauma or ulceration 
Chest pain 
COPD exacerbation (acute worsening of COPD symptoms) 
Death 
Depression 
Deep Vein Thromboembolism (DVT, blood clot) 
Dysphonia (hoarse or rough sounding voice) 
Empyema (presence of pus) 
Fever 
Formation of bronchial granulation (scab-like) tissue near the valve(s) 
Fractured Rib 
Headache 
Heart arrhythmias (irregular heartbeats) 

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Heart Attack 
Heart failure (heart function is impaired; could result in increased breathlessness or fluid retention) 
Hemoptysis (coughing up blood) 
Hemothorax (accumulation of blood between the lungs and the chest wall 
Iatrogenic injuries (injury caused by medical procedure) 
Impaired lung function 
Increased cough 
Increased dyspnea (shortness of breath) 
Increased hypercapnea (excess carbon dioxide in the blood) 
Increased hypoxemia (decreased oxygen in the blood) 
Infection  
Laryngospasm (throat spasm) 
Lethargy and disorientation 
Lung cancer or lung mass 
Nausea 
Pleural effusion (collection of fluid around the lungs) 
Pleuritis (inflammation of chest lining) 
Pneumonia 
Pneumothorax (air leak in the lung) 
Pulmonary shunting (uneven blood flow through the lung) 
Pulmonary embolism (a blood clot in the lung which can lead to chest pain and shortness of breath) 
Respiratory failure (poor lung function; could require you to have assistance with breathing using a 
mechanical ventilator) 
Septicemia (severe infection) 
Stroke or Transient Ischemic Attack (sudden temporary loss of neurological function) 
Valve expectoration, aspiration, or migration (valve moves from the place it was put by your 
physician) 
Vomiting 
Wheeze or whistling of valve 
 

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Other Potential Risks of Procedures that are Required by this Study 
 
Lung function and exercise tests:  You will be exerting yourself to your limits in these tests.  
Lightheadedness, dizziness, fainting, chest pain, irregular heartbeats, and rarely death have been seen 
during exercise tests.  You should inform the technicians or physicians if performing these tests makes 
you feel abnormal.  
 
Vein or artery blood tests:  The risks of drawing blood include temporary pain and discomfort and/or 
tenderness form the needle stick, redness, or bruising at the site, bleeding, fainting, and lightheadedness.  
While rare, there is a possibility of infection or a local blood clot with any procedure in which the skin is 
pierced by a needle.  
 
Radiation:  This study involves a radiation exposure from the CT scans and chest x-rays that is typical of 
other diagnostic tests using ionizing radiation.  The amount of radiation exposure received in this study 
is below the levels that are thought to result in a significant risk of harmful effects.  If you are especially 
concerned with radiation exposure, you should discuss this with your study doctor.   
 
Antibiotics:  Antibiotics will be provided to you around the time of the procedure and afterwards to 
minimize possible side effects.  All pharmaceutical drugs have side effects.  Antibiotics may also have 
side effects, including diarrhea, allergic reactions, and overgrowth of dangerous bacteria such as C. 
difficile which can result in a serious infection.  However, antibiotics are used routinely to treat COPD 
exacerbations.   
 
Anesthesia:  The side effects of moderate procedural sedation or general anesthesia medications and 
other medications required to perform bronchoscopy include, but are not limited to, allergic reaction, 
drowsiness, slurred speech, tremor, fatigue, low blood pressure, slowing of the heart rate, anxiety, 
confusion, dizziness, temporary loss of consciousness, and respiratory depression.  Trained medical 
professionals with extensive experience and expertise will administer the medications and will be 
responsible for your care during the course of the procedure.   
 
Voluntary Participation and Study Withdrawal 
Decisions regarding whether or not you should participate in this study are entirely voluntary.  If you 
decide not to participate, you will not lose any benefits to which you are entitled, nor will you be denied 
access to other available treatments for emphysema.  You will receive the standard treatment and care 
normally provided by your physician. 
 
Information obtained in the operating room after anesthesia is given to you will affect whether or not 
you are eligible to receive treatment during the bronchoscopy procedure.  This will happen, for instance, 
if it is determined that the air pressure and flow measured in the airways in your lungs make you 
ineligible to meet the study entry criteria or that the anatomy of your lung passageways does not allow 
the physician to place the EBV Implant.  In such an event, you will be sent to the recovery room without 
the valve treatment.   
 
Significant new findings discovered during the course of this study, which may affect your willingness 
to continue participating in the study, will be provided to you in writing.  You may withdraw your 
consent to participate in this study at any time without penalty or loss of benefits.  Also, your 

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physician may terminate your participation if continuing participation does not appear to be in your best 
medical interest, or if Pulmonx, the study Sponsor, terminates the study. 
 
Precautions 
Within 30 days before and 30 days after participating in this study, you should not take part in any other 
research project.  This is to protect you from possible injury arising from excessive blood drawing, 
excess x-rays, and interactions with other research devices or drugs, or similar hazards. 
 
Pregnancy and Contraception (Birth Control) 
Pregnant women may not participate in this research study as the risk of the procedure on an embryo or 
unborn fetus is unknown.  Women of childbearing potential must actively utilize appropriate means of 
birth control to avoid becoming pregnant throughout the course of the study.  
 
Confidentiality 
Information derived from this study and from your medical record may be reviewed and photocopied by 
the Food and Drug Administration (FDA) and/or state and federal regulatory agencies and by the device 
manufacturer, Pulmonx Inc., with protection of confidentiality so far as permitted by applicable law.  
Information resulting from this study and from your medical record may be used for research purposes 
and may be published; however, you will not be identified by name in such publications.    
 
Financial Responsibility 
The costs of any routine medical care administered during the study will be the responsibility of you 
and/or your health insurer. For such routine costs, you will be responsible for any co-payments or 
deductibles required under your insurance. You are not, however, expected to absorb the cost of any 
medical care specifically required by participation in this study. The study Sponsor (Pulmonx) will pay 
for tests and procedures performed solely for the purpose of this study.   
 
Research Related Injury 
In the event that you believe participation in this research study has led to injury, contact your physician 
and he will review the matter with you. You should understand that neither _____________________ 
(hospital) nor the Federal Government has any programs to provide compensation for persons 
participating in research projects who may experience injury. However, necessary facilities, emergency 
treatment and professional services will be available to you. You should not expect any one to pay you 
for pain, worry, lost income, or non-medical care costs that occur from taking part in this research study. 
No funds have been set aside by _________________ (hospital) to pay you in case of injury, nor will 
the study Sponsor provide direct compensation to patients in the event of an injury.  
 
Study Information at www.clinicaltrials.gov 
A description of this clinical trial will be available on the http:www.clinicaltrials.gov, as required by 
U.S. Law.  This web site will not include information that can identify you.  At most, the web site will 
include a summary of the results.  You can search this web site at any time.   
 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 20.  Example Crossover Informed Consent 
 
 
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Add Financial Compensation Section as Applicable 
This section is site specific – include financial compensation information as needed. 
 
Questions 
If you have any questions about the study, its procedures, risks or benefits, your alternatives or your 
rights, or if you experience a potentially research related injury you should contact your doctor. If you 
cannot reach your doctor, contact the alternate individual listed below. 
 
Physician Contact Information (24 hour): 
 
Name:  
______________________ 
 
Phone Number:______________________ 
Alternate Contact Information (24 hour): 
 
Name:  
______________________ 
 
Phone Number:______________________ 
 
 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 20.  Example Crossover Informed Consent 
 
 
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Authorization to Use and Disclose Health Information 
I agree to permit ____________________ (physician) and his/her staff (“Researchers”) to use and disclose 
health information that identifies me for the purposes described below.  I also agree to permit 
________________________ (hospital), my doctors, and my other health care providers to disclose health 
information in my medical records to the Researchers for the purposes described below.   
 
1. The health information that may be used and disclosed includes all information collected during 
the research described in this document and health information in my medical records that is 
relevant to the research described. 
2. The researchers and Pulmonx may use and share my health information to conduct research; 
disclose my health information to Pulmonx to confirm the research results; disclose my health 
information as required by law to representatives of government agencies and other persons who 
are required to watch over the safety, effectiveness and the conduct of the research; and remove 
from my health information my name and other information that could be used to identify me. 
3. Once information that could be used to identify me has been removed, the information that remains 
is no longer subject to this authorization and may be used and disclosed by the researchers and 
Pulmonx as permitted by law including for other research purposes. 
4. Once my health information has been disclosed to a third party, federal privacy laws may no longer 
protect it from further disclosure.  However, the researchers and Pulmonx agree to protect my 
health information by using and disclosing it only as permitted by me in this Authorization.  Also, 
no publication about the research will reveal my identity without my specific written permission.  
These limitations continue even if I revoke this Authorization.   
5. Please note that you do not have to sign this authorization, but if you do not, you may not be 
allowed to participate in this research study.  You may change your mind and revoke this 
authorization at any time.  However, if you revoke this authorization, you may no longer be 
allowed to participate in this research study.  Also, even if you revoke this authorization, the 
information already obtained may remain part of the research.  To revoke this authorization, you 
must write to: 
 
 
 
 
While the research is in progress, you will not be allowed to see your health information that is 
created or collected in the course of the research.  After the research is finished, however, you 
may see this information as described in (hospital) Notice of Information practices.     
 
6. This authorization does not have an expiration date. 
 
 
 
 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 20.  Example Crossover Informed Consent 
 
 
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Informed Consent 
I, ___________________________________, the undersigned hereby consent to my involvement in the 
research project titled: Lung Function Improvement after Bronchoscopic Lung Volume Reduction 
with Pulmonx Endobronchial Valves used in Emphysema. 
1) The nature, purpose, and contemplated effects of the project, so far as it affects me, have been fully 
explained to my satisfaction by the research worker.  My consent is informed and given voluntarily. 
2) The details of the procedure proposed have also been explained to me. 
3) It has been explained to me that the purpose of this research project is to improve the quality of 
medical care, and that my involvement may not be of any benefit to me. 
4) I have been given the opportunity to have a member of my family or a friend present while the 
project is explained to me. 
5) I am informed that no information regarding my medical history will be divulged, other than that 
described in the consent form, and that my identity will be kept confidential in all published results 
of the study. 
6) I have been informed that my involvement in the project will not affect my relationship with my 
medical advisors in their management of my health.  I have also been told that I am free to withdraw 
from the project at any stage without prejudice for future treatment at this hospital, and if I so 
choose, I can ask for any information collected up to that point to be withheld from use in the 
research. 
7) I declare that all of my questions have been answered to my satisfaction. 
 
If I agree to participate in the research study and if my questions are answered, I should sign this form.  
If I wish to refuse to participate in the study, I may do so without any loss of medical care or benefits.  
Once I have consented, I still have the right to withdraw at any time.  To withdraw, all I have to do is 
complete the Revocation of Consent portion of the form below and provide to or simply tell Dr. 
________________________. 
 
I will be given a copy of this form to keep and to refer to as needed. 
 
Printed Name of Participant (or legal representative):  
 
 
 
 
 
 
 
 
Signature: 
 
 
 
 
 
 
Date:  
 
 
 
 
 
I declare that I have been present when the research study was explained to the above participant and I 
believe that the participant has an application and understanding of the explanation given. 
 
Witness: 
 
 
 
 
 
 
Date:  
 
 
 
 
 
 

LIBERATE Study 
Clinical Investigational Plan #630-0012-H 
Appendix 20.  Example Crossover Informed Consent 
 
 
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REVOCATION OF CONSENT 
I hereby wish to WITHDRAW my consent to participate in the research proposal described above.  
Withdrawal WILL NOT jeopardize any treatment or my relationship with _________________ 
Hospital. 
 
Printed Name of Participant (or legal representative):  
 
 
 
 
 
 
 
Signature: 
 
 
 
 
 
 
Date: