A Prospective, Randomized, Controlled, Multi-Center Evaluation of a Powered Vascular Stapler in VAT Lobectomies
Phase: NA
Conditions: Non Small Cell Lung Cancer
Sponsor: Ethicon Endo-Surgery

Protocol ESC-15-001 
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A Prospective, Randomized, Controlled, Multi-Center Evaluation of a Powered Vascular 
Stapler in Video-Assisted Thoracoscopic Lobectomies 
Protocol #:   ESC-15-001 
Document 
Effective Date 
Original  
  November 11, 2015 
Sponsor:  
Ethicon Endo-Surgery, Inc. 
4545 Creek Road 
Cincinnati, OH 45242 
CONFIDENTIALITY STATEMENT 
The information in this document contains trade secrets and commercial information that are privileged or confidential 
and may not be disclosed unless such disclosure is required by federal or state law or regulations.  Subject to the 
foregoing, this information may be disclosed only to those persons involved in the study who have a need to know, but all 
such persons must be instructed not to further disseminate this information to others.  These restrictions on disclosure 
will apply equally to all future information supplied to you which is indicated as privileged or confidential. 
NCT ID: NCT02702921

 
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INVESTIGATOR SIGNATURE 
 
I have read, understood, and agree to: 
 
Ensure that the requirements for obtaining informed consent are met; 
 
Conduct the study in accordance with this protocol, including applicable local laws and 
regulations; 
 
Maintain the confidentiality of all information received or developed in connection with 
this protocol; 
 
Report all serious adverse events as soon as possible, but no later than 24 hours after 
becoming aware of the event; 
 
Adhere to the publication policy, as stated in the Clinical Study Agreement, for data 
collected during this study; and 
 
Ensure that all associates, colleagues, and employees assisting in the conduct of the 
study are informed of their obligations in meeting the above commitments. 
 
I will ensure that the Institutional Review Board (IRB)/Ethics Committee (EC) review complies 
with governmental requirements and will be responsible for the initial and continuing review and 
approval of the clinical investigation.  I also agree to promptly report to the IRB/EC all changes 
in the research activity and all unanticipated problems involving risks to human subjects or 
others.  Additionally, I will not make any changes in the research without sponsor and IRB/EC 
approval of an amended protocol, except where necessary to eliminate apparent immediate 
hazards to human subjects. 
I agree to comply with all other requirements regarding the obligation of clinical investigators 
and all other pertinent requirements of the sponsor and government agencies. 
 
 
 
 
 
 
 
 
 Investigator Signature 
 
Date 
 
 
 
 
 
 
Printed Name of Investigator 
 
 
 
 
 

 
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SYNOPSIS 
 
Regulatory 
Classification:   
Class II Staple Implantable; Stapler, Surgical 21CFR 
878.4750. Cleared 11/24/2014, 510(k) # K141952 
CE Mark granted 02/27/2015, Certificate, G7 15 02 
57666 049 
Indication:   
The ECHELON FLEXTM Powered Vascular Stapler 
(PVS) with Advanced Placement Tip and its reloads 
are intended for transection and resection of tissue and 
vasculature.  The instruments have application in 
multiple open or minimally invasive general, 
gynecologic, urologic, thoracic, and pediatric surgical 
procedures. The device will be utilized as described in 
the instruction for use (IFU). 

 
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Objective/Endpoint:   The primary objective of the study is to demonstrate 
that the frequency of hemostatic 
interventions/procedures required intra-operatively or 
post-operatively related to the transection of the 
pulmonary artery (PA) and pulmonary vein (PV) during 
VATS lobectomy with PVS is not increased when 
compared to standard of care (SOC). 
 
The primary performance endpoint will be: 
Incidence of hemostatic interventions/procedures 
completed for intra-operative bleeding related to the 
transection of the PA and PV during VATS lobectomy 
with the use of standard of care stapler (SOC) or 
powered vascular stapler (PVS) defined as: 
 
Hemostasis intervention:  bleeding 
detected and controlled intra-
operatively (additional stapling, 
over-sewing, clip placement, 
compression, use of suture, 
sealant, and/or buttress, and/or use 
of energy); or bleeding that occurs 
intra-operatively requiring blood or 
blood product transfusion or an 
additional surgical procedure (e.g. 
conversion to open). 
 
No hemostasis intervention is defined as no bleeding 
at the staple line or bleeding that stops after initial 
blotting of staple line. 
 
The primary safety endpoint will be: 
Incidence of hemostatic interventions /procedures 
completed for post-operative bleeding related to the 
transection of the PA and PV during VATS lobectomy 
with the use of SOC or PVS: 
 
Hemostasis intervention: bleeding 
that occurs post-operatively 
requiring blood or blood product 
transfusion or an additional surgical 
procedure (related to PA and PV 
transection). 
 
No hemostasis intervention is defined as no 
interventions needed for post-operative bleeding 
(related to PA and PV transection). 
 
 
 

 
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Study Design: 
This prospective, randomized, controlled, multi-center 
study will collect and compare data from the surgeon’s 
current SOC stapler (for PA/PV transection) and 
powered vascular stapler.   
Number of Subjects 
(Planned): 
Approximately 200 subjects will be randomized 
Diagnosis/Criteria 
for Inclusion:   
Subjects satisfying the following criteria will be eligible 
for participation in this study: 
 
1.  Subjects with a confirmed or suspected 
diagnosis of stage IA to stage IIIA non-
small cell lung cancer scheduled for a 
lobectomy (Lung Cancer Staging per 
American Joint Committee on Cancer,7th 
Edition)5;
2. Subjects scheduled for VATS lobectomy 
in accordance with their institution’s SOC; 
3. Performance status 0-1 (Eastern     
Cooperative Oncology Group 
classification); 
4. ASA score < 3;    
5. No prior history of VATS or open lung 
surgery (on the lung in which the 
procedure will be performed); 
6. Willing to give consent and comply with 
study-related evaluation and treatment 
schedule; and 
7. At least 18 years of age.  
 
Diagnosis/Criteria 
for Exclusion:   
Subjects will be excluded from the study for any of the 
following: 
1. Prior chemotherapy or radiation (within 30 
days prior to the procedure or the duration 
of the subject’s enrollment); 
2. Pregnancy; 
3. Physical or psychological condition which 
would impair study participation; or 
4. The subject is judged unsuitable for study 
participation by the Investigator for any 
other reason. 
 
Finished Product:   
ECHELON FLEXTM Powered Vascular Stapler with 
Advanced Placement Tip 

 
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Statistical  
Methods:   
Summary statistics and 95% confidence intervals will 
be provided for the number and frequency of 
interventions for the set of SOC and PVS subjects 
separately. This will be performed based on the total 
number of firings. An intervention is defined as any 
firing which is classified as hemostasis intervention.  
Given that it is expected to have at least 260 firings in 
each group, the sample size of approximately 200 
subjects is considered adequate for descriptive 
summarization of the number and frequency of surgical 
interventions. Assuming an approximate background 
intervention rate of 6%, the given sample size will 
provide reasonable precision in the estimation of the 
intervention rate to an expected margin of error for a 
95% confidence interval of at most 2.9% for each 
group. To establish that the intervention rate is not 
increased compared to SOC, a 95% confidence 
interval for the difference in proportion of firings 
requiring interventions for PVS minus SOC will be 
calculated and powered vascular stapler will be 
considered to have acceptable performance if the 
upper bound of the 95% confidence interval does not 
exceed 3%.  
The number and percentage of subjects requiring 
hemostasis interventions post-operatively that are 
classified as related to SOC or PVS for PA/PV 
transection (e.g. need for blood product transfusion or 
additional surgical procedure) will be summarized for 
each group as a primary safety endpoint.  
Additional endpoints will be summarized with 
descriptive statistics and 95% confidence intervals as 
appropriate for continuous or categorical 
measurements.  Safety will be assessed through the 
incidence of AEs and serious adverse events (SAEs), 
which will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA). 
 
 
 
 
 
 
 
 

 
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SCHEDULE OF EVENTS 
 
a. 
Two weeks prior to screening visit through study conclusion 
b. 
See section 4.7.3.1.2 for specific details 
c. 
Surgeon Device Questionnaire (PVS procedures only).  Surgeon Satisfaction and SURG-TLX (SOC and PVS 
procedures) 
d. 
Including pain medications given perioperative (i.e. spinal block, intercostal nerve blocks, etc.) and post-operative 
pain medications 
e. 
Phone call or office visit 
f. 
Anticoagulants taken preoperatively (up to 30 days prior to Visit 2/Procedure), including the stop date 
g. 
If applicable 
 
 
Study Activity  
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Screening Procedure
Post-Op 
through 
Discharge 
4 week 
follow-upe 
(post 
procedure)
Informed consent 
X 
 
 
 
Demographic information 
X 
 
 
 
Relevant medical/surgical history 
X 
X 
 
 
Inclusion/Exclusion Criteria 
X 
X 
 
 
Pain medication usagea,d 
X 
X 
X 
X 
ASES  Standardized Shoulder Assessment 
X 
 
X 
X 
Pain score assessment (incisional, trocar, 
chest tube pain) 
 
 
X 
X 
ASA score 
 
X 
 
 
Collection of procedure datab 
 
X 
 
 
Randomization (SOC or PVS) 
 
X 
 
 
Intra-operative interventions on PA/PV 
 
X 
 
 
Post-operative interventions on PA/PV 
 
 
X 
X 
Procedure duration  
 
X 
 
 
Daily volume and characteristics of chest 
tube(s) drainage 
 
 
X 
Xg
Concomitant procedures/interventions, if 
applicable 
 
 
X 
X 
Surgeon questionnairesc 
 
X 
 
 
Date of hospital admission 
 
X 
 
 
Overall Operating Room (OR) time 
 
X 
 
 
Adverse Events  
 
X 
X 
X 
Anticoagulantsf  
X 
 
 
 
Concomitant medications associated with 
adverse events/pain 
 
X 
X 
X 
Date(s) of chest tube(s) removal 
 
 
X 
Xg
Discharge date  
 
 
X 
 
Subject exited from study 
 
 
 
X 

 
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TABLE OF CONTENTS 
 
Page 
INVESTIGATOR SIGNATURE ................................................................................................. 3 
SYNOPSIS ................................................................................................................................ 4 
SCHEDULE OF EVENTS ...................................................................................................... 8 
ETHICS ................................................................................................................................... 11 
ADMINISTRATIVE REQUIREMENTS ................................................................................... 12 
1.0 
INTRODUCTION AND BACKGROUND ....................................................................... 13 
2.0 
STUDY OBJECTIVES ................................................................................................... 14 
2.1 
PRIMARY OBJECTIVE ................................................................................................. 14 
3.0 
INVESTIGATIONAL PLAN............................................................................................ 14 
3.1 
GENERAL DESIGN ...................................................................................................... 14 
3.2 
PRIMARY ENDPOINTS ................................................................................................ 14 
3.3 
ADDITIONAL MEASUREMENTS / DATA COLLECTED ............................................. 15 
4.0 
INVESTIGATIONAL PLAN............................................................................................ 16 
4.1 
OVERALL STUDY DESIGN ......................................................................................... 16 
4.2 
RANDOMIZATION ........................................................................................................ 16 
4.2.1  Inclusion Criteria ............................................................................................................ 16 
4.2.2  Exclusion Criteria .......................................................................................................... 16 
4.3 
PRIOR AND CONCOMITANT THERAPY .................................................................... 17 
4.3.1 
Concomitant Medications ..................................................................................... 17 
4.4 
REMOVAL OF SUBJECTS FROM STUDY ................................................................. 17 
4.5 
IDENTITY OF STUDY PRODUCT(S) ........................................................................... 19 
4.6 
PRODUCT ACCOUNTABILITY .................................................................................... 19 
4.7 
STUDY PROCEDURES ................................................................................................ 19 
4.7.1 
PROCEDURE DESCRIPTION ............................................................................. 19 
4.7.2 
VISIT 1 – SCREENING (CAN OCCUR OVER SEVERAL DATES WITHIN 1-2 
WEEKS OF VISIT 2- PROCEDURE) ................................................................... 19 
4.7.3 
VISIT 2 –PROCEDURE ........................................................................................ 20 
4.7.3.1.1 PRE-PROCEDURE ....................................................................................... 20 
4.7.3.1.2 INTRA-OPERATIVE ...................................................................................... 20 
4.7.4 
Visit 3 – Post-operative through Discharge .......................................................... 21 
4.7.5 
Visit 4- Final Visit (4 week follow up, post procedure) ......................................... 22 
5.0 
DATA MANAGEMENT AND INTEGRITY..................................................................... 22 
5.1 
DATA COMPLETION AND RECORD KEEPING ......................................................... 22 
5.1.2 
ELECTRONIC DATA CAPTURE .......................................................................... 23 
5.1.3 
DATA COLLECTION ............................................................................................ 23 
5.1.4 
DATA CORRECTION ........................................................................................... 23 
5.1.5 
DATA PRIVACY .................................................................................................... 23 
5.1.6 
RECORD RETENTION, INSPECTION, AND CUSTODY ................................... 24 
5.2 
MEDICAL DICTIONARY CODING ........................................................................... 24 
6.0 
DATA QUALITY ASSURANCE ..................................................................................... 24 
6.1 
Investigator Training .................................................................................................. 24 
6.2 
Monitoring .................................................................................................................. 24 
6.3 
PROTOCOL DEVIATIONS ....................................................................................... 25 
7.0 
STATISTICAL METHODS PLANNED IN THE PROTOCOL AND DETERMINATION OF 
SAMPLE SIZE ............................................................................................................... 25 
7.1 
Statistical and Analytical Plans ................................................................................. 25 
7.2 
Determination of Sample Size................................................................................... 25 
7.3 
Analysis Sets ............................................................................................................. 26 

 
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7.4 
Analysis of Effectiveness .......................................................................................... 26 
7.5 
Statistical/Analytical Issues ....................................................................................... 26 
7.5.1  Handling of Dropouts or Missing Data ...................................................................... 26 
7.5.2  Interim Analyses and Data Monitoring ...................................................................... 26 
7.5.3  Multicenter Studies .................................................................................................... 26 
7.5.4  Multiple Comparisons/Multiplicity .............................................................................. 26 
7.6 
Analysis of Safety ...................................................................................................... 27 
8.0 
RISKS AND BENEFITS OF THE STUDY DEVICE AND CLINICAL     INVESTIGATION
 ....................................................................................................................................... 27 
9.0 
ADVERSE EVENTS AND PRODUCT COMPLAINTS ................................................. 27 
9.1 
DEFINITIONS ................................................................................................................ 27 
9.1.1  ADVERSE EVENT ........................................................................................................ 27 
9.1.2  ANTICIPATED ADVERSE EVENTS ............................................................................ 27 
9.1.3  SERIOUS ADVERSE EVENT ....................................................................................... 28 
9.1.4  SEVERITY OF ADVERSE EVENTS ............................................................................ 28 
9.1.5  RELATIONSHIP OF ADVERSE EVENTS .................................................................... 28 
9.1.6  Product Complaints ....................................................................................................... 29 
9.2 
REPORTING PROCEDURES FOR ADVERSE EVENTS/PRODUCT   COMPLAINTS29 
9.2.1  REPORTING ADVERSE EVENTS ............................................................................... 29 
9.2.2  Reporting Serious Adverse Events ............................................................................... 29 
9.2.3  Reporting Product Complaints ...................................................................................... 30 
10.0  REFERENCE LIST ........................................................................................................ 30 
11.0  APPENDIX I:  ANTICIPATED ADVERSE EVENTS ..................................................... 31 
 
 
 

 
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ETHICS 
Institutional Review Board/Ethics Committee 
Participating investigators will ensure that this protocol, Informed Consent Document (ICD), ICD 
or protocol amendments, and if applicable, any other written information provided to the 
subjects that assist in the decision to participate are reviewed by an Institutional Review Board 
(IRB) or Ethics Committee (EC) that complies with governmental requirements. The approving 
IRB/EC will be responsible for the initial and continuing review and approval of this clinical 
investigation.  Participating investigators will be required to promptly report to the IRB/EC as 
required by the IRB/EC’s policies.  Additionally, investigators will be required to refrain from 
making any changes in the clinical investigation plan without Sponsor and IRB/EC approval of 
an amended protocol, except where necessary to eliminate apparent immediate hazards to 
study subjects or others. 
Applicable Regulations  
This study will be conducted in compliance with Good Clinical Practice and in accordance with 
the Declaration of Helsinki, ISO 14155: 2011, as well as any other applicable local and country 
regulatory requirements. 
Subject Information and Consent 
Regulations concerning the protection of subjects require that informed consent be obtained 
before a subject may participate in any clinical investigation.   
An IRB/EC approved informed consent must be sought from each subject and must be 
appropriately documented in the subject’s medical record prior to initiating the study. It is the 
Investigator’s responsibility to obtain written informed consent from the subject, the Investigator 
may delegate this responsibility if appropriately documented. 
The informed consent process involves the following: giving a subject adequate information 
concerning the study, providing adequate time for the subject to consider all available options, 
responding to the subject’s questions, ensuring that the subject has comprehended this 
information and finally, obtaining the subject’s written consent to participate in this study.  All 
subjects in this study should be completely informed about the purpose, risks, benefits, and 
other pertinent details of this study.  The informed consent process is careful to avoid the 
perception of any coercion or undue influence on, or inducement of, the subject to participate, 
and does not waive or appear to waive the subject's legal rights.  The ICD is presented in 
native, non-technical language that is understandable to the subject. 
Prior to a subject’s participation in this study, an ICD will be signed and dated by the subject and 
person who conducted the consent discussion. The subject will be provided a copy of the 
signed ICD.  The ICD and any other written materials provided to the subject to assist in the 
decision to participate must be revised whenever new information becomes available that may 
be relevant to their willingness to participate or continue participation in this study.  Revision to 
the ICD and other written materials will receive IRB/EC approval before implementation.  Each 
subject will be required to sign any amended ICD (as required by the IRB/EC) and will receive a 
copy of the signed ICD.   
 
 
 
 

 
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ADMINISTRATIVE REQUIREMENTS 
This study is sponsored by Ethicon Endo-Surgery, Inc. (EES, Cincinnati, OH, USA) and will be 
conducted in approximately six surgery centers in the United States and/or European Union 
under a single protocol approved by each participating site’s IRB/EC prior to implementation.   
The principal investigator at each study site is a surgeon qualified by education, experience, and 
training to perform the study procedure and to assume responsibility for the conduct of this 
study.  
The Data Management and Biostatistics groups of Ethicon Endo-Surgery, Inc.’s Global Surgery 
Clinical Development will be responsible for the analysis of data from this protocol.  An 
Electronic Data Capture (EDC) system will be utilized by study site personnel to transfer study 
data from source records (the first point of clinical data capture) onto common electronic case 
report forms (eCRFs). This system is a web-based, secure electronic software application 
(Medidata® Rave, 350 Hudson Street, 9th Floor, New York, New York, 10014).  This system 
was designed and is developed and maintained by Medidata in a manner that is compliant with 
national and international Good Clinical Practice (GCP) data protection/data privacy and 
electronic record/electronic signature (e.g. 21 CFR Part 11) regulatory requirements. 
 
Protocol Modifications 
All protocol amendments must be issued by the Sponsor, signed and dated by the Investigator, 
and should not be implemented without prior IRB/EC approval, except where necessary to 
eliminate immediate hazards to the subjects or when the change(s) involves only logistical or 
administrative aspects of the study (e.g., change in Sponsor personnel, change of telephone 
number(s)).  The Investigator will submit the protocol amendments to the IRB/EC as per their 
local requirements. 
 

 
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1.0 INTRODUCTION AND BACKGROUND 
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer.1   Surgical 
intervention is required in the treatment of lung cancer to remove localized tumors, as 
well as potentially affected lymph nodes, in order to prevent further spread of the 
disease.  International guidelines for NSCLC treatment are closely linked to the cancer 
stage and the patient’s general performance.2   Surgery is most common in patients with 
Stage 0 NSCLC, but may also be performed in patients with Stage I or Stage II NSCLC, 
if tumors remain localized.  Patients with Stage IIIA NSCLC could have resectable 
tumors or some form of metastases. Overall, the type of surgical procedure required 
varies depending on multiple factors, including the stage, location and cell types 
associated with the tumor. Limiting factors for surgery include poor overall performance 
status or an inadequate pulmonary reserve, as these patients will have a reduced 
chance of surviving the procedure.  Surgical interventions are not appropriate for 
patients with a poor overall performance status as the risk of serious complications or 
peri-operative death may be too high.  Surgical intervention decisions are made on the 
basis of the progression of the tumor as well as the general condition of the patient.    
 
The surgical procedure performed under this protocol is Video-Assisted Thoracoscopic 
Surgery (VATS) lobectomy.   VATS uses video technology to assist during thoracic 
surgical procedures. VATS is most commonly utilized in the treatment of lung cancer 
and can be used to extract cancerous tumors from the lungs through segmentectomy or 
lobectomy. A small video camera, for visualization of internal anatomy, is inserted into a 
patient’s chest via an incision in the chest wall termed a port. Additional ports are 
created to allow the entry of surgical instruments. The pulmonary artery, pulmonary vein, 
and bronchus to the involved pulmonary lobe are individually dissected, ligated and 
divided. VATS is commonly utilized in the treatment of lung cancer.   
  
Ethicon Endo-Surgery, Inc. has developed a powered vascular stapler, the ECHELON 
FLEXTM Powered Vascular Stapler with Advanced Placement Tip, which can transect 
pulmonary vessels in restricted narrow spaces near delicate vascular anatomy.    With 
its narrow anvil and curved dissection tip, this stapler enhances visibility and provides 
precise placement.   
 
 
 
 
 
 
 
 
 

 
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2.0 STUDY OBJECTIVES 
2.1 PRIMARY OBJECTIVE 
The primary objective of the study is to demonstrate that the frequency of hemostatic 
interventions/procedures required intra-operatively or post-operatively related to the 
transection of the pulmonary artery (PA) and pulmonary vein (PV) during VATS 
lobectomy with PVS is not increased when compared to standard of care (SOC).  
3.0   INVESTIGATIONAL PLAN 
3.1 GENERAL DESIGN  
This prospective, randomized, controlled, multi-center study will collect and compare 
data from the surgeon’s current SOC stapler (for PA/PV transection) and PVS.  
Approximately 200 individuals undergoing VATS lobectomy, and who meet study entry 
criteria, will be randomized in a 1:1 ratio to either the surgeon’s current SOC stapler or 
PVS.  Prospective subjects will be informed about the nature of the research, given the 
ICD to read, and if the subject understands the consent, will be asked to provide 
written consent (the ICD).   
 
3.2 PRIMARY ENDPOINTS 
 
The primary performance endpoint will be: 
Incidence of hemostatic interventions/procedures completed for intra-operative 
bleeding related to the transection of the PA and PV during VATS lobectomy with the 
use of standard of care stapler (SOC) or powered vascular stapler (PVS) defined as: 
 
Hemostasis intervention:  bleeding detected and controlled intra-operatively 
(additional stapling, over-sewing, clip placement, compression, use of 
suture, sealant, and/or buttress, and/or use of energy); or bleeding that 
occurs intra-operatively requiring blood or blood product transfusion or an 
additional surgical procedure (e.g. conversion to open). 
 
No hemostasis intervention is defined as no bleeding at the staple line or bleeding that 
stops after initial blotting of staple line. 
 
The primary safety endpoint will be: 
Incidence of hemostatic interventions /procedures completed for post-operative 
bleeding related to the transection of the PA and PV during VATS lobectomy with the 
use of SOC or PVS: 
 
Hemostasis intervention: bleeding that occurs post-operatively requiring 
blood or blood product transfusion or an additional surgical procedure 
(related to PA and PV transection). 
 
No hemostasis intervention is defined as no interventions needed for post-operative 

 
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bleeding (related to PA and PV transection). 
 
3.3 ADDITIONAL MEASUREMENTS / DATA COLLECTED 
a. Subject demographics;  
b. Pain medication usage (two weeks prior to procedure through final study visit); 
c. All adverse events; 
d. Anticoagulants taken preoperatively (up to 30 days prior to Visit 2/Procedure) and 
concomitant medications associated with AEs and pain; 
e. Relevant medical/surgical history (including hypertension and/or smoking history, if   
applicable); 
f. 
Pain score assessments; 
g. Procedure details; 
h. Number of ports; 
i. 
Overall operating room and procedure duration (including time to resection); 
j. 
Use of other stapling devices for bronchus and parenchyma transection (number 
and color of cartridges); 
k. Intra-operative and post-operative surgical interventions (not associated with 
transection of the PA/PV), if applicable; 
l. 
Volume of estimated intra-operative blood loss; 
m. Transfusion of blood or blood products;  
n. Date(s) of chest tube removal; 
o. Daily volume and characteristics of chest tube(s) drainage; 
p. Device usability /articulation questions;   
q. Surgeon assessment of visualization; 
r. Surgeon Questionnaires; 
s. American Shoulder and Elbow Surgeons (ASES) 3,4  Standardized Shoulder 
Assessment; 
t. 
Concomitant procedures/interventions, if applicable; and 
u. Length of stay (LOS) from admission through discharge. 
 
The data collected for this study may be used for future research or enhancement of 
similar surgical tools. 
 
 
 
 
 
 
 
 
 

 
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4.0   INVESTIGATIONAL PLAN 
4.1 OVERALL STUDY DESIGN  
This is a prospective, randomized, controlled, multi-center study that is intended to 
demonstrate that the frequency of hemostatic interventions/procedures required intra-
operatively or post-operatively related to the transection of the pulmonary artery (PA) and 
pulmonary vein (PV) during VATS lobectomy with PVS is not increased when compared to 
standard of care (SOC).  
Eligible subjects will be randomized pre procedure in a 1:1 ratio to either the surgeon’s 
current SOC stapler or PVS. Subjects will be followed post-operatively through discharge 
and at 4 weeks post-surgery (final visit can be conducted either by phone or office visit).   
If the study surgeons have not completed previous ECHELON FLEXTM Powered Vascular 
Stapler with Advanced Placement Tip training, each surgeon must complete two procedures 
with ECHELON FLEXTM Powered Vascular Stapler with Advanced Placement Tip prior to 
their first randomized subject.  These subjects will be considered part of a learning curve 
and will be analyzed separately from the randomized subjects.   
4.2 RANDOMIZATION 
In this non blinded study, randomization will be used to avoid bias in the assignment of 
the stapling device to be utilized for PA/PV transection for each subject, to increase the 
likelihood that attributes of the subject are evenly balanced between groups, and to 
enhance the validity of statistical comparisons between groups.  
The Sponsor will assign the stapling device randomly to each subject on a 1:1 basis to 
either the surgeon’s current SOC or PVS.  
In the event that a potential subject fails inclusion/exclusion criteria prior to 
randomization, this subject will be considered a screen failure. 
4.2.1 Inclusion Criteria 
Subjects satisfying the following criteria will be eligible for participation in this 
study: 
1. Subjects with a confirmed or suspected diagnosis of stage IA to stage IIIA 
non-small cell lung cancer scheduled for a lobectomy (Lung Cancer Staging 
per American Joint Committee on Cancer,7th Edition5); 
2. Subjects scheduled for VATS lobectomy in accordance with their institution’s 
SOC;       
3. Performance status 0-1 (Eastern Cooperative Oncology Group classification); 
4. ASA score < 3; 
5. No prior history of VATS or open lung surgery (on the lung in which the 
procedure will be performed); 
6. Willing to give consent and comply with study-related evaluation and treatment 
schedule; and 
7. At least 18 years of age.  
 
4.2.2 Exclusion Criteria 
Subjects will be excluded from the study for any of the following: 
1. Prior chemotherapy or radiation (within 30 days prior to the procedure or the 
duration of the subject’s enrollment); 

 
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2. Pregnancy; 
3. Physical or psychological condition which would impair study participation; or 
4. The subject is judged unsuitable for study participation by the Investigator for 
any other reason. 
 
All subjects signing consent who do not meet the inclusion/exclusion criteria and 
therefore do not proceed to Visit 2/Procedure, and are not randomized, will be 
recorded as screen failures. The relevant electronic Case Report Form (eCRF) 
pages will be completed for all screen failure subjects and the data will therefore 
be included in the study database. 
 
4.3 PRIOR AND CONCOMITANT THERAPY 
Study subjects may continue with their current medical care while in the study, including 
medications.   
 
4.3.1 Concomitant Medications  
Anticoagulants taken preoperatively (up to 30 days prior to Visit 2/Procedure) and 
peri-operative, intra-operative, and post-operative pain medication and/or 
medications prescribed due to an adverse event will be collected for this study.  No 
other concomitant medications will be collected. 
 
4.4 REMOVAL OF SUBJECTS FROM STUDY 
A subject has the right to withdraw from the study at any time for any reason without 
prejudice to his/her future medical care by the physician or the institution.  Should a 
subject (or subject’s legally authorized guardian/representative) decide to withdraw; all 
efforts will be made to collect and report the final visit observations as thoroughly and 
timely as possible.   
 
Subjects who withdraw from the study prior to randomization will be considered screen 
failures and will be replaced. Subjects who withdraw from the study post-randomization 
will not be replaced.  Subject participation may be terminated prior to completing the 
study for any of the reasons listed below.  When a subject’s participation is terminated 
prior to completing the study, the reason for withdrawal is to be documented on the 
Study Completion eCRF as well as in the source documentation:   
 
Withdrawal of Consent: 
The subject withdraws consent for participation in the study.  Any method of contact with 
the subject in which they state they no longer want to participate in the study specific 
activities constitutes withdrawal of consent.  When possible, the reason for withdrawal of 
consent will be documented. 
 
Surgical: 
The Investigator must withdraw a subject intra-operatively for the following reasons: 
 
Lobectomy not completed; 

 
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 
Conversion to an open procedure, unless directly related to transection of the 
PA/PV (subject will be followed for safety up to 30 days post-op); or 
 
Use of robotic assistance during surgery. 
 
Adverse Event: 
When the subject experiences an adverse event and the Principal Investigator or 
Medical Director believes it is in their best interest to discontinue participation in the 
study, they will be withdrawn.  
 
Death: 
When possible, the cause of death will be documented. 
 
Lost to follow-up: 
When contact with the subject has been lost without completing a final visit assessment, 
and every attempt to contact has failed, the subject will be considered lost to follow-up.  
Final documentation regarding all attempts to contact the subject requesting their return 
for the final visit should be documented.  
 
Site Termination or Study Termination: 
A site or study may be terminated.  When this occurs all subjects at the site will be 
withdrawn and documented as early termination.  Reasons for site or study termination 
may include, but are not limited to the following:   
 
Administrative Concerns (e.g., inadequate subject enrollment, 
investigator/institution non-compliance, change of business strategy, etc.); 
 
Safety Issues, including those due to non-compliance, which substantially affect 
the risk to benefit ratio of the study subjects at a site or for the study as a whole; 
and 
 
Regulatory Body Mandate(s). 
 
The Investigator has the right to terminate their participation at any time.  Should this be 
necessary, procedures for termination will be provided by the Sponsor. 
 
 
 
 
 
 
 
 
 
 

 
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4.5  IDENTITY OF STUDY PRODUCT(S)  
Product 
Code 
Product Name 
Manufacturer 
PVE35A 
ECHELON FLEX™ Powered Vascular Stapler 
with Advanced Placement Tip 
Ethicon Endo-Surgery, 
LLC (Guaynabo, Puerto 
Rico, USA) 
VASECR35
ENDOPATH ECHELON Vascular White 
Reload for Advanced Placement Tip 
Ethicon Endo-Surgery, 
LLC (Guaynabo, Puerto 
Rico, USA) 
 
The ECHELON FLEX™ Powered Vascular Stapler with Advanced Placement Tip is a 
sterile, single use instrument that simultaneously cuts and staples tissue. There are four 
staggered rows of staples, two on either side of the cut line. The  ECHELON FLEX™ 
Powered Vascular Stapler with Advanced Placement Tip and reloads have a staple line 
that is approximately 35mm long and a cut line that is approximately 30 mm long.  The 
shaft can rotate freely in both directions and an articulation mechanism enables the 
distal portion of the shaft to pivot to facilitate lateral access to the operative site. 
Powered vascular stapler has been cleared for marketing by the FDA and is CE marked 
which allows for commercial distribution in the EU.  The device will be used in 
accordance with product labeling and Instructions for Use (IFU). 
 
4.6 PRODUCT ACCOUNTABILITY 
The ECHELON FLEX™ Powered Vascular Stapler with Advanced Placement Tip and 
cartridges will be provided by the Sponsor  and will be tracked using shipping invoices 
and device accountability logs.  All product returns will be managed by contacting the 
Sponsor. 
The powered vascular staplers must be kept in a secure area.  Devices will only be used 
for treating subjects participating in the study, in accordance with the protocol.  The 
study device inventory must be available for periodic inspection/verification. 
 
4.7 STUDY PROCEDURES 
 4.7.1 
PROCEDURE DESCRIPTION 
 
  VATS lobectomy will be performed according to the institution’s SOC.    
 
4.7.2 VISIT 1 – SCREENING (CAN OCCUR OVER SEVERAL DATES WITHIN 
1-2 WEEKS OF VISIT 2- PROCEDURE) 
Subjects will be evaluated according to the local investigator’s preferred practice. 
Subjects will be selected for a surgical procedure based on the preoperative 
investigations and the local investigator’s interpretation of the clinical picture.  
Eligible subjects will be provided with the study information including the ICD.  

 
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The following screening activities will occur prior to the study procedure: 
 
The subject must be given ample time to review and sign the ICD; 
 
Collection of demographic information (year of birth, gender, ethnicity); 
 
Review and collection of relevant medical/surgical history, history of 
hypertension   or smoking if applicable; 
 
Review/collection of inclusion/exclusion criteria and determination as to 
whether the subject is eligible for participation (retrospective data, per site 
SOC, is permitted to determine eligibility);  
 
ASES Standardized Shoulder Assessment;  
 
Anticoagulants taken preoperatively (up to 30 days prior to Visit 
2/Procedure), including stop date; and  
 
Collection of current pain medications (within two weeks of the screening 
visit). 
4.7.3 VISIT 2 –PROCEDURE  
 
4.7.3.1.1 
 PRE-PROCEDURE  
The following must be obtained prior to the surgical procedure: 
 
Date of hospital admission; 
 
Update to medical / surgical history, if applicable; 
 
Confirm inclusion and exclusion criteria; 
 
ASA score;  
 
Pain Medication updates, including preoperative pain 
medications; and 
 
Randomization  
 
4.7.3.1.2 
 INTRA-OPERATIVE 
 Data collected during procedure: 
 
Overall Operating Room (OR) time; 
 
Duration of procedure (first incision to skin closure); 
- 
Includes time to completion of resection (capturing the time 
thoracoscopic camera is inserted until the specimen is 
received); 
 
Procedure data: 
- 
Location of affected lobe; 
- 
Number of pulmonary arteries (1, 2, or 3+); 
- 
Confirm visualization of the cut line indicator field prior to 
transection; 
- 
Confirm presence or absence of calcified hilar lymph 
nodes;  
- 
Use of other stapling devices for bronchus and 

 
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parenchyma transection (number and color of cartridges); 
- 
Number of ports; 
- 
Intra-operative surgical interventions (not associated with 
transection of the PA/PV), if applicable; 
- 
Reason for conversion to open surgery, if applicable; 
- 
Volume of estimated intra-operative blood loss; 
- 
Transfusion products (and rationale for use), if applicable; 
- 
Concomitant procedures/interventions performed, if 
applicable; 
- 
Number of chest tubes placed and anatomic position; 
- 
Tumor size and TNM staging, if available; 
 
Intra-operative interventions/procedures on PA/PV to stop 
bleeding, if applicable: 
- 
Hemostasis intervention:  bleeding detected and 
controlled intra-operatively (additional stapling, 
over-sewing, clip placement, compression, use of 
suture, sealant, and/or buttress, and/or use of 
energy); or bleeding that occurs intra-operatively 
requiring blood or blood product transfusion or an 
additional surgical procedure (e.g. conversion to 
open). 
 
Device usage data: 
- 
Usability and articulation questions; 
 
Surgeon Device Questionnaire (PVS procedures only);  
 
Surgeon Satisfaction Questionnaire (SOC and PVS 
procedures);  
 
SURG-TLX (SOC and PVS procedures); 
 
Adverse Events; 
 
Pain medications given perioperative (i.e. spinal block, 
intercostal nerve blocks, etc.); and 
 
Concomitant medication (associated with AEs and pain) 
 
4.7.4 Visit 3 – Post-operative through Discharge 
Post procedure assessments will be completed from OR discharge until hospital 
discharge.  Data to be collected includes: 
 
Post-operative  interventions/procedures related to PA/PV bleeding, if 
applicable: 
- 
Hemostasis intervention: bleeding that occurs post-
operatively requiring blood or blood product transfusion or 
an additional surgical procedure (and the relationship to 
SOC/PVS for PA/PV transection); 

 
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 
Post-operative pain medications used; 
 
Date(s) of chest tube(s) removal; 
 
Daily volume and characteristics of chest tube(s) drainage; 
 
ASES Standardized Shoulder Assessment; 
 
Pain score assessment (incisional, trocar, and chest tube pain); 
 
Concomitant procedures/ interventions performed, if applicable; 
 
Adverse Events;  
 
Concomitant medication (associated with AEs and/or pain); and 
 
Discharge date 
 
4.7.5 Visit 4- Final Visit (4 week follow up, post procedure) 
This visit can be either an office visit or a telephone follow-up visit.  Data to be 
collected includes: 
 
Post-operative  interventions/procedures related to PA/PV bleeding, if 
applicable: 
- 
Hemostasis intervention:  bleeding that occurs post-
operatively requiring blood or blood product transfusion or 
an additional surgical procedure (and the relationship to 
SOC/PVS for PA/PV transection); 
 
Post-operative pain medications used;  
 
ASES Standardized Shoulder Assessment; 
 
Date(s) of chest tube(s) removal, if applicable; 
 
Daily volume and characteristics of chest tube(s) drainage, if applicable; 
 
Concomitant procedures/interventions performed, if applicable; 
 
Pain score assessment (incisional, trocar, and chest tube pain) 
 
Adverse Events;  
 
Concomitant medication (associated with AEs and pain); and 
 
Subject exited from the study 
5.0 DATA MANAGEMENT AND INTEGRITY 
5.1 DATA COMPLETION AND RECORD KEEPING 
5.1.1 SOURCE DOCUMENTS 
Source documents are documents on which information regarding subjects is first 
recorded, including printed, hand written, or electronic documents.  Investigator 
subject files or hospital records generally are the basis of source document 
information.  This includes but is not limited to, original subject files; hospital/clinic 
records; original recordings /tracing; digital images from automated instruments 
(e.g., cameras); radiographs; device accountability records; photographic negatives; 
and records kept at the investigation site, at the laboratories and at other 
departments involved in the clinical investigation. 
Source documents must be retained by the Investigator as part of the subject’s 
permanent medical record. The information in the source documents is used to 

 
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complete the eCRFs. All information captured on the eCRFs should be completely 
and accurately supported in source documentation. Any additional information 
relevant to the study should be included in the source documents. The Investigator 
will retain originals of all source documents, subject consent forms, and study data. 
 
5.1.2 ELECTRONIC DATA CAPTURE 
An electronic data capture (EDC) system will be utilized by study site personnel to 
transfer study data from source records (medical records and/or source document 
worksheets) onto common eCRFs. This system is a web-based, secure electronic 
software application (Medidata® Rave, Medidata® Rave, 350 Hudson Street, 9th 
Floor, New York, New York, 10014). This system was designed and is developed 
and maintained by Medidata in a manner that is compliant with national and 
international GCP data protection/data privacy and electronic record/electronic 
signature (e.g., 21 CFR Part 11) regulatory requirements. The EDC system will be 
used to facilitate the collection of all study data at the site. Designated site 
personnel will be responsible for entering subject data into the EDC system. All 
external and Sponsor internal users will be trained on the EDC application at a level 
dependent on their planned function. An EDC digital User Manual will be available 
under the help menu within the Medidata® Rave website to assist in the collection 
and entry of source data into the electronic casebook.   
 
There is a 24/7/365 Help Desk Support line (and Email: helpdesk@mdsol.com) 
staffed by the outsourced vendor that will be available to respond to questions. 
 
5.1.3 DATA COLLECTION 
Each EDC eCRF will be completed by the PI or PI’s designee. Every effort should 
be made to respond to all monitoring and/or data management questions on each 
eCRF as completion of the data is required by the protocol. A unique ID number will 
identify each subject.  The subject’s unique ID number will be visible on each eCRF. 
At no time should the subject name appear on the eCRFs.  
All data should be recorded accurately and completely. The Investigator is 
responsible for reviewing and approving each completed eCRF. Assurance of 
overall review and approval will be documented by the Investigator electronically 
signing each subject’s electronic casebook. 
5.1.4 DATA CORRECTION 
Required data corrections to eCRFs will be prompted via automated electronic edit 
checks and/or queries manually created by Sponsor reviewers. The change(s), 
individual making the change(s), and time the change(s) were made to the eCRFs 
will be automatically captured in the audit trail within Medidata® Rave. 
5.1.5 DATA PRIVACY 
The collection, use, and disclosure of all personal data, including subject health and 
medical information, are to be maintained in compliance with applicable personal 
data protection and security laws and regulations that govern protected health 
information and the informed consent given by each study subject. When collecting 
and processing such personal data, appropriate measures are to be taken to 
maintain the confidentiality of subject health and medical information and to prevent 

 
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access by unauthorized persons. 
5.1.6 RECORD RETENTION, INSPECTION, AND CUSTODY 
The PI must maintain all documentation related to the study until they receive 
Sponsor notification.  The PI will allow representatives of the Sponsor, the FDA, or 
other applicable government regulatory agencies to inspect all study records, 
eCRFs, and corresponding portions of the subject’s office and/or hospital medical 
records at regular intervals during the study. These inspections are to verify 
adherence to the protocol, integrity of the data being captured on the eCRFs, and 
compliance with applicable regulations. 
Subject medical records will be maintained in a confidential manner. Study reports 
will not identify subjects by name. These reports may be submitted to the FDA and/or 
applicable regulatory authorities.  
If custody of the records is transferred, notice of such a transfer should be given to 
the Sponsor no later than 10 working days after the transfer occurs. 
5.2 
MEDICAL DICTIONARY CODING 
Medical dictionary coding of verbatim AE and SAEs captured on eCRFs will be 
performed using a coding thesaurus algorithm. The Medical Dictionary for Regulatory 
Activities and World Health Organization Drug Dictionary will be used after data entry 
and query resolution, via auto-encoding and interactive coding processes. 
 
6.0 DATA QUALITY ASSURANCE 
Steps to be taken to assure the accuracy and reliability of data include the selection of 
qualified investigators and appropriate study centers, review of protocol procedures with 
the Investigator and associated personnel prior to the study, and periodic monitoring 
visits by the Sponsor.  The Sponsor will review eCRFs for accuracy and completeness 
during on-site monitoring visits or periodic reviews of the EDC system; any 
discrepancies will be resolved with the Investigator or designees, as appropriate.  The 
data entered into the clinical study database will be verified for accuracy. 
 
6.1 
INVESTIGATOR TRAINING 
Prior to screening subjects for this study, the PI, sub-investigators, study coordinators, 
and other designated staff (as applicable) will be provided information on study 
execution, data collection, and procedures specific to this clinical protocol. 
 
6.2 
MONITORING 
This study will be monitored by the Sponsor to ensure: 
 
The rights and well-being of the subjects are protected; 
 
Reported study data is accurate, complete, and verifiable from source 
documents; and 
 
The conduct of the study is in compliance with the currently approved 
protocol/amendment(s), applicable GCPs, and with applicable local/regional 
regulatory requirements. 
The extent and nature of monitoring will be predetermined and based on 
considerations such as the objective, design, complexity, and endpoints of the study 
and mutually agreed to by the Sponsor and investigators. Monitors will comply with 
established written standard operating procedures as well as procedures (i.e., 

 
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monitoring plan) specified by the Sponsor for monitoring this study.  These monitoring 
procedures are characterized in the monitoring plan for this study. 
6.3 
PROTOCOL DEVIATIONS 
A deviation (any activity conducted outside the parameters established by the study 
protocol) can be identified from a number of sources.  Potential sources include, but 
are not limited to: a member of the Investigator’s staff, a Sponsor representative during 
monitoring visits, or a member of the data management or statistical groups when 
entering or analyzing data.  Regardless of the source, it is crucial to document the 
deviation.  The PI will report protocol deviations to the IRB/EC as required by the 
IRB/EC procedures.  All deviations will be captured in the source as well as the eCRF. 
7.0 
STATISTICAL METHODS PLANNED IN THE PROTOCOL AND 
DETERMINATION OF SAMPLE SIZE 
7.1 
STATISTICAL AND ANALYTICAL PLANS 
The Sposor’s Data Management and Biostatistics groups will be responsible for the 
analysis of data from this protocol. A comprehensive and detailed Statistical Analysis 
Plan (SAP) will be finalized prior to database lock and will supplement the statistical 
design and analysis described in this section. 
Categorical variables will be summarized descriptively by frequencies and associated 
percentages. Continuous variables will be summarized descriptively by number of 
subjects, mean, standard deviation, median, minimum, and maximum. 
 
7.2 
DETERMINATION OF SAMPLE SIZE 
Approximately 200 subjects will be randomized in the study in a 1:1 ratio to standard of 
care or powered vascular stapler.  Historical clinical study data on a similar powered 
surgical stapler demonstrated a need for staple line interventions in approximately 6% 
of firings on the pulmonary artery or pulmonary vein. This data also showed an 
average of 2.6 to 2.9 firings per subject, and it is expected, given differences in device 
design, that each subject will require 3 to 4 firings on the pulmonary vein or pulmonary 
artery in the current study with powered vascular stapler.  
Given that it is expected to have a minimum of 260 firings in each group, the sample 
size of approximately 200 subjects is considered adequate for descriptive 
summarization of the primary performance endpoint, i.e. number and frequency of 
intra-operative surgical interventions. Assuming an approximate background 
intervention rate of 6%, the given sample size will provide reasonable precision in the 
estimation of the intervention rate to an expected margin of error for a 95% confidence 
interval of at most 2.9% for each group. 
  
 
 
 
 
 

 
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7.3 ANALYSIS SETS 
There will be three analysis sets defined: 
 
The Full Analysis Set (FAS) will consist of all randomized subjects who had the 
procedure performed and provide data on number of surgical interventions;  
 
The Per Protocol (PP) Analysis Set will consist of all subjects in the FAS who had 
no major protocol violations; 
 
The Safety Set consists of all randomized subjects on whom the procedure is     
started. 
The primary performance endpoint analysis will be performed on the Full Analysis Set 
and subjects will be classified according to their randomized treatment group. The 
primary performance endpoint analysis will also be performed on the PP set as a 
sensitivity analysis to the results on the FAS.  The summary of additional endpoints will 
also be performed on the Full Analysis Set. Analysis of the primary safety endpoint 
and adverse events summaries will be performed on the Safety Set. 
7.4 ANALYSIS OF EFFECTIVENESS 
Summary statistics and 95% confidence intervals will be provided for the number and 
frequency of interventions for the set of SOC subjects and PVS subjects separately. 
This will be performed based on the total number of firings. An intervention is defined 
as any firing which is classified as hemostasis intervention.  To establish that the 
intervention rate is not increased compared to SOC, a 95% confidence interval for the 
difference in proportion of firings requiring interventions for PVS minus SOC will be 
calculated and powered vascular stapler will be considered to have acceptable 
performance if the upper bound of the 95% confidence interval does not exceed 3%.  
Additional endpoints will be summarized with descriptive statistics and 95% confidence 
intervals as appropriate for continuous or categorical measurements.   
7.5 STATISTICAL/ANALYTICAL ISSUES 
7.5.1 HANDLING OF DROPOUTS OR MISSING DATA 
All summaries will be performed only on subjects undergoing the surgical 
procedure and only observed data will be summarized. There will be no 
imputation of data for early terminated subjects or for missing data within the 
database. 
 
7.5.2 INTERIM ANALYSES AND DATA MONITORING 
No interim analysis is planned for this study. 
 
7.5.3 MULTICENTER STUDIES 
No adjustment for center is planned in the statistical analysis. Center specific 
analyses may be conducted pending within-center sample size to understand the 
effect that surgeon techniques and site standard of care may have on the overall 
results.  
 
7.5.4 MULTIPLE COMPARISONS/MULTIPLICITY 
No adjustment for multiplicity is necessary since multiple hypotheses are not 
being tested. 
 

 
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7.6 
ANALYSIS OF SAFETY 
The number and percentage of subjects requiring hemostasis interventions post-
operatively that are classified as related to SOC/PVS for PA/PV transection (e.g. need 
for blood product transfusion or additional surgical procedure) will be summarized for 
each group as a primary safety endpoint.  
Safety will be assessed through the incidence of AEs and serious adverse events 
(SAEs), which will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA). The incidence of AEs will be summarized at the MedDRA system organ 
class and preferred term level. Incidence of AEs will also be summarized by maximum 
severity. All reported adverse events will be listed.  
8.0 
RISKS AND BENEFITS OF THE STUDY DEVICE AND CLINICAL     
INVESTIGATION 
The procedure being performed with powered vascular stapler is identical to the 
procedure subjects would receive as part of their standard of care procedure. To date, 
no risks have been reported beyond standard risks associated with VATS 
lobectomy.   This study may or may not provide any benefits to the subject.  
9.0 
ADVERSE EVENTS AND PRODUCT COMPLAINTS 
9.1 
DEFINITIONS 
9.1.1 ADVERSE EVENT 
An adverse event is defined as any undesirable clinical occurrence in a subject that 
may or may not be attributable to the device or procedure. All AEs, regardless of 
their relationship to the procedure or device, are to be recorded in the eCRF and 
reported to the Sponsor.   
In addition, the Investigator is required to provide: 
 
The onset and resolution dates of the event; 
 
The severity of the event; 
 
The outcome of the event; 
 
The relationship of the event to procedure and/or device (ECHELON FLEX™ 
Powered Vascular Stapler with Advanced Placement Tip or standard of care 
stapler); and 
 
The action taken for the medical management of the event. 
Post-operative pain is expected and will not be documented as an adverse event 
unless the Investigator considers the pain to exceed what is typically anticipated 
following a VATS procedure. (This data is separate from incisional, trocar, and / or 
chest tube pain).  
9.1.2 ANTICIPATED ADVERSE EVENTS 
An expected morbidity/procedural complication is defined as an AE that is known to 
be common or usual in nature, severity, or incidence during VATS lobectomy in 
subjects with confirmed or suspected diagnosis of stage IA to stage IIIA non-small 

 
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cell lung cancer. 
A list of anticipated AEs that may occur during this study are listed in Appendix I. 
9.1.3 SERIOUS ADVERSE EVENT 
It is the Investigator’s responsibility to determine if an AE is an SAE.   
SAEs are AEs that: 
 Led to death, 
 Led to serious deterioration in the health of the subject, that either resulted in 
- 
a life-threatening illness or injury, or 
- 
a permanent impairment of a body structure or a body 
function, or 
- 
in-patient or prolonged hospitalization, or 
- 
medical or surgical intervention to prevent life-threatening 
illness or injury or permanent impairment to a body structure 
or a body function, 
- 
Led to fetal distress, fetal death or a congenital abnormality or 
birth defect 
 
 
Note:  “Death” should not be reported as an adverse event.  The cause of death 
should be reported as an adverse event.  The only exception is “Sudden Death” 
when the cause is unknown. 
 
9.1.4 SEVERITY OF ADVERSE EVENTS 
It is the Investigator’s responsibility to assess the severity of an AE.  A change in 
severity may constitute a new reportable AE. 
The following guideline should be used to determine the severity of each adverse 
event: 
 
MILD:  Awareness of experience, but easily tolerated. No medical 
intervention required. 
 
MODERATE: Enough discomfort to interfere with usual activities. Medical 
intervention required. 
 
SEVERE: Inability to carry out usual activities.  Medical intervention 
(including hospitalization or prolongation of hospitalization) required. 
 
9.1.5 RELATIONSHIP OF ADVERSE EVENTS 
It is the Investigator’s responsibility to assess the relationship of an AE to the study 
procedure (VATS lobectomy) and powered vascular stapler or SOC. 
The following guidelines should be used in determining the relationship of an 
adverse event to the study device, study procedure, or other causality: 
 
Not Related – A clinical event (including abnormal laboratory result) that 
results from causes extraneous to administration of device/procedure/other and 
is most likely due to alternative etiology, (i.e., pre-existing condition, underlying 
disease, intercurrent illness, concomitant medications); 
 
Possibly – A clinical event (including abnormal laboratory result) that presents 

 
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an unlikely association between device/procedure/other, which cannot be ruled 
out with certainty, but could also be explained by alternative etiology; 
 
Related– A clinical event (including abnormal laboratory result) that presents a 
strong temporal relationship between device/procedure/other, in which an 
alternative etiology is unlikely; or 
 
Unknown – A clinical event (including abnormal laboratory result) that cannot 
be determined to be related or unrelated to device/procedure/other given the 
information obtained. 
 
9.1.6 Product Complaints 
A product complaint is defined as any written, electronic or oral communication that 
alleges deficiencies related to the identity, labeling, quality, durability, reliability, 
safety, effectiveness, or performance of a device (i.e., stapler) after it is released 
for distribution (policy of Johnson and Johnson Medical Device Quality 
management).  A product complaint may or may not be associated with an 
AE/SAE.   
 
9.2 REPORTING PROCEDURES FOR ADVERSE EVENTS/PRODUCT   
COMPLAINTS 
9.2.1 REPORTING ADVERSE EVENTS 
Data related to AEs will be recorded in the source documentation from the time of 
study enrollment (first incision) until the subject completes the study or terminates 
early. All AEs that are unresolved at study completion (or early termination) will be 
recorded as ongoing at study end. 
Data related to SAEs will be collected until event resolution, or until the event is 
considered stable, or until all attempts to determine the resolution of the event are 
exhausted. 
9.2.2 Reporting Serious Adverse Events 
The site must complete the SAE eCRF within 24 hours of becoming aware of the 
event.    
 
Supporting SAE documentation can be faxed to: 
 
US sites: 
Fax:  1-513-337-1392 
Study Number: ESC-15-001 
 
EU sites: 
Fax: + 44-1506-5946-91 
Study Number: ESC-15-001 
The Investigator will also be required to assess if the SAE is considered anticipated 
(see Appendix I) and if the event involved a product complaint. The report of an 
SAE by a study site does not constitute an admission that study personnel or the 
user facility (hospital/clinic) caused or contributed to the event. 

 
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The study site is also responsible for submitting to the reviewing IRB/EC according 
to their IRB/EC procedures. 
9.2.3 Reporting Product Complaints 
All product complaints related to powered vascular stapler shall be documented 
throughout the clinical investigation.   
Product complaints related to powered vascular stapler must be reported to the 
Sponsor in a timely manner and no later than 24 hours after becoming aware of the 
event.  The Product Complaint Form must be emailed to the EES Customer 
Complaint team at the following email address: 
 
Productcomplaint1@its.jnj.com 
 
One copy of the processed form should be kept on-site and the device should be 
retained. EES representatives will organize collection of the device for evaluation 
as needed. 
 
 
10.0 REFERENCE LIST 
1. National Cancer Institute 
2. Diagnosis and Management of Lung Cancer:  ACCP Guidelines (2007) 
3. Michener, L. (2002). J Shoulder Elbow Surg;11:587-94 
4. Wilson W. (2003). European Journal of Cardio-thoracic Surgery; 23:390–396 
5. American Joint Committee on Cancer, Lung Cancer Staging 7th edition  
 
 
 
 

 
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11.0 APPENDIX I:  ANTICIPATED ADVERSE EVENTS 
 
Associated with Surgery and  
General Anesthesia 
Thoracic Surgery Specific 
Acute Lung Injury 
Air/Gas Embolism  
Acute Respiratory Distress Syndrome 
Angina 
Adhesions 
Broncho pleural fistula 
Altered Mental Status 
Chylothorax 
Anaphylaxis 
Diaphragmatic Injury 
Anemia 
Empyema 
Angina 
Esophageal Injury 
Atelectasis 
Hemothorax 
Bacteremia 
Hernia 
Bleeding 
Intercostal nerve injury 
Bradycardia 
Pneumothorax  
Cardiac Arrhythmia 
Prolonged Air Leak  
Central line infection 
Thoracic duct injury 
Cerebrovascular Accident / Stroke 
Thromboembolic Event 
Congestive Heart Failure 
Wound infection 
Constipation 
Tightness of the chest 
Death 
 
Deep Venous Thrombosis 
 
Dehydration 
 
Dementia 
 
Diarrhea 
 
DIC, Coagulopathy 
 
Dizziness 
 
Electrolyte Imbalance 
 
Fever, Pyrexia 
 
Headache 
 
Hematuria 
 
Hypertension 
 
Hypotension, shock 
 
Hypoxia 
 
Ileus 
 
Infection/SSI/Abscess 
 
Jaundice 
 
Lethargy 
 
Leukocytosis 
 
Liver Failure 
 

 
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Mesenteric Infarct  
 
Mesenteric Ischemia 
 
Myocardial Infarction 
 
Nausea 
 
Obtundation, Depressed Level of Consciousness 
 
Oliguria 
 
Pain (increased/severe/chronic) 
 
Pneumonia 
 
Pulmonary Embolism 
 
Renal Failure 
 
Respiratory Failure 
 
Respiratory Insufficiency 
 
Sepsis 
 
Somnolence 
 
Systemic Inflammatory Response Syndrome 
 
Tachycardia 
 
Thrombocytopenia 
 
Thromboembolic Event 
 
Thrombosis 
 
TIA 
 
Tightness of the chest, Angina 
 
Tinnitus 
 
Urinary Retention 
 
Urinary Tract Infection (UTI) 
 
Volume Depletion,  Hypovolemia 
 
Vomiting 
 
Wheezing 
 
Wound Dehiscence