A Prospective, Single-Arm, Multi-Center Study of the ECHELON ENDOPATH(TM) Staple Line Reinforcement Device in Gastric and Lung Resection Procedures
Phase: NA
Conditions: Gastric Procedures, Lung Resection Procedures
Sponsor: Ethicon Endo-Surgery

Trial Number: ESC_2018_03 
CONFIDENTIAL 
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Version: Amendment 3 – Gastric procedures only 
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A Prospective, Single-Arm, Multi-Center Study of the ECHELON ENDOPATHTM Staple Line 
Reinforcement Device in Gastric and Lung Resection Procedures 
Trial Number: ESC_2018_03 
Document 
Effective Date
Original 
5 SEP 2019
Amendment 1 
1 APR 2020
Amendment 2 
27 JAN 2021
Amendment 3 – Gastric procedures only 
11 JUN 2021
Sponsor: 
Ethicon Endo-Surgery, Inc. 
4545 Creek Road 
Cincinnati, Ohio 45242 
Anticipated Regulatory 
Classifications: 
Class II in the United States 
Name of Finished Product: 
ECHELON ENDOPATHTM Staple Line Reinforcement 
This is a sterile, bioabsorbable staple line 
reinforcement device intended for use in surgical 
procedures in which soft tissue transection or resection 
with staple line reinforcement is desired. 
Sponsor’s Medical Monitor: 
 
 Senior Medical Director for Endomechanical and 
Energy 
4545 Creek Rd. 
Cincinnati, OH 45242 
This study will be performed in compliance with Good Clinical Practice (GCP) and in accordance 
with the Declaration of Helsinki, as well as any other applicable local and country regulatory 
requirements. 
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. 

 
Trial Number: ESC_2018_03 
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INVESTIGATOR SIGNATURE PAGE 
 
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 (SAEs) as soon as possible, but no later than 72 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;  
• 
Ensure that all associates, colleagues, and employees assisting in the conduct of the 
study are informed of their obligations in meeting the above commitments; and 
• 
Provide copies of the protocol and all pertinent information to all individuals responsible 
to me who assist in the conduct of this study. I will discuss this material with them to 
ensure they are fully informed regarding the conduct of the study. 
I will ensure that the Institutional Review Board (IRB) 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 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 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. 
 
 
 
 
 
 
 
 
Signature of Principal Investigator (PI) 
 
Date 
 
 
 
 
Printed Name of PI 
 
 
 

 
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CLINICAL TRIAL PROTOCOL SYNOPSIS 
Anticipated 
Regulatory 
Classifications: 
Class II in United States 
Indication: 
ECHELON ENDOPATH Staple Line Reinforcement is indicated for use in 
surgical procedures in which soft tissue transection or resection with 
staple line reinforcement is needed. ECHELON ENDOPATH Staple Line 
Reinforcement can be used for reinforcement of staple lines during lung 
resection and bariatric surgical procedures. The device can also be used 
for reinforcement of staple lines during gastric, small bowel and colorectal 
procedures. 
Objective(s): 
The primary objective of this study is to evaluate safety following use of 
ECHELON ENDOPATH Staple Line Reinforcement (ECHELON SLR) in 
subjects undergoing indicated gastric and lung resection procedures. The 
secondary objective will be to capture usability data of the device. 
Overview of 
Study Design:   
This prospective, single-arm, multi-center study will collect clinical data in 
a post-market setting by procedure group (gastric and lung resection). 
Investigators will perform each procedure using the device in compliance 
with their standard surgical approach and the ECHELON SLR 
instructions for use (IFU).  
Subjects will be consented and screened anytime during a period of 8 
weeks prior to the date of surgery. Subjects will be considered treated 
when at least one ECHELON SLR has been placed during the 
procedure. All treated subjects will be followed post-operatively through 
discharge and again at 28, 70, and 135 days (± 14 days) post-surgery; 
therefore, from the surgery date to study exit, the duration will be 
approximately 19 weeks. 

 
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Number of 
Subjects:   
A minimum of 243 treated subjects (maximum of 431 treated subjects) 
will be included in the study from up to 16 sites in the United States with 
the following procedure targets: 
• 
A minimum of 112 treated subjects for gastric procedures; and 
• 
A minimum of 131 treated subjects for lung resection procedures. 
Given the lack of available clinical data on the ECHELON SLR, an 
adaptive approach to sample size re-estimation will occur after 
approximately 50% of the originally planned sample size in each group 
has been enrolled. The purpose of this interim analysis will be to estimate 
the rate of the primary endpoint in each procedure group as well as to 
understand the size of the relative reduction in the rate of the primary 
endpoint in relation to published literature. Based on these observed 
values, the sample size will be re-estimated.  Upon completion of the 
sample size re-estimation, the Sponsor will determine if enrollment will 
continue to the originally planned enrollment values above (the minimum 
number listed above for each procedure group), stop at the time of the 
interim analysis due to futility, or increase the sample size in one or both 
groups if the true endpoint rate or effect size differ from the original 
estimates.  
Criteria for 
Inclusion: 
Subjects satisfying the following criteria will be considered eligible for 
enrollment in this study: 
1. Primary procedure (gastric or lung resection) where the ECHELON 
SLR is planned to be used for reinforcement of staple lines per the 
IFU in either a or b: 
a. Gastric procedures limited to laparoscopic gastric resection, 
robotic laparoscopic gastric resection, partial gastrectomy, 
gastric wedge resection, subtotal gastrectomy, laparoscopic 
Roux-en-Y gastric bypass, and robotic laparoscopic gastric 
bypass; or 
b. Lung resection procedures that include lobectomy, 
segmentectomy or wedge resection, and lung volume reduction 
surgery, and may be video assisted thoracic surgery (VATS) or 
open procedures; 
2. Willingness to give consent and comply with all study-related 
evaluations and visit schedule; and 
3. At least 18 years of age. 
Criteria for 
Exclusion: 
Subjects meeting any of the following criteria will be considered ineligible 
for enrollment in this study: 
Preoperative 
1. Physical or psychological condition which would impair study 
participation; 
2. Gastric procedures: Body mass index (BMI) ≥ 50.0 kg/m2, or lung 
resection procedures: BMI ≥ 46.0 kg/m2; 

 
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3. The procedure is a revision/reoperation for the same indication or 
same anatomical location; 
4. A procedure where extended wound or organ support is required; 
5. Any medical condition that the investigator deems could impact 
inflammatory or immune response; 
6. Concurrent treatment with medications that the investigator 
deems could have influence on wound healing; 
7. History of hypersensitivity to polyglactin (Vicryl®), 
Polydioxanone (PDO or PDS), or hypersensitivity to related 
products (cross-allergy); or 
8. Enrollment in a concurrent interventional clinical study that could 
impact the study endpoints. 
Intraoperative 
1. Per surgeon discretion, presence of adhesions that could lead to 
an increased risk of leak occurrence at a different location than 
the staple line. 
2. Per surgeon discretion, medical finding intraoperatively such that 
the procedural plan is changed and ECHELON SLR is not used 
during the procedure. 
Test Product(s): 
ECHELON SLR: 
 
Product Code  Description 
Reinforcement 
Length 
ECH60R 
ECHELON ENDOPATHTM 
Staple Line Reinforcement 
60mm 
Reference 
Therapy/Product: 
No comparator product is being used in this study. 
Duration of 
Treatment: 
Subjects will be exposed to the study device during the procedure and 
will be followed for approximately 135 days. The device will be used as 
indicated in the IFU. The ECHELON SLR is composed of materials that 
are essentially absorbed within 120 days. 
Criteria for 
Evaluation: 
Primary endpoint: 
• 
Incidence of device-related adverse events (AEs) through the 70-
day post-procedure follow-up visit. Specific device-related AEs 
that will be captured and counted toward the primary endpoint are 
listed below. 
o Gastric 
 
Bleeding (defined as below) 
• 
Occurrence of post-operative blood 
transfusion deemed related to bleeding at 
the staple line; or  

 
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• 
Return to operating room before  70-day 
post-procedure follow-up visit due to 
bleeding deemed related to the staple line; 
 
Leak (defined as below) 
• 
Occurrence of intra-operative or post-
operative gastrointestinal leak related to the 
staple line as documented intra-operatively, 
by clinical exam, or radiographically; 
 
Stricture (defined as below) 
• 
Occurrence of stricture documented 
radiographically or by endoscopy along the 
staple line; 
o Lung Resection 
 
Prolonged air leak deemed related to the staple 
line (defined as below) 
• 
Greater than postoperative day 7 
(procedure=day 0); 
 
Empyema (defined as below) 
• 
Purulent fluid collection in the pleural space 
documented radiographically, excluding 
chronic empyema 
Secondary performance endpoints: 
• 
Number of study devices replaced during surgery due to slipping 
or bunching or not properly loaded onto stapler cartridge; and 
• 
Device questionnaire by procedure group (gastric and lung 
resection) to capture usability. 
Statistical 
Analysis: 
Analysis Sets 
The summary of all performance and safety endpoints will be performed 
on the set of subjects in whom the ECHELON SLR is utilized during the 
surgical procedure. The summary of all primary and secondary endpoints 
will be performed by procedure group (gastric or lung resection).  
  
Primary Endpoint Analyses 
The following hypotheses will be evaluated for the primary endpoint for 
gastric procedures: 
H0: pG ≥ 14.0% 
H1: pG < 14.0% 
Where pG is the percentage of subjects experiencing at least one 
occurrence of bleeding, leak, or stricture through 70 days. A 95% 
confidence interval will be calculated for p based on the sample 
proportion of subjects experiencing the endpoint using the Normal 
approximation to the Binomial distribution, and the upper limit of this 
confidence interval will be compared to 14.0% to evaluate the above 
hypotheses. A p-value will be determined based on the same Normal 

 
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approximation methodology.  
A similar methodology will be applied to the data observed in lung 
procedures to evaluate the following hypotheses:  
H0: pL ≥ 12.0% 
H1: pL < 12.0% 
Where pL is the percentage of subjects experiencing at least one 
occurrence of prolonged air leak or empyema through 70 days.  
 
Secondary Endpoint and Safety Analyses 
Summary statistics will be provided by procedure group for all procedure-
related variables measured in this study including number of study 
device(s) replaced during surgery due to slipping or bunching and device 
questionnaires to capture usability. Counts and percentages will be 
provided for number of staple line reinforcement devices used during the 
procedure. 
All device- and procedure-related AEs reported during the study will be 
coded to the Medical Dictionary for Regulatory Activities (MedDRA). 
Adverse events will be assessed for seriousness, severity, action taken, 
and outcome. Adverse events will be summarized by MedDRA system 
organ class and preferred term by procedure group and in total. Serious 
AEs will be summarized in a similar manner. 
 
 

 
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TABLE OF CONTENTS 
 
Page 
PROTOCOL SIGNATURE PAGE........................................................................................2 
INVESTIGATOR SIGNATURE PAGE .................................................................................3 
CLINICAL TRIAL PROTOCOL SYNOPSIS .........................................................................4 
PROTOCOL-SPECIFIC ACRONYMS AND ABBREVIATIONS ..........................................11 
ETHICS ............................................................................................................................12 
ADMINISTRATIVE REQUIREMENTS ...............................................................................13 
1.0 
INTRODUCTION .....................................................................................................14 
2.0 
STUDY OBJECTIVES .............................................................................................14 
2.1 
Primary Endpoint .................................................................................................14 
2.2 
Secondary Performance Endpoints ......................................................................14 
2.3 
Additional Key Data Collected ..............................................................................15 
3.0 
INVESTIGATIONAL PLAN.......................................................................................15 
3.1 
OVERALL STUDY DESIGN AND PLAN - DESCRIPTION ....................................15 
3.2 
STUDY POPULATION .........................................................................................15 
3.2.1 Enrollment .......................................................................................................15 
3.2.2 Inclusion Criteria ..............................................................................................16 
3.2.3 Exclusion Criteria.............................................................................................16 
3.2.4 Removal of Subjects from Study ......................................................................17 
3.2.5 Subject Replacement in Study .........................................................................18 
3.3 
STUDY PROCEDURES .......................................................................................18 
3.3.1 Procedure Description .....................................................................................18 
3.3.2 Identity of Study Products ................................................................................18 
3.3.2.1 Device Description....................................................................................18 
3.3.2.2 Indications ................................................................................................19 
3.3.2.3 Labeling of Study Products .......................................................................19 
3.3.2.4 Accountability of Study Products ...............................................................19 
3.3.3 Prior and Concomitant Therapy........................................................................19 
3.3.3.1 Restricted Therapy ...................................................................................19 
3.4 
STUDY VARIABLES ............................................................................................20 
3.4.1 Demographic and Baseline Characteristics ......................................................20 
3.4.2 Surgical Variables............................................................................................20 
3.4.3 Device Questionnaire.......................................................................................21 
3.4.4 Safety Data Variables ......................................................................................21 
3.5 
SCHEDULE OF EVENTS ....................................................................................22 
3.6 
STUDY PROCEDURES .......................................................................................22 
3.6.1 Visit 1 – Screening (may occur over visits within 8 weeks of Visit 2) ..................22 
3.6.2 Visit 2 – Procedure Through Discharge Visit.....................................................22 
3.6.3 Visit 3 – Post-procedure Follow-up Visit ...........................................................23 
3.6.4 Visit 4 – Post-procedure Follow-up Visit ...........................................................23 
3.6.5 Visit 5 – Post-procedure Follow-up Visit ...........................................................23 
3.6.6 Unscheduled Visit(s) ........................................................................................23 
4.0 
DATA MANAGEMENT AND INTEGRITY .................................................................23 
4.1 
DATA COMPLETION AND RECORD KEEPING ..................................................23 
4.1.1 Source Documents ..........................................................................................23 
4.1.2 Electronic Data Capture ...................................................................................23 
4.1.3 Data Collection ................................................................................................24 
4.1.4 Data Correction ...............................................................................................24 
4.1.5 Data Privacy ....................................................................................................24 

 
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4.1.6 Record Retention, Inspection, and Custody ......................................................24 
4.2 
MEDICAL DICTIONARY CODING .......................................................................24 
4.3 
VIDEO RECORDING AND ANALYSIS .................................................................25 
4.4 
DATA QUALITY ASSURANCE ............................................................................25 
4.4.1 Site Personnel Training....................................................................................26 
4.4.2 Monitoring .......................................................................................................26 
4.4.3 Quality Assurance ...........................................................................................26 
4.5 
PROTOCOL DEVIATIONS...................................................................................26 
5.0 
STATISTICAL METHODS PLANNED IN THE PROTOCOL AND DETERMINATION OF 
SAMPLE SIZE .........................................................................................................26 
5.1 
Study Design .......................................................................................................26 
5.2 
Treatment Assignment .........................................................................................26 
5.3 
Interval Windows .................................................................................................27 
5.4 
Primary and Secondary Endpoints and Associated Hypotheses ............................27 
5.5 
Levels of Significance ..........................................................................................27 
5.6 
Analysis Sets .......................................................................................................27 
5.7 
Sample Size Justification .....................................................................................27 
5.8 
Data Monitoring Committee ..................................................................................28 
5.9 
Analyses to be Conducted ...................................................................................28 
5.9.1 General Conventions .......................................................................................28 
5.9.2 Disposition of Study Subjects ...........................................................................28 
5.9.3 Demographic, Baseline, and Surgical Characteristics .......................................29 
5.9.4 Primary and Secondary Endpoint Analyses ......................................................29 
5.9.5 Plans for Interim Analyses ...............................................................................29 
5.9.6 Handling of Missing Data .................................................................................29 
5.9.7 Subgroup Analyses..........................................................................................29 
6.0 
ADVERSE EVENTS ................................................................................................29 
6.1 
DEFINITIONS ......................................................................................................30 
6.1.1 Adverse Event .................................................................................................30 
6.1.2 Adverse Device Effect......................................................................................30 
6.1.3 Serious Adverse Event ....................................................................................30 
6.1.4 Serious Adverse Device Effect (SADE) ............................................................30 
6.1.5 Unanticipated Serious Adverse Device Effect (USADE) ....................................30 
6.1.6 Pre-existing Condition......................................................................................30 
6.2 
SEVERITY OF ADVERSE EVENTS .....................................................................31 
6.3 
RELATIONSHIP OF ADVERSE EVENTS.............................................................31 
6.4 
REPORTING PROCEDURES FOR ADVERSE EVENTS......................................32 
6.4.1 Recording Adverse Events...............................................................................32 
6.4.2 Reporting Adverse Events ...............................................................................33 
6.4.3 Reporting Serious Adverse Events ...................................................................33 
7.0 
PRODUCT COMPLAINTS .......................................................................................33 
7.1 
REPORTING PRODUCT COMPLAINTS FOR MARKETED DEVICES..................33 
7.1.1 Reporting of Approved EES Marketed Devices.................................................33 
8.0 
REFERENCES ........................................................................................................33 
 

 
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PROTOCOL-SPECIFIC ACRONYMS AND ABBREVIATIONS 
Acronyms/Abbreviations  
Terms 
ADE 
 
Adverse device effect 
AE 
 
Adverse event 
ASA 
 
American Society of Anesthesiologists 
BMI 
 
Body mass index 
CFR 
 
Code of Federal Regulations 
C-SATS 
 
Crowd-sourced assessment of technical skills 
ECHELON SLR 
 
ECHELON ENDOPATH™ Staple Line Reinforcement 
eCRF 
 
Electronic case report form 
EDC 
 
Electronic Data Capture 
EES 
 
Ethicon Endo-Surgery, Inc. 
FDA 
 
Food and Drug Administration 
GCP 
 
Good clinical practice 
ICD 
 
Informed consent document 
IFU 
 
Instructions for use 
IRB 
 
Institutional review board 
MedDRA 
 
Medical Dictionary for Regulatory Activities 
PI 
 
Principal Investigator 
SADE 
 
Serious adverse device effect 
SAE 
 
Serious adverse event 
SAP 
 
Statistical analysis plan 
SOC 
   Standard of care 
USADE 
 
Unanticipated serious adverse device effect 
VATS 
 
Video-assisted thoracic surgery 
 
 

 
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ETHICS 
Institutional Review Board 
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) that complies with governmental requirements. The approving IRB will be responsible for 
the initial and continuing review and approval of this clinical study. Participating investigators will 
be required to promptly report to the IRB as required by the IRB’s policies. Additionally, 
investigators will be required to refrain from making any changes in the clinical investigation 
plan without Sponsor and IRB 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 GCP and in accordance with the Declaration of 
Helsinki, 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 study. An IRB 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 approval before implementation. Each 
subject will be required to sign any amended ICD (as required by the IRB) 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 up to sixteen surgery centers in the United States under a single protocol 
approved by each participating site’s IRB 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 the Sponsor 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 GCP data protection/data 
privacy and electronic record/electronic signature (e.g. 21 Code of Federal Regulations [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 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 medical monitor(s), change of telephone 
number(s)). The Investigator reports the protocol amendments to the IRB as per their local 
requirements. 
 
 

 
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1.0 INTRODUCTION 
Staple line complications are an important issue to consider in gastric and lung resection 
surgical procedures. Various types of staple line reinforcement devices currently exist and are 
used for reinforcing staple lines including fibrin glue and other sealants, suture oversewing, and 
buttressing. For buttressing, some of the most commonly used reinforcement buttressing 
materials include bovine pericardium and biocompatible glycolide copolymer.    
The Sponsor, EES, has developed the ECHELON ENDOPATH Staple Line Reinforcement 
(ECHELON SLR) for use in surgical procedures in which soft tissue transection or resection with 
staple line reinforcement is needed. ECHELON ENDOPATH Staple Line Reinforcement can be 
used for reinforcement of staple lines during lung resection and bariatric surgical procedures. 
The device can also be used for reinforcement of staple lines during gastric, small bowel and 
colorectal procedures. 
2.0 STUDY OBJECTIVES 
The primary objective of this post-market study is to evaluate safety following use of the 
ECHELON SLR in subjects undergoing indicated gastric and lung resection procedures. The 
secondary objective will be to capture usability data of the device.  
2.1 PRIMARY ENDPOINT  
The primary endpoint for this study is the incidence of device-related AEs through the 70-day 
post-procedure follow-up visit. Specific device-related AEs that will be captured and counted 
toward the primary endpoint are listed below. 
• 
Gastric 
o Bleeding (defined as below) 
 
Occurrence of post-operative blood transfusion deemed related to 
bleeding at the staple line; or  
 
Return to operating room before 70-day post-procedure follow-up visit 
due to bleeding deemed related to the staple line; 
o Leak (defined as below) 
 
Occurrence of intra-operative or post-operative gastrointestinal leak 
related to the staple line as documented intra-operatively, by clinical 
exam, or radiographically; 
o Stricture (defined as below) 
 
Occurrence of stricture documented radiographically or by endoscopy 
along the staple line; 
• 
Lung Resection 
o Prolonged air leak deemed related to the staple line (defined as below) 
 
 Greater than postoperative day 7 (procedure=day 0); 
o Empyema (defined as below) 
 
Purulent fluid collection in the pleural space documented 
radiographically, excluding chronic empyema 
2.2 SECONDARY PERFORMANCE ENDPOINTS  
The secondary performance endpoints for this study are listed below. 
• 
Number of study devices replaced during surgery due to slipping or bunching or not 
properly loaded onto stapler cartridge; and 

 
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• 
Device questionnaire by procedure group (gastric and lung resection) to capture 
usability. 
2.3 ADDITIONAL KEY DATA COLLECTED  
Additional key data collected for evaluation in this study are: 
• 
Endocutter and reload used (type, name, and color [for reload]) for each firing during 
the procedure along with which firings are associated with the study device; 
• 
Total number of study devices used during the procedure; 
• 
If intervention used for intra-operative bleeding on the staple line, capture type and 
number of interventions used; 
• 
Occurrence of blood transfusion (record the total required units of blood, rationale, 
and if related to staple line); 
• 
Date(s) of chest tube placement and removal, daily volume and characteristics of 
chest tube drainage; 
• 
Air leak duration in lung resection procedures; 
• 
Surgical procedure conducted (and technique used); 
• 
Procedure duration; 
• 
Hospital stay duration; and 
• 
Readmission for procedural-related complications. 
3.0 INVESTIGATIONAL PLAN 
3.1 OVERALL STUDY DESIGN AND PLAN - DESCRIPTION 
This prospective, single-arm, multi-center study will collect clinical data in a post-market 
setting by procedure group (gastric and lung resection). Investigators will perform each 
procedure using the device in compliance with their standard surgical approach and the 
ECHELON SLR IFU.  
Subjects will be consented and screened anytime during a period of 8 weeks prior to the date 
of surgery. Subjects will be considered treated when at least one ECHELON SLR has been 
placed during the procedure. All treated subjects will be followed post-operatively through 
discharge and again at 28, 70, and 135 days (± 14 days) post-surgery; therefore, from the 
surgery date to study exit, the duration will be approximately 19 weeks.  
3.2 STUDY POPULATION 
3.2.1 
Enrollment 
Subjects will be recruited from the PI’s existing patient population who plan to have an 
elective gastric or lung resection surgical procedure. Eligible subjects will be consecutively 
approached for participation so as to remove the potential of subject selection bias. 
Subjects will be considered enrolled at the time of consent signing. Subjects will be 
considered treated when at least one ECHELON SLR has been placed during the 
procedure. Gastric procedures are limited to laparoscopic gastric resection, robotic 
laparoscopic gastric resection, partial gastrectomy, gastric wedge resection, subtotal 
gastrectomy, laparoscopic Roux-en-Y gastric bypass, and robotic laparoscopic gastric 
bypass. Lung resection procedures include lobectomy, segmentectomy or wedge 

 
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resection and lung volume reduction surgery, and may be VATS or open procedures. Up 
to 16 centers in the United States will be selected as study sites. Each participating 
investigator is expected to perform a minimum of five gastric or lung resection procedures 
using the ECHELON SLR. A minimum of 243 treated subjects (maximum of 431 treated 
subjects) are planned to be in the study with a minimum of 112 treated subjects for gastric 
procedures and a minimum of 131 treated subjects for lung resection procedures.   
3.2.2 
Inclusion Criteria 
Subjects satisfying the following criteria will be considered eligible for enrollment in this 
study: 
1. Primary procedure (gastric or lung resection) where ECHELON SLR is planned to 
be used for reinforcement of staple lines per the IFU in either a. or b.: 
a. Gastric procedures limited to laparoscopic gastric resection, robotic 
laparoscopic gastric resection, partial gastrectomy, gastric wedge 
resection, subtotal gastrectomy, laparoscopic Roux-en-Y gastric bypass, 
and robotic laparoscopic gastric bypass; or 
b. Lung resection procedures that include lobectomy, segmentectomy or 
wedge resection, and lung volume reduction surgery, and may be VATS or 
open procedures; 
2. Willingness to give consent and comply with all study-related evaluations and visit 
schedule; and 
3. At least 18 years of age. 
3.2.3 
Exclusion Criteria 
Subjects meeting any of the following criteria will be considered not eligible for enrollment 
in this study: 
Preoperative 
1. Physical or psychological condition which would impair study participation; 
2. Gastric procedures: Body mass index (BMI) ≥ 50.0 kg/m2, or lung resection 
procedures: BMI ≥ 46.0 kg/m2; 
3. The procedure is a revision/reoperation for the same indication or same anatomical 
location; 
4. A procedure where extended wound or organ support is required; 
5. Any medical condition that the investigator deems could impact inflammatory or 
immune response; 
6. Concurrent treatment with medications that the investigator deems could have 
influence on wound healing; 
7. History of hypersensitivity to polyglactin (Vicryl®), Polydioxanone (PDO or PDS), or 
hypersensitivity to related products (cross-allergy); or 
8. Enrollment in a concurrent interventional clinical study that could impact the study 
endpoints. 

 
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Intraoperative 
1. Per surgeon discretion, presence of adhesions that could lead to an increased risk 
of leak occurrence at a different location than the staple line. 
2. Per surgeon discretion, medical finding intraoperatively such that the procedural 
plan is changed and ECHELON SLR is not used during the procedure. 
3.2.4 
Screening Failures 
All subjects signing consent who do not have at least one ECHELON SLR placed during 
their procedures will be recorded as screen failures. For subjects who are determined to 
be screen failures, only the relevant eCRF pages (inclusion/exclusion criteria, 
demographics, AEs, subject completion/discontinuation) will be completed. 
3.2.5 
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, 1) all data 
collected up to the point of withdrawal will be considered for analysis; and 2) all efforts will 
be made to collect and report the final visit observations as thoroughly and timely as 
possible. Participation may be terminated prior to completing the study for any of the 
reasons listed below (reasons that do not fit the categories below will be documented as 
“other”). 
Adverse Event 
When the subject experiences an AE and the Investigator or Medical Monitor believes it is 
in the best interest of the subject to discontinue participation in the study, the subject will 
be withdrawn from the study.  
Lost to follow-up 
When contact with the subject has been lost without completing a final contact 
assessment, and every attempt to contact the subject has failed, the subject will be 
considered lost to follow-up. All attempts to contact the subject requesting his/her return 
for the final visit must be documented.  
Withdrawal of consent 
Any method of contact with the subject (or subject’s legally authorized 
guardian/representative) in which he/she state they no longer want to participate in the 
study specific activities constitutes withdrawal of consent for participation in the study. 
When possible, the reason for withdrawal of consent will be documented. 
Site Termination or Study Termination 
A study site or the entire study may be terminated. When this occurs, all subjects currently 
enrolled at the site will be withdrawn and documented as early terminations. 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, or those that substantially 
affect the risk to benefit ratio of the study subjects at a site or for the study as a 
whole; or 
• 
Regulatory Body Mandate(s). 

 
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The Investigator has the right to terminate the subject’s participation at any time. Should 
this be necessary, procedures for termination will be provided by the Sponsor. 
Death 
• 
When possible, the cause of death will be documented. 
Other (which may include) 
• 
Investigator recommendation. 
3.2.6 
Subject Replacement in Study 
Treated subjects who withdraw or are terminated early from the study will not be replaced. 
3.3 STUDY PROCEDURES 
3.3.1 
Procedure Description 
Elective gastric and lung resection procedures where ECHELON SLR is indicated for use 
(See Section 3.2.1 for the study specific procedures) will be performed per the institution’s 
standard of care (SOC).  
3.3.2 
Identity of Study Products 
The ECHELON SLR is the study product for this study. Per the ECHELON SLR IFU, it 
should only be used with ECHELON ENDOPATH GST 60 mm reload cartridges.  
For this study, only the ECHELON FLEX™ Powered Plus Stapler (with ECHELON 
ENDOPATH GST 60 mm cartridges) should be used with the ECHELON SLR.  
3.3.2.1 Device Description 
The ECHELON SLR (Figure 1) is a sterile, bioabsorbable staple line reinforcement. The 
applicator contains a set of reinforcement materials: one each for the upper and lower 
stapler jaws.  
 
 
Figure 1: Image of the ECHELON SLR. 
 
The reinforcement material is composed of a VICRYL® material coated with a thin 
polydioxanone film on each side. The VICRYL component is prepared from polyglactin 
910, a synthetic absorbable copolymer of glycolide and lactide, derived respectively from 
glycolic acid and lactic acids. The polyglactin 910 component is essentially absorbed 

 
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within 120 days. The VICRYL material is degraded via a combination of hydrolytic and 
enzymatic pathways and has been found to be both biocompatible and nonantigenic, 
with a history of use as bioabsorbable sutures, membranes and other implantable 
devices.  
The polydioxanone which coats the VICRYL is a poly (p-dioxanone) polymer. The 
polydioxanone is essentially absorbed within 120 days. The reinforcement material 
elicits a mild tissue reaction during absorption. The polydioxanone material is degraded 
via a combination of hydrolytic and enzymatic pathways and has been found to be both 
biocompatible and nonantigenic, with a history of use as bioabsorbable sutures. 
The ECHELON SLR contains a pre-applied, patterned adhesive composed of a mixture 
of water soluble alkylene oxide copolymers, which attaches the reinforcement material to 
the stapler reload and anvil.  
3.3.2.2 Indications 
ECHELON ENDOPATH Staple Line Reinforcement is indicated for use in surgical 
procedures in which soft tissue transection or resection with staple line reinforcement is 
needed. ECHELON ENDOPATH Staple Line Reinforcement can be used for 
reinforcement of staple lines during lung resection and bariatric surgical procedures. The 
device can also be used for reinforcement of staple lines during gastric, small bowel and 
colorectal procedures. 
3.3.2.3 Labeling of Study Products 
The ECHELON SLR has received 510(k) clearance in the United States from the Food 
and Drug Administration (FDA). The study device will use the cleared labeling. The 
Sponsor requires no additional labeling in this study. 
3.3.2.4 Accountability of Study Products 
The ECHELON SLR will be provided to the participating institutions. Devices will be 
tracked using shipping receipts and device accountability logs and all device returns will 
be managed by contacting EES. Devices provided for the study must be kept in a secure 
area and used only for treating subjects participating in the study, in accordance with the 
protocol. If applicable, the study device inventory must be available for periodic 
inspection/verification. 
3.3.3 
Prior and Concomitant Therapy 
Subjects will be assessed for prior medication therapy history (30 days prior) during Visit 1 
(Screening Visit).  
Any medications administered during the study must be documented on the concomitant 
medication eCRF except for medications used by the site as standard of care for surgical 
procedures (i.e., standard perioperative medications, including anesthesia, etc.). 
3.3.3.1 Restricted Therapy 
Treatments restricted during the course of this study because of potential influence on 
study variables include: 
• 
Concurrent treatment with medications that the investigator deems could have an 
influence on wound healing, unless deemed in the subject’s best medical interest 
and then it would be allowed (rationale for use must also be collected).  

 
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3.4 STUDY VARIABLES 
Specific variables assessed in the study are provided in the following sections. Refer to 
Section 3.5 Schedule of Events for the time when the study variables will be collected 
throughout the course of the study. 
3.4.1 
Demographic and Baseline Characteristics  
The following will be collected preoperatively: 
• 
Age (years); 
• 
Gender; 
• 
Race; 
• 
Ethnicity; 
• 
Body weight (kg or lbs; no shoes); 
• 
Body height (cm or in; no shoes); 
• 
American Society of Anesthesiologists (ASA) Physical Status Classification; 
• 
Incidence and location of cancer and occurrence of pre-surgical 
radiation/chemotherapy within 90 days prior to surgery (when and how many 
doses), if applicable. 
• 
Review and collection of medical history and surgical history including the 
following: 
o Surgical procedure to be conducted (and technique used), including 
primary indication for surgery; 
o Smoking history; and 
o Tumor details (including staging information), if applicable. 
3.4.2 
Surgical Variables 
The following will be recorded preoperatively, intraoperatively, or postoperatively: 
• 
Date/time of hospital admission; 
• 
Endocutter and reload used (type, name, and color [for reload]) for each firing 
during the procedure along with which firings are associated with the study device; 
• 
Total number of study devices used during the procedure; 
• 
Number of study device(s) replaced during surgery due to slipping or bunching or 
not properly loaded onto stapler cartridge (these are product complaints and 
should be reported; refer to section 7.0); 
• 
If any intervention used for intra-operative bleeding on the staple line, capture type 
and number of interventions used; 
• 
Occurrence of blood transfusion (record the total required units of blood, rationale, 
and if related to staple line); 
• 
If applicable, date(s) of chest tube placement and removal, daily volume and 
characteristics of chest tube drainage;   
• 
Air leak duration in lung resection procedures; 

 
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• 
Procedure duration, defined as first skin incision to final skin closure; 
• 
Volume of estimated intra-operative blood loss; 
• 
Conversion to open, if it occurs (with rationale); 
• 
For the gastric procedure group, if it occurs: 
o Bleeding (defined in section 2.1); 
o Leak (occurrence of intra-operative or post-operative gastrointestinal leak 
related to the staple line as documented intra-operatively, by clinical exam, 
or radiographically); 
o Stricture (occurrence of stricture documented radiographically or by 
endoscopy along the staple line); 
• 
For the lung resection procedure group, if it occurs: 
o Prolonged air leak related to the staple line greater than postoperative day 
7 (procedure=day 0); and 
o Empyema (purulent fluid collection in the pleural space documented 
radiographically, excluding chronic empyema. 
• 
If available, video recordings (refer to Section 4.3). Video footage will not be 
considered source documentation for purposes of data collection for this study. 
Video may be used for the assessment of: 
o Number of study device(s) replaced during surgery due to slipping or 
bunching; 
o Endocutter and reload used (type, name, and color [for reload]) for each 
firing during the procedure along with which firings are associated with the 
study device; 
o If intervention used for intra-operative bleeding on the staple line, capture 
length of time, type and number of interventions used; and 
o Total video operative time and breakdown of time by major steps of the 
procedure; 
• 
Concomitant procedures, if applicable (defined as any medical or surgical 
procedure beyond activities associated with primary study procedure); 
• 
Concomitant medication usage, except for medications used by the site as 
standard of care for surgical procedures; 
• 
Date/time of hospital discharge. 
3.4.3 
Device Questionnaire 
Investigators will be asked to answer a non-validated device questionnaire related to 
his/her experience using the ECHELON SLR. The questionnaire will be completed by the 
Investigators as soon as possible after the investigator’s 1st, 3rd, and 5th procedure, 
preferably on the same day. The questionnaire responses will then be transcribed onto 
eCRFs.  
3.4.4 
Safety Data Variables 
All device-related and procedure-related AEs will be collected and captured as outlined in 

 
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Intra-operative and Post-operative 
Data collected during and after the procedure as defined in Section 3.4. 
3.6.3 
Visit 3 – Post-procedure Follow-up Visit 
After the surgery, subjects will have a follow-up visit approximately 28 days later (+/- 14 
days). This visit can be either an office visit or a telephone follow-up. Data to be collected 
is defined in Section 3.5.  
3.6.4 
Visit 4 – Post-procedure Follow-up Visit 
After the surgery, subjects will have a follow-up visit approximately 70 days later (+/- 14 
days). This visit can be either an office visit or a telephone follow-up. Data to be collected 
is defined in Section 3.5.  
3.6.5 
Visit 5 – Post-procedure Follow-up Visit 
After the surgery, subjects will have a follow-up visit approximately 135 days later (+/- 14 
days). This visit can be either an office visit or a telephone follow-up. Data to be collected 
is defined in Section 3.5.  
3.6.6 
Unscheduled Visit(s) 
Any unscheduled visit between Visit 2 and Visit 5 will be documented including the reason 
for the visit. These visits can be either an office visit or a telephone follow-up. 
4.0 DATA MANAGEMENT AND INTEGRITY 
4.1 DATA COMPLETION AND RECORD KEEPING 
4.1.1 
Source Documents 
Source documents are documents on which information regarding subjects is first 
recorded, including printed, optical, 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; 
radiographs; device accountability records; photographic negatives; and records kept at 
the investigation site, at the laboratories and at other departments involved in the clinical 
study. Source document worksheets may also be used to facilitate data collection and 
entry into eCRFs.  
Source documents must be retained by the Investigator as part of the subject’s study 
record. The information in the source documents is used to 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. Any deviations from the study protocol or procedures should be 
recorded in the source documents. The Investigator will retain originals of all source 
documents, subject consent forms, and study data per site policy. 
4.1.2 
Electronic Data Capture 
An 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
 
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 

 
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Dictionary for Regulatory Activities (MedDRA) and World Health Organization Drug 
Dictionary will be used after data entry and query resolution, via auto-encoding and 
interactive coding processes. 
4.3 VIDEO RECORDING AND ANALYSIS 
Video will be used in an exploratory analysis to validate the utility of video analysis to assess 
several study variables. Video footage will not be considered source documentation for 
purposes of data collection for this study. C-SATS, part of the Johnson & Johnson Institute, 
is a performance management system for healthcare professionals that may be used to 
assess and improve performance continuously, accurately, and objectively. In this study, the 
C-SATS platform may be used for video upload and analysis. 
Videos of the surgical procedure will be recorded at applicable investigational sites. Videos 
should be of the entire procedure, as per physician/hospital standard of care.  
Upon completion of the surgical procedure, the video will be sent to the Sponsor via one of 
the following methodologies, based on local requirements: 
• 
Upload videos to Sponsor from the hospital source video or hospital cloud storage; or 
• 
Send video via encrypted hard drive to the Sponsor. 
Specific instructions for each delivery method will be included in the Investigator Site File.  
The following variables will be reviewed through videos obtained during the procedure (as 
mentioned in Section 3.4.2): 1) counts of number of study device(s) replaced during surgery 
due to slipping or bunching, 2) endocutter and reload used (type, name, and color [for 
reload]) for each firing during the procedure along with which firings are associated with the 
study device, 3) if intervention used for intra-operative bleeding on the staple line, capturing 
length of time, type and number of interventions used, and 4) total video operative time will 
be captured. Additional post-hoc data collection and analysis of other variables from the 
videos may be performed. 
The video collected will be used for an exploratory comparison analysis to data entered into 
eCRFs (based on source document worksheets, subject files, and/or hospital records), in 
order to validate the use of video for possible endpoint assessment in future studies.  
Any issues observed by independent reviewers that may constitute a device deficiency shall 
be reported following the sponsor’s product complaints reporting process for medical 
devices. For any discrepancies noted as a result of the comparison analysis, only the site-
reported data will be considered for purposes of study endpoint assessment, as the videos 
are not considered source documentation for purposes of study data collection.  
In order to maintain independence of the video reviewers, access to the EDC database will 
not be granted to the video reviewers. 
Participation with video recording of the surgical cases is not mandatory. Surgeons or 
subjects who decide to opt out will still be included in the study.  
4.4 DATA QUALITY ASSURANCE 
Steps to be taken to assure the accuracy and reliability of data include the selection of 
qualified investigators and appropriate sites, 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 monitoring 
visits and periodic reviews; any discrepancies will be resolved with the Investigator or 
designees, as appropriate. 

 
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4.4.1 
Site Personnel Training 
Prior to completing any study-related assessments, the PI, Sub-Investigator(s), Study 
Coordinator, and other designated staff (as applicable) will be trained on study execution, 
data collection, and procedures specific to this clinical protocol. 
4.4.2 
Monitoring 
This study will be monitored by the Sponsor or its representative to ensure: 
• 
The rights and well-being of the subjects are protected; 
• 
The 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 agreed to by the Sponsor 
and investigators. Monitors will comply with established written standard operating 
procedures as well as procedures specified by the Sponsor for monitoring this study as 
characterized in the monitoring plan for this study. 
4.4.3 
Quality Assurance 
The extent and nature of quality assurance audits will be predetermined and based on 
considerations such as the regulatory classification, objective, and complexity of the study. 
Any audits performed will comply with established written standard operating procedures 
and the audit plan for this study. 
4.5 PROTOCOL DEVIATIONS 
A deviation (any activity conducted outside the parameters established by the protocol) can 
be identified from a number of sources. Potential sources for identification of deviations 
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 
in the source documentation as well as the eCRF. The PI will report protocol deviations to 
the IRB as required by the IRB procedures. 
5.0 STATISTICAL METHODS PLANNED IN THE PROTOCOL AND 
DETERMINATION OF SAMPLE SIZE 
The Sponsor will be responsible for the analysis of data from this protocol. A detailed Statistical 
Analysis Plan (SAP) will be written and approved prior to final database lock. The SAP will 
describe all planned analyses based on the statistical design of this study and the subsequent 
data collected. A brief overview of key statistical analyses is provided below. 
5.1 STUDY DESIGN 
Study design is described in Section 3.1. 
5.2 TREATMENT ASSIGNMENT 
This is a single-arm study where all enrolled subjects will have the ECHELON SLR utilized 
during the surgical procedure. 

 
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5.3 INTERVAL WINDOWS 
Interval windows for the purpose of analysis in this study will not be defined outside of those 
already specified in the protocol for visit scheduling. The final visit occurs approximately 19 
weeks after surgery, thus no interval windows need to be defined given the absence of long-
term follow-up in this study. The Schedule of Events specifies a window of 14 days around 
the scheduling of the follow-up visits, and any information entered in the eCRFs at this visit 
will correspond to the associated visit. There will be no assigning of observations to time 
points outside of the visit to which they are recorded in the eCRFs. 
5.4 PRIMARY AND SECONDARY ENDPOINTS AND ASSOCIATED HYPOTHESES 
All study endpoints are described in Section 2.1 through Section 2.3. The following 
hypotheses will be evaluated for the primary endpoint for gastric procedures: 
H0: pG ≥ 14.0% 
H1: pG < 14.0% 
Where pG is the percentage of subjects experiencing at least one occurrence of bleeding, 
leak, or stricture through 70 days. A 95% confidence interval will be calculated for pG based 
on the sample proportion of subjects experiencing the endpoint using the Normal 
approximation to the Binomial distribution and the upper limit of this confidence interval will 
be compared to 14.0% to evaluate the above hypotheses. A p-value will be determined 
based on the same Normal approximation methodology.  
A similar methodology will be applied to the data observed in lung procedures to evaluate the 
following hypotheses:  
H0: pL ≥ 12.0% 
H1: pL < 12.0% 
Where pL is the percentage of subjects experiencing at least one occurrence of prolonged air 
leak or empyema through 70 days.  
5.5 LEVELS OF SIGNIFICANCE 
Each of the sets hypotheses above will be evaluated using a one-sided significance level of 
0.025 and the overall level of significance across the study will be controlled at a value that 
does not exceed 0.05. Estimation of all additional endpoints will be performed using 95% 
confidence intervals. 
5.6 ANALYSIS SETS 
The summary of all performance and safety endpoints will be performed on the set of 
subjects in whom the ECHELON SLR is utilized during the surgical procedure. The summary 
of all primary and secondary endpoints will be performed by procedure group and in total.   
5.7 SAMPLE SIZE JUSTIFICATION 
For the gastric procedure group, a sample size of at least 99 subjects is required to have a 
minimum of 80% power for rejecting the null hypothesis when the expected rate of the 
primary endpoint is 7% based on current available literature1,2. Similarly, for the lung 
resection group, a sample size of at least 116 subjects is required to have a minimum of 80% 
power for rejecting the null hypothesis when the expected rate of the primary endpoint is 6% 
based on current available literature3. Each calculation is determined using the Normal 
approximation with a one-sided significance level of 0.025 and makes the assumption of a 
20% reduction in the expected rate of the primary endpoint with the ECHELON SLR. The 

 
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performance goal-based hypotheses specified in Section 5.4 are based on establishing 
acceptable initial performance of the ECHELON SLR by ruling out a doubling of the expected 
risk that has been reported in the literature for these procedures.  
Accounting for an anticipated dropout rate as high as 12.5% in each procedure group leads 
to an initial planned sample size of 112 subjects in the gastric group and 131 subjects in the 
lung resection group.  
Given the lack of available clinical data on the performance of the ECHELON SLR, an 
adaptive approach to sample size re-estimation will occur after approximately 50% of the 
originally planned sample size has been enrolled into each procedure group. The purpose of 
this interim analysis will be to estimate the rate of the primary endpoint in each group or 
concurrently to estimate the size of the relative reduction of this endpoint relative to the 
values reported in current literature. The current sample size calculation assumes an 
expected background rate of 7% in the gastric group, 6% in the lung resection group, and 
that a 20% relative reduction will be observed with the ECHELON SLR. Based on the values 
observed at the interim analysis time points for each group, the within-group sample sizes will 
be re-estimated. A sample size of 200 subjects has been set as the maximum sample size 
that will be pursued following the interim analysis and sample size re-estimation process in 
the gastric group and a maximum of 231 subjects has been set in the lung resection group.  
The sample size re-estimation for each group will apply the methodology described in Lan 
and Trost4 and Wang, Keller, and Lan5.  Following that methodology, the prespecified 
conditional power lower limit for futility is set at 10%, and the upper limit for maintaining the 
original sample size is set at 80%. Specifically, if the conditional power evaluated at the time 
of the interim analysis is ≤ 0.10, the trial within that procedure group will be stopped for futility 
and the null hypothesis will be accepted. If the conditional power is ≥ 0.80, then the study will 
continue to its originally planned completion with no sample size adjustment. If the 
conditional power is between 0.10 and 0.80, the sample size will be increased so as to 
maintain the conditional power at a target of 0.80 under the current trend of the data, up to 
the maximum values specified above. 
As discussed in Lan and Trost, given that the lower limit of conditional power for futility is at 
least 0.10, the Type I error rate is controlled at the nominal level, and no adjustment to the 
planned significance level of 0.025 is required under this approach.  
5.8 DATA MONITORING COMMITTEE 
There are no plans to utilize a data monitoring committee during this study. 
5.9 ANALYSES TO BE CONDUCTED 
5.9.1 
General Conventions 
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. Confidence 
intervals will also be provided for procedure-related variables. 
5.9.2 
Disposition of Study Subjects 
Subject disposition will be summarized in total and by procedure group using counts and 
percentages. The number and percentage of subjects completed and discontinued will be 
tabulated along with the specific reasons for discontinuation. 

 
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5.9.3 
Demographic, Baseline, and Surgical Characteristics 
Summary statistics of subject demographics (age, gender, race and ethnicity) will be 
presented in total and by procedure group. Similar summaries will also be provided for 
baseline and surgical characteristics including body mass index, surgical procedure, 
smoking history, ASA physical status classification, procedure duration, and additional 
surgical data outlined in earlier sections.  
5.9.4 
Primary and Secondary Endpoint Analyses 
Within each procedure group, the number and percentage of subjects experiencing an 
occurrence of the primary endpoint will be summarized and a 95% confidence interval for 
each rate will be estimated. The performance goal hypotheses will be tested based on 
methodology as described above in Section 5.4.  
The number and percentage of subjects experiencing each component of the composite 
endpoint will be summarized in each procedure group.  
All device-related and procedure-related AEs reported during the study will be coded to 
MedDRA. All AEs will be summarized by MedDRA system organ class and preferred term 
by procedure group and in total. Separate summaries will be provided for device-related 
and procedure-related AEs. Serious AEs will be summarized in a similar manner. 
Counts and percentages will be provided for usability data collected via surgeon 
questionnaire and summary statistics will be provided for the number of study devices 
attempted and used during the surgical procedure. 
5.9.5 
Plans for Interim Analyses 
One interim analysis in each procedure group is planned for sample size re-estimation. 
Details are provided in Section 5.7 above. Study enrollment may continue while the interim 
analysis is ongoing. 
5.9.6 
Handling of Missing Data 
All summaries will be performed only on subjects undergoing the scheduled 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 for the primary evaluation of 
the hypotheses specified above. Sensitivity analyses will be detailed in the SAP that will 
be designed to assess the robustness of the primary study conclusions to missing data or 
incomplete data on early terminated subjects.  
5.9.7 
Subgroup Analyses 
Descriptive summaries are planned to be provided for each procedure within the lung 
resection group (lobectomy, segmentectomy, etc.). Subgroup analyses may be performed 
for additional groups pending the distributions of baseline demographic or clinical 
characteristics. These analyses will be exploratory, and summary statistics for the 
procedure-related parameters will be provided for each subgroup.  
6.0 ADVERSE EVENTS 
All adverse events considered unlikely, possibly, probably, or causally related to the device or 
the procedure will be collected during this study. 

 
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6.1 DEFINITIONS 
6.1.1 
Adverse Event 
An AE is defined as any untoward medical occurrence, regardless of its relationship to the 
study device or the study procedure. An untoward medical occurrence includes any new, 
undesirable medical experience or worsening of a pre-existing condition, which occurs 
throughout the duration of the clinical study.  
6.1.2 
Adverse Device Effect 
An adverse device effect (ADE) is an AE related to the use of a study device. This 
includes any AE resulting from insufficient or inadequate IFU, deployment, implantation, 
installation, operation, or any malfunction of the study device. An ADE may also include 
any event resulting from user error or from intentional misuse of the study device. 
6.1.3 
Serious Adverse Event 
It is the Investigator’s responsibility to determine the “seriousness” of a reportable AE. 
A SAE is defined as an AE (as defined in Section 6.1.1) that results in any of the following: 
• 
Death; 
• 
A life-threatening illness or injury; 
• 
A permanent impairment of a body structure or a body function; 
• 
Required in-patient hospitalization or prolongation of existing hospitalization; 
• 
Resulted in medical or surgical intervention to prevent life-threatening illness or 
injury or permanent impairment to a body structure or a body function; or 
• 
Led to a fetal distress, fetal death, or a congenital abnormality or birth defect. 
Note: “Death” should not be reported as an AE. The cause of death should be reported as 
the AE. The only exception is “Sudden Death” when the cause is unknown. 
Note: Planned hospitalization for a pre-existing condition, or a procedure required by the 
protocol, without serious deterioration in health, is not considered a SAE. 
6.1.4 
Serious Adverse Device Effect (SADE) 
A serious ADE (SADE) is an ADE that has resulted in any of the consequences 
characteristic of a SAE or that might have led to any of these consequences if suitable 
action had not been taken or intervention had not been made or if circumstance had been 
less opportune. 
6.1.5 
Unanticipated Serious Adverse Device Effect (USADE) 
An unanticipated serious adverse device effect (USADE) is an effect which, by its nature, 
incidence, severity or outcome, has not been identified. An anticipated SADE is an effect 
which by its nature, incidence, severity, or outcome, has been identified in the IFU. 
6.1.6 
Pre-existing Condition 
A pre-existing condition is defined as a medical condition that is present at the initiation of 
the study and is to be reported as part of the subject’s medical history with a listed start 
date. Any pre-existing condition that has worsened in intensity, frequency, or the character 
of the condition should be recorded as a new AE on the AE eCRF, as an exacerbation of 
the pre-existing condition and the start date will be recorded as the time when the 
exacerbation occurred. 

 
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6.2 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 AE: 
• 
MILD: Awareness of signs or symptoms, but does not interfere with the patient’s 
usual activity, or is a transient event that resolves without treatment and with no 
sequelae. 
• 
MODERATE: A sign or symptom, which interferes with the patient’s usual activity. 
• 
SEVERE: Incapacity with inability to do work or usual activities. 
6.3 RELATIONSHIP OF ADVERSE EVENTS 
It is the Investigator’s responsibility to assess the relationship of a reportable AE (as defined 
in Section 6.1.1). Only AEs considered unlikely, possibly, probably, or causally related to the 
study procedures or the ECHELON SLR device are to be recorded in the eCRF and 
reported to the Sponsor. 
The following guidelines should be used in determining the relationship of an AE in the 
study: 
• 
Not related – Relationship to the procedures or device can be excluded when: 
o The event is not a known side effect of the product category the device 
belongs to or of similar devices and procedures; 
o The event has no temporal relationship with the use of the device or the 
procedures; 
o The event does not follow a known response pattern to the device (if the 
response pattern is previously known) and is biologically implausible; 
o The discontinuation of the device application or the reduction of the level 
activation/exposure (when clinically feasible) and reintroduction of its use (or 
increase of the level of activation/exposure), does not impact on the event; 
o The event involves a body site or an organ not expected to be affected by the 
device or the procedure; 
o The event can be attributed to another cause (e.g. an underlying or 
concurrent illness/clinical condition, an effect of another device, drug, 
treatment, or other risk factors); 
o Harms to the subject are not clearly due to use error; or 
o To establish the non-relatedness, not all the criteria listed above might be met 
at the same time, depending on the type of device/procedure and the event. 
• 
Unlikely – The relationship with the use of the device seems not relevant and/or the 
event can be reasonably explained by another cause, but additional information may 
be obtained. 
• 
Possible – The relationship with the use of the device is weak but cannot be ruled 
out completely. Alternative causes are also possible (e.g. an underlying or 
concurrent illness/condition and/or an effect of another device, drug, or treatment). 
Cases where relatedness cannot be assessed, or no information has been obtained 

 
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should also be classified as possible. 
• 
Probable – The relationship with the use of the device seems relevant and/or the 
event cannot reasonably be explained by another cause, but additional information 
may be obtained. 
• 
Causal relationship – The event is associated with the device or with procedures 
beyond reasonable doubt when: 
o The event is a known side effect of the product category the device belongs 
to or of similar devices and procedures; 
o The event has a temporal relationship with the device uses/application or 
procedures; 
o The event involves a body-site or organ that: 
 
The device or procedures are applied to or is adjacent to; 
 
The device or procedures have an effect on; 
o The event follows a known response pattern to the medical device (if the 
response pattern is previously known); 
o The discontinuation of medical device application (or reduction of the level of 
activation/exposure) and reintroduction of its use (or increase of the level of 
activation/exposure), impact on the event (when clinically feasible); 
o Other possible causes (e.g. an underlying or concurrent illness/clinical 
condition and/or an effect of another device, drug, or treatment) have been 
adequately ruled out; 
o Harm to the subject is due to error in use; or 
o To establish the relatedness, not all the criteria listed above might be met at 
the same time, depending on the type of device/procedure and the event. 
6.4 REPORTING PROCEDURES FOR ADVERSE EVENTS 
6.4.1 
Recording Adverse Events 
The Investigator will record all AEs (both AEs and SAEs) considered attributable 
(relationship of possible, probable, causal relationship) to the study procedure or the 
ECHELON SLR in the source documents and eCRF.  
Standard medical terminology should be used when recording AEs. In addition, the 
following information should be recorded: 
• 
Onset date; 
• 
Resolution date or date of death; 
• 
Severity of the event; 
• 
Indication of whether the event is serious; 
• 
Relationship of AE to the device used in the study; 
• 
Relationship of AE to the study procedure; 
• 
Action taken; 
• 
Event status; and 
• 
Was AE anticipated or not (only for SAEs). 
Data related to AEs will be collected until the event resolution, or until the event is 
considered stable, or until all attempts to determine the resolution of the event are 

 
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(2007). The approach of fused fissures with fissureless technique decreases the 
incidence of persistent air leak after lobectomy. European journal of cardio-thoracic 
surgery, 31(2), 203-208. 
4. Lan, K. K. G., & Trost, D. C. (1997). Estimation of parameters and sample size re-
estimation. In Proceedings-Biopharmaceutical Section American Statistical 
Association (pp. 48-51). American Statistical Association. 
5. Wang, C., Keller, D. S., & Lan, K. K. G. (2002). Sample size re-estimation for binary 
data via conditional power. In American Statistical Association Proceedings of the 
Joint Statistical Meetings (pp. 3621-3626).