A Prospective, Single-Arm Multi-Center Study of the ENSEAL X1 Curved Jaw Tissue Sealer and Generator G11 in Upper Gastrointestinal, Lower Gastrointestinal, and Gynecological Procedures
Phase: NA
Conditions: Upper GI; Lower GI; Gynecological
Sponsor: Ethicon Endo-Surgery

 
Trial Number: ENG_2019_01 
CONFIDENTIAL 
Page 1 of 34 
Version: Amendment 5  
 
11 NOV 2022 
A Prospective, Single-Arm Multi-Center Study of the ENSEAL® X1 Curved Jaw Tissue 
Sealer and Generator G11 in Upper Gastrointestinal, Lower Gastrointestinal, and 
Gynecological Procedures 
 
Trial Number: ENG_2019_01 
 
Document 
Effective Date
Original 
01 APR 2020
Amendment 1 
15 MAY 2020
Amendment 2 
10 SEP 2020
Amendment 3 
01 MAR 2021
Amendment 4 
16 JUL 2021
Amendment 5 
11 NOV 2022
 
Sponsor: 
Ethicon Endo-Surgery, Inc. 
4545 Creek Road 
Cincinnati, Ohio 45242 
Regulatory Classifications: 
Class II in the United States and Class IIb in European 
Union and United Kingdom for both devices 
Name of Finished 
Product(s): 
ENSEAL® X1 Curved Jaw Tissue Sealer 
Generator G11 
Sponsor’s Medical Monitor: 
Giovanni A. Tommaselli, M.D. 
 
Medical Director LCM Compliance 
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. 
 

 
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PROTOCOL SIGNATURE PAGE 
 
A Prospective, Single-Arm Multi-Center Study of the ENSEAL® X1 Curved Jaw Tissue 
Sealer and Generator G11 in Upper Gastrointestinal, Lower Gastrointestinal, and 
Gynecological Procedures 
 
 
Trial Number: ENG_2019_01 
 
Document 
Effective Date
Original 
01 APR 2020
Amendment 1 
15 MAY 2020
Amendment 2 
10 SEP 2020
Amendment 3 
01 MAR 2021
Amendment 4
16 JUL 2021
Amendment 5 
11 NOV 2022
 
 
 
 
 
Approvals: 
 
 
 
 
 
 
 
 
 
Franchise Clinical Head 
 
Date 
Ethicon Endo-Surgery, Inc. 
 
 
This study will be performed in compliance with GCP, and in accordance with the Declaration of 
Helsinki, as well as any other applicable local and country regulatory requirements. 
KATHRINE LORENZ
Digitally signed by KATHRINE LORENZ 
DN: c=US, o=JNJ, ou=Subscribers, 0.9.2342.19200300.100.1.1=7354, 
cn=KATHRINE LORENZ 
Reason: I am approving this document. 
Date: 2022.11.14 11:11:19 -05'00' 
Adobe Acrobat version: 2020.013.20064

 
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INVESTIGATOR SIGNATURE PAGE 
 
 
I have read, understood, and agree to: 
x 
Ensure that the requirements for obtaining informed consent are met; 
x 
Conduct the study in accordance with this protocol, including applicable local laws and 
regulations; 
x 
Maintain the confidentiality of all information received or developed in connection with this 
protocol; 
x 
Report all serious adverse events (SAEs) as soon as possible, but no later than 72 hours 
after becoming aware of the event; 
x 
Adhere to the publication policy, as stated in the Clinical Study Agreement, for data 
collected during this study;  
x 
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 
x 
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) / 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. 
 
 
 
 
 
 
 
 
Signature of Principal Investigator 
 
Date 
 
 
 
 
Printed Name of Principal Investigator 
 
 
 
Site Identification Number 
 
 

 
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CLINICAL STUDY PROTOCOL SYNOPSIS 
Regulatory 
Classification: 
Class II in the United States and Class IIb in European Union and United 
Kingdom for both devices 
Indication: 
ENSEAL® X1 Tissue Sealers (ENSEAL X1)  
The ENSEAL X1 devices are bipolar electrosurgical instruments for use 
with an electrosurgical generator. They are intended for use during open or 
laparoscopic surgical procedures to cut and seal vessels, and to cut, grasp 
and dissect tissue during surgery. 
Indications for use include open and laparoscopic general, gynecological, 
urologic, thoracic, and ENT surgical procedures or any procedure where 
vessel ligation (cutting and sealing), tissue grasping, dissection, and 
division of vessels, lymphatics, and tissue bundles is performed (e.g. bowel 
resections, hysterectomies, gall bladder procedures, Nissen Fundoplication, 
adhesiolysis, and oophorectomies). The devices can be used on vessels up 
to and including 7 mm and bundles as large as will fit in the jaws of the 
instruments. 
The ENSEAL X1 Tissue Sealers have not been shown to be effective for 
tubal sterilization or tubal coagulation for sterilization procedures.  
Generator G11 (GEN11) 
The GEN11 provides radiofrequency power to drive ENSEAL electrosurgical 
instruments that are used during open or laparoscopic general and 
gynecological surgery to cut and seal vessels and to cut, grasp, and dissect 
tissues. In addition, the generator provides power to drive HARMONIC 
ultrasonic surgical instruments that are indicated for soft tissue incisions 
when bleeding control and minimal thermal injury are desired. 
ENSEAL and HARMONIC instruments, when used with the GEN11, have 
not been shown to be effective for sterilization procedures or tubal 
coagulation. 
Objective(s): 
The primary objective of this study is to demonstrate the acceptable 
performance and safety of the ENSEAL X1 and GEN11 devices when used 
per the instructions for use (IFU). 
Overview of 
Study Design:   
This prospective, single-arm, multi-center study will collect clinical data in a 
post-market setting by procedure group (upper gastrointestinal [GI], lower 
GI, and gynecological). Investigators will perform each procedure using the 
device in compliance with their standard surgical approach and the 
ENSEAL X1 and GEN11 IFUs.  
Subjects will be consented and screened anytime during a period of 8 
weeks prior to the date of surgery. Subjects will be considered enrolled 
when the ENSEAL X1 device has been attempted to be used for a vessel 
transection during upper GI, lower GI, or gynecological procedures. All 
enrolled subjects will be followed post-operatively through discharge and 
again at 28 days (± 14 days) post-surgery; therefore, from the surgery date 
to study exit, the duration will be approximately 6 weeks.  

 
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Number of 
Subjects:   
In order to achieve a total of 230 vessel transections for analysis with a 
minimum of  27 vessel transections in each group (including 4 subgroups in 
upper GI procedure), a minimum of  133 subjects (maximum of 149 
subjects) will be included in the study from up to 16 surgery centers in the 
United States and/or European Union and/or United Kingdom. The 
minimum number of subjects is determined based on the number of 
subjects enrolled at the time of amendment 5 and projection of subjects 
needed to achieve a minimum of 27 vessels per group, deemed to be 
adequate to ensure optimum representation of each of the procedure 
groups in the whole study sample.  The enrollment is planned with the 
following procedure targets: 
x 
A minimum of 77 subjects enrolled to a maximum of 89 subjects 
enrolled for upper GI procedures to achieve 27 vessel transections 
in each of the four subgroups. Subjects will be enrolled to the 
following subgroups with corresponding enrollment restrictions: 
o A minimum of 14 subjects enrolled to a maximum of 17 
subjects enrolled for fundoplication (Nissen, anterior or 
posterior [Toupet]) or hiatal hernia procedures); 
o A minimum of 27 subjects enrolled to a maximum of 30 
subjects enrolled for gall bladder procedures; 
o A minimum of 10 subjects enrolled to a maximum of 13 
subjects enrolled for sleeve gastrectomy procedures; 
o A minimum of 26 subjects enrolled to a maximum of 29 
subjects enrolled for small intestine resection procedures 
(also includes Roux-en-Y gastric bypass [RYGB] and 
biliopancreatic diversion with duodenal switch [BPD/DS]); 
x 
A minimum of 28 subjects enrolled to a maximum of 30 subjects 
enrolled for lower GI procedures (e.g., large intestine resections); 
and 
x 
A minimum of 28 subjects enrolled to a maximum of 30 subjects 
enrolled for gynecological procedures (hysterectomies associated 
with oophorectomies). 
Criteria for 
Inclusion: 
Subjects satisfying the following criteria will be considered eligible for 
enrollment in this study: 
1. Primary laparoscopic or open procedure (upper GI, lower GI, or 
gynecological) where at least one vessel is planned to be transected 
by the ENSEAL X1 device per the IFU; 
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: 
1. Physical or psychological condition which would impair study 
participation; or 

 
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2. Enrollment in a concurrent interventional clinical study that could 
impact the study endpoints. 
Test Product: 
ENSEAL® X1 Curved Jaw Tissue Sealer (Product Codes: NSLX125C, 
NSLX137C, or NSLX145C) and Generator G11 (GEN11). 
Reference 
Therapy/ 
Product: 
No comparator product is being used in this study. 
Duration of 
Treatment: 
Subjects will be exposed to the ENSEAL X1 device during the procedure 
and while the device is used as indicated in the IFU. The device nor any 
device components remain in the patient after use. 
Criteria for 
Evaluation: 
The primary performance endpoint will be: 
x 
Achievement of Grade 3 or lower hemostasis for each vessel 
transection (per the grading scale below): 
o Grade 1: no bleeding at transection site; 
o Grade 2: minor bleeding at transection site, no intervention 
needed; 
o Grade 3: minor bleeding at transection site, mild intervention 
needed, use of compression, basic energy devices 
(monopolar and/or bipolar) and/or touch-ups with ENSEAL 
X1; or 
o Grade 4: significant bleeding (e.g., pulsatile blood flow, 
venous pooling) requiring intervention such as extensive 
coagulation or ligation with use of additional hemostatic 
measures (e.g., hemoclips, staples, sutures, fibrin sealants, 
other advanced energy products); 
The secondary performance endpoints will be: 
x 
Distribution of 5-point scale scores for various tasks completed by 
the ENSEAL X1 device (adhesiolysis, lymphatics or tissue bundles 
divided, tissue grasping, tissue cutting, or tissue dissection); 
x 
Distribution of hemostasis grading scale for each vessel transected; 
and 
x 
Type, name, and number of additional hemostasis products required 
to achieved hemostasis for Grade 4 vessel transections. 
The safety endpoint will be:
x 
Occurrence of device-related adverse events (AEs). 
Statistical 
Analysis: 
Analysis Sets 
The summary of all performance and safety endpoints will be performed on 
the set of subjects in whom the ENSEAL X1 device is utilized during the 
surgical procedure. The summary of all performance and safety endpoints 
will be performed by procedure group, procedure subgroup, and on the 
entire pooled set of subjects.  

 
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Sample Size Determination 
A sample size of at least 230 vessel transections is required to have a 
minimum of 90% power for rejecting the null hypothesis that the rate of 
Grade 3 or lower hemostatic transections is less than 87.5% when the 
expected rate of Grade 3 hemostatic transections is at least 94.0% based 
on exact binomial test and a one-sided significance level of 0.025. The 
hemostatic transection grades for vessels are assumed to be independent 
within a subject and a procedure.  
In order to achieve a total of 230 vessel transections for analysis with a 
minimum of 27 vessel transections in each group (including 4 subgroups in 
upper GI procedure), a minimum of 133 subjects (a maximum of 149 
subjects) will be enrolled in the study.  
The original sample size of the study was based on the assumption of one 
vessel transection per subject. At the time of amendment 5 the number of 
transections per subject was estimated to be 1.9 on average. The primary 
endpoint and the study hypothesis are based on hemostasis of vessel 
transection; therefore, the number of subjects to be enrolled was updated to 
ensure 230 vessel transections. 
 
Performance Analyses 
The number and percentage of vessels where hemostasis is achieved (≤ 
Grade 3) will be summarized and an exact 95% confidence interval will be 
estimated for each procedure group (upper GI, lower GI, and 
gynecological), the six individual procedure subgroups, and in total. The 
performance goal hypothesis will be evaluated using the lower bound of the 
exact 95% confidence interval and a p-value will be calculated using  exact 
binomial test. The 95% confidence interval will be estimated based on the 
Clopper-Pearson method. Counts and percentages will be provided for 
type, size, and number of vessels transected, grading scale distribution for 
all vessels transected, number of times ENSEAL X1 touch-ups were 
required, and incidence of requirement for additional measures to obtain 
hemostasis on vessels (other advanced energy devices or hemostatic 
measures).  
Safety Analyses 
All device-related and procedure-related AEs reported during the study will 
be coded to the Medical Dictionary for Regulatory Activities (MedDRA). All 
AEs will be summarized by MedDRA system organ class and preferred 
term by procedure group, procedure subgroup and in total. Separate 
summaries will be provided for device-related and procedure-related AEs. 
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 STUDY PROTOCOL SYNOPSIS ......................................................................... 4 
PROTOCOL-SPECIFIC ACRONYMS AND ABBREVIATIONS ........................................... 10 
ETHICS ............................................................................................................................... 11 
ADMINISTRATIVE REQUIREMENTS ................................................................................. 12 
1.0 
INTRODUCTION ....................................................................................................... 13 
2.0 
STUDY OBJECTIVES ................................................................................................ 14 
2.1 
Primary Performance Endpoint .............................................................................. 14 
2.2 
Secondary Performance Endpoints ........................................................................ 14 
2.3 
Safety Endpoint ...................................................................................................... 14 
2.4 
Additional Key Data Collected ................................................................................ 14 
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 
Screening Failures ............................................................................................. 16 
3.2.3 
Inclusion Criteria ................................................................................................ 16 
3.2.4 
Exclusion Criteria ............................................................................................... 17 
3.2.5 
Removal of Subjects from Study ........................................................................ 17 
3.2.6
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 
Contraindications ........................................................................................ 19 
3.3.2.4 
Labeling of Study Products ......................................................................... 19 
3.3.2.5 
Accountability of Study Products ................................................................. 19 
3.3.3 
Prior and Concomitant Therapy ......................................................................... 20 
3.4 
STUDY VARIABLES .............................................................................................. 20 
3.4.1 
Demographic and Baseline Characteristics ........................................................ 20 
3.4.2 
Surgical Variables .............................................................................................. 21 
3.4.3 
Questionnaires ................................................................................................... 22 
3.4.4 
Safety Data Variables ........................................................................................ 23 
3.5 
SCHEDULE OF EVENTS....................................................................................... 23 
3.6 
STUDY PROCEDURES ......................................................................................... 24 
3.6.1 
Visit 1 – Screening (may occur over visits within 8 weeks of Visit 2 
including up to the day of the procedure) ........................................................... 24 
3.6.2 
Visit 2 – Procedure Through Discharge Visit ...................................................... 24 
3.6.3 
Visit 3 – Post-procedure Follow-up Visit ............................................................. 24 
3.6.4 
Unscheduled Visit(s) .......................................................................................... 24 
3.6.5 
Vessel Image Capture........................................................................................ 24 
4.0 
DATA MANAGEMENT AND INTEGRITY ................................................................... 24 
4.1 
DATA COMPLETION AND RECORD KEEPING .................................................... 24 
4.1.1 
Source Documents ............................................................................................ 24 
4.1.2 
Electronic Data Capture ..................................................................................... 25 
4.1.3 
Data Collection .................................................................................................. 25 

 
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4.1.4 
Data Correction .................................................................................................. 25 
4.1.5 
Data Privacy ...................................................................................................... 26 
4.1.6 
Record Retention, Inspection, and Custody ....................................................... 26 
4.2 
MEDICAL DICTIONARY CODING ......................................................................... 26 
4.3 
DATA QUALITY ASSURANCE .............................................................................. 26 
4.3.1 
Site Personnel Training ...................................................................................... 26 
4.3.2 
Monitoring .......................................................................................................... 26 
4.3.3 
Quality Assurance .............................................................................................. 27 
4.4 
PROTOCOL DEVIATIONS ..................................................................................... 27 
5.0 
STATISTICAL METHODS PLANNED IN THE PROTOCOL AND DETERMINATION OF 
SAMPLE SIZE ........................................................................................................... 27 
5.1 
STUDY DESIGN .................................................................................................... 27 
5.2 
TREATMENT ASSIGNMENT ................................................................................. 27 
5.3 
INTERVAL WINDOWS ........................................................................................... 27 
5.4 
PRIMARY AND SECONDARY ENDPOINTS AND ASSOCIATED 
HYPOTHESES ....................................................................................................... 27 
5.5 
LEVELS OF SIGNIFICANCE ................................................................................. 28 
5.6 
ANALYSIS SETS ................................................................................................... 28 
5.7 
SAMPLE SIZE JUSTIFICATION ............................................................................ 28 
5.8 
DATA MONITORING COMMITTEE ....................................................................... 29 
5.9 
ANALYSES TO BE CONDUCTED ......................................................................... 29 
5.9.1 
General Conventions ......................................................................................... 29 
5.9.2
Disposition of Study Subjects.............................................................................29
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 ................................................................................... 30 
5.9.7 
Subgroup Analyses ............................................................................................ 30 
6.0 
ADVERSE EVENTS................................................................................................... 30 
6.1 
DEFINITIONS ........................................................................................................ 30 
6.1.1 
Adverse Event ................................................................................................... 30 
6.1.2 
Serious Adverse Event....................................................................................... 30 
6.1.3 
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 
7.1.2 
Reporting of Approved Marketed Devices and Commercially Available 
Devices (not Ethicon) ......................................................................................... 33 
8.0 
REFERENCES .......................................................................................................... 34 
 

 
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PROTOCOL-SPECIFIC ACRONYMS AND ABBREVIATIONS 
Acronyms/Abbreviations 
 
Terms 
AE 
 
Adverse event 
ASA 
 
American Society of Anesthesiologists Physical Status 
Classification System 
EC 
 
Ethics committee 
eCRF 
 
Electronic case report form 
EDC 
 
Electronic Data Capture 
EES 
 
Ethicon Endo-Surgery, Inc. 
ENSEAL G2 
 
ENSEAL® G2 Tissue Sealer 
ENSEAL X1 
 
ENSEAL® X1 Curved Jaw Tissue Sealer 
GEN11 
 
Ethicon Endo-Surgery Generator G11 
FDA 
 
Food and Drug Administration 
GCP 
 
Good clinical practice 
GI 
 
Gastrointestinal 
ICD 
 
Informed consent document 
IFU 
 
Instructions for use 
IRB 
 
Institutional review board 
MedDRA 
 
Medical Dictionary for Regulatory Activities 
OR 
   Operating room 
PCF 
 
Product complaint form 
PHI 
 
Protected health information 
PMCF 
 
Post-market clinical follow-up 
RYGB 
 
Roux-en-Y gastric bypass 
SAE 
 
Serious adverse event 
SAP 
 
Statistical analysis plan 
SOC 
   Standard of care 
 
 
 

 
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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 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 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 up to sixteen surgery centers in the United States and/or European Union and/or 
United Kingdom 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 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).  
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 monitor(s), change of telephone number(s)). 
The Investigator reports the protocol amendments to the IRB/EC as per their local requirements. 
 
 

 
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1.0 INTRODUCTION 
The ENSEAL X1 device is a sterile, single-patient-use advanced bipolar surgical instrument 
intended for use during open or laparoscopic surgical procedures to seal and transect vessels up 
to and including 7mm in diameter and lymphatics, and to cut, grasp and dissect tissue during 
surgery.  
ENSEAL X1 differs primarily in three ways from the earlier version of the device, the ENSEAL® 
G2 Tissue Sealer (ENSEAL G2). 
1. The ENSEAL G2 relied on I-BLADE® Technology to provide compression along the 
device tip, whereas the ENSEAL X1 has a redesigned jaw that provides uniform 
compression without the need for an I-BLADE. 
2. The ENSEAL G2 used a positive temperature coefficient technology to modulate energy 
flow and control temperature at the blade, whereas ENSEAL X1 uses electrical 
impedance feedback to intelligently monitor tissue conditions and modulate energy 
delivery to ensure effective sealing while minimizing tissue damage. 
3. The ENSEAL G2 had an integrated seal-and-cut steps for use, whereas ENSEAL X1 
has separated these into intuitive, simplified functions, so that surgeons may now seal 
without cutting, cut without sealing, or both seal and cut. 
The ENSEAL X1 devices have undergone extensive preclinical testing to ensure that they are 
capable of producing strong and durable seals for vessels up to 7mm in diameter. Beginning in 
2018, the open-surgery version, ENSEAL X1 Large Jaw, was successfully launched. Now, a 
laparoscopic version, ENSEAL X1 Curved Jaw (Figure 1) is being introduced to the market. 
With a shaft diameter of 5 mm, the device will be available in lengths of 25, 37, and 45 cm. The 
curved tapered tip of the device is designed for fine dissection, while being able to capture more 
tissue per bite with stronger grasping than the predicate device. The shaft can be rotated a full 
360° for easier access to targeted tissue. 
 
Figure 1: Image of the ENSEAL X1. 
The GEN11 supplies energy to the HARMONIC and ENSEAL surgical instruments. It also has a 
touchscreen for easy setup and operation, and a high-resolution display with wider viewing 
angles. Software updates to ensure that the system is operating optimally are available via USB 
memory stick. The generator uses a touchscreen display interface and has a unique receptable 

 
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port that accepts either a HARMONIC or an ENSEAL instrument. Connectors (HGA11 for 
HARMONIC and EGA11 for ENSEAL) are used to enable the generator to power legacy 
instruments. 
The ENSEAL X1 device includes several incremental enhancements of the same basic 
technology used with predicate devices. This study is being initiated to evaluate the subject 
devices when used per their instructions for use (IFU) in the following types of procedures: 
upper GI, lower GI, and gynecological.   
2.0 STUDY OBJECTIVES 
The primary objective of this study is to demonstrate the acceptable performance and safety of 
the ENSEAL X1 and GEN11 devices when used per the instructions for use (IFU).  
2.1 PRIMARY PERFORMANCE ENDPOINT  
A hemostasis grading scale was adopted from Siegel et al.1 The primary performance 
endpoint will be: 
x 
Achievement of Grade 3 or lower hemostasis for each vessel transection (per the 
grading scale below): 
o Grade 1: no bleeding at transection site; 
o Grade 2: minor bleeding at transection site, no intervention needed; 
o Grade 3: minor bleeding at transection site, mild intervention needed, use of 
compression, basic energy devices (monopolar and/or bipolar) and/or touch-
ups with ENSEAL X1; or 
o Grade 4: significant bleeding (e.g., pulsatile blood flow, venous pooling) 
requiring intervention such as extensive coagulation or ligation with use of 
additional hemostatic measures (e.g., hemoclips, staples, sutures, fibrin 
sealants, other advanced energy products). 
2.2 SECONDARY PERFORMANCE ENDPOINTS  
The secondary performance endpoints will be: 
x 
Distribution of 5-point scale scores for various tasks completed by the ENSEAL X1 
device (adhesiolysis, lymphatics or tissue bundles divided, tissue grasping, tissue 
cutting, or tissue dissection). The scale will be a 5-point scale (very dissatisfied, 
dissatisfied, neither satisfied or dissatisfied, satisfied, or very satisfied) asking how 
satisfied the surgeon was with the use of the device for each of the tasks; 
x 
Distribution of hemostasis grading scale for each vessel transected; and 
x 
Type, name, and number of additional hemostasis products required to achieve 
hemostasis for Grade 4 vessel transections. 
2.3 SAFETY ENDPOINT  
The safety endpoint will be occurrence of device-related adverse events (AEs). 
2.4 ADDITIONAL KEY DATA COLLECTED  
Additional key data collected for evaluation in this study are: 
x 
Procedure duration; 

 
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x 
Use of any other energy device (basic [monopolar and traditional bipolar], advanced 
bipolar, ultrasonic) in primary procedure (type, name, and number of device and 
reason for use), if applicable; 
x 
Overall assessment questionnaire of how device performed in various tasks for lower 
GI/large intestine resection and gynecological procedures; 
x 
Surgeon questionnaire administered once per investigator; 
x 
Task questionnaire after each lower GI/large intestine resection and gynecological 
procedure; 
x 
Generator questionnaire after each procedure for each GEN11 used; 
x 
Surgical procedure conducted; 
x 
Hospital stay duration; 
x 
Name and number of vessels that were transected, surgeon determination of 
diameter size range (< 3 mm, 3 to 5 mm, and > 5 to 7 mm); 
x 
Occurrence and location of cancer and occurrence of pre-surgical 
radiation/chemotherapy within 90 days prior to surgery, if applicable; 
x 
Occurrence of vessel skeletonization; 
x 
Presence of inflamed tissue, calcified tissues/vessels, atherosclerotic tissue, fibrotic 
tissue, or presence of adhesions, if applicable; 
x 
Volume of estimated intra-operative blood loss; 
x 
Occurrence of blood transfusion, if applicable (record the total required units of blood 
and rationale); 
x 
Type of additional mild interventions (use of compression, basic energy devices 
[monopolar and/or bipolar] and/or touch-ups with ENSEAL X1) required to achieve 
hemostasis for Grade 3 vessel transections including number of times when 
ENSEAL X1 touch-ups were used; and 
x 
Procedure-related AEs. 
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 (upper GI, lower GI, and gynecological). Investigators will perform 
each procedure using the device in compliance with their standard surgical approach and the 
ENSEAL X1 and GEN11 IFUs.  
Subjects will be consented and screened anytime during a period of 8 weeks prior to the date 
of surgery. Subjects will be considered enrolled when the ENSEAL X1 device has been 
attempted to be used for a vessel transection during upper GI, lower GI, and gynecological 
procedures. All subjects enrolled will be followed post-operatively through discharge and 
again at 28 days (± 14 days) post-surgery; therefore, from the surgery date to study exit, the 
duration will be approximately 6 weeks. 
3.2 STUDY POPULATION 
3.2.1 
Enrollment 
Subjects will be recruited from the existing patient population who plan to have a 
procedure from the proposed procedure groups (upper GI, lower GI, and gynecological) 

 
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utilizing consecutive screening and enrollment in an effort to generate a random and 
representative patient population sample. All eligible subjects (Sections 3.2.3 and 3.2.4) 
will be considered enrolled at the time when the ENSEAL X1 device has been attempted 
to be used for a vessel transection during one of the proposed procedure groups. Up to 16 
surgery centers (United States and/or European Union and/or United Kingdom) will be 
selected as study sites. Each participating investigator is expected to perform a minimum 
of two procedures using the ENSEAL X1 device. A minimum of 133 subjects (maximum of 
149 subjects) will be included in the study to achieve a total of 230 vessel transections. 
The enrollment is planned with the following procedure targets: 
x 
A minimum of 77 subjects enrolled to a maximum of 89 subjects enrolled for upper 
GI procedures which will contain the following subgroups with corresponding 
enrollment restrictions: 
o A minimum of 14 subjects enrolled to a maximum of 17 subjects enrolled 
for fundoplication (Nissen, anterior or posterior [Toupet]) or hiatal hernia 
procedures); 
o A minimum of 27 subjects enrolled to a maximum of 30 subjects enrolled 
for gall bladder procedures; 
o A minimum of 10 subjects enrolled to a maximum of 13 subjects enrolled 
for sleeve gastrectomy procedures; 
o A minimum of 26 subjects enrolled to a maximum of 29 subjects enrolled 
for small intestine resection procedures (also includes RYGB and BPD/DS),  
x 
A minimum of 28 subjects enrolled to a maximum of 30 subjects enrolled for lower 
GI procedures (e.g., large intestine resections); and 
x 
A minimum of 28 subjects enrolled to a maximum of 30 subjects enrolled for 
gynecological procedures (hysterectomies associated with oophorectomies). The 
planned use of the ENSEAL X1 device should be for both the hysterectomy and 
oophorectomy steps of the procedures.    
3.2.2 
Screening Failures 
All subjects signing consent who do not have at least one vessel transection attempted by 
ENSEAL X1 during their procedures will be recorded as screen failures. For subjects who 
are determined to be screen failures, only the relevant electronic eCRF pages 
(inclusion/exclusion criteria, demographics, AEs, subject completion/discontinuation) will 
be completed. 
3.2.3 
Inclusion Criteria 
Subjects satisfying the following criteria will be considered eligible for enrollment in this 
study: 
1. Primary laparoscopic or open procedure (upper GI, lower GI, and gynecological) 
where at least one vessel is planned to be transected by the ENSEAL X1 device 
per the IFU; 
2. Willingness to give consent and comply with all study-related evaluations and 
treatment schedule; and 

 
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3. At least 18 years of age. 
3.2.4 
Exclusion Criteria 
Subjects meeting the following criteria will be considered ineligible for enrollment in this 
study: 
1. Physical or psychological condition which would impair study participation; or 
2. Enrollment in a concurrent interventional clinical study that could impact the study 
endpoints. 
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 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: 
x 
Administrative concerns (e.g., inadequate subject enrollment, 
Investigator/institution non-compliance, change of business strategy, etc.); 
x 
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; or 
x 
Regulatory Body Mandate(s). 
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. 

 
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Death 
x 
When possible, the cause of death will be documented. 
Other (which may include) 
x 
Investigator recommendation. 
3.2.6 
Subject Replacement in Study 
Subjects who withdraw or are terminated early from the study will not be replaced. 
3.3 STUDY PROCEDURES 
3.3.1 
Procedure Description 
Elective upper GI, lower GI, and gynecological procedures where ENSEAL X1 is indicated 
for use will be performed per the institution’s SOC. Only the principal investigator or sub-
Investigator can use the device during the vessel transections. For the gynecological 
procedures, the planned use of the ENSEAL X1 device should be for both the hysterectomy 
and oophorectomy steps of the procedures.  
3.3.2 
Identity of Study Products 
The ENSEAL X1 and the GEN11 are the study products for this study.  
3.3.2.1 Device Description 
ENSEAL X1 
The ENSEAL X1 instrument is a sterile, single-patient-use surgical instrument to 
coagulate and transect vessels up to and including 7 mm in diameter, tissue and/or 
vascular bundles. This device is to be used for soft tissue only. The instrument consists 
of a grip housing assembly, a rotating shaft, a moveable jaw, and a knife. The instrument 
shaft can be rotated 360° to facilitate visualization and enable easy access to targeted 
tissue. The jaws are in a normally-opened position and can be partially or fully closed by 
squeezing the closing handle. The jaws are designed for grasping and holding targeted 
tissue when clamped. The ENSEAL X1 has separate seal and cut capabilities. The lower 
jaw of the ENSEAL X1 can be used in the open or closed position to deliver energy 
based on the electrode configuration and jaw design. Bipolar energy is delivered when 
the SEAL button on the device or the MIN foot pedal is pressed. Pressing the CUT 
button advances the knife the length of the jaws to cut the targeted tissue. The power 
cord is permanently attached to the device and connects the instrument to the generator. 
The ENSEAL X1 instrument is designed for use exclusively with the GEN11 software 
version 2016-1 or later, packaged separately. 
GEN11 
The GEN11 device supplies energy to the HARMONIC and ENSEAL surgical 
instruments. The generator uses a touchscreen display interface and has a unique 
receptacle port that accepts either a HARMONIC or an ENSEAL instrument. Connectors 
(HGA11 for HARMONIC and EGA11 for ENSEAL) are used to enable the generator to 
power legacy instruments. 

 
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3.3.2.2 Indications 
ENSEAL X1 
The ENSEAL X1 are bipolar electrosurgical instruments for use with an electrosurgical 
generator. They are intended for use during open or laparoscopic surgical procedures to 
cut and seal vessels, and to cut, grasp and dissect tissue during surgery. 
Indications for use include open and laparoscopic general, gynecological, urologic, 
thoracic, and ENT surgical procedures or any procedure where vessel ligation (cutting 
and sealing), tissue grasping, dissection, and division of vessels, lymphatics, and tissue 
bundles is performed (e.g. bowel resections, hysterectomies, gall bladder procedures, 
Nissen Fundoplication, adhesiolysis, and oophorectomies). The devices can be used on 
vessels up to and including 7 mm and bundles as large as will fit in the jaws of the 
instruments. 
The ENSEAL X1 have not been shown to be effective for tubal sterilization or tubal 
coagulation for sterilization procedures. 
GEN11 
The GEN11 provides radiofrequency power to drive ENSEAL electrosurgical instruments 
that are used during open or laparoscopic general and gynecological surgery to cut and 
seal vessels and to cut, grasp, and dissect tissues. In addition, the generator provides 
power to drive HARMONIC ultrasonic surgical instruments that are indicated for soft 
tissue incisions when bleeding control and minimal thermal injury are desired. 
ENSEAL and HARMONIC instruments, when used with the GEN11, have not been 
shown to be effective for sterilization procedures or tubal coagulation.  
3.3.2.3 Contraindications 
ENSEAL X1 
The efficacy of the ENSEAL X1 for the indication of contraceptive tubal coagulation 
(permanent female sterilization) has not been evaluated and is unknown. The design of 
the ENSEAL tissue sealing device is significantly different from bipolar designs that are 
marketed for the indication of contraceptive tubal coagulation. The design differences 
may affect the efficacy of the procedure and failure rates may not be comparable. 
GEN11 
The use of the GEN11 and the attached instruments are contraindicated when, in the 
judgement of the physician, radiofrequency or ultrasonic surgery would be contrary to 
the best interest of the patient. The instruments are not indicated for incising bone. 
3.3.2.4 Labeling of Study Products 
The ENSEAL X1 has received 510(k) clearance in the United States by the Food and 
Drug Administration (FDA) and has CE Mark in the European Union and United 
Kingdom. The GEN11 has clearance for distribution in the United States by the FDA and 
is CE marked in the European Union and United Kingdom. The study devices will use 
the cleared labeling. The Sponsor requires no additional labeling in this study. 
3.3.2.5 Accountability of Study Products 
The ENSEAL X1 may be provided to the participating institutions. The GEN11 (including 
footswitches) may be loaned to any institution in the study. Each institution not provided 
with ENSEAL X1 will use devices acquired through normal procurement process. If 

 
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institutions are provided ENSEAL X1, the 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 certain prior medication therapy used up to 30 days prior to 
surgery. These medications include aspirin, antiplatelet agents, nonsteroidal anti-
inflammatory drugs, and anticoagulants. Review will occur during Visit 1 (Screening Visit) 
and Visit 2 (Procedure Visit). 
Subjects will be assessed for occurrence of pre-surgical radiation/chemotherapy used up 
to 90 days prior to surgery. Review will occur during Visit 1 (Screening Visit) and Visit 2 
(Procedure Visit). 
Subjects may continue with their current medical care while in the study and the following 
medications will be collected for this study: 
x 
Certain prior medication therapy used up to 30 days prior to surgery (listed above); 
and 
x 
Any medications administered during the study due to a device-related or 
procedure-related AE.  
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: 
x 
Age (years); 
x 
Gender; 
x 
Race; 
x 
Ethnicity; 
x 
Pregnancy test result, if taken as per standard of care; 
x 
American Society of Anesthesiologists Physical Status Classification System 
(ASA) score; 
x 
Occurrence and location of cancer, if applicable; 
x 
Review and collection of relevant medical history and surgical history including the 
following: 
o For the gynecological procedure group, the gravidity and parity; 
o Surgical procedure to be conducted, including primary indication for 
surgery; and 
o Smoking history (current smoking status, if stopped, length of time [months 
and years]). 

 
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3.4.2 
Surgical Variables 
The following variables will be recorded preoperatively, intraoperatively, or postoperatively: 
x 
Date/time of hospital admission; 
x 
Body weight (kg or lbs; no shoes); 
x 
Body height (cm or in; no shoes); 
x 
Procedure duration, defined as first skin incision to final skin closure; 
x 
Did vessel skeletonization occur (Yes/No; if Yes, describe vessel skeletonized and 
device used); 
x 
Was there presence of inflamed tissue, calcified tissues/vessels, atherosclerotic 
tissue, fibrotic tissue, or presence of adhesions, if applicable (Yes/No; if Yes, 
describe the tissue along with location); 
x 
Were adhesions removed or divided by ENSEAL X1 (Yes/No; if Yes, describe 
adhesions along with location and complete 5-point scale); 
x 
Were lymphatics and tissue bundles divided by ENSEAL X1 (Yes/No; if Yes, 
describe lymphatics and tissue bundles along with location and complete 5-point 
scale); 
x 
Was ENSEAL X1 used for grasping tissue, tissue cutting, or tissue dissection 
(Yes/No; if Yes, describe activity along with location and complete 5-point scale); 
x 
Conversion to open with reason, if applicable; 
x 
Volume of estimated intra-operative blood loss; 
x 
Use of any other energy device (monopolar, traditional bipolar, advanced bipolar, 
ultrasonic) in primary procedure (type, name, and number of device and reason for 
use), if applicable; 
x 
Name, product code, and number of Ethicon trocars used with ENSEAL X1, if 
applicable; 
x 
Was there prophylactic use of clips as standard of surgical care before vessel 
transection (Yes/No; if Yes, name vessel transected, and number of clips 
prophylactically applied); 
x 
For each vessel transected with ENSEAL X1: 
o Name of each vessel; 
o Hemostasis grading scale assessment; 
o Surgeon determination of diameter size range (< 3 mm, 3 to 5 mm, and > 5 
to 7 mm); 
o Image captured where the vessel is perpendicular and below the open jaw 
of the ENSEAL X1 device; 
o For every Grade 3 vessel transection: 
 
Compression used as a mild intervention, if applicable (Yes/No); 
 
Touch-ups with a monopolar device, if applicable (Yes/No; if Yes, 
record number of touch-ups); 

 
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 
Touch-ups with a bipolar device, if applicable (Yes/No; if Yes, record 
number of touch-ups); 
 
Touch-ups with ENSEAL X1 (Yes/No; if Yes, record number of 
touch-ups); 
o For every Grade 4 vessel transection intervention: 
 
Type, name, and number of times used for each additional 
hemostatic measure used along with a description of why it was 
considered Grade 4; 
x 
For the gynecological procedure group, if applicable: 
o Estimated uterine size;  
x 
Occurrence of blood transfusion, if applicable (record the total required units of 
blood and rationale); 
x 
Concomitant procedures, if applicable (defined as any medical or surgical 
procedure beyond activities associated with primary study procedure). If a 
concomitant procedure requires vessel transection by ENSEAL X1, each vessel 
transected will have the same information collected as stated above for vessel 
transections, but these will not be included as part of the primary endpoint; 
x 
Concomitant medication usage associated with device-related or procedure-related 
AEs and specific drugs used up to 30 days prior to surgery (aspirin, antiplatelet 
agents, nonsteroidal anti-inflammatory drugs, anticoagulants) and 90 days prior to 
surgery (pre-surgical radiation/chemotherapy); and 
x 
Date/time of hospital discharge. 
3.4.3 
Questionnaires 
Data related to the following study variables will be obtained from the Task Questionnaire 
after every completed procedure (only for lower GI/large intestine resection and 
gynecological procedures), the Surgeon Questionnaire for every investigator after they 
have completed his/her second procedure (upper GI, lower GI, and gynecological 
procedures), and a GEN11 Questionnaire after every completed procedure.  
Task Questionnaire 
Investigators will be asked to answer a non-validated device questionnaire related to 
his/her experience using the ENSEAL X1 and overall assessment of how the device 
performed in various tasks during the procedures. The survey will be completed by the 
Investigators as soon as possible after each lower GI/large intestine resection and 
gynecological procedures, preferably on the same day. The survey responses will then be 
transcribed onto eCRFs.  
Surgeon Questionnaire 
Investigators will be asked to answer a non-validated surgeon questionnaire related to 
his/her experience using the ENSEAL X1. The survey will be completed by the 
Investigators as soon as possible after they have completed his/her second procedure in 
any of the six procedure groups. The survey responses will then be transcribed onto 
eCRFs. The questionnaire will be completed for the upper GI, lower GI, and gynecological 
procedures. 

 
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Generator Questionnaire 
Investigators will be asked to answer a non-validated generator questionnaire related to 
his/her experience using the GEN11 and any ENSEAL and/or HARMONIC device. The 
survey will be completed by the Investigators as soon as possible after each procedure, 
preferably on the same day for each GEN11 used. The survey responses will then be 
transcribed onto eCRFs.    
3.4.4 
Safety Data Variables 
All device-related and procedure-related AEs will be collected as outlined in Section 5.0.  
3.5 SCHEDULE OF EVENTS 
Table 1: Schedule of Events 
Activity 
Visit 1a 
Visit 2a 
Visit 3 
Unscheduled 
Visit, if 
applicable 
Screening Visit 
(-56 to 0 Days) 
Procedure Through 
Discharge Visit 
(Day 0) 
Post Procedure 
Follow Up Visit 
(28 ± 14 Days)b 
Informed consent 
X 
 
 
 
Demographics (age, gender, race, and 
ethnicity) 
X 
 
 
 
Administer pregnancy test as per 
standard of care 
X 
 
 
 
Height and weight (both with no shoes) 
 
X 
 
 
Medical and surgical history (including 
diagnosis) 
X 
X 
 
 
Background information (including 
smoking history) 
X 
X 
 
 
Review of inclusion/exclusion criteria 
X 
X 
 
 
Concomitant medications 
X 
X 
X 
X 
Surgical data collected for evaluation 
 
X 
 
 
Collect vessel imagec 
 
X 
 
 
Collect task questionnaired 
 
X 
 
 
Collect generator questionnairee 
 
X 
 
 
Collect surgeon reported questionnairef 
 
X 
 
 
Concomitant procedures conducted 
besides primary procedure 
 
X 
 
 
Re-operation(s) associated with the 
primary procedure 
 
 
X 
X 
Assess for device-related and 
procedure-related AEs 
 
X 
X 
X 
Subject completion/discontinuation 
 
X 
X 
X 
a. Visit 1 and Visit 2 may be combined; 
b. This can be either an office visit or telephone follow-up;
c. The image captured where the vessel is below the open jaw of the ENSEAL X1 device perpendicular to the vessel during the primary 
procedure at Visit 2; 
d. The task questionnaire will be completed after every lower GI/large intestine resection and gynecological procedure; 
e. The generator questionnaire will be completed after every procedure; 
f. The surgeon questionnaire will be completed after the investigator has completed their second procedure in any of the six procedure 
groups; 
AE = adverse events. 

 
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3.6 STUDY PROCEDURES 
3.6.1 
Visit 1 – Screening (may occur over visits within 8 weeks of Visit 2 including 
up to the day of the procedure) 
Prospective subjects will be provided with the study information including the ICD. The 
subject must be given ample time to review and sign the ICD. The screening activities 
noted in Section 3.4 will occur prior to the study procedure. 
3.6.2 
Visit 2 – Procedure Through Discharge Visit 
Pre-procedure 
The following must be obtained prior to the surgical procedure: 
x 
Height and weight (both with no shoes); and 
x 
Updates to concomitant medication and medical/surgical/smoking history; 
x 
Confirm inclusion and exclusion criteria. 
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 date of surgery, subjects will have a follow-up visit approximately 28 days (± 14 
days) later. 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 
Unscheduled Visit(s) 
Any unscheduled visit between Visit 2 and Visit 3 will be documented including the reason 
for the visit. This visit can be either an office visit or a telephone follow-up. Data to be 
collected is listed in Section 3.5. 
3.6.5 
Vessel Image Capture 
The preferred image should be captured during the primary procedure at Visit 2 where the 
vessel (or the tissue bundle containing the vessel) is below the open jaw of the ENSEAL 
X1 device. The image should show the device perpendicular to the vessel. The image 
should have the entire length of the jaw of the ENSEAL X1 device in view. The image will 
be uploaded to the electronic database capture (EDC) system as either jpeg or pdf file. 
The Sponsor will determine if the image is analyzable and then each image will be 
reviewed and have a vessel size determined (if measurement is feasible) to the nearest 
quarter decimal (e.g., 5.0 mm, 5.25 mm, 5.50 mm, etc.) by the Sponsor utilizing computer 
software with the measurement captured in the EDC. No reconciliation will be performed 
between the surgeon determination of vessel size (see Section 3.4.2) and the vessel size 
determined by the image analysis. The primary vessel size determination will be by the 
surgeon determination. 
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 

 
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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 
investigation. 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 electronic database 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, 350 Hudson St. 9th Floor, NY, NY 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 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.  
A 24/7/365 Help Desk Support line (telephone: 973-659-6780; fax: 973-954-5621; toll free: 
866-633-4328; Email: helpdesk@mdsol.com) staffed by the outsourced vendor will also be 
available to respond to site and monitor questions. 
4.1.3 
Data Collection 
Each EDC eCRF will be completed by the principal investigator or principal investigator’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 and 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 principal investigator is 
responsible for reviewing and approving each completed eCRF. Assurance of overall 
review and approval will be documented by the principal investigator electronically signing 
each subject’s electronic casebook. 
4.1.4 
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) was made to the eCRFs will be automatically 
captured in the audit trail within Medidata® Rave. 

 
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4.1.5 
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 access by unauthorized persons. 
4.1.6 
Record Retention, Inspection, and Custody 
The principal investigator must maintain all documentation related to the study until 
notified by the Sponsor. The principal investigator will allow representatives of the Sponsor 
or other 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 study records will be maintained in a confidential manner. Study reports will not 
identify subjects by name. These reports may be submitted to 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 before the transfer occurs. 
4.2 MEDICAL DICTIONARY CODING 
Medical dictionary coding of medical history and verbatim AEs captured on eCRFs will be 
performed using a coding thesaurus algorithm. The Medical Dictionary for Regulatory 
Activities (MedDRA) will be used after data entry and query resolution, via auto-encoding and 
interactive coding processes. 
4.3 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 either onsite 
or offsite monitoring visits; any discrepancies will be resolved with the Investigator or 
designees, as appropriate. 
4.3.1 
Site Personnel Training 
Prior to screening subjects for this study, the principal investigator, 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. 
4.3.2 
Monitoring 
This study will be monitored by the Sponsor or its representative to ensure: 
x 
The rights and well-being of the subjects are protected; 
x 
The reported study data is accurate, complete, and verifiable from source 
documents; and 
x 
The conduct of the study is in compliance with the currently approved 
protocol/amendment(s), applicable GCPs, and with applicable local/regional 
regulatory requirements. 

 
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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. 
4.3.3 
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. 
4.4 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. 
Protocol deviations will be captured in the eCRFs. The principal investigator will report 
protocol deviations to the IRB/EC as required by the IRB/EC 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 ENSEAL X1 device 
utilized for transection of a least one vessel. 
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 as the collection of data for the primary 
and secondary performance endpoints occurs intra-operatively. The final visit occurs 
approximately 4 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 4-week follow-up visit, and any information entered in 
the eCRFs at this visit will correspond to the 4-week 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 2.4. The following 
hypothesis will be evaluated for the primary endpoint: 
H0: p ≤ 87.5% 
H1: p > 87.5% 

 
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Where p is the percentage of transections achieving a Grade 3 or lower hemostasis rating 
and 87.5% is set as a performance goal for the lower bound of acceptable hemostasis. A 
95% confidence interval will be calculated for p based on the sample proportion of 
transections where Grade 3 or lower hemostasis was achieved using Clopper-Pearson’s 
method  and the lower limit of this confidence interval will be compared to 87.5% to evaluate 
the above hypotheses. A p-value will be determined based on exact binomial test.  
Given that multiple transections per subject may occur, a sensitivity analysis will be 
performed using appropriate methods to account for the potential correlation among the 
outcomes of multiple transections within the same subject and procedure. Further details of 
this approach will be provided in the SAP. 
5.5 LEVELS OF SIGNIFICANCE 
The hypotheses above will be evaluated using a one-sided significance level of 0.025. 
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 ENSEAL X1 device is utilized during the surgical procedure. The 
summary of all performance and safety endpoints will be performed by procedure group and 
procedure subgroup on the entire pooled set of subjects. The hypotheses described in 
Section 5.4 will be evaluated on the pooled set of subjects as data on the ENSEAL X1 Large 
Jaw device demonstrated consistent performance across procedure groups in a similar study 
(>94% Grade 3 or lower hemostasis achieved for each procedure group).  
5.7 SAMPLE SIZE JUSTIFICATION 
A sample size of at least 230 vessel transections is required to have a minimum of 90% 
power for rejecting the null hypothesis when the expected rate of Grade 3 hemostatic 
transections is at least 94.0% based on exact binomial test and a one-sided significance level 
of 0.025. The hemostatic transection grades for vessels are assumed to be independent 
within a subject and procedure.   
In order to achieve a total of 230 vessel transections for analysis with a minimum of 27 vessel 
transections in each group (including 4 subgroups in upper GI procedure), a minimum of 133 
subjects (a maximum of 149 subjects) will be enrolled in the study. 
The original sample size of the study was based on the assumption of one vessel transection 
per subject. At the time of amendment 5 the number of transections per subject was 
estimated to be 1.9 on average. The primary endpoint and the study hypothesis are based on 
hemostasis of vessel transection; therefore, the number of subject to be enrolled was 
updated to ensure 230 vessel transections. 
Given that the primary endpoint is being evaluated intra-operatively, it is not anticipated that 
there will be subject dropout prior to evaluating this endpoint, thus no adjustment or increase 
in subject enrollment is planned to account for dropout. A minimum of 27 vessel transections 
in each group (including 4 subgroups in upper GI procedure) is planned to attain optimum 
representation of each of the procedure groups to the whole study sample.    
From a safety perspective on the pooled analysis of 133 subjects and in consideration of rare 
AEs that may occur (e.g., bleeding requiring blood product transfusion), for an event that has 
an incidence rate of, for example, 1%, then in a sample of 133 subjects, the probability of 
observing at least 1 event is 73.7% under a binomial probability model. Thus, this sample 
size provides a high probability of observing rare events if they do occur, and provides 
reasonable assurance to conclude that the likelihood of such AEs is less than 2.8% if they do 

 
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not occur based on the upper limit of an exact 95% confidence interval when 0 events out of 
133 subjects are observed. 
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 and procedure 
subgroups using counts and percentages. The number and percentage of subjects 
completed and discontinued will be tabulated along with the specific reasons for 
discontinuation. 
5.9.3 
Demographic, Baseline, and Surgical Characteristics 
Summary statistics of subject demographics (age, gender, and race) will be presented in 
total and by procedure group and procedure subgroups. Surgical characteristics including, 
at minimum, estimated blood loss, requirement for blood transfusion, and procedure 
duration will be summarized by procedure group, procedure subgroup and in total. 
5.9.4 
Primary and Secondary Endpoint Analyses 
The number and percentage of vessels where hemostasis is achieved (≤ Grade 3) will be 
summarized and an exact 95% confidence interval will be estimated for each procedure 
group, procedure subgroup, and in total based on Clopper-Pearson’s method. The 
performance goal hypothesis will be tested as described in Section 5.4. 
The analysis of primary endpoint is based on the assumption of independence of 
hemostatic grades within subject and procedure. This assumption of independence and its 
impact on the overall study conclusion will be evaluated through sensitivity analyses and 
will be described in SAP. 
Counts and percentages will be provided for type, size, and number of vessels transected, 
as well as for the grading scale distribution for all vessels transected, number of times 
ENSEAL X1 touch-ups were required, incidence of requirement for additional measures to 
obtain hemostasis on vessels (other advanced energy devices or hemostatic measures), 
and 5-point scale scores for various tasks completed by the ENSEAL X1 device 
(adhesiolysis, lymphatics or tissue bundles divided, tissue grasping, tissue cutting, or 
tissue dissection).  
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, procedure subgroup, and in total. Separate summaries will be 
provided for device-related and procedure-related AEs. Serious AEs will be summarized in 
a similar manner. 
5.9.5 
Plans for Interim Analyses 
No interim analyses are planned for this study. 

 
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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. 
5.9.7 
Subgroup Analyses 
Subgroup analyses are planned to be performed for the subgroup of subjects who have a 
medical history of treatment for cancer (e.g. chemotherapy or radiation) and 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 
Only AEs considered possibly, probably, or causally related to the device or the procedure will 
be collected during this study. 
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 
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: 
x 
Death; 
x 
A life-threatening illness or injury; 
x 
A permanent impairment of a body structure or a body function; 
x 
Required in-patient hospitalization or prolongation of existing hospitalization; 
x 
Resulted in medical or surgical intervention to prevent life-threatening illness or 
injury or permanent impairment to a body structure or a body function; 
x 
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. 
6.1.3 
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: 
x 
MILD: A type of AE that is usually transient and may require only minimal 
treatment or therapeutic intervention. The event does not generally interfere with 
usual activities of daily living. 
x 
MODERATE: A type of AE that is usually alleviated with additional specific 
therapeutic intervention. The event interferes with usual activities of daily living, 
causing discomfort but poses no significant or permanent risk of harm to the 
research participant. 
x 
SEVERE: A type of AE that interrupts usual activities of daily living, or significantly 
affects clinical status, or may require intensive therapeutic intervention. 
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 possibly, probably, or causally related to the study 
procedures or the ENSEAL X1 or GEN11 devices 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: 
x 
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. 
x 
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). 

 
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Cases where relatedness cannot be assessed or no information has been obtained 
should also be classified as possible. 
x 
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. 
x 
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; 
 
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 
ENSEAL X1 or GEN11 devices in the source documents and eCRF.  
Standard medical terminology should be used when recording AEs. In addition, the 
following information should be recorded: 
x 
Onset date; 
x 
Resolution date or date of death; 
x 
Severity of the event; 
x 
Indication of whether the event is serious; 
x 
Relationship of AE to the study devices; 
x 
Relationship of AE to the study procedure; 
x 
Action taken; 
x 
Event status; and 
x 
Was AE anticipated or not (only for SAEs). 
Data related to AEs will be collected until the event resolution, or until the event is 

 
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considered stable, or until all attempts to determine the resolution of the event are 
exhausted. All AEs that are unresolved at study completion (or at the last visit completed 
for early withdrawal subjects) will be recorded as ongoing at study end. 
6.4.2 
Reporting Adverse Events 
The Investigator is required to report AEs to the Sponsor within 2 weeks from when the 
study site becomes aware of the event. All AEs must be reported on the AE eCRF and be 
documented in a timely manner throughout the study duration. 
6.4.3 
Reporting Serious Adverse Events 
Any AE that the Investigator determines to be a SAE must be reported by the study site 
within 72 hours of becoming aware of the event to the Sponsor by completing the AE 
eCRF. A notification containing the pertinent data will be automatically generated by the 
EDC system and forwarded to the Sponsor. If applicable, supporting SAE documentation 
should be de-identified and provided to the Clinical Trial Leader. 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. The study site is also responsible for 
submitting SAEs to the reviewing IRB/EC per their IRB/EC procedures. 
7.0 PRODUCT COMPLAINTS 
A product complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, labeling, quality, durability, reliability, safety, effectiveness, or 
performance of a device after it is released for distribution. A product complaint may or may not 
be associated with an AE/SAE.
7.1 REPORTING PRODUCT COMPLAINTS FOR MARKETED DEVICES 
7.1.1 
Reporting of Approved EES Marketed Devices 
All product complaints related to devices in the procedure shall be documented throughout 
the clinical investigation. Product complaints related to an Ethicon-manufactured ENSEAL 
X1 or GEN11 devices must be reported to the Sponsor in a timely manner and no later 
than 24 hours after becoming aware of the event. When a sponsor representative 
becomes aware of a product complaint, the Product Complaint Team must be notified 
within 24 hours after becoming aware of the event. The Product Complaint Form must be 
emailed to the Sponsor Customer Complaint team at the following email address: 
Productcomplaint1@its.jnj.com 
The sites will report Product Complaints by completing the Product Complaint Form. If a 
product complaint is related to a safety event, the site must complete an AE eCRF as well. 
One copy of the processed form should be kept on-site and the device should be retained. 
Sponsor representatives will organize collection of the device for evaluation as needed. 
7.1.2 
Reporting of Approved Marketed Devices and Commercially Available 
Devices (not Ethicon) 
The site should report Product Complaints of non-Ethicon devices that are approved 
marketed devices or commercially available medical devices according to the specific 
product’s manufacturer specifications/guidelines. 
 

 
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8.0 REFERENCES 
1. Siegel JM, Cummings JF, Clymer JW. Reproducible, repeatable and clinically-relevant 
hemostasis scoring. J Adv Med Pharm Sci 2014;1:30-39.