MANTIS Clip Study: A Prospective, Multi-Center, All-Comer MANTIS Endoscopic Clipping Study:
Conditions: Hemostasis, Perforation Colon, Feeding Tube Complication, Endoscopy
Sponsor: Boston Scientific Corporation

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Prospective, Multi-Center, All-Comer MANTIS Endoscopic 
Clipping Study 
 
 
MANTIS Clip Study 
E7170 
 
CLINICAL INVESTIGATION PLAN 
Sponsored By 
Boston Scientific Corporation 
300 Boston Scientific Way 
Marlborough, MA 01752-1234 
USA 
Boston Scientific International S.A. 
Parc Val Saint-Quentin, Bâtiment H 
2 Rue René Caudron 
78960 Voisins le Bretonneux 
France 
 
Boston Scientific India Private Ltd. 
Bestech Business Tower, 3rd Floor  
 Sohna Road, Sector – 48 
Gurugram – 122019, Haryana  
 India 
 
Boston Scientific Pty Ltd  
 Building 1, Level 6, Connect Corporate Centre 
 191 O’Riordan Street  
 Mascot, NSW 2020  
Australia 
 
 
This protocol contains confidential information for use by the Investigators and their 
designated representatives participating in this clinical investigation. The protocol should be 
held confidential and maintained in a secure location. 
Do not copy or distribute without written permission from Boston Scientific Corporation. 

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Contact Information 
Role 
Contact  
Clinical Contact 
Andrea Burbage 
Clinical Project Manager  
Clinical Endoscopy  
Boston Scientific Corporation 
200 Boston Scientific Way 
Marlborough, MA 01752-1234 
USA 
Phone: +1-781-254-4679 
Email: Andrea.Burbage@bsci.com 
 
Coordinating Principal 
Investigators 
Dr. Daniel von Renteln  
Centre hospitalier de l'Université de Montréal (CHUM) 
900, rue St-Denis, porte R05-652 
Montréal, Québec 
Canada  H2X 0A9 
Phone: +1-514-890-8000 X30912 
Email: danielrenteln@gmail.com 
 
Dr. Jeff Mosko   
St. Michael’s Hospital 
30 Bond St.  
Toronto, Onterio  
Canada M5B 1W8 
Phone: +1-416-864-5684 
Email: Jeff.Mosko@unityhealth.to 
 
 
 
 

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Original Release: August 01 2022 
Current Version: February 17 2023 
 
 
Revision 
Version 
Protocol 
Date 
Template 
number 
and version 
Protocol 
Section 
Modified 
Summary of Changes 
 
Justification for Modification 
 
Ver. B 
12Oct2022 
90702637   
Ver AQ 
None 
No changes to 
content  
Protocol not initially stored  
in  BSC Document Repository 
(WindChill)  as trainable 
document. Upreved only to allow 
BSC employees to assign and 
complete training.      
Ver. C 
17Feb2023 
90702637   
Ver AQ 
2, 6, 7, 8, 9, 11, 
12, 16, 19, 20 
 
Changes to Initial 
and Continued 
Enrollment Cohort 
and associated 
sections 
Modified objective to include 
evaluation of the procedural and 
clinical merit of specific attributes 
and expand enrollment to 
countries where the device is not 
yet approved   
Ver. D 
24Jul2023 
90702637   
Ver AQ 
2, 6, 8 
Change to Study 
Design and Objective 
to include 
consecutive 
enrollment   
Modified to clarify that there will 
be consecutive enrollment   

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2. Protocol Synopsis 
MANTIS Clip Study 
Objectives 
Initial Cohort 
To document performance of the MANTISTM Clip in all indications for 
endoscopic clipping. 
 
Continued Enrollment Cohort 
To evaluate the procedural and clinical merit in consecutive cases in 
which at least one MANTIS clip is selected, of specific attributes of the 
MANTISTM Clips, including but not limited to the ability of this new 
endoscopic clipping device: 
o to provide prophylaxis to reduce the risk of delayed bleeding post 
lesion resection 
o to close post mucosal resections/polypectomy ulcers, post 
submucosal dissection ulcers, or mucosal incisions made in 
conjunction with endoscopic myotomy procedures 
o to close lumenal perforations, fistulas, or leaks   
o to close perforations after full thickness resection of lesions in the 
gastrointestinal (GI) tract 
Indications for 
Use 
Resolution™ Clip family is indicated for clip placement within the GI 
tract for the purpose of: 
1. Endoscopic marking 
2. Hemostasis for:  
o Mucosal/sub-mucosal defects < 3 cm 
o Bleeding ulcers 
o Arteries < 2 mm 
o Polyps < 1.5 cm in diameter 
o Diverticula in the colon 
o Prophylactic clipping to reduce the risk of delayed bleeding 
post lesion resection 
3. Anchoring to affix jejunal feeding tubes to the wall of the small 
bowel  
4. As a supplementary method, closure of GI tract luminal 
perforations < 20 mm that can be treated conservatively  

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MANTIS Clip Study 
Study Device 
MANTISTM is a clip in the Resolution 360 Clip product family.   
Study 
Procedure 
The portion of the endoscopic procedure where the MANTISTM Clip is 
used  for hemostasis, closure, anchoring or marking.   
Study Design 
Prospective, multi-center, open label, consecutive enrollment  
• Group A: Hemostasis  
• Group B: Closure  
• Group C: Anchoring 
• Group D: Endoscopic Marking  
• Group E: Other  
Number of 
Subjects and 
Sites 
• Initial Cohort: Up to 50 cases  
• Continued Enrollment Cohort: 240 cases 
• Up to 15 sites globally 
Primary 
Effectiveness 
Endpoint 
Initial Cohort 
Ability to complete the indication for the use of endoscopic clipping 
Continued Enrollment Cohort 
Clinical success defined as, where applicable,  
o Absence of delayed bleeding 
o Sustained closure of the targeted leasion  
up to 30 days after the endoscopic clipping procedure  
Primary Safety 
Endpoint 
Rate of serious adverse events (SAEs) related to the MANTISTM clip or 
the endoscopic study portion of the procedure. 
NOTE: If providing hemostasis to an active bleed requires possible 
additional hemostasis after the index study procedure for management of 
bleeding SAEs within 7 days36 of the index study procedure, then such 
bleeding SAEs are not counted for the Primary Safety Endpoint.  
Additional 
Endpoints 
1. Technical success at placement defined as ability to deploy the 
endoscopic clips in satisfactory position.  
2. Ability to anchor device, mobilize the tissue, and approximate defect 
edges for secured closure. (Group B only).  

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MANTIS Clip Study 
3. Post procedural bleeding, defined as a severe bleeding event that 
required hospitalization, a blood transfusion (>5 units), or another 
invasive intervention (angiographic or surgery) within 30 days after 
the study clip placement. 
4. For active bleeding hemostasis cases only  
a. Rate of patients requiring additional modalities of hemostasis.   
b. Report of hemostasis of active bleeding 7 days after the index 
study procedure, defined as ability to stop the active bleed at the 
time of the study procedure and/or with additional clipping 
procedures to provide hemostasis of continued or recurrent 
bleeding within 7 days of the index study procedure 
Follow-up 
Schedule 
• Baseline 
• Procedure 
• 30 day follow up (both Initial and Continued Enrollment Cohort) 
Study Duration Enrollment is expected to be completed in approximately 12 months; 
therefore the total study duration is estimated to be approximately 13 
months as Subjects will be on the study for up to 30 days. 
Key Inclusion 
Criteria 
1. Subject indicated for endoscopic clipping per local standard of 
practice.  
2. Willing and able to comply with the study procedures and provide 
written informed consent to participate in the study. 
NOTE: Hemostasis and closure can be needed in the setting of 
complications such as perforations or acute bleeding that are typically 
rare and sometimes emergent. In such circumstances consenting the 
patient before the procedure is not feasible and consent shall be 
obtained from the patient after the procedure but before any study data 
is collected.   
Key Exclusion 
Criteria 
1. Subjects who are currently enrolled in another investigational study 
that would directly interfere with the current study, without prior 
written approval from the sponsor. 
2. Subjects who the investigator deems at risk for study device or 
procedure related complications per the Instructions for Use (IFU), 
where commercially available or the Investigator Brochure (IB) for 
countries where the study device is not approved.  
 

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MANTIS Clip Study 
Statistical 
Methods 
Initial cohort: 
No hypotheses will be tested, only observational, summary statistics will 
be performed.   
Continued enrollment cohort: 
A systematic literature search was conducted on PubMed and Embase 
from January 1, 2016 to September 2022 to identify studies that 
evaluated the safety and effectiveness of an endoscopic clip device for 
closing various types of incisions, lesions, or defects in the 
gastrointestinal tract resulting from endoscopic mucosal resection 
(EMR), endoscopic submucosal dissection (ESD), polypectomy of 
polyps or adenomas, perforations, and fistulas. The primary objective of 
the search strategy was to identify studies that examined the closure of 
large mucosal defects by endoscopic clipping. Twenty studies were 
identified through a post-market literature review activity were included 
to the analysis with a total of 2257 patients. 
We hypothesize that the clinical success rate of MANTISTM clip will be 
greater than the performance goal of 89% with expected clinical success 
rate of 94%. These assumptions are based in the following meta-analyses 
of clinical success for closure of a defect:  
• 20 publications representing 2257 patients: 93.9% (95% CI 
88.6%-97.6%) 
We hypothesize that the serious adverse event (SAE) rate related to 
MANTISTM clip or the endoscopic clipping portion of the procedure will 
be lower than the performance goal of 19% with expected related SAE 
rate of  10%. These assumptions are based in the following meta-
analyses of clinical success for closure of a defect: 
• 9 publications representing 1019 patients: 9.8% (95% CI 3.7%-
18.5%) 
Using an exact test with an alpha level of 0.05, 240 subjects enrolled 
will provide at least 80% power for the performance and safety metrics. 
These tests will only be performed for cases in the continued enrollment 
cohort. 

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3. Table of Contents 
1. 
TITLE PAGE  .......................................................................................................................1 
2. 
PROTOCOL SYNOPSIS .........................................................................................................4 
3. 
TABLE OF CONTENTS .........................................................................................................8 
3.1. Table of Figures .....................................................................................................11 
3.2. Table of Tables ......................................................................................................11 
4. 
INTRODUCTION.................................................................................................................12 
4.1. Background ............................................................................................................12 
4.2. Study Rationale .....................................................................................................13 
5. 
DEVICE DESCRIPTION ......................................................................................................13 
5.1. Device Under Study...............................................................................................13 
6. 
STUDY OBJECTIVES .........................................................................................................14 
7. 
STUDY ENDPOINTS ...........................................................................................................15 
7.1. Primary effectiveness endpoints ..........................................................................15 
7.2. Primary Safety endpoint .......................................................................................15 
8. STUDY DESIGN .....................................................................................................................16 
8.1 
Scale and Duration ................................................................................................16 
8.2 
Justification for the Study Design ........................................................................16 
9 
SUBJECT SELECTION ........................................................................................................17 
9.1 
Inclusion Criteria ..................................................................................................17 
9.2 
Exclusion Criteria .................................................................................................17 
10 SUBJECT ACCOUNTABILITY .............................................................................................17 
10.1 Point of Enrollment ...............................................................................................17 
10.2 Withdrawal ............................................................................................................18 
10.3 Lost to Follow-Up ..................................................................................................18 
10.4 End-of-Study Definition........................................................................................18 
11 STUDY METHODS .............................................................................................................19 
11.1 Data Collection ......................................................................................................19 
11.2 Study Candidate Screening ..................................................................................19 

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11.3 Strategies for Recruitment and Retention ..........................................................19 
11.4 Informed Consent..................................................................................................19 
11.5 Baseline...................................................................................................................19 
11.6 Study Procedure ....................................................................................................19 
11.7 30 Day (± 5 days) Telephone Interview Assessments .........................................20 
11.8 Study Completion ..................................................................................................20 
11.9 Source Documents .................................................................................................20 
12 STATISTICAL CONSIDERATIONS ......................................................................................20 
12.1 Endpoints ...............................................................................................................20 
12.1.1 
Primary Endpoints ....................................................................................20 
12.1.1.1 Primary Effectiveness Endpoint: .............................................20 
12.1.1.2 Primary Safety Endpoint: .........................................................20 
12.1.1.3 Hypotheses and Sample Size Justification ...............................21 
12.2 General Statistical Methods .................................................................................21 
12.2.1 
Analysis Sets .............................................................................................21 
12.3 Data Analyses ........................................................................................................22 
12.3.1 
Other Endpoints/Measurements ................................................................22 
12.3.2 
Procedure Data ..........................................................................................22 
12.3.3 
Post-Procedure Data .................................................................................22 
12.3.4 
Interim Analyses .......................................................................................23 
12.3.5 
Subgroup Analyses ...................................................................................23 
12.3.6 
Justification of Pooling .............................................................................23 
12.3.7 
Multivariable Analyses .............................................................................23 
12.3.8 
Changes to Planned Analyses ...................................................................23 
13 DATA MANAGEMENT .......................................................................................................23 
13.1 Data Collection, Processing, and Review ............................................................23 
13.2 Data Retention .......................................................................................................24 
13.3 Technical Source Forms .......................................................................................24 
14 DEVIATIONS......................................................................................................................24 
15 DEVICE ACCOUNTABILITY ..............................................................................................25 
15.1 Investigationally-Labelled Devices ......................................................................25 
16 COMPLIANCE ....................................................................................................................26 
16.1 Statement of Compliance ......................................................................................26 

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16.2 Investigator Responsibilities ................................................................................26 
16.2.1 
Delegation of Responsibility ....................................................................28 
16.3 Institutional Review Board/ Ethics Committee ..................................................28 
16.4 Sponsor Responsibilities .......................................................................................28 
16.4.1 
Role of Boston Scientific Representatives ...............................................29 
16.5 Insurance ................................................................................................................30 
17 MONITORING ....................................................................................................................30 
18 POTENTIAL RISKS AND BENEFITS ...................................................................................30 
18.1 Instructions for Use or Investigator Brochure ...................................................30 
18.2 Risks associated with Participation in the Clinical Study .................................30 
18.3 Risk Minimization Actions ...................................................................................30 
18.4 Anticipated Benefits ..............................................................................................31 
18.5 Risk to Benefit Rationale ......................................................................................31 
19 SAFETY REPORTING .........................................................................................................31 
19.1 Reportable Events by investigational site to Boston Scientific .........................31 
19.2 Definitions and Classification...............................................................................32 
19.3 Relationship to Study Device(s) and/or Study Procedure .................................35 
19.4 Investigator Reporting Requirements .................................................................37 
19.5 Device Deficiencies ................................................................................................39 
19.6 Reporting to Regulatory Authorities / IRBs / ECs / REBs/ Investigators .......39 
20 INFORMED CONSENT ........................................................................................................40 
21 COMMITTEES ...................................................................................................................41 
21.1 Safety Monitoring Process ....................................................................................41 
22 SUSPENSION OR TERMINATION........................................................................................42 
22.1 Premature Termination of the Study ..................................................................42 
22.1.1 
Criteria for Premature Termination of the Study ......................................42 
22.2 Termination of Study Participation by the Investigator or Withdrawal of 
IRB/ EC/REB Approval .......................................................................................42 
22.3 Requirements for Documentation and Subject Follow-up ................................42 
22.4 Criteria for Suspending/Terminating a Study Site ............................................43 
23 STUDY REGISTRATION AND RESULTS .............................................................................43 

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23.1 Study Registration .................................................................................................43 
23.2 Clinical Investigation Report ...............................................................................43 
23.3 Publication Policy ..................................................................................................43 
24 REIMBURSEMENT AND COMPENSATION FOR SUBJECTS .................................................44 
24.1 Compensation for Subject’s Health Injury.........................................................44 
25 BIBLIOGRAPHY .................................................................................................................44 
26 ABBREVIATIONS AND DEFINITIONS .................................................................................47 
26.1 Abbreviations.........................................................................................................47 
26.2 Definitions ..............................................................................................................48 
 
 
3.1. Table of Figures 
Figure 1. Jaw geometry comparison (full and augmented view) Resolution 360 (left) vs 
MANTIS clip (Right) .......................................................................................... 14 
 
3.2. Table of Tables 
Table 9.1-1: Inclusion Criteria ................................................................................................ 17 
Table 9.2-1: Exclusion Criteria ............................................................................................... 17 
Table 19.2-1: Safety Definitions ............................................................................................. 32 
Table 26.1-1: Abbreviations ................................................................................................... 47 
 

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4. Introduction 
4.1. Background 
The endoscopic clip, endoclip or hemoclip, was first introduced by Hayashi for the treatment 
of gastrointestinal (GI) bleeding in Japan in 1975.1 Over the past decades, the hemostatic clips 
technology has evolved and it has become the standard of care for gastrointestinal bleeding. 
Endoscopic clips achieve gastrointestinal hemostasis by clamping the vessel and/or 
approximating the edges of the lesion, producing mechanical compression without causing 
tissue injury.2, 3 
Gastrointestinal bleeding (GIB) is one of the major causes of emergency hospital admission. 
In the United States, GIB accounted for more than 500,000 hospitalizations and consumed 
nearly US$5 billion in 2014.4 GIB is usually categorized according to its anatomic location as 
either upper GIB (UGIB) or lower GIB (LGIB). Acute UGIB may originate in the esophagus, 
stomach, and duodenum. The common causes of acute UGIB are peptic ulcer disease including 
from the use of aspirin and other non-steroidal anti-inflammatory drugs, variceal hemorrhage, 
Mallory-Weiss tear and neoplasms including gastric cancers. Other relatively common causes 
include esophagitis, erosive gastritis/duodenitis, vascular ectasias and Dieulafoy’s lesion.5 
Among 16%-20% of acute UGIB cases, more than one endoscopic diagnosis may be identified 
as the cause of GIB. Acute UGIB is a common condition worldwide that has an estimated 
annual incidence of 40-150 cases per 100,000 population, frequently leads to hospital 
admission, and has significant associated morbidity and mortality, especially in the elderly.6 
LGIB is defined as bleeding that emanates from a source distal to the ligament of Treitz. LGIB 
is approximately one-fifth as common as UGIB and accounts for approximately 20 to 30 
hospitalizations per 100,000 adults per year. The incidence of LGIB increases substantially 
with age, presumably due to the high incidence of diverticulosis and vascular disease in this 
group. Prognosis in LGIB varies and given that most acute LGIB is self-limited, outcomes are 
typically favorable. However, the mortality associated with LGIB is generally considered to 
be less than 5% and when it occurs, is often a result of comorbid condition.7  
UGIB usually presents with hematemesis and/or melena. Hematochezia usually indicates      
bleeding from the lower GI tract but can occasionally be the presentation for a briskly bleeding 
upper gastrointestinal source. Variceal hemorrhage is life threatening and should be a major 
consideration in diagnosis as it accounts for up to 30% of all cases of acute UGIB and up to 
90% in patients with liver cirrhosis. LGIB classically presents with hematochezia, however 
bleeding from the right colon or the small intestine can present with melena. Bleeding from 
the left side of the colon tends to present bright red in color, whereas bleeding from the right 
side of the colon often appears dark or maroon-colored and may be mixed with stool.5  
Following the publication of Hayashi et al, Binmoeller KF et al popularized the endoclip use 
in 1993 by conducting an uncontrolled study to evaluate performance of an improved metallic 
clip (Olympus hemoclip) for the endoscopic treatment of nonvariceal GIB.8 Initial designs 
were cumbersome and performed inconsistently. Improvements appeared in the mid-1990s 
from the Olympus Company with the introduction of a reloadable clip. It was reusable rotatable 
device that required manually reloading a disposable clip onto a small hook at the end of a 
metal cable running through a plastic sheath.  Followed by the pre-loaded QuickClip in 2002 

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and rotatable QuickClip2 in 2005. The preloaded version is easier and faster to use, especially 
in the setting of a bleeding lesion. Cook’s TriClip and Boston Scientific’s Resolution clip both 
were launched in 2003. At the end of 2010, a new type of clip, developed by Ovesco Endoscopy 
AG as an over-the-scope-clip device and commonly known as the bear claw, was introduced. 
Its design was fundamentally different from through-the-scope devices in that the clip is held 
on the outside of the tip of the endoscope until it is released, by a deployment much like a 
band-ligation handle.9, 10 A new clip by Cook Medical was introduced on a limited basis in the 
United States in 2011. The Instinct Endoscopic Hemoclip has similarities and differences from 
its predecessors. It has two arms with anchoring teeth and nitinol strips for added strength, 
controlled 360-degree bidirectional rotation, no plastic sheath, can be opened and closed 
multiple times and has a very simple, one-directional deployment mechanism. Resolution 
360™ Clip was launched by Boston Scientific Corporation, and CE marked in December 2016 
with the features such as controlled 360-degree bidirectional rotation, radiopacity and MR 
conditional. 
This overtime improvement in design and performance of endoclip devices resulted in use of 
hemostatic clips for variety of GIB conditions such as prevention of bleeding from ulcers11, 
Mallory Weiss tears 12, Dieulafoy’s lesion13, polypectomy sites14, varices15-17, and 
diverticulae18; to close mucosal defects resulting from endoscopic mucosal resection19, 
hemostasis of GI fistula20; and perforations of the esophagus21, stomach22, and colon23. Clips 
have also been used to secure feeding tubes24, esophageal stents, and manometry catheters to 
the GI wall. Endoscopic clipping using the currently available devices appears effective and 
safe.25-33 
4.2. Study Rationale 
The MANTIS Clip is designed to be delivered Through-The-Scope (TTS) and has features 
intended to optimize ability to close mucosal/submucosal defects by anchoring the device, 
mobilizing the tissue, and approximating defect edges for secure closure. This clinical study 
aims to document in a prospective manner the use of the MANTIS TTS clip and the impact 
of its enhanced capabilities when used for hemostasis, closure, anchoring and marking. 
Compared to prior endoscopic clips in the Resolution 360 Platform the MANTIS™ clip has 
newly designed jaws which have increased jaw thickness and modified teeth geometry aimed 
to provide enhanced tissue grasping capabilities. 
 
This study will prospectively document the performance of the MANTIS clip when used per 
standard of practice. It is designed to be a multicenter study to assure broad representation of 
use of the MANTIS clip. 
5. Device Description 
5.1. Device Under Study 
The MANTIS™ clip, which is manufactured by Boston Scientific Corporation is a Through-
The-Scope (TTS) device that leverages all features and advantages on the delivery system 
and the deployment system from the Resolution 360 product family.  

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The MANTIS Clip is indicated for clip placement within the Gastrointestinal (GI) tract for 
the purpose of Endoscopic marking, Hemostasis for: Mucosal/sub-mucosal defects < 3 cm, 
Bleeding ulcers, Arteries < 2 mm, Polyps < 1.5 cm in diameter, Diverticula 
in the colon, Prophylactic clipping to reduce the risk of delayed bleeding post lesion 
resection, Anchoring to affix jejunal feeding tubes to the wall of the small bowel, and as a 
supplementary method, closure of GI tract luminal perforations < 20 mm that can be treated 
conservatively. 
 
The MANTIS clip consists of a radiopaque, single-use clip with an 11mm clip opening, pre-
loaded on a flexible, rotatable delivery system. The clip is designed to be compatible with 
forward viewing endoscopes with working channels equal to or greater than 2.8 mm. 
 
The radiopaque MANTIS clip is engineered to enable opening and closing no more than five 
times prior to deployment, aiding in repositioning of the clip at the lesion site. Re-opening, 
closing and rotation capability may be limited by clinical circumstances and patient anatomy, 
among other factors. 
 
Study devices are labeled on the box and inner pouch and include information not limited to 
name of legal manufacturer, device name and dimensions, lot number and expiration date. 
Device labeling will be provided in local language(s) as per national regulations. For a 
detailed description of each device, please reference the Instructions for Use (IFU) included 
in each device package where commercially available or the Investigator Brochure (IB) for 
countries where the study device is not approved.   
 
Figure 1. Jaw geometry comparison (full and augmented view) Resolution 360 (left) vs 
MANTIS™ clip (Right) 
 
 
6. Study Objectives  
Initial Cohort:  
To document performance of the MANTISTM Clip in all indications for endoscopic clipping. 
Continued Enrollment Cohort: 

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To evaluate the procedural and clinical merit in consecutive cases in which at least one 
MANTIS clip is selected, of specific attributes of the MANTISTM Clips, including but not 
limited to  the ability of this new endoscopic clipping device: 
o to provide prophylaxis to reduce the risk of delayed bleeding post lesion resection 
o to close post mucosal resections/polypectomy ulcers, post submucosal dissection 
ulcers, or mucosal incisions made in conjunction with endoscopic myotomy 
procedures 
o to close lumenal perforations, fistulas, or leaks   
o to close perforations after full thickness resection of lesions in the gastrointestinal 
(GI) tract 
7. Study Endpoints  
7.1. Primary effectiveness endpoints  
Initial Cohort 
Ability to complete the indication for the use of endoscopic clipping 
Continued Enrollment Cohort 
Clinical success defined as, where applicable,  
• Absence of delayed bleeding 
• Sustained closure of the targeted leasion  (up to 30 days after the endoscopic clipping 
procedure)  
7.2. Primary Safety endpoint 
Rate of serious adverse events (SAEs) related to the MANTISTM clip or the endoscopic study 
portion of the procedure. 
NOTE: If providing hemostasis to an active bleeding in Group A requires possible additional 
hemostasis after the index study procedure for management of bleeding SAEs within 7 days 
of the index study procedure, then such bleeding SAEs are not counted for the Primary 
Safety Endpoint.  
 
Additional endpoints: 
• Technical success at placement defined as ability to deploy the endoscopic clips in 
satisfactory position.   
• Ability to anchor device, mobilize the tissue, and approximate defect edges for a 
secured closure. 
• Post procedural bleeding, defined as a severe bleeding event that required 
hospitalization, a blood transfusion (>5 units) , or another invasive intervention 
(angiographic or surgical) within 30 days after completion of the study clip placement 
procedure.   

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• For active bleeding hemostasis cases only  
o Rate of patients requiring additional modalities of hemostasis.   
o Report of hemostasis of active bleeding 7 days after the index study 
procedure, and/or with additional clipping procedures to provide hemostasis 
of continued or recurrent bleeding within 7 days of the index study procedure 
8.   Study Design 
Prospective, multi-center, multi-national, open label, consecutive enrollment. The population 
will be split up into 5 groups, namely: 
• Group A: Hemostasis  
• Group B: Closure  
• Group C: Anchoring 
• Group D: Endoscopic Marking  
• Group E: Other 
8.1 Scale and Duration 
Scope of the series: 
• Initial Cohort:  
o Up to 50 cases    
• Continued Enrollment Cohort:  
o Up to 240 cases not including Initial Cohort 
• Up to 15 sites 
The study duration for each subject is expected to be approximately 1 month. Enrollment is 
expected to be completed in approximately 18 months per cohort. 
Study visits: 
• Screening/Enrollment and Baseline: Informed consent process, including informed 
consent signature date   
• Procedure   
• 30-day follow-up Telephone Interview  
8.2 Justification for the Study Design 
The study is designed to demonstrate that physicians are able to complete standard of care  
procedures using of a new endoscopic clipping device when used for hemostasis, closure, 
anchoring and marking.  

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9 Subject Selection  
9.1 Inclusion Criteria 
Subjects who meet all of the following criteria (see Table 9.1-1) may be given consideration 
for inclusion in this clinical investigation, provided no exclusion criterion (see Section 9.2) is 
met.  
Table 9.1-1: Inclusion Criteria 
Inclusion 
Criteria 
1.  Subject indicated for endoscopic clipping per local standard of practice. 
2. Willing and able to comply with the study procedures and provide written 
informed consent to participate in the study 
NOTE: Hemostasis and closure can be needed in the setting of complications 
such as perforations or acute bleeding that are typically rare and sometimes 
emergent. In such circumstances consenting the patient before the procedure 
is not feasible and consent shall be obtained from the patient after the 
procedure but before any study data is collected.   
 
9.2 Exclusion Criteria 
Subjects who meet any one of the following criteria (Table 9.2-1) cannot be included in this 
study or will be excluded from this clinical study. No vulnerable populations will be enrolled 
in this study per the local standard of care at the institution/IRB.  
Table 9.2-1: Exclusion Criteria 
Exclusion 
Criteria 
1. Subjects who are currently enrolled in another investigational study   that 
would directly interfere with the current study, without prior written 
approval from the sponsor 
2. Subjects who the investigator deems at risk for study device or procedure 
related complications per the Instructions for Use (IFU) where 
commercially available or the Investigator Brochure (IB) for countries 
where the study device is not approved. 
 
10 Subject Accountability 
10.1 
Point of Enrollment 
Subjects will be considered enrolled into the study at the time of the study-specific Informed 
Consent Form (ICF) execution. Subjects who have signed informed consent but do not 
undergo the study procedure are considered screen failures. Screen failures will be recorded 

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in the Electronic Data Capture (EDC) system by each study site and will not count toward 
total study enrollment. 
In the case it is determined that the subject failed to meet the inclusion/exclusion criteria after 
the subject has agreed to participate in the study and has signed the informed consent, the 
study personnel will complete the Screening form and the End of Study form.  
10.2 
Withdrawal 
Subjects will participate in the study voluntarily and may withdraw at any time without 
prejudice to further treatment. All subjects enrolled in the clinical study (including those 
withdrawn from the clinical study) shall be accounted for and documented. If a subject 
withdraws from the clinical investigation, the reason(s) shall be reported. If such withdrawal 
is due to problems related to study device safety or performance, the investigator shall ask for 
the subject’s permission to follow his/her status/condition outside of the clinical study.   
 
Applicable case report forms up to the point of subject withdrawal, including an End of 
Study form must be completed.  Unless the withdrawal is due to a Serious Adverse Event, 
additional subject data will not be collected after the point at which the subject has been 
withdrawn or withdraws consent from the study. Data collected up to the point of withdrawal 
may be used by the investigators as permitted in the ICF. 
10.3 
Lost to Follow-Up 
A subject will be considered lost to follow-up if he/she fails to return for their scheduled 
follow-up visits and is unable to be contacted by the study site staff after at least three 
documented attempts, at which point an End of Study form should be completed.  Before a 
participant is deemed lost to follow up, the investigator or designee will make every effort to 
regain contact with the participant (where possible, 3 telephone calls and, if necessary, a 
certified letter to the participant’s last known mailing address or local equivalent methods).  
These contact attempts should be documented in the participant’s medical record or study 
file. 
10.4 
End-of-Study Definition  
A clinical trial is considered completed when participants are no longer being examined or 
the last participant’s last study visit has occurred.  
Subjects will be followed through 30 days post index procedure. At study completion, an End 
of Study form will be completed. The end of study is defined as completion of the last visit 
or a reason for the last study visit not having been completed has been determined by the 
investigator or designee.  If the last follow up visit was not completed, the investigator will 
note the reason on the study completion form (e.g. subject withdrawn by investigator, subject 
withdrew consent, lost to follow-up, AE, death, etc.)  

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11 Study Methods 
11.1 
Data Collection 
The data collection schedule is shown in Table 10-1.1. 
Table 10-1.1: Data Collection Schedule  
Procedure/Assessment 
Screening 
Baseline 
Study 
Procedure 
30 Days (± 5 days)    
Follow Up 
Informed consent process, 
including informed consent 
signature date 
X 
 
 
 
Demographics, Medical 
History 
 
X 
 
 
Procedure 
 
 
X 
 
Device Deficiency Assessment 
 
 
X 
X 
Adverse Event Assessment 
 
 
X 
X 
End of Study 
 
 
X 
X 
X=required 
 
 
 
 
 
11.2 
Study Candidate Screening 
No study-specific data will be collected until after the subject has signed an Informed 
Consent Form (ICF). A Screen Failure/Enrollment Log will be maintained in the EDC 
system by the center to document select information about candidates who signed consent.   
11.3 
Strategies for Recruitment and Retention 
All patients under the care of a study investigator during the enrollment period of a site will 
be considered for recruitment. 
11.4 
Informed Consent 
Data collection will not occur prior to the subject signing the ICF. Patients will be considered 
enrolled in the study once they sign the ICF. Once a subject is considered enrolled in the 
study, baseline information may be obtained. 
11.5 
Baseline 
Baseline information will include the following data points: age at time of consent, gender, 
and relevant medical history. 
11.6 
Study Procedure 
During the index procedure, the endoscopist or designated member of study staff will record:  
Clip information, and any activities completed or attempted during the procedure, regardless 
of original intent.  Any ensuing adverse or device events will be recorded and reported. 

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11.7 
30 Day (± 5 days) Telephone Interview Assessments 
All enrolled subjects will be evaluated via telephone to screen for any post-procedure adverse 
events, and to evaluate the resolution of any previously noted adverse events or sequelae, as 
applicable. 
11.8 
Study Completion 
Subjects will be followed for 30 days (± 5 days) post index procedure. Subjects will continue 
to receive care from their doctor as they normally would. At study completion, an End of 
Study form will be completed, indicating whether the subject completed the study. If the last 
follow-up visit was not completed, the reason will be noted on the study completion form 
(e.g. subject withdrawn by investigator, subject withdrew consent, lost to follow-up, AE, 
death, etc.) and a Protocol Deviation form will be completed.  
11.9 
Source Documents 
It is preferable that original source documents are maintained, when available. In lieu of 
original source documents, certified copies are required to be maintained.  A certified copy is 
a copy (irrespective of the type of media used) of the original record that has been verified 
(i.e., by a dated signature or by generation through a validated process) to have the same 
information, including data that describe the context, content, and structure, as the original. 
12 Statistical Considerations 
12.1 
Endpoints 
12.1.1 Primary Endpoints 
12.1.1.1 
Primary Effectiveness Endpoint: 
Initial Cohort 
Ability to complete the indication for the use of endoscopic clipping 
Continued Enrollment Cohort 
Clinical success defined as, where applicable,  
o Absence of delayed bleeding 
o Sustained closure of the targeted leasion  
up to 30 days after the endoscopic clipping procedure  
12.1.1.2 
Primary Safety Endpoint: 
Rate of serious adverse events (SAEs) related to the MANTISTM clip or the endoscopic study 
portion of the procedure. 
NOTE: If providing hemostasis to an active bleeding in Group A requires possible additional 
hemostasis after the index study procedure for management of bleeding SAEs within 7 days 

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of the index study procedure, then such bleeding SAEs are not counted for the Primary 
Safety Endpoint.  
12.1.1.3 
Hypotheses and Sample Size Justification 
Initial cohort: 
No hypotheses will be tested, only observational, summary statistics will be performed.   
Continued enrollment cohort: 
A systematic literature search was conducted on PubMed and Embase from January 1, 2016 
to September 2022 to identify studies that evaluated the safety and effectiveness of an 
endoscopic clip device for closing various types of incisions, lesions, or defects in the 
gastrointestinal tract resulting from endoscopic mucosal resection (EMR), endoscopic 
submucosal dissection (ESD), polypectomy of polyps or adenomas, perforations, and fistulas. 
The primary objective of the search strategy was to identify studies that examined the closure 
of large mucosal defects by endoscopic clipping. Twenty studies were identified through a 
post-market literature review activity were included to the analysis with a total of 2257 
patients. 
 
We hypothesize that the clinical success rate of MANTISTM clip will be greater than the 
performance goal of 89% with expected clinical success rate of 94%. These assumptions are 
based in the following meta-analyses of clinical success for closure of a defect:  
• 20 publications representing 2257 patients: 93.9% (95% CI 88.6%-97.6%) 
We hypothesize that the serious adverse event (SAE) rate related to MANTISTM clip or the 
endoscopic clipping portion of the procedure will be lower than the performance goal of 
19% with expected related SAE rate of  10%. These assumptions are based in the following 
meta-analyses of clinical success for closure of a defect: 
• 9 publications representing 1019 patients: 9.8% (95% CI 3.7%-18.5%) 
12.2 
Using an exact test with an alpha level of 0.05, 217 subjects enrolled will 
provide at least 80% power for the performance and safety metrics. An 
additional 10% will be added for attrition, so total enrollment will be 240 
subjects. These tests will only be performed for cases in the continued 
enrollment cohort General Statistical Methods 
12.2.1 Analysis Sets 
Enrolled Cohort 
A subject is considered enrolled after signing the study-specific ICF.  Subjects who sign the 
ICF, but subsequently do not meet one or more of the eligibility criteria provided in Section 
8.1 and Section 8.2 will be considered screen failures and excluded from the study.   
Intent-to-Treat Cohort (ITT) 

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This cohort consists of enrolled subjects who are planned to have a MANTISTM clip placed 
regardless if they met I/E criteria. 
Treated Cohort 
The treated cohort is a subset of the ITT subjects who have a MANTISTM clip placed. 
12.3 
Data Analyses 
All statistical analyses will be done using The SAS System software, version 8 or higher 
(Copyright © 2000 SAS Institute Inc., SAS Campus Drive, Cary, North Carolina 27513, 
USA. All rights reserved). 
12.3.1 Other Endpoints/Measurements  
• Technical success at placement defined as ability to deploy the endoscopic clips in 
satisfactory position.  
• Post procedural bleeding, defined as a severe bleeding event that required 
hospitalization, a blood transfusion (>5 units), or another invasive intervention 
(angiographic or surgery) within 30 days after the study clip placement. 
• For active bleeding hemostasis cases only  
• Rate of patients requiring additional modalities of hemostasis.   
• Report of hemostasis of active bleeding 7 days after the index study 
procedure, defined as ability to stop the active bleed at the time of the study 
procedure and/or with additional clipping procedures to provide hemostasis of 
continued or recurrent bleeding within 7 days of the index study procedure 
12.3.2 Baseline Data 
Subject demographics and medical history will be summarized using descriptive statistics 
(e.g., mean, standard deviation, n, minimum, maximum) for continuous variables and 
frequency statistics for discrete variables.  
12.3.3 Procedure Data 
Procedure data including qualitative evaluation will be collected and reported using 
descriptive statistics (e.g., mean, standard deviation, n, minimum, maximum) for continuous 
variables and frequency statistics for discrete variables. 
12.3.4 Post-Procedure Data 
Post-procedure information will be collected as detailed in Table 11-1.1 Data Collection 
Schedule and will be summarized using descriptive statistics for continuous variables (e.g., 
mean, standard deviation, n, minimum, maximum) and frequency statistics for discrete 
variables.   

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12.3.5 Interim Analyses  
12.3.6 There will be no formal interim analyses performed. irlSubgroup 
Analyses 
Stratified analyses will include tabulating the primary and select secondary endpoints by 
gender, polyp location, polyp size, or use of periprocedural antithrombotic medications. 
12.3.7 Justification of Pooling 
The analyses will be performed using data pooled across institutions. An assessment of the 
poolability of patients across sites will be made by fitting generalized linear models with site 
as the factor of interest and the primary endpoints as the outcome variable. 
12.3.8 Multivariable Analyses 
Multivariable analyses may be performed to assess the effect of potential predictors on the 
primary endpoint. 
12.3.9 Changes to Planned Analyses 
Any changes to the planned statistical analyses made prior to performing the analyses will be 
documented in an amended Statistical Analysis Plan approved prior to performing the 
analyses.  
13 Data Management 
13.1 
Data Collection, Processing, and Review 
Subject data will be recorded in a limited access secure electronic data capture (EDC) 
system.  
The clinical database will reside on a production server hosted by Medidata. All changes 
made to the clinical data will be captured in an electronic audit trail and available for review 
by the sponsor or its representative. The associated Rave software and database have been 
designed to meet regulatory compliance for deployment as part of a validated system 
compliant with laws and regulations applicable to the conduct of clinical studies pertaining to 
the use of electronic records and signatures. Database backups are performed regularly. 
The Investigator provides his/her electronic signature on the appropriate electronic case 
report forms (eCRFs) in compliance with local regulations. A written signature on printouts 
of the eCRFs must also be provided if required by local regulation. Changes to data 
previously submitted to the sponsor require a new electronic signature by the Investigator 
acknowledging and approving the changes. 
Visual and/or electronic data review will be performed to identify possible data 
discrepancies. Manual and/or automatic queries will be created in the Medidata EDC system 
and will be issued to the site for appropriate response. Site staff will be responsible for 
resolving queries in the database. 

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Access to the clinical database will be changed to “Read only” after data is either “Hard 
Locked” or “Entry Locked”. Once acceptance of the final report or finalization of 
publications (as applicable) is received, final database storage and archiving activities can 
begin. Once the closeout activities are completed a request to IT is submitted to have the 
“Database Locked” or Decommissioned and database access revoked. 
13.2 
Data Retention 
The Principal Investigator or his/her designee or Investigational site will maintain all 
essential study documents and source documentation that support the data collected on the 
study subjects in compliance with applicable regulatory requirements.   
The Principal Investigator or his/her designee will take measures to prevent accidental or 
premature destruction of these documents. If for any reason the Principal Investigator or 
his/her designee withdraws responsibility for maintaining these essential documents, custody 
must be transferred to an individual who will assume responsibility and BSC must receive 
written notification of this custodial change. Sites are required to inform Boston Scientific in 
writing where paper or electronic files are maintained in case files are stored off site and are 
not readily available. 
13.3 
Technical Source Forms 
A Technical Source Form (TSF) may be developed by Boston Scientific or by the 
investigational site to capture protocol required data elements that are not duplicated in any 
other source documents. This form is to be used by the study sites as a source document. A 
Boston Scientific representative may complete the TSF at the request of the Principal 
Investigator. The TSF will be reviewed and signed for approval by the Principal Investigator 
or his/her designee at the end of each procedure.  
14 Deviations 
An Investigator must not make any changes or deviate from this protocol, except to protect 
the life and physical well-being of a subject in an emergency. An investigator shall notify the 
sponsor and the reviewing IRB/EC/REB, and the regulatory authority if applicable of any 
deviation from the investigational plan to protect the life or physical well-being of a subject 
in an emergency, and those deviations which affect the scientific integrity of the clinical 
investigation. Such notice shall be given as soon as possible, but no later than 5 working days 
after the emergency occurred, or per prevailing local requirements, if sooner than 5 working 
days.  
Deviations from the investigational plan, with the reason for the deviation must be 
documented and reported to the sponsor using EDC. Sites may also be required to report 
deviations to the IRB/EC/REB, and the regulatory authority, per local guidelines and 
national/government regulations.  
Deviations will be reviewed and evaluated on an ongoing basis and, as necessary, appropriate 
corrective and preventive actions including IRB/EC/REB/Regulatory Authority/FDA 

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notification, site re-training, or site discontinuation/termination) will be put into place by the 
sponsor. 
The sponsor will not approve protocol waivers.  
15 Device Accountability 
15.1 
Investigationally-Labelled Devices 
This section applies to items being distributed with investigational use indication on the 
device packaging. 
For investigationally-labelled items, the principal investigator or an authorized designee shall 
do the following: 
• Securely maintain and control access to these items to ensure they are used only 
in this clinical study and only per the protocol.  
• Ensure the storage environment for these items is appropriate for maintaining 
conditions per the items’ labeling (e.g. temperature, humidity, etc., as applicable)  
• Maintain accurate and timely Device Accountability Records, providing copies to 
Sponsor upon request. Such records shall include the following content, at 
minimum: 
o Identification, quantity and expiry date (if applicable) of each item received. 
Include batch number, serial number or unique code, as applicable; 
o Date of receipt; open/use, and end disposition of each item and name of 
person(s) who performed those activities; 
o Subject identification / subject exposure to device and, if applicable, the date 
on which the item was returned/explanted from subject, if applicable; 
o Reason for repair, disposal or return to Sponsor (e.g. advisory/recall, sponsor 
request, other 
• Return or dispose of items as directed by Sponsor 
o Complaint / deficiency related items should be returned whenever possible 
o Opened non-complaint / non-deficiency related items should be returned or 
disposed as directed by Sponsor 
o Unopened and reusable items should be returned to Sponsor or designee upon 
Sponsor request and in the condition in which they were provided, reasonable 
wear and tear excepted. 

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16 Compliance 
16.1 
Statement of Compliance 
This clinical investigation is financed by the study sponsor. Before the investigational site 
can be “Authorized to Enroll,” the investigational site must enter into a Clinical Study 
Agreement with the sponsor that details the financing of the study as well as the rights and 
obligations of the investigational site and the investigator. This study will be conducted in 
accordance with European Medical Device Regulation, ISO 14155: Clinical Investigation of 
Medical Devices for Human Subjects – Good Clinical Practice, ICH Guidelines for GCP, 
Japan Medical Device GCP, ethical principles that have their origins in the Declaration of 
Helsinki, and applicable individual country laws and regulations. The study shall not begin 
until the required approval/favorable opinion from the IRB/EC/REB and/or regulatory 
authority has been obtained, if appropriate. Also, the study shall not begin prior to issuance 
of the site Authorization to Enroll, as provided by the sponsor. Any additional requirements 
imposed by the IRB/EC/REB or regulatory authority shall be followed, if appropriate.  
16.2 
Investigator Responsibilities 
The Principal Investigator of an investigational site is responsible for ensuring that the study 
is conducted in accordance with the Clinical Study Agreement, the clinical investigation 
plan/, ISO 14155, ethical principles that have their origins in the Declaration of Helsinki, any 
conditions of approval imposed by the reviewing IRB/EC/REB, and prevailing local and/or 
country laws and/or regulations, whichever affords the greater protection to the subject. 
The Principal Investigator’s responsibilities include, but are not limited to, the following.  
• Prior to beginning the study, sign the Clinical Study Agreement and comply with the 
Investigator responsibilities as described in such Agreement.   
• Prior to beginning the study, sign the Investigator Brochure Signature Page if applicable 
and Protocol Signature page documenting his/her agreement to conduct the study in 
accordance with the protocol. 
 
• Provide his/her qualifications and experience to assume responsibility for the proper 
conduct of the study and that of key members of the site team through up-to-date 
curriculum vitae or other relevant documentation and disclose potential conflicts of 
interest, including financial, that may interfere with the conduct of the clinical study or 
interpretation of results. 
• Make no changes in or deviate from this protocol, except to protect the life and physical 
well-being of a subject in an emergency; document and explain any deviation from the 
approved protocol that occurred during the course of the clinical investigation. 
• Create and maintain source documents throughout the clinical study and ensure their 
availability with direct access during monitoring visits or audits; ensure that all clinical-
investigation-related records are retained per requirements. 

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• Ensure the accuracy, completeness, legibility, and timeliness of the data reported to the 
sponsor in the CRFs and in all required reports. 
• Record, report, and assess (seriousness and relationship to the device/procedure) every 
adverse event as applicable per the protocol and observed device deficiency. 
• Report to sponsor, per the protocol requirements, all reportable events. 
• Report to the IRB/EC/REB and regulatory authorities any SAEs and device deficiencies 
that could have led to a SADE and potential/USADE or UADE, if required by applicable 
laws or regulations or this protocol or by the IRB/EC/REB, and supply BSC with any 
additional requested information related to the safety reporting of a particular event. 
• In the event where commercial product is provided to sites for free, maintain records and 
control of the device, ensuring that the study device is used only by authorized/designated 
users and in accordance with this protocol and instructions for use or investigator 
brochure. 
• Allow the sponsor to perform monitoring and auditing activities, and be accessible to the 
clinical research monitor or auditor and respond to questions during monitoring visits or 
audit(s). 
• Allow and support regulatory authorities and the IRB/EC/REB when performing auditing 
activities. 
• Ensure that informed consent is obtained in accordance with applicable laws, this 
protocol and local IRB/EC/REB requirements. 
• Provide adequate medical care to a subject during and after a subject’s participation in a 
clinical study in the case of adverse events, as described in the Informed Consent Form 
(ICF). 
• Inform the subject of the nature and possible cause of any adverse events experienced. 
• As applicable, provide the subject with necessary instructions on proper use, handling, 
storage, and return of the device when it is used/operated by the subject. 
• Inform the subject of any new significant findings occurring during the clinical 
investigation, including the need for additional medical care that may be required. 
• Provide the subject with well-defined procedures for possible emergency situations 
related to the clinical study, and make the necessary arrangements for emergency 
treatment, including decoding procedures for blinded/masked clinical investigations, as 
needed. 
• Ensure that clinical medical records are clearly marked to indicate that the subject is 
enrolled in this clinical study. 
• Ensure that, if appropriate, subjects enrolled in the clinical investigation are provided 
with some means of showing their participation in the clinical investigation, together with 
identification and compliance information for concomitant treatment measures (contact 
address and telephone numbers shall be provided). 

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• Inform, with the subject’s approval or when required by national regulations, the 
subject’s personal physician about the subject’s participation in the clinical investigation. 
• Make all reasonable efforts to ascertain the reason(s) for a subject’s premature 
withdrawal from clinical investigation while fully respecting the subject’s rights. 
• Ensure that an adequate investigation site team and facilities exist and are maintained and 
documented during the clinical investigation. 
All investigators will provide their qualifications and experience to assume responsibility for 
their delegated tasks through up-to-date curriculum vitae or other relevant documentation and 
disclose potential conflicts of interest, including financial, that may interfere with the conduct 
of the clinical study or interpretation of results. 
16.2.1 Delegation of Responsibility 
When specific tasks are delegated by an investigator, including but not limited to conducting 
the informed consent process, the Principal Investigator is responsible for providing 
appropriate training, are competent to perform the tasks they have been delegated and 
adequate supervision of those to whom tasks are delegated. Where there is a sub investigator 
at a site, the sub investigator should not be delegated the primary supervisory responsibility 
for the site. The investigator is accountable for regulatory violations resulting from failure to 
adequately supervise the conduct of the clinical study.  
16.3 
Institutional Review Board/ Ethics Committee 
The investigational site will obtain the written and dated approval/favorable opinion of the 
IRB/EC/REB for the clinical investigation before recruiting subjects and implementing all 
subsequent amendments, if required. 
A copy of the written IRB/EC/REB and/or competent authority (CA) approval of the 
protocol (or permission to conduct the study) and ICF, must be received by the sponsor 
before recruitment of subjects into the. Prior approval must also be obtained for other 
materials related to subject recruitment or which will be provided to the subject. 
 
Any amendment to the protocol will require review and approval by the IRB/EC/REB before 
the changes are implemented to the study.  All changes to the ICF will be IRB/EC/REB 
approved; a determination will be made regarding whether a new ICF needs to be obtained 
from participants who provided consent, using a previously approved ICF.  
Annual IRB/EC/REB approval and renewals will be obtained throughout the duration of the 
study as required by applicable local/country laws or regulations or IRB/EC/REB 
requirements. Copies of the study reports and the IRB/EC/REB continuance of approval must 
be provided to the sponsor.  
16.4 
Sponsor Responsibilities 
All information and data sent to BSC concerning subjects or their participation in this study 
will be considered confidential by BSC and will be kept confidential in accordance with all 

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applicable laws and regulations. Only authorized BSC personnel and/or a BSC representative 
including, but not limited to Contract Research Organization (CRO), will have access to this 
information. Authorized regulatory personnel have the right to inspect and copy all records 
pertinent to this study. Study data collected during this study may be used by BSC for the 
purposes of this study, publication, and to support future research and/or other business 
purposes, such as overseeing and improving the performance of its device, new medical 
research and proposals for developing new medical products and procedures. All data used in 
the analysis and reporting of this study or shared with a third-party researcher will be without 
identifiable reference to specific subjects. 
Information received during the study will not be used to market to subjects; subject names 
will not be placed on any mailing lists or sold to anyone for marketing purposes.  
16.4.1 Role of Boston Scientific Representatives 
Boston Scientific personnel can provide technical support to the investigator and other health 
care personnel (collectively HCP) as needed during implant, testing required by the protocol, 
and follow-ups. Support may include HCP training, addressing HCP questions, or providing 
clarifications to HCPs concerning the operation of BSC equipment/devices (including 
programmers, analyzers, and other support equipment). 
At the request of the investigator and while under investigator supervision, BSC personnel 
may operate equipment during implant or follow-up, assist with the conduct of testing 
specified in the protocol, and interact with the subject to accomplish requested activities.  
Typical tasks may include the following: 
• Provide instructions for the safe return of products. For potentially hazardous items, 
provide specialized instruction and materials as applicable.  
• Clarifying device behavior, operation or diagnostic output as requested by the 
investigator or other health care personnel 
• Entering technical data on technical source form as long as the responsible investigator 
verifies and signs the completed form  
• Provide technical expertise/support to subjects during office visits and/or during 
teleconference calls/electronic communications with the principal investigator or their 
delegated site staff and the subject.  
In addition, BSC personnel may perform certain activities to ensure study quality. These 
activities may include the following. 
• Observing testing or medical procedures to provide information relevant to protocol 
compliance 
• Reviewing collected data and study documentation for completeness and accuracy 
Boston Scientific personnel will not do the following.  
• Practice medicine 
• Provide medical diagnosis or treatment to subjects 

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• Discuss a subject’s condition or treatment with a subject  
• Independently collect critical study data (defined as primary or secondary endpoint data) 
• Enter data in electronic data capture systems or on paper case report forms 
16.5 
Insurance  
Where required by local/country regulation, proof and type of insurance coverage, by BSC 
for subjects in the study will be obtained. 
17 Monitoring 
Monitoring will be performed during the study to assess continued compliance with the 
protocol and applicable regulations. In addition, the clinical research monitor verifies that 
study records are adequately maintained, that data are reported in a satisfactory manner with 
respect to timeliness, adequacy, and accuracy, and that the Principal Investigator continues to 
have sufficient staff and facilities to conduct the study safely and effectively. The Principal 
Investigator/institution guarantees direct access to original source documents by BSC 
personnel, their designees, and appropriate regulatory authorities. 
The sponsor will put a plan in place to document the specific monitoring requirements.  
The study may also be subject to a quality assurance audit by BSC or its designees, as well as 
inspection by appropriate regulatory authorities. It is important that the Principal Investigator 
and relevant study personnel are available during on-site monitoring visits or audits and that 
sufficient time is devoted to the process. 
18 Potential Risks and Benefits 
18.1 
Instructions for Use or Investigator Brochure 
Please refer to the Instructions for Use or Investigator Brochure for an overview of 
anticipated adverse (device) effects, and risks associated to the device(s). 
18.2 
Risks associated with Participation in the Clinical Study 
Risk associated with participation in the Clinical Study are similar to that of use of an 
endoscopic clipping device when used for hemostasis, closure, anchoring or marking.  
18.3 
Risk Minimization Actions 
Additional risks may exist. Risks can be minimized through compliance with this protocol, 
performing procedures in the appropriate hospital environment, adherence to subject 
selection criteria, close monitoring of the subject's physiologic status during research 
procedures and/or follow-ups and by promptly supplying BSC with all pertinent information 
required by this protocol. 

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18.4 
Anticipated Benefits 
The safety and performance of the BSC endoscopic hemostatic clip devices have been  
established through studies reported in the literature and the market experience data. Medical 
science and future patients may benefit from this study.  
18.5 
Risk to Benefit Rationale 
Based on collected reports in literature to-date, the risk-to-benefit ratio is within reason for 
foreseeable risks. However, literature reports do not always capture all side effects. 
Observation and follow-up of patients is required as outlined in the protocol. 
19 Safety Reporting 
19.1 
Reportable Events by investigational site to Boston Scientific 
It is the responsibility of the investigator to assess and report to BSC any event which occurs 
in any of following categories: 
• All Non-Serious Adverse Events related to the Study Device and/or Study Procedure  
• All Serious Adverse Events including those related to the Study Device and/or Study 
Procedure 
• All events with a Fatal Outcome  
• All Device Deficiencies  
• Unanticipated Adverse Device Effects/Unanticipated Serious Adverse Device Effects 
• New findings/updates in relation to already reported events 
When possible, the medical diagnosis should be reported as the Event Term instead of 
individual symptoms. 
If it is unclear whether or not an event fits one of the above categories, or if the event cannot 
be isolated from the device or procedure, it should be submitted as an adverse event and/or 
device deficiency. 
Any reportable event, experienced by the study subject after informed consent, whether prior 
to, during or subsequent to the procedure, must be recorded in the eCRF. 
Underlying diseases and chronic conditions are not reported as AEs unless there is an 
increase in severity or frequency during the course of the investigation. Death should not be 
recorded as an AE, but should only be reflected as an outcome of one (1) specific SAE (see 
Table 19.2-1 for AE definitions). 
Refer to Instructions for Use or Investigator Brochure for the known risks associated with the 
device(s). 

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19.2 
Definitions and Classification 
Adverse event definitions are provided in Table 19.2-1. Administrative edits were made on 
the safety definitions from applicable regulations and guidance including (but not limited to) 
21 CFR Part 812, ISO 14155 and EU MDR 2017/745/MDCG 2020-10/1 Guidance on Safety 
Reporting in Clinical Investigations for clarification purposes. 
 
Table 19.2-1: Safety Definitions 
Term 
Definition 
Adverse Event (AE) 
 
Ref: ISO 14155 
 
Ref: MDCG 2020-10/1 
 
 
 
 
Any untoward medical occurrence, unintended disease or injury, 
or any untoward clinical signs (including an abnormal 
laboratory finding) in subjects, users or other persons, in the 
context of a clinical investigation, whether or not related to the 
study medical device and whether anticipated or unanticipated.  
NOTE 1: This includes events related to the study medical 
device or comparator. 
NOTE 2: This definition includes events related to the 
procedures involved. 
NOTE 3: For users or other persons, this definition is restricted 
to events related to the study medical device.  
Adverse Device Effect (ADE) 
 
Ref: ISO 14155 
 
Ref: MDCG 2020-10/1 
 
Adverse event related to the use of the study medical device 
NOTE 1: This includes any adverse event resulting from 
insufficiencies or inadequacies in the instructions for use, the 
deployment, the implantation, the installation, the operation, 
or any malfunction of the study medical device. 
NOTE 2: This definition includes any event resulting from 
use error or from intentional misuse of the study medical 
device. 
NOTE 3: This includes ‘comparator’ if the comparator is a 
medical device. 
Serious Adverse Event (SAE) 
 
Ref: ISO 14155 
 
Ref: MDCG 2020-10/1 
 
Adverse event that led to any of the following: 
a) death, 
b) serious deterioration in the health of the subject, users or 
other persons as defined by either: 
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body 
function, including chronic diseases, or  
3) in-patient hospitalization or prolongation of existing 
hospitalization, or 
4) medical or surgical intervention to prevent life-
threatening illness or injury or permanent impairment 
to a body structure or a body function 
c) foetal distress, foetal death, or a congenital abnormality or 
birth defect including physical or mental impairment. 
NOTE 1: Planned hospitalization for a pre-existing condition, 
or a procedure required by the clinical investigational plan, 
without a serious deterioration in health, is not considered a 
serious adverse event.  

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Table 19.2-1: Safety Definitions 
Term 
Definition 
Serious Adverse Device Effect (SADE) 
Ref: ISO 14155 
 
Ref: MDCG 2020-10/1 
Adverse device effect that has resulted in any of the 
consequences characteristic of a serious adverse event. 
Unanticipated Adverse Device Effect 
(UADE) 
 
Ref: 21 CFR Part 812 
 
Any serious adverse effect on health or safety or any life-
threatening problem or death caused by, or associated with, a 
device, if that effect, problem, or death was not previously 
identified in nature, severity, or degree of incidence in the 
investigational plan or application (including a supplementary 
plan or application), or any other unanticipated serious problem 
associated with a device that relates to the rights, safety, or 
welfare of subjects.   
Unanticipated Serious Adverse Device 
Effect (USADE) 
 
Ref: ISO 14155 
 
Ref: MDCG 2020-10/1 
Serious adverse device effect which by its nature, incidence, 
severity, or outcome has not been identified in the current risk 
assessment. 
NOTE 1: Anticipated serious adverse device effect (ASADE) is 
an effect which by its nature, incidence, severity or outcome has 
been identified in the risk assessment. 
Serious Health Threat 
 
Ref: ISO 14155 
 
Signal from any adverse event or device deficiency that 
indicates an  imminent risk of death or a serious deterioration in 
the health in subjects, users or other persons, and that requires 
prompt remedial action 
for other subjects, users or other persons. 
NOTE 1: This would include events that are of significant and 
unexpected nature such that they become alarming as a potential 
serious health hazard or possibility of multiple deaths occurring 
at short intervals. 
Device Deficiency 
 
Ref: ISO 14155 
 
Ref: MDCG 2020-10/1 
 
An inadequacy of a medical device related to its identity, 
quality, durability, reliability, usability, safety or performance.  
NOTE 1: Device deficiencies include malfunctions, use errors, 
and inadequacy in the information supplied by the manufacturer 
including labelling. 
NOTE 2: This definition includes device deficiencies related to 
the  device under study.  
The following definitions will be used for defining hospitalization or prolongation of hospitalization for SAE 
classification purposes: 
Hospitalizations  
Hospitalization does not include: 
• 
emergency room visit that does not result in in-patient 
admission  
Note: although an emergency room visit does not itself 
meet the definition for hospitalization, it may meet 
other serious criteria (e.g. medical or surgical 
intervention to prevent permanent impairment or 
damage) 

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Table 19.2-1: Safety Definitions 
Term 
Definition 
• 
elective and pre-planned treatment/surgery for a pre-
existing condition that is documented in the subject’s 
record at the time of consent/enrollment 
• 
admission for social reasons and/or respite care in the 
absence of any deterioration in the subject’s general 
condition (e.g. subject is homeless, caregiver relief) 
• 
pre-planned, protocol-specified admission related to 
the clinical study (e.g. procedure required by protocol) 
Prolongation of hospitalization  
In-patient admission to the hospital that is prolonged beyond the 
expected standard duration for the condition under treatment. 
Note: new adverse events occurring during the hospitalization 
are evaluated to determine if they prolonged hospitalization or 
meet another SAE criteria. 
The following definitions will be used to determine the severity criteria for bleeding events. 
Bleeding Severity Criteria  
Ref: ASGE Guidelines (Adverse Events 
associated with ERCP 2017) 
Cotton et al⁶ 
 
 
 
 
Mild Bleeding: 
• 
Clinical (i.e. not just endoscopic) evidence of bleeding 
• 
Hemoglobin drop <3 g/dL and no need for transfusion 
Moderate Bleeding: 
• 
Transfusion (≤ 4 units) 
• 
No angiographic intervention or surgery 
Severe Bleeding: 
• 
Transfusion ≥ 5 units or intervention (angiographic or 
surgical)  
The following definitions will be used to determine the severity criteria for perforation events  
 
Perforation Severity Criteria 
Ref: Odom, S. (2022, May). Overview of 
gastrointestinal tract perforation. UpToDate.   
Perforation: A full thickness hole in the wall of the 
Gastrointestinal Tract. 
Limited: 
• 
Micro perforation, minor or no medical intervention  
Moderate: 
• 
Medical Intervention (Nothing by mouth, 
antibiotics, etc)  
 
Severe: 
• 
Surgical intervention 
The following definitions will be used to describe the procedures performed in this study. 
Procedures: 
Endoscopic Procedure:  
The procedure that will be done for hemostasis, closure, 
anchoring or marking in the gastrointestinal tract as a part of 
this study. 
Study Procedure: 
The portion of the endoscopic procedure where the study device 
is used  for hemostasis, closure, anchoring or marking.   

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Table 19.2-1: Safety Definitions 
Term 
Definition 
The following definitions will be used to describe the severity level of adverse events. 
Severity Level:  
Severe: Significant illness or injury that results in 
permanent damage to a body structure or permanent 
impairment of a body function, or necessitates 
medical or surgical intervention to prevent 
permanent damage to a body structure or permanent 
impairment of a body function; immediate or 
substantial risk of death 
Moderate: Significant illness or injury that is 
temporary or reversible with moderate medical or 
surgical interventions 
Mild: No adverse health consequence nor clinically 
significant health consequence; the event is transient, 
minor illness or injury that is temporary or reversible 
with minor or no medical intervention 
19.3 
Relationship to Study Device(s) and/or Study Procedure 
The Investigator must assess the relationship of the reportable AE to the study device(s), 
and/or study procedure. See criteria in Table 19.3 1:  
Table 19.3 1: Criteria for Assessing Relationship of Study Device or Procedure to 
Adverse Event 
Classification 
Description 

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Not Related 
Ref: MDCG 
2020-10/1 
Relationship to the device, comparator or procedures can be excluded when: 
- the event has no temporal relationship with the use of the study device or the procedures 
related to the use of the study device; 
- the serious event does not follow a known response pattern to the medical device (if the 
response pattern is previously known) and is biologically implausible; 
- the discontinuation of medical device application or the reduction of the level of 
activation/exposure - when clinically feasible – and reintroduction of its use (or increase of 
the level of activation/exposure), do not impact on the serious event; 
- the event involves a body-site or an organ that cannot be affected by the device or 
procedure;  
- the serious 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); 
- the event does not depend on a false result given by the study device used for diagnosis, 
when applicable; - In order to establish the non-relatedness, not all the criteria listed above 
might be met at the same time, depending on the type of device/procedures and the serious 
event. 
Possibly 
Related 
Ref: MDCG 
2020-10/1 
The relationship with the use of the study device or comparator, or the relationship with 
procedures is weak but cannot be ruled out completely. Alternative causes are also possible 
(e.g. an underlying or concurrent illness/ clinical condition or/and an effect of another 
device, drug or treatment). Cases where relatedness cannot be assessed or no information 
has been obtained should also be classified as possible. 
Probably 
Related 
Ref: MDCG 
2020-10/1 
The relationship with the use of the study device or, comparator, or the relationship with 
procedures seems relevant and/or the event cannot be reasonably explained by another 
cause. 
 

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Causal 
Relationship 
Ref: MDCG 
2020-10/1 
The serious event is associated with the study device, comparator or with procedures 
beyond reasonable doubt when: 
- the event is a known side effect of the product category the device belongs to or of 
similar devices and procedures; 
- the event has a temporal relationship with the study device use/application or 
procedures; 
- the event involves a body-site or organ that 
-the study device or procedures are applied to; 
-the study device or procedures have an effect on; 
- the serious event follows a known response pattern to the medical device (if the 
response pattern is previously known); 
- 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 serious event (when clinically feasible); 
- other possible causes (e.g. an underlying or concurrent illness/ clinical condition or/and 
an effect of another device, drug or treatment) have been adequately ruled out; 
- harm to the subject is due to error in use; 
- the event depends on a false result given by the study device used for diagnosis, when 
applicable; 
- In order to establish the relatedness, not all the criteria listed above might be met at the 
same time, depending on the type of device/procedures and the serious event. 
19.4 
Investigator Reporting Requirements 
The communication requirements for reporting to BSC are as shown in below 
 
Table 19.4 1: Investigator Reporting Requirements 
Event 
Classification 
Communication 
Method  
Communication Timeline 
pre-market studies 
(21 CFR Part 812, MDCG 
2020-10/1) 
Communication Timeline 
post-market studies*  
(EU MDR 2017/745, MDCG 
2020-10/1MEDDEV 2.12/1:  
GUIDELINES ON A 
MEDICAL DEVICE 
VIGILANCE SYSTEM) 
Unanticipated 
Adverse Device 
Effect / 
Unanticipated 
Serious Adverse 
Device Effect  
 
Complete AE eCRF 
page with all available 
new and updated 
information.  
• 
Within 1 business day 
of first becoming aware 
of the event. 
• 
Terminating at the end 
of the study 
• 
Within 1 business day of 
first becoming aware of 
the event.  
• 
Terminating at the end 
of the study. 
 
 
Provide all relevant 
source documentation 
(de-identified/ 
pseudonymized) for 
reported event.  
• 
Upon request of 
sponsor. 
 
• 
Upon request of 
sponsor.  

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Event 
Classification 
Communication 
Method  
Communication Timeline 
pre-market studies 
(21 CFR Part 812, MDCG 
2020-10/1) 
Communication Timeline 
post-market studies*  
(EU MDR 2017/745, MDCG 
2020-10/1MEDDEV 2.12/1:  
GUIDELINES ON A 
MEDICAL DEVICE 
VIGILANCE SYSTEM) 
Serious Adverse 
Event  
Complete AE eCRF 
page with all available 
new and updated 
information.  
• 
Within 3 calendar days 
of first becoming aware 
of the event or as per 
local/regional 
regulations.  
• 
Reporting required 
through the end of the 
study 
• 
Within 10 calendar days 
after becoming aware of 
the event or as per 
local/regional 
regulations.  
 
• 
Reporting required 
through end of study. 
Provide all relevant 
source documentation 
(de-identified/ 
pseudonymized) for 
reported event as 
requested. 
• 
Upon request of sponsor 
 
• 
When documentation is 
available 
• 
Upon request of sponsor 
Serious Adverse 
Device Effects 
Complete AE eCRF 
page with all available 
new and updated 
information. 
• 
Within 3 calendar days 
of first becoming aware 
of the event or as per 
local/regional 
regulations. 
• 
Reporting required 
through the end of the 
study 
• 
Within 3 calendar days 
of first becoming aware 
of the event or as per 
local/regional 
regulations. 
• 
Reporting required 
through the end of the 
study 
Provide all relevant 
source documentation 
(de-identified/ 
pseudonymized) for 
reported event.  
• 
Upon request of sponsor 
 
• 
When documentation is 
available 
• 
Upon request of sponsor 
Device Deficiencies 
(including but not 
limited to 
malfunctions, use 
errors, and 
inadequacy in 
information supplied 
by the manufacturer, 
including labelling) 
Note:  Any Study 
Device Deficiency 
that might have led 
to a serious adverse 
event if appropriate 
action had not been 
taken, intervention 
had not occurred, 
circumstances had 
Complete Device 
Deficiency CRF with 
all available new and 
updated information.  
• 
Within 3 calendar days 
of first becoming aware 
of the event. Reporting 
required through the end 
of the study 
 
• 
Within 3 calendar days 
of first becoming aware 
of the event. Reporting 
required through the end 
of the study 
Provide all relevant 
source documentation 
(de-identified/ 
pseudonymized) for 
reported event. 
• 
Upon request of sponsor 
 
• 
Upon request of sponsor  

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Event 
Classification 
Communication 
Method  
Communication Timeline 
pre-market studies 
(21 CFR Part 812, MDCG 
2020-10/1) 
Communication Timeline 
post-market studies*  
(EU MDR 2017/745, MDCG 
2020-10/1MEDDEV 2.12/1:  
GUIDELINES ON A 
MEDICAL DEVICE 
VIGILANCE SYSTEM) 
been less fortunate is 
considered a 
reportable event. 
Adverse Event 
including Adverse 
Device Effects 
Complete AE eCRF 
page, which contains 
such information as 
date of AE, treatment 
of AE resolution, 
assessment of 
seriousness and 
relationship to the 
device.  
• 
In a timely manner (e.g. 
recommend within 10 
business days) after 
becoming aware of the 
information 
• 
Reporting required 
through end of study  
• 
Upon request of sponsor 
 
• 
Adverse Device Effects 
(or other key events of 
interest, e.g., Heart 
Failure): In a timely 
manner but not later 
than 30 business days 
after becoming aware of 
the information  
• 
Adverse Events: In a 
timely manner but 
recommend within 30 
business days after 
becoming aware of the 
information  
• 
Reporting required 
through end of study.  
• 
Upon request of sponsor 
Provide all relevant 
source documentation 
(de-identified/ 
pseudonymized) for 
reported event.  
 
19.5 
Device Deficiencies 
Device deficiencies will be documented and reported to BSC.  If possible, the device(s) 
under study should be returned to BSC for analysis. Instructions for returning the device(s) 
will be provided in site initiation visit slides. Device deficiencies should also be documented 
in the subject’s source records. 
Device deficiencies are not adverse events. However, an adverse event that results from a 
device deficiency, would be recorded as an adverse event on the appropriate eCRF. 
19.6 
Reporting to Regulatory Authorities / IRBs / ECs / REBs/ Investigators 
BSC is responsible for reporting adverse event information to all participating Principal 
Investigators, IRBs/ECs/REBs and regulatory authorities, as applicable.  
The Principal Investigator is responsible for informing the IRB/EC/REB, and regulatory 
authorities of UADEs/USADEs and SAEs as required by local/regional regulations. 

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20 Informed Consent 
Subject participation in this clinical study is voluntary.  Informed Consent is required from 
each subject or his/her legally authorized representative. NOTE: Hemostasis and closure can 
be needed in the setting of complications such as perforations or acute bleeding that are 
typically rare and sometimes emergent. In such circumstances consenting the patient before 
the procedure is not feasible and consent shall be obtained from the patient after the 
procedure but before any study data is collected.   
The Principal Investigator may enroll a subject without obtaining the informed consent of the 
subject or his/her legally authorized representative only when the following conditions are 
fulfilled. 
o The prospective subject fulfils the emergency conditions and is obviously in a 
life-threatening situation. 
o There is a fair possibility that the life-threatening risk to the prospective 
subject can be avoided if the device is used. 
o Anticipated risks are outweighed by the potential benefits of applying the 
device. 
o The legally authorized representative cannot be promptly reached and 
informed. 
In either situation, arrangements shall be made to inform the subject or legally authorized 
representative as soon as possible about a) all aspects of the clinical study and b) the subject's 
inclusion in the clinical study. ] 
The obtaining and documentation of Informed Consent must be in accordance with the 
principles of the Declaration of Helsinki, ISO 14155, any applicable national regulations, and 
local Ethics Committee and/or Regulatory authority, as applicable. The ICF must be accepted 
by BSC or its delegate (e.g. CRO), and approved by the site’s IRB/EC/REB, or central IRB, 
if applicable. 
Boston Scientific will provide a study-specific template of the ICF to investigators 
participating in this study. The ICF template may be modified to meet the requirements of the 
investigative site’s IRB/EC/REB.  Any modification requires acceptance from BSC prior to 
use of the form.  The ICF must be in a language understandable to the subject and if needed, 
BSC will assist the site in obtaining a written consent translation. Translated consent forms 
must also have IRB/EC/REB approval prior to their use.  Privacy language shall be included 
in the body of the form or as a separate form as applicable.   
The process of obtaining Informed Consent shall at a minimum include the following steps, 
as well as any other steps required by applicable laws, rules, regulations and guidelines: 
• be conducted by the Principal Investigator or designee authorized to conduct the process,  
• include a description of all aspects of the clinical study that are relevant to the subject’s 
decision to participate throughout the clinical study, 
• avoid any coercion of or undue influence of subjects to participate, 

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• not waive or appear to waive subject’s legal rights, 
• use native language that is non-technical and understandable to the subject or his/her 
legal representative, 
• provide ample time for the subject to consider participation and ask questions if 
necessary, 
• ensure important new information is provided to new and existing subjects throughout the 
clinical study.  
The ICF shall always be signed and personally dated by the subject or legal representative 
competent to sign the ICF under the applicable laws, rules, regulations and guidelines and by 
the investigator and/or an authorized designee responsible for conducting the informed 
consent process. If a legal representative signs, the subject shall be asked to provide informed 
consent for continued participation as soon as his/her medical condition allows. The original 
signed ICF will be retained by the site and a copy of the signed and dated document and any 
other written information must be given to the person signing the form.  
Failure to obtain subject consent will be reported by BSC to the applicable regulatory 
authority according to their requirements (e.g., FDA requirement is within 5 working days of 
learning of such an event). Any violations of the informed consent process must be reported 
as deviations to the sponsor and local regulatory authorities (e.g. IRB/EC/REB), as 
appropriate. 
If new information becomes available that can significantly affect a subject's future health 
and medical care, that information shall be provided to the affected subject(s) in written form 
via a revised ICF or, in some situations, enrolled subjects may be requested to sign and date 
an addendum to the ICF. In addition to new significant information during the course of a 
study, other situations may necessitate revision of the ICF, such as if there are amendments 
to the applicable laws, protocol, a change in Principal Investigator, administrative changes, or 
following annual review by the IRB/EC/REB. The new version of the ICF must be approved 
by the IRB/EC/REB. Acceptance by Boston Scientific is required if changes to the revised 
ICF are requested by the site’s IRB/EC/REB. The IRB/EC/REB will determine the subject 
population to be re-consented. 
21 Committees 
21.1 
Safety Monitoring Process 
The BSC personnel from the Medical Safety and Safety Trial Operation group review safety 
data as it is reported by the sites throughout the duration of the study. During scheduled 
monitoring activities, clinical research monitors further support this review through their 
review of source documents and other data information. The BSC Medical Safety and Safety 
Trial Operations team include health care providers with expertise and with the necessary 
therapeutic and subject matter expertise to evaluate and classify the events into the categories 
outlined above. 
 

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There will be no other committees (e.g., Clinical Events Committee, Data Monitoring 
Committee, Independent Data Reviewer, Morbidity and Mortality Events Committee, etc.) 
used in this study. 
22 Suspension or Termination 
22.1 Premature Termination of the Study 
Boston Scientific reserves the right to terminate the study at any stage but intends to exercise 
this right only for valid scientific or business reasons and reasons related to protection of 
subjects.  Investigators, associated IRBs/ECs/REBs, and regulatory authorities, as applicable, 
will be notified in writing in the event of study termination. 
22.1.1 Criteria for Premature Termination of the Study 
Possible reasons for premature study termination include, but are not limited to, the 
following: 
• Suspicion of an unacceptable risk, including serious health threat. In this case, the 
sponsor shall suspend the clinical investigation while the risk is assessed. The sponsor 
shall terminate the clinical investigation if an unacceptable risk which cannot be 
controlled is confirmed. 
• Instructions by the IRB/EC/REB or regulatory authorities to suspend or terminate the 
clinical investigation. 
• An enrollment rate far below expectation that prejudices the conclusion of the study.  
• A decision on the part of Boston Scientific to suspend or discontinue 
development/marketing of the device. 
22.2 Termination of Study Participation by the Investigator or Withdrawal of IRB/ 
EC/REB Approval 
Any investigator, or associated IRB/EC/REB or regulatory authority may discontinue 
participation in the study or withdraw approval of the study, respectively, with suitable 
written notice to Boston Scientific. Investigators, associated IRBs/ECs/REBs, and regulatory 
authorities, as applicable, will be notified in writing in the event of these occurrences. 
22.3 Requirements for Documentation and Subject Follow-up 
In the event of premature study termination a written statement as to why the premature 
termination has occurred will be provided to all participating sites by Boston Scientific. The 
IRB/EC/REB and regulatory authorities, as applicable, will be notified. Detailed information 
on how enrolled subjects will be managed thereafter will be provided.  
In the event an IRB/EC/REB terminates participation in the study, participating investigators, 
associated IRBs/ECs/REBs, and regulatory authorities, as applicable, will be notified in 

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writing. Detailed information on how enrolled subjects will be managed thereafter will be 
provided by Boston Scientific. 
In the event a Principal Investigator terminates participation in the study, study responsibility 
will be transferred to another investigator, if possible. In the event there are no opportunities 
to transfer Principal Investigator responsibility; detailed information on how enrolled 
subjects will be managed thereafter will be provided by Boston Scientific. 
The Principal Investigator or his/her designee must return all study-related documents and 
devices, if supplied by Boston Scientific, unless this action would jeopardize the rights, 
safety, or welfare of the subjects. 
22.4 Criteria for Suspending/Terminating a Study Site 
Boston Scientific reserves the right to stop the inclusion of subjects at a study site at any time 
after the study initiation visit if no subjects have been enrolled  for a period beyond 12 
months after site initiation, or if the site has multiple or severe protocol 
violations/noncompliance without justification and/or fails to follow remedial actions. 
In the event of termination of site participation, all devices and testing equipment, as 
applicable, will be returned to BSC unless this action would jeopardize the rights, safety or 
well-being of the subjects. The IRB/EC/REB and regulatory authorities, as applicable, will 
be notified. Study participants will be contacted, as applicable, and be informed of changes to 
study visit schedule. 
23 Study Registration and Results 
23.1 
Study Registration 
To comply with applicable laws and regulations, the study will be registered on a publicly 
accessible database. 
23.2 
Clinical Investigation Report 
Study results will be made available in accordance with the legal requirements and the 
recognized ethical principles, in accordance with the Boston Scientific Policy. A Clinical 
Investigation Report will be made available to all investigators, IRB/EC/REB and regulatory 
authorities, as applicable in accordance with the Boston Scientific Policy and local 
requirements.  As applicable an abbreviated Clinical Investigation Report will be made 
available on a publicly accessible database. 
23.3 
Publication Policy 
BSC requires disclosure of its involvement as a sponsor or financial supporter in any 
publication or presentation relating to a BSC study or its results. BSC may submit study 
results for publication (regardless of study outcome) following the conclusion or termination 
of the study. Boston Scientific adheres to the Contributorship Criteria set forth in the 
Uniform Requirements of the International Committee of Medical Journal Editors (ICMJE; 

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http://www.icmje.org). In order to ensure the public disclosure of study results in a timely 
manner, while maintaining an unbiased presentation of study outcomes, BSC personnel may 
assist authors and investigators in publication preparation provided the following guidelines 
are followed:  
• All authorship and contributorship requirements as described above must be followed. 
• BSC involvement in the publication preparation and the BSC Publication Policy should 
be discussed with the Coordinating Principal Investigator(s) and/or Executive/Steering 
Committee at the onset of the project. 
• The First and Senior authors are the primary drivers of decisions regarding publication 
content, review, approval, and submission.  
The data, analytic methods, and study materials for this clinical trial may be made available 
to other researchers in accordance with the Boston Scientific Data Sharing Policy 
(https://www.bostonscientific.com/).  
24 Reimbursement and Compensation for Subjects 
24.1 
Compensation for Subject’s Health Injury 
Boston Scientific will purchase an insurance policy to cover the cost of potential health 
injury for study subjects, if required by applicable law.  
 
25 Bibliography 
Uncategorized References 
1. 
Hayashi T. The study on stanch clips for the treatment by endoscopy. 
Gastroenterological Endoscopy. 1975;17(1):92-101. 
2. 
Lin H-J, Hsieh Y-H, Tseng G-Y, Perng C-L, Chang F-Y, Lee S-D. A prospective, 
randomized trial of endoscopic hemoclip versus heater probe thermocoagulation for peptic 
ulcer bleeding. The American journal of gastroenterology. 2002;97(9):2250-4. 
3. 
Shin EJ, Ko C-W, Magno P, Giday SA, Clarke JO, Buscaglia JM, et al. Comparative 
study of endoscopic clips: duration of attachment at the site of clip application. 
Gastrointestinal endoscopy. 2007;66(4):757-61. 
4. 
Peery AF, Crockett SD, Murphy CC, Lund JL, Dellon ES, Williams JL, et al. Burden 
and Cost of Gastrointestinal, Liver, and Pancreatic Diseases in the United States: Update 
2018. Gastroenterology. 2019;156(1):254-72.e11. Epub 2018/10/14. doi: 
10.1053/j.gastro.2018.08.063. PubMed PMID: 30315778; PubMed Central PMCID: 
PMCPMC6689327. 
5. 
Kim BSM, Li BT, Engel A, Samra JS, Clarke S, Norton ID, et al. Diagnosis of 
gastrointestinal bleeding: A practical guide for clinicians. World journal of gastrointestinal 
pathophysiology. 2014;5(4):467. 

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6. 
Gralnek IM, Dumonceau J-M, Kuipers EJ, Lanas A, Sanders DS, Kurien M, et al. 
Diagnosis and management of nonvariceal upper gastrointestinal hemorrhage: European 
Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2015;47(10):a1-a46. 
7. 
Rockey DC. Lower gastrointestinal bleeding. Gastroenterology. 2006;130(1):165-71. 
8. 
Binmoeller K, Thonke F, Soehendra N. Endoscopic hemoclip treatment for 
gastrointestinal bleeding. Endoscopy. 1993;25(02):167-70. 
9. 
Romagnuolo J. Endoscopic clips: past, present and future. Canadian Journal of 
Gastroenterology. 2009;23(3):158-60. 
10. 
Carr-Locke DL. The History of Clips in Endoscopy 2013 [cited 2021 12/13/2021]. 
Available from: https://www.cookmedical.com/endoscopy/the-history-of-clips-in-
endoscopy/. 
11. 
Cipolletta L, Bianco MA, Marmo R, Rotondano G, Piscopo R, Vingiani AM, et al. 
Endoclips versus heater probe in preventing early recurrent bleeding from peptic ulcer: a 
prospective and randomized trial. Gastrointestinal endoscopy. 2001;53(2):147-51. 
12. 
Huang S-P, Wang H-P, Lee Y-C, Lin C-C, Yang C-S, Wu M-S, et al. Endoscopic 
hemoclip placement and epinephrine injection for Mallory-Weiss syndrome with active 
bleeding. Gastrointestinal endoscopy. 2002;55(7):842-6. 
13. 
Chung I-K, Kim E-J, Lee M-S, Kim H-S, Park S-H, Lee M-H, et al. Bleeding 
Dieulafoy's lesions and the choice of endoscopic method: comparing the hemostatic efficacy 
of mechanical and injection methods. Gastrointestinal endoscopy. 2000;52(6):721-4. 
14. 
Shioji K, Suzuki Y, Kobayashi M, Nakamura A, Azumaya M, Takeuchi M, et al. 
Prophylactic clip application does not decrease delayed bleeding after colonoscopic 
polypectomy. Gastrointestinal endoscopy. 2003;57(6):691-4. 
15. 
Cordon JP, Torres CF, García AB, Rodriguez FG, de Parga JMS. Endoscopic 
management of esophageal varices. World journal of gastrointestinal endoscopy. 
2012;4(7):312. 
16. 
Yol S, Belviranli M, Kartal A. Endoscopic clipping versus band ligation in the 
management of bleeding esophageal varices. Surgical Endoscopy And Other Interventional 
Techniques. 2003;17(1):38-42. 
17. 
Ahmad N, Ginsberg GG. Variceal ligation with bands and clips. Gastrointest Endosc 
Clin N Am. 1999;9(2):207-30. Epub 1999/05/20. PubMed PMID: 10333439. 
18. 
Rustagi T, McCarty TR. Endoscopic management of diverticular bleeding. 
Gastroenterol Res Pract. 2014;2014:353508. Epub 2014/12/31. doi: 10.1155/2014/353508. 
PubMed PMID: 25548554; PubMed Central PMCID: PMCPMC4274660. 
19. 
Nishiyama N, Mori H, Kobara H, Rafiq K, Fujihara S, Kobayashi M, et al. Efficacy 
and safety of over-the-scope clip: including complications after endoscopic submucosal 
dissection. World journal of gastroenterology: WJG. 2013;19(18):2752. 
20. 
Raymer GS, Sadana A, Campbell DB, Rowe WA. Endoscopic clip application as an 
adjunct to closure of mature esophageal perforation with fistulae. Clinical Gastroenterology 
and Hepatology. 2003;1(1):44-50. 

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21. 
Wewalka F, Clodi P, Haidinger D. Endoscopic clipping of esophageal perforation 
after pneumatic dilation for achalasia. Endoscopy. 1995;27(08):608-11. 
22. 
Tsunada S, Ogata S, Ohyama T, Ootani H, Oda K, Kikkawa A, et al. Endoscopic 
closure of perforations caused by EMR in the stomach by application of metallic clips. 
Gastrointestinal endoscopy. 2003;57(7):948-51. 
23. 
Mana F, De Vogelaere K, Urban D. latrogenic perforation of the colon during 
diagnostic colonoscopy: endoscopic treatment with clips. Gastrointestinal endoscopy. 
2001;54(2):258-9. 
24. 
Hirdes MM, Monkelbaan JF, Haringman JJ, Van Oijen MG, Siersema PD, Pullens 
PH, et al. Endoscopic clip-assisted feeding tube placement reduces repeat endoscopy rate: 
results from a randomized controlled trial. Official journal of the American College of 
Gastroenterology| ACG. 2012;107(8):1220-7. 
25. 
Kaltenbach T, Watson R, Shah J, Friedland S, Sato T, Shergill A, et al. Colonoscopy 
with clipping is useful in the diagnosis and treatment of diverticular bleeding. Clinical 
Gastroenterology and Hepatology. 2012;10(2):131-7. 
26. 
Yen EF, Ladabaum U, Muthusamy VR, Cello JP, McQuaid KR, Shah JN. 
Colonoscopic treatment of acute diverticular hemorrhage using endoclips. Digestive diseases 
and sciences. 2008;53(9):2480-5. 
27. 
Setoyama T, Ishii N, Fujita Y. Enodoscopic band ligation (EBL) is superior to 
endoscopic clipping for the treatment of colonic diverticular hemorrhage. Surgical 
endoscopy. 2011;25(11):3574-8. 
28. 
Boo S-J, Byeon J-S, Park SY, Rew JS, Lee DM, Shin SJ, et al. Clipping for the 
prevention of immediate bleeding after polypectomy of pedunculated polyps: a pilot study. 
Clinical endoscopy. 2012;45(1):84. 
29. 
Luigiano C, Ferrara F, Ghersi S, Fabbri C, Cennamo V, Landi P, et al. Endoclip-
assisted resection of large pedunculated colorectal polyps: technical aspects and outcome. 
Digestive diseases and sciences. 2010;55(6):1726-31. 
30. 
Kouklakis G, Mpoumponaris A, Gatopoulou A, Efraimidou E, Manolas K, 
Lirantzopoulos N. Endoscopic resection of large pedunculated colonic polyps and risk of 
postpolypectomy bleeding with adrenaline injection versus endoloop and hemoclip: a 
prospective, randomized study. Surgical endoscopy. 2009;23(12):2732-7. 
31. 
Magdeburg R, Collet P, Post S, Kaehler G. Endoclipping of iatrogenic colonic 
perforation to avoid surgery. Surgical endoscopy. 2008;22(6):1500-4. 
32. 
Cho SB, Lee WS, Joo YE, Kim HR, Park SW, Park CH, et al. Therapeutic options for 
iatrogenic colon perforation: feasibility of endoscopic clip closure and predictors of the need 
for early surgery. Surgical endoscopy. 2012;26(2):473-9. 
33. 
Hokama A, Kishimoto K, Kinjo F, Fujita J. Endoscopic clipping in the lower 
gastrointestinal tract. World journal of gastrointestinal endoscopy. 2009;1(1):7. 

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34. 
Fujishiro M, Iguchi M, Kakushima N, Kato M, Sakata Y, Hoteya S, et al. Guidelines 
for endoscopic management of non-variceal upper gastrointestinal bleeding. Dig Endosc. 
2016;28(4):363-78. Epub 2016/02/24. doi: 10.1111/den.12639. PubMed PMID: 26900095. 
35.      Cotton PB, Lehman G, Vennes J, et al. Endoscopic sphincterotomy 
complications and their management: an attempt at consensus. Gastrointest 
Endosc 1991;37:383-93. 
36.       Meier B, Wannhoff A, Denzer U, et al. Gut Epub doi:10.1136/gutjnl-2021-325300 
37. 
Odom, S. (2022, May). Overview of gastrointestinal tract perforation. UpToDate. 
 
26 Abbreviations and Definitions  
26.1 
Abbreviations 
Abbreviations are shown in Table 26.1-1.   
Table 26.1-1: Abbreviations 
Abbreviation/Acronym 
Term 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
BSC 
Boston Scientific Corporation 
CA 
Competent Authority 
CRF 
Case Report Form 
CRO  
Contract Research Organization 
EC 
Ethics Committee 
ERCP 
Endoscopic Retrograde Cholangio-Pancreatography 
EDC 
Electronic Data Capture 
FDA 
U.S. Food and Drug Administration 
GCP 
Good Clinical Practice 
GI 
Gastrointestinal 
HCP 
Health Care Personnel 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IRB 
Institutional Review Board 
ITT 
Intent-to-Treat 
REB 
Research Ethics Board 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
UADE 
Unanticipated Adverse Device Effect 
USADE 
Unanticipated Serious Adverse Device Effect 
 

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26.2 
Definitions 
Definitions are shown in Table 26.2-1. 
Table 26.2-1: Definitions 
Term 
Definition 
Source data 
Ref: ISO 14155 
All information in original records, certified copies of original records of 
clinical findings, observations, or other activities in a clinical investigation, 
necessary for the reconstruction and evaluation of the clinical investigation 
Note 1 to entry: This includes source data initially recorded in an electronic 
format. 
Source document 
Ref: ISO 14155 
Original or certified copy of printed, optical or electronic document containing 
source data. 
Vulnerable Subject 
Ref: ISO 14155 
Individuals who are unable to fully understand all aspects of the investigation 
that are relevant to the decision to participate, or who could be manipulated or 
unduly influenced as a result of a compromised position, expectation of benefits 
or fear of retaliatory response