Prospective, Multi-center, Randomized Controlled Study Comparing Endoscopic Clearance of Non-Complex Biliary Stones Using Fluoroscopy/Radiation-Free Direct Solitary Cholangioscopy (DSC) to Standard of Care Endoscopic Retrograde Cholangiography (ERC)
Phase: NA
Conditions: Biliary Stones
Sponsor: Boston Scientific Corporation

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT  
Confidential 
                        Template 90702637 Rev/Ver AH 
                                                                                                                               Page 1 of 51 
  
 
 
Prospective, Multi-center, Randomized Controlled Study Comparing 
Endoscopic Clearance of Non-Complex Biliary Stones Using 
Fluoroscopy/Radiation-Free Direct Solitary Cholangioscopy (DSC) to 
Standard of Care Endoscopic Retrograde Cholangiography (ERC) 
 
 
Non-Complex Biliary Stones DSC vs ERC RCT  
CLINICAL INVESTIGATION PLAN 
 
 
E7131 
 
 
Sponsored By 
Boston Scientific Corporation 
300 Boston Scientific Way 
Marlborough, MA 01752-1234 
USA 
 
Boston Scientific International SA,  
Le Val Saint-Quentin  
2 Rue René Caudron 
78960 Voisins le  
Bretonneux, France 
  
Boston Scientific India Private Ltd.  
Building No. 5, Tower A 8th Floor 
Cyber Terraces 
DLF Cyber City-Phase 3 
Gurgaon 12002, India 
 
 
 
 
 
 
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. 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT  
Confidential 
                        Template 90702637 Rev/Ver AH 
                                                                                                                               Page 2 of 51 
  
Contact Information 
Role 
Contact  
Clinical Contact 
Pooja G. Goswamy 
Clinical Project Manager 
Boston Scientific Corporation 
300 Boston Scientific Way 
Marlborough, MA 01752-1234 USA 
Phone: +1 (508) 683-4335 
Email: Pooja.Goswamy@bsci.com 
 
Raquel Mazariegos 
Clinical Project Specialist 
Boston Scientific Corporation 
300 Boston Scientific Way 
Marlborough, MA 01752-1234 USA 
Phone: +1 (508) 683-4174 
e-mail: Raquel.Mazariegos@bsci.com 
Principal Investigator 
Subhas Banerjee, MD 
Stanford University Medical Center 
300 Pasteur Drive, H0262A MC: 5244 
Stanford, CA 94305 
USA 
 
 
 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT  
Confidential 
                        Template 90702637 Rev/Ver AH 
                                                                                                                               Page 3 of 51 
  
 
Original Release: November 15, 2017 
Current Version: June 12, 2018 
Protocol Synopsis 
 
E7131 – Non-Complex Biliary Stones DSC vs ERC RCT  
Study Objective To prospectively compare non-complex biliary stone clearance using 
fluoroscopy/radiation-free direct solitary cholangioscopy (DSC) 
utilizing the SpyGlass™ system with non-complex biliary stone 
clearance using standard endoscopic retrograde cholangiography 
(ERC).  
Indication(s) for 
Use  
• SpyGlass™ DS Digital Controller is intended to provide 
illumination and receive, process, and output images from the 
SpyScope™ DS Access and Delivery Catheter for diagnostic and 
therapeutic applications during endoscopic procedures in the 
pancreatico-biliary system including the hepatic ducts. 
• SpyScope™ DS Access and Delivery Catheter is intended to 
provide direct visualization and to guide both optical and 
accessory devices for diagnostic and therapeutic applications 
during endoscopic procedures in the pancreatico-biliary system 
including the hepatic ducts. 
• The following devices will be available upon commercialization:  
o SpyScope™ DS II Access and Delivery Catheter is 
intended to provide direct visualization and to guide both 
optical and accessory devices for diagnostic and 
therapeutic applications during endoscopic procedures in 
the pancreatico-biliary system including the hepatic ducts. 
o SpyGlass™ Retrieval Basket is indicated for the 
endoscopic removal of stones, stone fragments, or foreign 
bodies in the pancreaticobiliary system. 
Device 
SpyGlass™ Digital System 
Study Design 
• Prospective 
• Consecutive cases 
• Multi-center 
• Randomized 1:1 ratio: 
o Group A (ERC arm): Clearance of bile duct stones using 
standard-of-practice ERCP techniques 
o Group B (DSC arm): Clearance of bile duct stones using DSC 
techniques 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT  
Confidential 
                        Template 90702637 Rev/Ver AH 
                                                                                                                               Page 4 of 51 
  
E7131 – Non-Complex Biliary Stones DSC vs ERC RCT  
o Block-randomization by site  
• Non-inferiority hypothesis 
• Validation of stone clearance by ERC in DSC arm and by DSC in 
ERC arm. 
Number of 
Subjects 
• 250 subjects  
• An additional 5 Roll-in cases. Each participating endoscopist at 
each of the participating centers must perform 5 Roll-in cases. 
These roll-in cases will not count towards the enrollment ceiling 
of 250 cases. 
• Procedures to be conducted only by the Principal Investigator. 
Sub-Investigators will be authorized to do study procedures only 
on an exception basis.  Such exception may be granted by the 
Sponsor in consultation with the Principal Investigator of the site 
and Lead Principal Investigator to the study.  
Number of Sites  Up to 15 global sites 
Primary 
Endpoint 
Complete stone clearance by extraction of bile duct stones from the 
common bile duct (CBD) into duodenum as determined by 
fluoroscopy free cholangioscopy in the DSC arm and by 
cholangiography in the ERC arm. 
Secondary 
Endpoints  
1. Evaluation of all serious adverse events (SAEs) including all 
deaths (related and unrelated), severity, onset, time to resolution 
related to the DSC devices and/or procedure and/or the ERC 
procedure through 30 days post procedure. 
2. Radiation exposure to the patient (total fluoroscopy time, total 
radiation dose, Dose Area Product (DAP), effective dose), from 
duodenoscope in to completion of stone clearance, not 
including the validation DSC procedure in ERC arm and ERC 
procedure in DSC arm. 
3. Duration of procedure defined as time from duodenoscope in to 
completion of stone clearance, not including the validation DSC 
procedure in ERC arm and ERC procedure in DSC arm.  
Follow-up 
Schedule 
Telephone follow-up during the following post-procedure intervals: 
• 24 hours 
• 7 days 
• 30 days 
Study duration 
Approximately 2 years 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT  
Confidential 
                        Template 90702637 Rev/Ver AH 
                                                                                                                               Page 5 of 51 
  
E7131 – Non-Complex Biliary Stones DSC vs ERC RCT  
Inclusion 
Criteria 
1. 18 years or older 
2. Abdominal pain consistent with choledocholithiasis (procedure 
possible within 72 hours of onset of symptoms and imaging 
suggesting choledocholithiasis, contingent on persistent 
abdominal pain) 
3. Abnormal LFTs 
4. Non-complex biliary stone disease, defined as 5 or fewer stones 
in the common bile or common hepatic duct with largest stone no 
larger than 10 mm in size.  If stones not seen on imaging (US, 
CT) the bile duct diameter should be ≤12 mm* 
* Given the poor sensitivity (approximately 20%) for biliary 
stones of CT and US, the diameter of the dilated CBD is used as 
a surrogate for largest stone diameter 
5. Availability of non-invasive imaging to determine the diameter 
of the bile duct and number and size of bile duct stones if visible 
on imaging 
a. If probability of stones is high per investigator assessment 
based on ASGE criteria, any standard of practice imaging 
modality (eg. abdominal US) is acceptable. 
b. If the probability of stones is either intermediate or low 
per investigator assessment based on ASGE criteria, 
MRCP or EUS imaging is required to confirm presence of 
stones. 
6. Willing and able to comply with the study procedures and 
provide written informed consent to participate in the study 
Exclusion 
Criteria 
1. Potentially vulnerable subjects, including but not limited to 
pregnant women and subjects in whom an endoscopic procedure 
is contraindicated 
2. Location of the stones in intrahepatic ducts, cystic duct or 
proximal to strictures 
3. Bile duct stricture noted distal to stone on MRCP, which would 
make extraction without lithotripsy impossible  
4. Ongoing cholangitis at time of randomization, manifested by 
fever with tachycardia and hypotension or evidence of pus at the 
ampulla 
5. Patients with prior biliary sphincterotomy  

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT  
Confidential 
                        Template 90702637 Rev/Ver AH 
                                                                                                                               Page 6 of 51 
  
E7131 – Non-Complex Biliary Stones DSC vs ERC RCT  
6. Patients with Primary Sclerosing Cholangitis (PSC) 
7. Acute pancreatitis, defined as abdominal pain and serum 
concentration of pancreatic enzymes [lipase (required), amylase 
(optional)] three or more times the upper limit of normal 
8. Surgically altered gastro-duodenal luminal anatomy other than 
prior Billroth I reconstruction, as these would be anticipated to 
lead to more complicated procedures  
9. Coagulopathy or ongoing need for anti-coagulation  
Statistics 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• Preliminary DSC-guided stone clearance rate was established in a 
Pilot study1 and found to be comparable to that of ERC-guided 
stone clearance. 
• Eight relevant peer-reviewed publications2-9 reporting on ERC-
guided biliary stone clearance rates, representing 2721 patients 
were analyzed. A meta-analysis was conducted of the biliary stone 
clearance rates, yielding a point estimate of 90% with a 95% CI of 
[85%, 94%] (see Forest plot below). 
• Based on the two observations provided above, we hypothesize 
that the DSC-guided stone clearance rate is non-inferior to that of 
the ERC-guided stone clearance rate.  We assume a DSC-guided 
and ERC-guided stone clearance rate of 90% and use a 10% non-
inferiority margin for the sample size calculation provided below.  
The 10% non-inferiority margin is based on the fact that in the 
references used for the meta-analysis2-9 stone clearance rates above 
80% eliminate the lowest performing publications.   
 
Test Method:  
An exact test will be used to test the one-sided hypothesis of non-
inferiority of the DSC-guided vs ERC-guided stone clearance rates.  
 
Sample Size:  
To detect non-inferiority of the clearance rate in DSC arm compared 
to the ERC arm with 80% power and one-sided alpha=0.05, a sample 
of 250 total is needed.  
 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT  
Confidential 
                        Template 90702637 Rev/Ver AH 
                                                                                                                               Page 7 of 51 
  
E7131 – Non-Complex Biliary Stones DSC vs ERC RCT  
 
 
 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT  
Confidential 
                        Template 90702637 Rev/Ver AH 
                                                                                                                               Page 8 of 51 
  
TABLE OF CONTENTS 
1. 
INTRODUCTION ................................................................................................................12 
2. 
DEVICE DESCRIPTION ......................................................................................................14 
2.1. SpyScope™ DS Access and Delivery Catheter ...................................................14 
2.2. SpyGlass™ DS Digital Controller .......................................................................14 
2.3. SpyScope™ DS II Access and Delivery Catheter ...............................................14 
2.4. SpyGlass™ Retrieval Basket ................................................................................15 
2.5. Device Labeling .....................................................................................................15 
3. 
STUDY OBJECTIVES .........................................................................................................15 
4. 
STUDY ENDPOINTS ...........................................................................................................15 
4.1. Primary Endpoint .................................................................................................15 
4.2. Secondary Endpoint ..............................................................................................15 
5. 
STUDY DESIGN .................................................................................................................16 
5.1. Scale and Duration ................................................................................................16 
5.2. Treatment Assignment..........................................................................................17 
5.3. Justification for the Study Design ........................................................................17 
6. 
SUBJECT SELECTION ........................................................................................................17 
6.1. Study Population and Eligibility ..........................................................................17 
6.2. Inclusion Criteria ..................................................................................................17 
6.3. Exclusion Criteria .................................................................................................18 
7. 
SUBJECT ACCOUNTABILITY .............................................................................................19 
7.1. Point of Enrollment ...............................................................................................19 
7.2. Withdrawal ............................................................................................................19 
8. 
STUDY METHODS .............................................................................................................19 
8.1. Data Collection ......................................................................................................19 
8.2. Study Candidate Screening ..................................................................................21 
8.3. Informed Consent .................................................................................................21 
8.4. Baseline ..................................................................................................................21 
8.5. Randomization ......................................................................................................21 
8.6. Procedure ...............................................................................................................21 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT  
Confidential 
                        Template 90702637 Rev/Ver AH 
                                                                                                                               Page 9 of 51 
  
8.7. 24-Hour, 7-Day, and 30-Day Follow-up ..............................................................26 
8.8. Study Completion ..................................................................................................26 
9. 
STATISTICAL CONSIDERATIONS ......................................................................................26 
9.1. Primary Endpoint .................................................................................................26 
9.1.1. 
Hypotheses ................................................................................................26 
9.1.2. 
Sample Size ..............................................................................................27 
9.1.3. 
Statistical Methods ....................................................................................27 
9.2. Analysis Populations .............................................................................................27 
9.2.1. 
Enrolled Cohort ........................................................................................27 
9.2.2. 
Intent-to-Treat Cohort (ITT) .....................................................................27 
9.2.3. 
Per-Protocol Cohort (PP) ..........................................................................27 
9.3. Data Analyses ........................................................................................................27 
9.3.1. 
Baseline .....................................................................................................27 
9.3.2. 
Procedure Data ..........................................................................................28 
9.3.3. 
Post-Procedure Data .................................................................................28 
9.3.4. 
Interim Analyses .......................................................................................28 
9.3.5. 
Subgroup Analyses ...................................................................................28 
9.3.6. 
Justification of Pooling .............................................................................28 
9.3.7. 
Multivariable Analyses .............................................................................28 
9.3.8. 
Learning Curve Analysis ..........................................................................28 
9.3.9. 
Changes to Planned Analyses ...................................................................28 
10. DATA MANAGEMENT .......................................................................................................29 
10.1. Data Collection, Processing, and Review ............................................................29 
10.2. Data Retention .......................................................................................................29 
11. AMENDMENTS ..................................................................................................................30 
12. DEVIATIONS .....................................................................................................................30 
13. DEVICE/EQUIPMENT ACCOUNTABILITY .........................................................................30 
14. COMPLIANCE ....................................................................................................................31 
14.1. Statement of Compliance ......................................................................................31 
14.2. Investigator Responsibilities ................................................................................31 
14.2.1. Delegation of Responsibility ....................................................................33 
14.3. Institutional Review Board/ Ethics Committee ..................................................33 
14.4. Sponsor Responsibilities .......................................................................................33 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT  
Confidential 
                        Template 90702637 Rev/Ver AH 
                                                                                                                               Page 10 of 51 
  
14.4.1. Role of Boston Scientific Representatives ...............................................34 
14.5. Insurance ................................................................................................................34 
15. MONITORING ....................................................................................................................35 
16. POTENTIAL RISKS AND BENEFITS ...................................................................................35 
16.1. Anticipated Adverse Device Effects .....................................................................35 
16.2. Risk Minimization Actions ...................................................................................36 
16.3. Anticipated Benefits ..............................................................................................37 
16.4. Risk to Benefit Rationale ......................................................................................37 
17. SAFETY REPORTING .........................................................................................................37 
17.1. Reportable Events by investigational site to Boston Scientific .........................37 
17.2. Definitions and Classification ..............................................................................38 
17.3. Relationship to Study Device(s) ...........................................................................39 
17.4. Investigator Reporting Requirements .................................................................41 
17.5. Boston Scientific Device Deficiencies ...................................................................42 
17.6. Reporting to Regulatory Authorities / IRBs / ECs / Investigators ...................42 
18. INFORMED CONSENT........................................................................................................43 
19. SUSPENSION OR TERMINATION .......................................................................................44 
19.1 Premature Termination of the Study ..................................................................44 
19.1.1 
Criteria for Premature Termination of the Study ......................................44 
19.2 Termination of Study Participation by the Investigator or Withdrawal of 
IRB/ EC Approval .................................................................................................44 
19.3 Requirements for Documentation and Subject Follow-up ................................44 
19.4 Criteria for Suspending/Terminating a Study Site ............................................45 
20. PUBLICATION POLICY ......................................................................................................45 
21. BIBLIOGRAPHY .................................................................................................................46 
22. ABBREVIATIONS AND DEFINITIONS .................................................................................48 
22.1. Abbreviations ........................................................................................................48 
22.2. Definitions ..............................................................................................................49 
 
 
 
 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT  
Confidential 
                        Template 90702637 Rev/Ver AH 
                                                                                                                               Page 11 of 51 
  
2.1 Table of Figures 
Figure 5.1-1: Non-Complex Biliary Stone DSC vs ERC RCT Study Design ........................ 17 
 
2.2 Table of Tables 
Table 8.1-1: Data Collection Schedule ................................................................................... 19 
Table 16.2-1: Potential Risks Rates of Occurrence ................................................................ 36 
SpyScope™ DS Access and Delivery Catheter 
Table 16.2-2: Potential Risks Rates of Occurrence ................................................................ 36 
SpyGlass™ Retrieval Basket  
Table 17.2-1: Safety Definitions ............................................................................................. 38 
Table 17.3-1: Criteria for Assessing Relationship of Study Device, Including Accessory 
Device(s) and/or Procedure(s) to Adverse Event ................................................ 39 
Table 17.4-1: Investigator Reporting Requirements ............................................................... 41 
Table 22.1-1: Abbreviations ................................................................................................... 48 
Table 22.2-1: Definitions ........................................................................................................ 49 
Table 22.3-1: Predictors of Choledocholithiasis ..................................................................... 50 
 
 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT  
Confidential 
                        Template 90702637 Rev/Ver AH 
                                                                                                                               Page 12 of 51 
  
1. Introduction 
Prior to the advent of flexible endoscopy, imaging of the gastrointestinal lumen was 
performed predominantly using barium contrast studies.  Over the last few decades, contrast 
studies for the upper and lower GI tract (barium swallow/barium meal) have largely been 
replaced by upper gastrointestinal endoscopy and colonoscopy.  Similarly, balloon assisted 
enteroscopy and capsule endoscopy are replacing small bowel follow-through contrast 
studies for small bowel evaluation.  This shift from radiological to endoscopic evaluation was 
driven by the many advantages of endoscopy, including the ability to provide more accurate 
real-time imaging with fewer false negative and false positive results, the ability to obtain 
biopsies to confirm visual impressions, and finally, the ability to deliver therapeutic 
interventions in the same procedure. 
 
The bile and pancreatic ducts remain the “final frontiers” in the GI lumen where endoscopy 
is not yet the primary modality for diagnosis and therapy.  Here, a hybrid 
endoscopic/radiological procedure, endoscopic retrograde cholangio-pancreatography 
(ERCP), remains the predominant diagnostic and therapeutic modality.  Given the inevitable 
evolution of technology, it is possible in the future, that as with other GI luminal organs, 
direct endoscopic evaluation of the bile duct with cholangioscopy may replace 
cholangiography for the evaluation and management of at least some kinds of biliary disease.  
Non-complex biliary stone disease represents a potential such disease process, suitable for 
study.  Development of a fluoroscopy-free cholangioscopy based approach to bile duct 
disease is desirable for several reasons that are discussed below.   
 
From the viewpoint of endoscopy unit efficiency and safety, the requirement for fluoroscopy 
during ERCP creates several issues.  A separate fluoroscopy room is necessary within the 
endoscopy unit to perform ERCP, which requires additional capital investment.  The 
fluoroscopy room is typically busy and is often a bottleneck at high volume ERCP centers. A 
full schedule in the fluoroscopy room will result in delays for additional patients needing 
ERCP, even if other endoscopy rooms have availability, thereby impacting endoscopy unit 
efficiency and the timely delivery of patient care.  Additionally, low volume ERCP centers 
often do not have a dedicated fluoroscopy room within the endoscopy unit and the 
endoscopist has to await availability of an open room within the Radiology Department.   
 
If fluoroscopy-free cholangioscopy based clearance of uncomplicated common bile duct 
(CBD) stones becomes a safe and broadly accepted methodology, then one might envision 
that non-complex CBD stone removal might be performed in non-fluoroscopy endoscopy 
rooms.  This would alleviate the scheduling delays inherent in requiring a specialized 
fluoroscopy room for the procedures.  Additionally, in the future, one might envisage this 
procedure becoming possible in bedside settings in the Emergency Department, for patients 
presenting with symptomatic choledocholithiasis.  A rapid procedure performed in the 
Emergency Department would accelerate the delivery of therapeutic care to the patient, while 
avoiding the need for admission, thereby resulting in cost savings.  Similarly, bedside 
cholangioscopy based procedures performed in Intensive Care Unit settings would avoid the 
need for transfer of gravely ill patients to the endoscopy unit, thereby enhancing patient 
safety. 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT  
Confidential 
                        Template 90702637 Rev/Ver AH 
                                                                                                                               Page 13 of 51 
  
 
An additional concern with ERCP is that patients and endoscopy room personnel are exposed 
to ionizing radiation, which some consider to carry deleterious health consequences. The U.S 
per capita annual effective radiation dose from radiological procedures has increased six-fold 
over the last three decades and it is estimated that up to 2% of all cancers in the U.S. today 
may be attributable to medical radiation.10 Therefore, in recent years, there has been growing 
interest in monitoring and minimizing radiation exposure to patients. The World 
Gastroenterology Organization, the American Society for Gastrointestinal Endoscopy, and 
the International Atomic Energy Agency together developed guidelines in 2009 for 
minimizing radiation exposure to patients and endoscopy room staff during endoscopy.12  
The U.S. Food and Drug Administration has published a White Paper entitled ‘Initiative to 
Reduce Unnecessary Radiation Exposure From Medical Imaging’.11  The European Society 
of Gastrointestinal Endoscopy has also published guidelines for radiation protection in 
digestive endoscopy.13  Finally, the Stanford Endoscopy Research Group has done 
pioneering work in the field of minimizing patient radiation exposure during ERCP.14,15,16  
However, additional novel methods to further reduce or even eliminate radiation exposure 
are needed. 
 
Radiation-free cholangioscopy based biliary procedures offer one such opportunity.  
Although previously predominantly utilized as a complementary technique to ERCP, digital 
cholangioscopy has now evolved sufficiently that it may finally offer a viable, robust, and 
purely endoscopic alternative to ERCP, allowing liberation from the fluoroscopy room and 
from associated radiation exposure. The platform is small and readily deployable in non-
fluoroscopy rooms which are typically smaller.   
 
In light of the current interests in minimizing patient radiation exposure during ERCP, 
eventually lowering healthcare costs and maximizing endoscopy room efficiency, we 
hypothesize that the Spyglass cholangioscopy system may be able to provide a radiation-free 
alternative to ERCP in patients with non-complex choledocholithiasis.  We propose that in 
patients with non-complex choledocholithiasis who have undergone prior non-invasive 
imaging (US/MRCP/CT) that clearly defines the diameter of the bile duct and underlying 
pathology, the objectives of standard-of-care ERCP may be achievable with cholangioscopy 
alone, without the need for fluoroscopy.   
 
Radiation-free biliary procedures are already sometimes performed in pregnant women with 
choledocholithiasis or ICU patients who cannot travel, utilizing endoscopic ultrasound (EUS) 
to provide information regarding bile duct diameter and the number of stones present in the 
bile duct.  A cholangioscopy based approach offers advantages over the EUS guided 
approach, including ensuring that the guidewire has been advanced into the bile duct and not 
into the cystic duct, allowing measurement of the distance from the ampulla to the bile duct 
bifurcation to guide subsequent balloon sweeps, and allowing direct visual confirmation of 
clearance of all stones from the bile duct.  We wish to determine if Spyglass cholangioscopy 
can reliably facilitate radiation-free stone removal, thereby avoiding the costs of an 
additional EUS procedure preceding stone extraction.   
 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT  
Confidential 
                        Template 90702637 Rev/Ver AH 
                                                                                                                               Page 14 of 51 
  
Proof of concept was demonstrated in two single-arm, consecutive series reflecting 
experience in 31 patients at Stanford University Medical Center1 and in 50 patients at King 
Chulalongkorn Memorial Hospital in Bangkok.14  Fluoroscopy free CBD clearance of 
uncomplicated (CBD) stones <15mm in diameter was achieved in 93% and 90% of patients 
respectively in these two series. Post procedure complications reported in the 81 patients 
combined include pancreatitis in 4 patients, bleeding in 3 patients, and cholangitis in 1 
patient. These series support the feasibility and safety for radiation-free cholangioscopic 
based management of uncomplicated CBD stones with success and complication rates 
comparable to those of standard ERCP. The present study aims to expand that concept to a 
multi-center, multi-national study, comparing fluoroscopy-free endoscopic and 
cholangioscopic stone clearance to ERCP-guided stone clearance in symptomatic patients 
with non-complex bile duct stones.  
2. Device Description 
This study will be conducted using commercially available devices.  All devices will be used 
in accordance with the appropriate Directions for Use (DFU). 
2.1. SpyScope™ DS Access and Delivery Catheter 
The SpyScope™ DS Access and Delivery Catheter (SpyScope™ DS Catheter) is a 
sterile, single-use endoscope that enables access and delivery of accessories to 
targeted pancreatico-biliary anatomy and displays live video when connected to 
a SpyGlass DS Digital Controller. 
2.2. SpyGlass™ DS Digital Controller  
The SpyGlass™ DS Digital Controller is an electronic device that: receives video signals 
from a SpyScope DS Catheter, processes the video signals and outputs video images to a 
video monitor. The controller also generates and controls the light transmitted to the tip of 
the SpyScope DS Catheter to illuminate the area of interest within the anatomy. Buttons on 
the controller’s front panel enable you to control the brightness level of the light. 
To use the controller, connect it to a video monitor with a video cable and then connect a 
SpyScope DS Catheter to the controller. The controller provides direct visualization of the 
pancreatico-biliary duct anatomy and enables exploratory and endotherapy procedures. 
 
The following devices will be available for use upon commercialization. 
2.3. SpyScope™ DS II Access and Delivery Catheter 
The SpyScope™ DS II Access and Delivery Catheter is intended to provide direct 
visualization and to guide both optical and accessory devices for diagnostic and therapeutic 
applications during endoscopic procedures in the pancreatico-biliary system including the 
hepatic ducts. 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT  
Confidential 
                        Template 90702637 Rev/Ver AH 
                                                                                                                               Page 15 of 51 
  
2.4. SpyGlass™ Retrieval Basket  
The SpyGlass™ Retrieval Basket is indicated for the endoscopic removal of stones, stone 
fragments, or foreign bodies in the pancreaticobiliary system. 
2.5. Device Labeling 
A copy of the DFU for each product will be included in each device package. The study 
devices are labeled on the outer packaging of each device. The SpyScope™ Access and 
Delivery Catheter, SpyScope™ DS II Access and Delivery Catheter, SpyGlass™ Retrieval 
Basket, and SpyGlass™ DS Digital Controller labels contain the following information:  
• Device name 
• Device number 
• SI units 
• Graphical description 
• Device diameter, length, channel inside diameter 
• Lot number 
• Expiration (use before) date or date of manufacture 
3. Study Objectives 
The objective of this study is to prospectively compare non-complex biliary stone clearance 
using fluoroscopy/radiation-free direct solitary cholangioscopy (DSC) utilizing the 
SpyGlass™ system with non-complex biliary stone clearance using standard endoscopic 
retrograde cholangioscopy (ERC).  
4. Study Endpoints 
4.1. Primary Endpoint 
The primary endpoint is complete stone clearance by extraction of bile duct stones from the 
common bile duct (CBD) into duodenum by fluoroscopy free cholangioscopy in the DSC 
arm and by cholangiography in the ERC arm. 
4.2. Secondary Endpoint 
The following will be recorded as secondary outcomes during baseline and follow-up 
procedures: 
1. Evaluation of all serious adverse events (SAEs) including all deaths (related and 
unrelated), severity, onset, time to resolution related to the DSC devices and/or procedure 
and/or the ERC procedure through 30 days post procedure. 
2. Radiation exposure to the patient (total fluoroscopy time, total radiation dose, Dose Area 
Product (DAP), effective dose), from duodenoscope in to completion of stone clearance, 
not including the validation DSC procedure in ERC arm and ERC procedure in DSC arm. 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT  
Confidential 
                        Template 90702637 Rev/Ver AH 
                                                                                                                               Page 16 of 51 
  
3. Duration of procedure defined as time from duodenoscope in to completion of stone 
clearance, not including the validation DSC procedure in ERC arm and ERC procedure in 
DSC arm.  
5. Study Design 
This is a prospective, multi-center, randomized controlled study comparing endoscopic 
clearance of non-complex biliary stones using fluoroscopy/radiation free direct solitary 
cholangioscopy (DSC) versus standard of care endoscopic retrograde cholangiography 
(ERC) at up to 15 global sites. 
   
5.1. Scale and Duration 
A total of 250 patients will be randomized on a 1:1 ratio.  Block randomization through an 
online database system will be used. Randomization will be stratified by study center. Prior 
to randomization each participating endoscopist at each of the participating centers must 
perform up to 5 Roll-in cases.   These roll-in cases will not count towards the enrollment 
ceiling of 250 cases.  
The study duration is anticipated to be approximately 2 years, namely 18 months for 
completion of enrollment of 250 randomized cases, 1 month follow-up per subject, and 3 
months for data clean up and final data analysis. 
 
  
 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT  
Confidential 
                        Template 90702637 Rev/Ver AH 
                                                                                                                               Page 17 of 51 
  
Figure 5.1-1: Non-Complex Biliary Stone DSC vs ERC RCT Study Design 
5.2. Treatment Assignment 
All consecutive patients seen at an investigational site during the enrollment period: 
• 
Presenting with confirmed non-complex bile duct stones 
Patients will be screened relative to the Inclusion and Exclusion Criteria provided below. 
Patients will sign the Informed Consent Form, and then undergo screening examinations. 
Once Inclusion and Exclusion criteria are met, and presence of non-complex bile duct 
stone(s) is confirmed by imaging, patients will be randomized to either DSC arm or the ERC 
arm. 
5.3. Justification for the Study Design 
• 
During ERCP, patients and staff are exposed to radiation associated with the 
fluoroscopy.  This may increase their lifetime risk of developing cancer along with 
other harmful radiation effects. 
• 
In 2010, the FDA and the Center for Devices and Radiological Health published an 
initiative to reduce unnecessary radiation exposure from medical imaging10. 
Cholangioscopy (direct visualization of the bile duct) using the SpyGlass™ DS System and 
the SpyGlass™ accessories can reduce the duration of radiation exposure and may even 
eliminate the need for radiation exposure by allowing radiation-free management of non-
complex bile duct stones. This will cause a paradigm shift from a hybrid endoscopic-
fluoroscopic procedure to a purely endoscopic procedure. 
6. Subject Selection  
6.1. Study Population and Eligibility  
All consecutive patients who meet the selection criteria below will be invited for 
participation in the study.  Patients who sign the informed consent form will be considered 
enrolled. All the patients will have documented biliary obstruction based on the labs and 
imaging performed as standard of care. 
6.2. Inclusion Criteria 
Subjects who meet all of the following criteria may be given consideration for inclusion in 
this clinical investigation, provided no exclusion criterion (see Section 6.3) is met.  
1. 18 years or older 
2. Abdominal pain consistent with choledocholithiasis (possible procedure within 72 
hours of onset of symptoms and imaging suggesting choledocholithiasis, contingent 
on persistent abdominal pain) 
3. Abnormal LFTs 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT  
Confidential 
                        Template 90702637 Rev/Ver AH 
                                                                                                                               Page 18 of 51 
  
4. Non-complex biliary stone disease, defined as 5 or fewer stones in the common bile 
or common hepatic duct with largest stone no larger than 10 mm in size.  If stones not 
seen on imaging (US, CT) the bile duct diameter should be ≤12 mm.* 
* Given the poor sensitivity (approximately 20%) for biliary stones of CT and US, the 
diameter of the dilated CBD is used as a surrogate for largest stone diameter  
5. Availability of prior non-invasive imaging to determine the diameter of the bile duct 
and number and size of bile duct stones if visible on imaging. 
a. If probability of stones is high per investigator assessment based on ASGE 
criteria, any standard of practice imaging modality (eg. abdominal US) is 
acceptable. (see Figure 22.3-1, page 49). 
b. If the probability of stones is either intermediate or low per investigator 
assessment based on ASGE criteria, MRCP or EUS imaging is required to 
confirm presence of stones.  (see Figure 22.3-1, page 49). 
6. Willing and able to comply with the study procedures and provide written informed 
consent to participate in the study. 
6.3. Exclusion Criteria 
Subjects who meet any one of the following criteria will be excluded from this clinical study. 
1. Potentially vulnerable subjects, including but not limited to pregnant women and 
subjects in whom an endoscopic procedure is contraindicated. 
2. Location of the stones in intrahepatic ducts, cystic duct or proximal to strictures  
3. Bile duct stricture noted distal to stone on MRCP, which would make extraction 
without lithotripsy impossible. 
4. Ongoing cholangitis at time of randomization, manifested by fever with tachycardia 
and hypotension or evidence of pus at the ampulla 
5. Patients with prior biliary sphincterotomy 
6. Patients with Primary Sclerosing Cholangitis (PSC) 
7. Acute pancreatitis, defined as abdominal pain and serum concentration of pancreatic 
enzymes (lipase (required), amylase (optional) three or more times the upper limit of 
normal. 
8. Surgically altered gastro-duodenal luminal anatomy other than prior Billroth I 
reconstruction, as these would be anticipated to lead to more complicated procedures. 
9. Coagulopathy or ongoing need for anti-coagulation 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT  
Confidential 
                        Template 90702637 Rev/Ver AH 
                                                                                                                               Page 19 of 51 
  
7. Subject Accountability 
7.1. Point of Enrollment 
Patients who are considered for participation into the study but do not provide informed 
consent or do not meet eligibility criteria are considered screen failures. Screen failures will 
be tallied at each study site.  
In the case it is determined that the patient failed to meet the inclusion/exclusion criteria after 
the patient has agreed to participate in the study and has signed the informed consent, the 
study personnel will complete the Screening form as well as the End of Study form and 
indicate the specific inclusion/exclusion criterion that was not met. 
7.2. Withdrawal 
Subjects will participate in the study voluntarily and may withdraw at any time without 
prejudice to further treatment. If a subject withdraws from the clinical investigation, the 
primary reason shall be reported.  
All applicable case report forms up to the point of subject withdrawal, including an End of 
Study form must be completed.  
Subjects who are “lost-to-follow-up” should have three documented attempts to contact them 
prior to completion of the End of Study form. If withdrawal is due to investigator’s 
discretion, the investigator will describe what follow-up activities the investigator is 
obligated to perform.  
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. 
8. Study Methods 
8.1. Data Collection 
Data collection will occur according to the Data Collection Schedule shown in Table 8.1-1. 
Table 8.1-1: Data Collection Schedule  
Procedure/Assessment 
Screening 
 Baseline 
Index 
Procedure 
Follow-up Visits 
Unscheduled 
Reintervention 
24 hours 
 
Telephone 
Follow-up 
7 Days 
(± 2 Days) 
 Telephone 
Follow-up 
30 Days  
(± 10 Days) 
Telephone 
Follow-up 
Informed consent, 
Inclusion/Exclusion 
Criteria 
X 
 
 
 
 
 
 
Demographics 
 
X 
 
 
 
 
 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT  
Confidential 
                        Template 90702637 Rev/Ver AH 
                                                                                                                               Page 20 of 51 
  
Procedure/Assessment 
Screening 
 Baseline 
Index 
Procedure 
Follow-up Visits 
Unscheduled 
Reintervention 
24 hours 
 
Telephone 
Follow-up 
7 Days 
(± 2 Days) 
 Telephone 
Follow-up 
30 Days  
(± 10 Days) 
Telephone 
Follow-up 
Non-Invasive Imaging 
(Ultrasound, CT or 
MRCP) 
 
X 
 
 
 
 
 
Medical history 
 
X 
 
 
 
 
 
Lab Results  
 
X 
 
 
 
 
 
Probability of bile duct 
stone based on ASGE 
criteria:  high, 
intermediate or low 
 
X 
 
 
 
 
 
Need for MRCP or EUS 
based on intermediate or 
low ASGE criteria 
 
X 
 
 
 
 
 
Procedural details 
 
 
X 
 
 
 
 
Post-procedure Follow up 
 
 
 
X 
X 
X 
 
Biliary Re-interventions 
 
 
 
X 
X 
X 
X 
Serious Adverse Events 
assessment 
 
 
X 
X 
X 
X 
 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT 
Confidential                                            
 
            Template 90702637 Rev/Ver AH 
                                                                                                                       Page 21 of 51 
  
8.2. Study Candidate Screening 
Patients who present with abdominal symptoms of choledocholithiasis, or who have 
undergone imaging demonstrating choledocholithiasis as listed in Inclusion Criteria will be 
screened for trial enrollment. A Screen Failure/Enrollment Log will be maintained by the 
center to document select information about candidates who signed consent. 
8.3. Informed Consent 
Data collection or study procedure will not occur prior to the patient signing the ICF. Patients 
will be considered enrolled in the study once they sign the informed consent and affirm that 
they agree to participate in the study and adhere to the study schedule. Once a patient is 
considered enrolled in the study, baseline information may be obtained.  
8.4. Baseline 
The following baseline data will be collected for all subjects: 
• Demographics 
• Results of Non-Invasive Imaging (including Ultrasound, CT or MRCP) 
• Medical History 
• Lab Results (LFTs, Lipase, Hct, Platelet Count) 
• Probability of bile duct stone based on ASGE criteria:  high, intermediate or low 
• Need for MRCP or EUS based on intermediate or low ASGE criteria 
8.5. Randomization 
Randomization is to occur only after verification of all inclusion/exclusion criteria. Once the 
patient has signed the IRB/EC-approved study ICF and has met all general inclusion and 
none of the exclusion criteria, the patient will be eligible for randomization. 
Randomization will be stratified by clinical site. Within each site, eligible subjects will be 
randomized in a 1:1 ratio to receive each treatment method. This study is not blinded. 
For back-up randomization, sites will be instructed to randomize patients via back-up 
envelopes only in cases of unsuccessful access to the online database system. Envelopes are 
sequentially numbered sealed opaque envelopes containing randomized treatments.   
8.6. Procedure 
The following procedural data will be collected for all subjects: 
• Achievement of cannulation portion of procedure 
• Biliary Sphincterotomy performed 
• Additional sphincteroplasty performed 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT 
Confidential                                            
 
            Template 90702637 Rev/Ver AH 
                                                                                                                       Page 22 of 51 
  
• Number and approximate size of stones extracted 
• Time Stamps: 
o Duodenoscope in  
o Time cannulation commenced 
o Time biliary cannulation achieved (defined as free advancement of guidewire) 
o SpyGlass™ DS in (For DSC Procedure) 
o SpyGlass™ DS out (For DSC procedure) 
o Time stone clearance achieved 
o Duodenoscope out 
• Total radiation exposure to patient (fluoroscopy time, total radiation dose, Dose Area 
Product (DAP), effective dose) 
• Volume of injected saline during DSC procedure 
• Total number of endoscopic devices used during the procedure. 
• Procedure outcome: all stones successfully extracted during the procedure? 
• Serious Adverse Events and Device Events and all cases of Cholangitis, Pancreatitis, 
Perforation and Bleeding. 
 
The following steps are procedural guidelines: 
In both arms: 
1. Prior non-invasive imaging will be reviewed to determine the number and size of bile 
duct stones (if possible) and the diameter of the bile duct.   
2. Once bile duct stones are deemed to be a high probability based on clinical presentation 
imaging and ASGE criteria, patients will be randomized to either the DSC arm or the 
ERC arm. 
3. Patient will receive prophylactic antibiotics and rectal indomethacin. 
4. The duodenoscope will be advanced to the duodenum and the major papilla will be 
identified. 
5.  Needle knife pre-cut sphincterotomy may be utilized for stones visibly impacted at the 
ampulla. 
6.  A sphincterotome with guidewire will be used to cannulate the bile duct following 
needle knife sphincterotomy AND for all other patients without visibly impacted stones.   
 
In Group A (ERC arm): 
1.  Needle knife pre-cut sphincterotomy may be utilized for stones visibly impacted at the 
ampulla. 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT 
Confidential                                            
 
            Template 90702637 Rev/Ver AH 
                                                                                                                       Page 23 of 51 
  
2. For all other patients, standard cannulation techniques with a sphincterotome to gain 
biliary access; contrast medium injected. 
3. If initial cannulation has not been achieved within 15 minutes, a double wire technique 
and/or transpancreatic septotomy cannulation technique should be attempted.  
4. If cannulation failure persists despite these advanced cannulation techniques for an 
additional 15 minutes, this will be considered a cannulation failure.  Participating 
institutions may proceed with their standard of care interventions at this point.   
5. Use of needle-knife other than for visibly impacted stones will be considered a 
cannulation failure. Patients will be followed through 30 days post index procedure as 
indicated in the follow-up schedule. 
6. After cannulation succeeds, number and estimated size of biliary stones will be 
confirmed following contrast injection.  Biliary sphincterotomy will be performed.  
Additional papillary large balloon dilation can be performed if the sphincterotomy is felt 
to be inadequate.  
7. Stone removal using standard techniques.  If unexpectedly large stones are encountered, 
papillary large balloon dilation or mechanical lithotripsy may be applied. 
8. If stone clearance fails due to size/shape of the stone(s), stone extraction failure will 
have occurred. However, participating institutions may proceed with their standard of 
care interventions at this point, including cholangioscopy and EHL/LL or stent placement 
with repeat ERC on another day. Patients will be followed through 30 days post index 
procedure as indicated in the follow-up schedule. 
 
Post ERC validation by DSC: 
9. In patients in whom stone extraction is deemed to be complete, the SpyGlass™ 
cholangioscope will then be advanced to confirm complete clearance of the bile duct. 
10. If residual stone(s) are noted, then additional balloon sweeps, and/or stone retrieval using 
a SpyGlass™ Retrieval Basket, of the bile duct will be performed with fluoroscopy 
assistance and supplemented by papillary large balloon dilation, mechanical lithotripsy 
and EHL/LL as needed. 
11. The number of “missed stones” equal to or greater than 5 mm in size per endoscopist’s 
estimate will be documented. 
 
In Group B (DSC arm): 
1. Needle knife pre-cut sphincterotomy may be utilized for stones visibly impacted at the 
ampulla. 
2. Fluoroscopy-free cannulation technique to gain biliary access for all other patients.   
• Do not prime the sphincterotome with contrast. 
• Following deep cannulation, confirm free advancement of the guidewire into a 
ductal system. 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT 
Confidential                                            
 
            Template 90702637 Rev/Ver AH 
                                                                                                                       Page 24 of 51 
  
• Aspiration of bile via the sphincterotome using a syringe to confirm bile duct 
cannulation.  
• If clear fluid is aspirated, this may indicate that the pancreatic duct has been 
accessed. Re-attempt to access the bile duct. If no fluid is aspirated, or if there is 
remaining uncertainty over which duct was accessed, physicians if they wish, 
may use a brief tap on the fluoroscopy pedal to assess whether the guidewire 
appears to be in the bile duct.  Alternatively, they may proceed to an early double 
wire and/or transpancreatic septotomy cannulation technique.  They MUST 
proceed to double wire and/or transpancreatic septotomy cannulation techniques 
if fluoroscopy-free cannulation failure persists for 15 minutes.  If brief 
fluoroscopy is used to confirm biliary cannulation, then the case is considered a 
primary endpoint failure, but the DSC technique for stone evaluation and 
clearance may be continued.  Secondary endpoints will be assessed in these 
patients, including patient radiation exposure. 
• If initial fluoroscopy-free cannulation failure persists for 15 minutes, a double 
wire and/or transpancreatic septotomy cannulation technique should be 
attempted.  
• If cannulation failure persists despite these advanced cannulation techniques for 
an additional 15 minutes, this will be considered a cannulation failure. The 
patient will crossover to the ERC arm where these cannulation techniques will 
be continued with full fluoroscopy support. If cannulation in the ERC arm fails 
despite use of fluoroscopy and basic/advanced cannulation techniques for an 
additional 15 min then participating institutions may then proceed with their 
standard of care interventions at this point. Use of needle-knife other than for 
visibly impacted stones will be considered a cannulation failure for these 
crossover patients.   
• Patients will be followed through 30 days post index procedure as indicated in 
the follow-up schedule. 
3. After fluoroscopy-free cannulation succeeds, biliary sphincterotomy will be performed.  
Additional papillary large balloon dilation can be performed if the sphincterotomy is felt 
to be inadequate 
4. The sphincterotome will be exchanged for the SpyGlass cholangioscope over the 
guidewire. 
5. The cholangioscope will be advanced into the bile duct up to the bifurcation (hilum) and 
distance from ampulla to the bifurcation (hilum) will be noted.  (Adhesive tapes placed 
on SpyGlass shaft where it exits the duodenoscope working channel when 
cholangioscope is at the bifurcation, and again when it just exits ampulla will allow 
measurement of this distance). 
6. Injection of saline/water to be minimized to avoid driving stones more proximally (inject 
gently with a syringe rather than using the pump).  Suction applied through the Spyglass 
cholangioscope and gentle ‘head-up’ tilt of the fluoroscopy table may be utilized.  
7. Number and estimated size of biliary stones will be confirmed during cholangioscopy.  

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT 
Confidential                                            
 
            Template 90702637 Rev/Ver AH 
                                                                                                                       Page 25 of 51 
  
8. Visualized stones may then be extracted using a Balloon catheter and/or SpyGlass™ 
Retrieval Basket. 
Retrieval using Balloon Catheter: 
9. The cholangioscope will be exchanged for a stone extraction balloon catheter.   This 
exchange should be performed over a long 0.035” guidewire; if a short guidewire or a 
0.025” guidewire was used earlier in the procedure, it should ideally be changed prior to 
next steps.  The balloon catheter should be of appropriate size to fill the bile duct lumen 
(based on known diameter from prior non-invasive imaging).  The balloon catheter will 
have distance markings.  
10. A stone extraction balloon catheter marked with the distance from ampulla to hilum will 
then be advanced over the guidewire long 0.035” guidewire.   
11. For patients with multiple stones, the balloon will be sequentially advanced more 
proximally up the bile duct for balloon sweeps, and eventually advanced to the hilum 
guided by previously measured distance from ampulla to hilum. Where only a single 
stone is noted, a single sweep commencing at the hilum may be performed.  Balloon 
sweeps will be performed and the number of extracted stones will be counted to confirm 
complete extraction. 
12. Saline irrigation will be performed via the balloon catheter, with the catheter positioned 
at proximal to the bifurcation prior to the last 2 balloon sweeps, to ensure clearance of 
any residual sludge/stone fragments/debris.  If possible a gentle head up tilt of the table 
may be performed prior to irrigation to encourage downward movement of stones. 
13. The cholangioscope will then be re-inserted and advanced to the hilum to confirm 
complete clearance of the bile duct. 
14. If residual stone/stones are noted, additional balloon sweeps will be performed followed 
by repeat cholangioscopy to confirm clearance.  This cycle may be repeated as necessary 
until all stones are believed to have been successfully extracted. 
Retrieval using SpyGlass™ Retrieval Basket: 
15. Stones visualized at cholangioscopy may also be captured and retrieved sequentially 
using the SpyGlass™ Retrieval Basket, commencing distally and progressing proximally 
to the hilum as with balloon extraction.  Extracted stones will be counted.  If stone 
capture is difficult using the basket, the endoscopist may switch to balloon extraction at 
any point.  Where retrieval is successful using purely SpyGlass™ Retrieval Basket alone 
(without need for balloon catheter), or if retrieval using SpyGlass™ Retrieval Basket is 
utilized for the final visualized stone, saline irrigation (Step 12) and cholangioscope re-
insertion (Steps 13/14) will not be necessary. 
16. EHL or LL may be performed for unexpectedly large/complex stones. 
• If stone clearance fails due to size/shape of the stone(s), electro-hydraulic 
lithotripsy (EHL) or laser lithotripsy (LL) can be performed.   
• If stone clearance still fails stone extraction failure will have occurred. 
However, participating institutions may proceed with their standard of care 
interventions at this point, including ERC with mechanical lithotripsy or stent 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT 
Confidential                                            
 
            Template 90702637 Rev/Ver AH 
                                                                                                                       Page 26 of 51 
  
placement followed by repeat ERC on another day. Patients will be followed 
through 30 days post index procedure as indicated in the follow-up schedule. 
 
Post DSC validation by ERC: 
17. An occlusion cholangiogram will be performed using the stone extraction balloon 
catheter and presence or absence of filling defects will be documented. 
18. If filling defects are noted, then balloon sweeps of the bile duct will be performed to 
determine if the filling defects are “missed” bile duct stones or simply air bubbles. 
The number of “missed stones” > 5 mm per endoscopist’s estimate will be documented. 
8.7. 24-Hour, 7-Day, and 30-Day Follow-up 
The following data will be collected for all subjects (including Roll-in cases) during these 
follow up periods: 
• Phone call to patient 
• Serious Adverse Events, all events of Cholangitis, Pancreatitis, Perforation, and 
Bleeding, and Device Events, including discharge summaries for any device-related 
hospitalizations. 
8.8. Study Completion 
Subjects will be followed for 30 days post-index procedure. 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 investigator will note the reason on the study 
completion form (e.g. subject withdrawn by investigator, subject withdrew consent, lost to 
follow-up, SAE, death, etc.).  
9. Statistical Considerations 
9.1. Primary Endpoint 
Preliminary DSC-guided stone clearance rate was established in a pilot study1 and found to 
be comparable to that of ERC-guided stone clearance. Eight relevant peer reviewed 
publications2-9 reporting on ERC-guided biliary stone clearance rates representing 2721 
patients were analyzed. A meta-analysis was conducted of the biliary stone clearance rates, 
yielding a point estimate of 90% with a 95% CI of [85%, 94%]. 
9.1.1. Hypotheses 
We hypothesize that the DSC-guided stone clearance rate is non-inferior to that of the ERC-
guided stone clearance rate. We assume a DSC-guided and ERC-guided stone clearance rate 
of 90% with a 10% non-inferiority margin. The following hypothesis will be tested:  
H0: PDSC minus PERC ≤ -∆ (Inferior) 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT 
Confidential                                            
 
            Template 90702637 Rev/Ver AH 
                                                                                                                       Page 27 of 51 
  
H1: PDSC minus PERC > -∆ (Non-inferior) 
where PDSC and PERC are the stone clearance rates for the DSC arm (test) and the ERC arm 
(control), respectively, and (∆delta) is the non-inferiority absolute margin. 
9.1.2. Sample Size  
The sample size was estimated based on the following assumptions: 
- 
Expected stone clearance rate of 90% in DSC-guided and ERC-guided group 
- 
Non-inferiority margin: 10% 
- 
Alpha (1-sided): 0.05 
- 
Power: 80% 
With the above assumptions, a sample of 250 patients (125 in each arm) is needed to detect 
the non-inferiority of the clearance rate in the DSC arm compared to the ERC arm. This 
sample size was calculated using StatXact 9®. 
9.1.3. Statistical Methods 
An exact test will be used to test the non-inferiority hypothesis of the DSC-guided vs. ERC-
guided stone clearance rates. 
9.2. Analysis Populations 
9.2.1. Enrolled Cohort 
A subject is considered enrolled after signing the study-specific Informed Consent Form 
(ICF). Patients who sign the ICF but subsequently do not meet one or more of the selection 
criteria will be considered screen failures and will be excluded from the study.  
9.2.2. Intent-to-Treat Cohort (ITT) 
This cohort consists of those enrolled patients who meet all inclusion/exclusion criteria and 
are subsequently randomized.  
9.2.3. Per-Protocol Cohort (PP) 
The per-protocol cohort is a subset of the ITT subjects who are treated per protocol post 
randomization with no major protocol deviations (ICH E9 definitions). 
9.3. Data Analyses 
9.3.1.Baseline 
Baseline data will be summarized using but not limited to the following variables: subject 
demographics, medical history, and history of prior ERCP or sphincterotomy. Descriptive 
statistics (e.g., mean, standard deviation, n, minimum, maximum) will be reported for 
continuous variables and frequency tables for discrete variables.  

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT 
Confidential                                            
 
            Template 90702637 Rev/Ver AH 
                                                                                                                       Page 28 of 51 
  
9.3.2. Procedure Data 
Procedure data, such as cannulation success, biliary sphincterotomy and stone removal will 
be collected and reported using descriptive statistics (e.g., mean, standard deviation, n, 
minimum, maximum) for continuous variables and frequency tables for discrete variables. 
9.3.3. Post-Procedure Data 
Post-procedure data will be collected as described in Table 8.1-1 Data Collection Schedule 
and will be summarized using descriptive statistics (e.g., mean, standard deviation, n, 
minimum, maximum) for continuous variables and frequency tables for discrete variables. 
9.3.4. Interim Analyses  
 No formal interim analyses are planned for this study.  
9.3.5. Subgroup Analyses 
Stratified analyses will include tabulating the primary and select secondary endpoints by 
gender. 
9.3.6. 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 endpoint as the outcome variable.  
9.3.7. Multivariable Analyses 
Multivariable analyses may be performed to identify potential predictors and assess their 
effect on the primary endpoint. 
9.3.8. Learning Curve Analysis 
A generalized linear model will be fit to investigate the effect of time since first enrollment 
and sites/physicians (and potential interaction between time and sites/physicians) on the 
primary and select secondary endpoints.  
9.3.9. 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.  

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT 
Confidential                                            
 
            Template 90702637 Rev/Ver AH 
                                                                                                                       Page 29 of 51 
  
10. Data Management 
10.1. 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 Rave. All 
changes made to the clinical data will be captured in an electronic audit trail and available for 
review by Boston Scientific Corporation (BSC) 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 EDC system and will 
be issued to the site for appropriate response. Site staff will be responsible for resolving 
applicable queries in the database. 
10.2. Data Retention 
The Principal Investigator or his/her designee or Investigational site will maintain, at the 
investigative site, all essential study documents and source documentation that support the 
data collected on the study subjects in compliance with ICH/GCP guidelines.  Documents 
must be retained for at least 2 years after the last approval of a marketing application or until 
at least 2 years have elapsed since the formal discontinuation of the clinical investigation of 
the product. These documents will be retained for a longer period of time by agreement with 
BSC or in compliance with other country/regional/local regulations.  
The Principal Investigator or his/her designee will take measures to ensure that these 
essential documents are not accidentally damaged or destroyed. 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. 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT 
Confidential                                            
 
            Template 90702637 Rev/Ver AH 
                                                                                                                       Page 30 of 51 
  
11. Amendments  
If a protocol revision is necessary which affects the rights, safety or welfare of the subject or 
scientific integrity of the data, an amendment is required. Appropriate approvals (e.g., 
IRB/EC/FDA/CA) of the revised protocol must be obtained prior to implementation. 
12. 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 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.  
All deviations from the investigational plan, with the reason for the deviation must be 
documented and reported to the sponsor using the protocol deviation form in the EDC. Sites 
may also be required to report deviations to the IRB/EC, per local guidelines and government 
regulations.  
Deviations will be reviewed and evaluated on an ongoing basis and, as necessary, appropriate 
corrective and preventive actions (including IRB/EC notification, site re-training, or site 
discontinuation/termination) will be put into place by the sponsor. 
13. Device/Equipment Accountability 
The devices/equipment shall be securely maintained, controlled, and used only in this clinical 
study. The Device Accountability Log will be used to track subjects and device allocations 
during the study. Equipment shall be returned in the condition in which it was provided, 
reasonable wear and tear excepted. 
The sponsor shall keep records to document the physical location of all devices/ equipment 
from shipment of devices from BSC or designated facility/equipment to the investigation 
sites until return or disposal. 
Records shall be kept by the site to document the physical location and conditions of storage 
of all devices/equipment.  
The principal investigator or an authorized designee shall keep records documenting the 
receipt, use, return and disposal of the devices/equipment, which shall include the following 
• Date of receipt 
• Identification of each device/piece of equipment (batch number or unique code) 
• Expiry date, as applicable 
• Date or dates of use 
• Subject identification 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT 
Confidential                                            
 
            Template 90702637 Rev/Ver AH 
                                                                                                                       Page 31 of 51 
  
• Date on which the device/piece of equipment was returned/explanted from subject, if 
applicable 
• Date of return (and number) of unused, expired, or malfunctioning devices/equipment, if 
applicable. 
Written procedures may be required by national regulations. 
14. Compliance 
14.1. Statement of Compliance 
This study will be conducted in accordance with Good Clinical Practices as outlined in the 
ISO 14155:2011, ICH Guidelines for GCP, ethical principles that have their origins in the 
Declaration of Helsinki, and pertinent individual country laws and regulations. The study 
shall not begin until the required approval/favorable opinion from the IRB/EC and/or 
regulatory authority has been obtained, if appropriate. Any additional requirements imposed 
by the IRB/EC or regulatory authority shall be followed, if appropriate.  
14.2. 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 14155:2011, ethical principles that have their origins in the Declaration of 
Helsinki, any conditions of approval imposed by the reviewing IRB/EC, 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 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. 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT 
Confidential                                            
 
            Template 90702637 Rev/Ver AH 
                                                                                                                       Page 32 of 51 
  
• 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. 
• Maintain the device accountability records and control of the device, ensuring that the 
device is used only by authorized/designated users and in accordance with this protocol 
and instructions/directions for use. 
• 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 when performing auditing 
activities. 
• Ensure that informed consent is obtained in accordance with applicable laws, this 
protocol and local IRB/EC 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 investigational 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). 
• 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. 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT 
Confidential                                            
 
            Template 90702637 Rev/Ver AH 
                                                                                                                       Page 33 of 51 
  
• Ensure that maintenance and calibration of the equipment relevant for the assessment of 
the clinical investigation is appropriately performed and documented, where applicable. 
14.2.1. 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 and adequate supervision of those to whom tasks are delegated. The 
investigator is accountable for regulatory violations resulting from failure to adequately 
supervise the conduct of the clinical study.  
14.3. Institutional Review Board/ Ethics Committee 
Prior to gaining Approval-to-Enroll status, the investigational site will provide to the sponsor 
documentation verifying that their IRB/EC is registered or that registration has been 
submitted to the appropriate agency, as applicable according to national/regulatory 
requirements.   
A copy of the written IRB/EC and/or competent authority approval of the protocol (or 
permission to conduct the study) and Informed Consent Form, must be received by the 
sponsor before recruitment of subjects into the study and shipment of investigational 
product/equipment. Prior approval must also be obtained for other materials related to subject 
recruitment or which will be provided to the subject. 
Annual IRB/EC approval and renewals will be obtained throughout the duration of the study 
as required by local/country or IRB/EC requirements. Copies of the Investigator’s reports 
and the IRB/EC continuance of approval must be provided to the sponsor.  
14.4. Sponsor Responsibilities 
All information and data sent to BSC concerning subjects or their participation in this study 
will be considered confidential by BSC. Only authorized BSC personnel or a BSC 
representative including, but not limited to Contract Research Organization (CRO) will have 
access to these confidential records. 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. All data used in the analysis and reporting of this study will be 
without identifiable reference to specific subject name. 
Boston Scientific will keep subjects’ identifiable health information confidential in 
accordance with all applicable laws and regulations.  Boston Scientific may use subjects’ 
health information to conduct this research, as well as for additional purposes, such as 
overseeing and improving the performance of its device, new medical research and proposals 
for developing new medical products or procedures, and other business purposes. 
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.  

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT 
Confidential                                            
 
            Template 90702637 Rev/Ver AH 
                                                                                                                       Page 34 of 51 
  
14.4.1. 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. 
• 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 worksheet  
• Print out programming reports directly from the clinician programmer and provide 
original to clinical site as source documentation 
• 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 
• Discuss a subject’s condition or treatment with a subject without the approval and 
presence of the investigator 
• 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 
14.5. Insurance  
Where required by local/country regulation, proof and type of insurance coverage, by BSC 
for subjects in the study will be obtained. 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT 
Confidential                                            
 
            Template 90702637 Rev/Ver AH 
                                                                                                                       Page 35 of 51 
  
15. 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 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. 
16. Potential Risks and Benefits 
16.1. Anticipated Adverse Device Effects  
From the Anticipated Adverse Events listed above, the following anticipated adverse device 
effects (ADE) have been identified for SpyGlass DS™ System 
The primary risks associated with the SpyScope™ DS Access and Delivery Catheter, and 
SpyGlass™ Retrieval Basket listed in the DFU include the following: 
• Pancreatitis 
• Perforation 
• Hemorrhage 
• Septicemia/Infection 
• Cholangitis 
• Allergic reaction  
Additional primary risks associated with the SpyScope™ DS Access and Delivery Catheter 
listed in the DFU include: 
• Mucous membrane damage 
• Hematoma 
 
The additional primary risks included in the DFU associated with the SpyGlass™ Retrieval 
Basket include: 
• Basket impaction 
• Cholecystitis 
 
 
Any of these must be reported on the Adverse Event page of the eCRF if they are serious.  If 
cholangitis, pancreatitis, perforation, or bleeding, all cases (AE and SAEs) should be 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT 
Confidential                                            
 
            Template 90702637 Rev/Ver AH 
                                                                                                                       Page 36 of 51 
  
reported. If death occurs, it must be entered as an outcome to a specific SAE, rather than the 
SAE itself. 
The rate of occurrence of potential risks and side effects associated with taking part in this 
study are listed in the table 16.2-1 and 16.2-2. 
 
Table 16.1-1: Potential Risks Rates of Occurrence 
SpyScope™ DS Access and Delivery Catheter 
 
 
 
Table 16.1-2: Potential Risks Rates of Occurrence 
SpyGlass™ Retrieval Basket  
Risk Term 
Rate of 
Occurrence 
Post-ERCP Pancreatitis 
3% - 6.6%, .13%  
Cholangitis 
6.6% - 7.5% 
Bleeding 
1.3% 
Broken basket and impaction 
6 case reports, .88% 
 
16.2. 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. 
Risk Term 
Rate of Occurrence 
Sources 
Pancreatitis 
1.1% - 18.1% 
15, 16, 17, 18 
Abdominal pain 
5.1% - 15.3% 
19, 16 
Sustained DSC-related bacteremia 
13.9% 
20 
Cholangitis 
1.4%-11% 
21, 22, 23, 24, 15, 25, 26, 17 
Mild pancreatitis 
1.6% - 8.5% 
22, 23, 24, 25, 28 
Unexpected hospitalization 
7.6% 
16 
Fever 
5.8% 
19 
Self-limited pancreatitis 
5.8% 
19 
Mild perforation 
4.2% 
24 
Post-EST bleeding 
0.8%-3.8% 
21, 22, 28 
Self-limited abdominal pain 
3.5% 
23 
Asymptomatic amylasemia 
3.5% 
23 
Bleeding 
1%-2% 
15, 25 
Hemobilia 
1.1% 
23 
Perforation 
0.7%-1.1% 
15, 16, 25 
Aspiration pneumonia 
0.8% 
22 
Infection 
0.34% 
 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT 
Confidential                                            
 
            Template 90702637 Rev/Ver AH 
                                                                                                                       Page 37 of 51 
  
16.3. Anticipated Benefits 
There may be no benefit from participation this study. Medical science and future patients 
may benefit from this study; notably reducing radiation exposure, and wait times for 
procedure rooms.  
16.4. Risk to Benefit Rationale 
The SpyGlass™ DS is intended to provide direct visualization of the pancreaticobiliary 
system, including the hepatic ducts as stated in the DFU.     
Benefits to the subject could potentially include reducing radiation exposure and wait times 
for procedure rooms, better diagnostic accuracy and therapeutic efficacy as compared to 
ERCP alone when SpyScope™ DS Access and Delivery Catheter is used with SpyGlass™ 
DS Digital Controller. Indeed, potential benefits may include for example, successful 
visualization and diagnosis of lesions, better identification of filling defects, and removal of 
large and and/or impacted bile duct stone(s). 
The risks associated with the use of the SpyGlass DS are documented in the Directions for 
Use and clinical data for the system is currently reviewed by the Sponsor. The following 
conclusion was reported as it pertains to SpyGlass-related adverse events: Evaluation of bile 
duct disease and biliary stone therapy can be safely performed with a high success rate by 
using the single-operated cholangioscopy system.   
17. Safety Reporting 
17.1. 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 Serious Adverse Events 
• All events of Cholangitis, Pancreatitis, Perforation, and Bleeding 
• All Device Events, including Deficiencies  
• New findings/updates in relation to already reported events 
• All study Device related Adverse Events 
• All Accessory Device related Adverse Events 
• All study Procedure related Adverse Events 
• All ERCP Procedure related Adverse 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. 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT 
Confidential                                            
 
            Template 90702637 Rev/Ver AH 
                                                                                                                       Page 38 of 51 
  
Any AE required by the protocol, experienced by the study subject after informed consent 
and once considered enrolled in the study (as defined in study subject classification section), 
whether during or subsequent to the procedure, must be recorded in the eCRF. 
Underlying diseases are not reported as AEs unless there is an increase in severity of 
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 17.2-1 for AE 
definitions). 
Unrelated AEs, except for any event of Cholangitis, Pancreatitis, Perforation and Bleeding, 
will not be collected in this study 
Refer to Section 16 for the known risks associated with the study device(s). 
17.2. Definitions and Classification 
Adverse event definitions are provided in Table 17.2-1. Administrative edits were made on 
the definition of serious adverse event from ISO 14155:2011and MEDDEV 2.7/3 for 
clarification purposes. 
 
Table 17.2-1: Safety Definitions 
Term 
Definition 
Adverse Event (AE) 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
 
 
Any untoward medical occurrence, unintended disease or injury, or any 
untoward clinical signs (including an abnormal laboratory finding) in 
subjects, users or other persons, whether or not related to the 
investigational medical device.  
NOTE 1: This includes events related to the investigational 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 investigational medical device.  
Adverse Device Effect (ADE) 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
Adverse event related to the use of an investigational 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 
investigational medical device. 
NOTE 2: This definition includes any event resulting from use error or 
intentional abnormal use of the investigational medical device. 
Serious Adverse Event (SAE) 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
Note: This definition meets the reporting objectives and requirements of  
ISO 14155  and  MEDDEV 2.7/3. 
Adverse event that: 
a) Led to death, 
b) Led to  serious deterioration in the health of the subject as defined by 
either: 
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body function, 
or 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT 
Confidential                                            
 
            Template 90702637 Rev/Ver AH 
                                                                                                                       Page 39 of 51 
  
Table 17.2-1: Safety Definitions 
Term 
Definition 
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) Led to fetal distress, fetal death, or a congenital abnormality or birth 
defect. 
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.  
Serious Adverse Device Effect 
(SADE) 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
Adverse device effect that has resulted in any of the consequences 
characteristic of a serious adverse event. 
 
Device Deficiency 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
A inadequacy of an investigational medical device related to its identity, 
quality, durability, reliability, safety or performance. This may include 
malfunctions, use error, or inadequacy in the information supplied by the 
manufacturer. 
 
Abbreviations: EC=Ethics Committee; IRB=Institutional Review Board 
17.3. Relationship to Study Device(s) 
The Investigator must assess the relationship of the AE to the study device, including 
accessory devices and/ or procedure(s). See criteria in Table 17.3-1:  
Table 17.3-1: Criteria for Assessing Relationship of Study Device, Including 
Accessory Device(s) and/or Procedure(s) to Adverse Event 
Classification 
Description 
Not Related 
Relationship to the device or procedures can be excluded when: 
- the event is not a known side effect of the product category the device belongs to 
or of similar devices and procedures; 
- the event has no temporal relationship with the use of the investigational device or 
the procedures; 
- 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 not expected to be affected by the 
device or procedure; the serious event can be attributed to another cause (e.g. an 
underlying 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT 
Confidential                                            
 
            Template 90702637 Rev/Ver AH 
                                                                                                                       Page 40 of 51 
  
 
Table 17.3-1: Criteria for Assessing Relationship of Study Device, Including 
Accessory Device(s) and/or Procedure(s) to Adverse Event 
Classification 
Description 
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 investigational device 
used for diagnosis, when applicable; harms to the subject are not clearly due to use 
error; 
- 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. 
Unlikely Related 
The relationship with the use of the device seems not relevant and/or the event can 
be reasonably explained by another cause, but additional information may be 
obtained. 
Possibly Related 
The relationship with the use of the investigational device 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 were relatedness cannot be assessed or no information has been 
obtained should also be classified as possible. 
Probably Related 
The relationship with the use of the investigational device seems relevant and/or 
the event cannot reasonably explained by another cause, but additional information 
may be obtained. 
Causal Relationship 
The serious event is associated with the investigational device 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 investigational device use/application 
or procedures; 
- the event involves a body-site or organ that 
o the investigational device or procedures are applied to; 
o the investigational 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 investigational 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. 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT 
Confidential                                            
 
            Template 90702637 Rev/Ver AH 
                                                                                                                       Page 41 of 51 
  
17.4. Investigator Reporting Requirements 
The communication requirements for reporting to BSC are as shown in 17.4-1. 
Table 17.44-1: Investigator Reporting Requirements 
Event Classification 
Communication Method  
Communication Timeline post-
market studies**  
(MEDDEV 2.12/2:  
GUIDELINES ON A MEDICAL 
DEVICE VIGILANCE SYSTEM) 
Adverse Event 
Complete AE eCRF page 
with all available new and 
updated information.  
a) Within 10 business days after 
becoming aware of the event or as 
per local/regional regulations. 
b) Reporting required through the 
12-month Follow-up time point 
Provide all relevant source 
documentation (unidentified) 
for reported event upon 
request of the sponsor 
c) When documentation is available 
Serious Adverse Event  
Complete AE eCRF page 
with all available new and 
updated information.  
d) Within 10 business days after 
becoming aware of the event or as 
per local/regional regulations.  
e) Reporting required through the 
end of study 
Provide all relevant source 
documentation (unidentified) 
for reported event upon 
request of the sponsor 
f) When documentation is available 
Serious Adverse Device Effects 
Complete AE eCRF page 
with all available new and 
updated information. 
g) Within 2 business days of first 
becoming aware of the event or as 
per local/regional regulations. 
h) Reporting required through the 
end of the study 
Provide all relevant source 
documentation (unidentified) 
for reported event 
i) When documentation is available 
Device Deficiencies (including but not 
limited to failures, malfunctions, and 
product nonconformities) 
Note:  Any Investigational Device 
Deficiency that might have led to a 
serious adverse event if a) suitable 
action had not been taken or b) 
intervention had not been made or c) if 
circumstances had been less fortunate 
is considered a reportable event. 
 
Complete Device Event CRF 
with all available new and 
updated information.  
j) Within 2 business days of first 
becoming aware of the event. 
Reporting required through the 
end of the study 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT 
Confidential                                            
 
            Template 90702637 Rev/Ver AH 
                                                                                                                       Page 42 of 51 
  
Abbreviations: AE=adverse event; CRF=case report form;  
**Please note that post-market studies are clinical studies where the medical devices used in the study bear the 
regulatory approval and are used for the same approved indications. 
 
17.5. Boston Scientific Device Deficiencies 
All device deficiencies (including but not limited to failures, malfunctions, use errors, 
product nonconformities, and inadequacy in the information supplied by the manufacturer) 
will be documented and reported to BSC.  
Device deficiencies (including but not limited to failures, malfunctions, and product 
nonconformities) are not adverse events. However, an adverse event that results from a 
device failure or malfunction would be recorded as an adverse event on the appropriate 
eCRF. 
Any Device Deficiency that might have led to a serious adverse event if a) suitable action 
had not been taken or b) intervention had not been made or c) if circumstances had been less 
fortunate is considered a reportable event. 
17.6. Reporting to Regulatory Authorities / IRBs / ECs / Investigators 
BSC is responsible for reporting adverse event information to all participating Principal 
Investigators and regulatory authorities, as applicable.  
Event Classification 
Communication Method  
Communication Timeline post-
market studies**  
(MEDDEV 2.12/2:  
GUIDELINES ON A MEDICAL 
DEVICE VIGILANCE SYSTEM) 
Adverse Event 
Complete AE eCRF page 
with all available new and 
updated information.  
a) Within 10 business days after 
becoming aware of the event or as 
per local/regional regulations. 
b) Reporting required through the 
12-month Follow-up time point 
Provide all relevant source 
documentation (unidentified) 
for reported event upon 
request of the sponsor 
c) When documentation is available 
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.  
k) In a timely manner  (e.g. 
recommend within 30 business 
days) after becoming aware of the 
information 
l) Reporting required through end of 
study 
 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT 
Confidential                                            
 
            Template 90702637 Rev/Ver AH 
                                                                                                                       Page 43 of 51 
  
18. Informed Consent 
Subject participation in this clinical study is voluntary.  Informed Consent is required from 
each subject or his/her legally authorized representative. The Investigator is responsible for 
ensuring that Informed Consent is obtained prior to the use of any investigational devices, 
study-required procedures and/or testing, or data collection.  
The obtaining and documentation of Informed Consent must be in accordance with the 
principles of the Declaration of Helsinki, ISO 14155:2011, any applicable national 
regulations, and local Ethics Committee and/or Regulatory authority body, as applicable. The 
ICF must be accepted by BSC or its delegate (e.g. CRO), and approved by the site’s IRB/EC, 
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.  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 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, 
• 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 body 
according to their requirements (e.g., FDA requirement is within 5 working days of learning 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT 
Confidential                                            
 
            Template 90702637 Rev/Ver AH 
                                                                                                                       Page 44 of 51 
  
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), 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. The new version of the ICF must be approved by 
the IRB/EC. Acceptance by Boston Scientific is required if changes to the revised ICF are 
requested by the site’s IRB/EC. The IRB/EC will determine the subject population to be re-
consented. 
19. Suspension or Termination 
19.1 Premature Termination of the Study 
Boston Scientific Corporation reserves the right to terminate the study at any stage but 
intends to exercise this right only for valid scientific or administrative reasons and reasons 
related to protection of subjects.  Investigators, associated IRBs/ECs, and regulatory 
authorities, as applicable, will be notified in writing in the event of study termination. 
19.1.1 Criteria for Premature Termination of the Study 
Possible reasons for premature study termination include, but are not limited to, the 
following. 
• The occurrence of unanticipated adverse device effects that present a significant or 
unreasonable risk to subjects enrolled in the study. 
• 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 of the 
device. 
19.2 Termination of Study Participation by the Investigator or Withdrawal of IRB/ EC 
Approval 
Any investigator, or IRB/ EC in the Non-Complex Biliary Stones DSC vs ERC RCT may 
discontinue participation in the study or withdrawal approval of the study, respectively, with 
suitable written notice to Boston Scientific. Investigators, associated IRBs/ECs, and 
regulatory authorities, as applicable, will be notified in writing in the event of these 
occurrences. 
19.3 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 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT 
Confidential                                            
 
            Template 90702637 Rev/Ver AH 
                                                                                                                       Page 45 of 51 
  
IRB/EC 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 or EC terminates participation in the study, participating investigators, 
associated IRBs/ECs, and regulatory authorities, as applicable, will be notified in 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 
investigational product to Boston Scientific, unless this action would jeopardize the rights, 
safety, or welfare of the subjects. 
19.4 Criteria for Suspending/Terminating a Study Site 
Boston Scientific Corporation 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 6 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 study 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 and regulatory authorities, as applicable, will be 
notified. All subjects enrolled in the study at the site will continue to be followed for 30 days 
after index procedure per the study protocol. The Principal Investigator at the site must make 
provision for these follow-up visits unless BSC notifies the investigational site otherwise. 
20. 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 will submit study 
results for publication (regardless of study outcome) following the conclusion or termination 
of the study. Boston Scientific Corporation adheres to the Contributorship Criteria set forth in 
the Uniform Requirements of the International Committee of Medical Journal Editors 
(ICMJE; 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. 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT 
Confidential                                            
 
            Template 90702637 Rev/Ver AH 
                                                                                                                       Page 46 of 51 
  
• The First and Senior authors are the primary drivers of decisions regarding publication 
content, review, approval, and submission.  
 
 
 
 
 
 
 
 
 
21. Bibliography 
1. Barakat MT, Girotra M, Choudhary A, Huang R, Sethi S, Banerjee S. A prospective evaluation 
of radiation-free direct solitary cholangioscopy for the management of choledocholithiasis. 
Gastrointestinal Endoscopy 2017, 1-6,6.e1. 
2. Samardzic J, Latic F, Kraljik D, Pitlovic V, Mrkovic H, Miskic D, Latic A, Delibegovic S, 
Bencevic J, Brod S. Treatment of common bile duct stones-is the role of ERCP changed in era of 
minimally invasive surgery? Medical Archives 2010; Vol 64, No 3, 187-8. 
3. Kim HJ, Choi HS, Park JH, Park DI, Cho YK, Sohn CI, Jeon WK, Kim BI, Choi SH. Factors 
influencing the technical difficulty of endoscopic clearance of bile duct stones. Gastrointestinal 
Endoscopy 2007, Vol 66, No 6, 1154-1160. 
4. Wan X-J, Xu Z-J, Zhu F, Li L. Success rate and complications of endoscopic extraction of 
common bile duct stones over 2 cm in diameter. Hepatobiliary & Pancreatic Diseases 
International 2011, Vol 10, No 4, 403-407. 
5. Nathanson L, O’Rourke NA, Martin IJ, Fielding GA, Cowen, AE, Roberts RK, Kendall BJ, 
Kerlin P, Devereux BM. Postoperative ERCP versus laparoscopic choledochotomy for clearance 
of selected bile duct calculi: a randomized trial. Annals of surgery 2005, Vol 242, No 2, 188-
192. 
6. Heo JH, Kang DH, Jung HJ, Kwon DS, An JK, Kim BS, Suh KD, Lee SY, Lee JH, Kim GH, 
Kim TO, Heo J, Song GA, Cho M. Endoscopic sphincterotomy plus large-balloon dilation 
versus endoscopic sphincterotomy for removal of bile-duct stones. Gastrointestinal Endoscopy 
2007, Vol 66, No 4, 720-726. 
7. DiSario JA, Freeman ML, Bjorkman DJ, MacMathuna P, Petersen BT, Jaffe PE, Morales TG, 
Hixson LJ, Sherman S, Lehman GA, Jamal MM, Al-Kawas FH, Khandelwal M, Moore JP, 
Derfus GA, Jamidar PA, Ramirez FC, Ryan ME, Woods KL, Carr-Locke D, Alder SC. 
Endoscopic balloon dilation compared with sphincterotomy for extraction of bile duct stones. 
Gastroenterology 2004, Vol 127, No 5, 1291-1299. 
8. Obana T, Fujita N, Noda Y, Kobayashi G, Ito K, Horaguchi J, Koshita S, Kanno Y, Yamashita 
Y, Kato Y, Ogawa T. Efficacy and safety of therapeutic ERCP for the elderly with 
choledocholithiasis: comparison with younger patients. Internal Medicine 2010, Vol 49, No 18, 
1935-1941. 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT 
Confidential                                            
 
            Template 90702637 Rev/Ver AH 
                                                                                                                       Page 47 of 51 
  
9. Ödemiş B, Kuzu UB, Öztas E, Saygılı F, Suna N, Coskun O, Aksoy A, Sırtaş, Arı D, Akpınar Y. 
Endoscopic Management of the Difficult Bile Duct Stones: A Single Tertiary Center Experience. 
Gastroenterology Research and Practice 2016, Vol 2016, 1-7. 
10. Berrington de González A, Mahesh M, Kim KP, Bhargavan M, Lewis R, Mettler F, Land C.. 
“Projected Cancer Risks from Computed Tomographic Scans Performed in the United States in 
2007,” Archives of Internal Medicine, December 2009, Vol. 169, No. 22, pp. 2071-2077.   
11. Initiative to Reduce Unnecessary Radiation Exposure from Medical Imaging.  US Food and 
Drug Administration, White Paper February 2010. Available from: 
http://www.fda.gov/Radiation-EmittingProducts/RadiationSafety/ 
RadiationDoseReduction/ucm199994.htm. 
12. Radiation protection in the endoscopy suite - Minimizing radiation exposure for patients and 
staff in endoscopy: a joint ASGE/IAEA/WGO guideline. Available at: 
2009:http://www.worldgastroenterology.org/global-guidelines.html.  
13. Dumonceau JM, Garcia-Fernandez FJ, Verdun FR, et al. Radiation protection in digestive 
endoscopy: European Society of Digestive Endoscopy (ESGE) guideline. Endoscopy 
2012;44:408-21. 
14. Ridtitid W, Luangsukrerk T, Angsuwatcharakon P, Piyachaturatwat P, Aumpansub P, Jurst C, 
Chaiteerakij R, Kongkam P, Rerknimitr R. Uncomplicated common bile duct stone removal 
guided by cholangioscopy versus conventional endoscopic retrograde 
cholangiopancreatography. Surgical Endoscopy 2017; DOI 10.1007/s00464-017-5966-2; 
15. Lübbe J, Arnelo U, Lundell L, et al. ERCP-guided cholangioscopy using a single-use system: 
Nationwide register-based study of its use in clinical practice. Endoscopy. 2015;47(9):802-807. 
16. Tieu AH, Kumbhari V, Jakhete N, et al. Diagnostic and therapeutic utility of SpyGlass® peroral 
cholangioscopy in intraductal biliary disease: Single-center, retrospective, cohort study. 
Digestive Endoscopy. 2015;27(4):479-485. 
17. Kalaitzakis E, Sturgess R, Kaltsidis H, et al. Diagnostic utility of single-user peroral 
cholangioscopy in sclerosing cholangitis. Scandinavian Journal of Gastroenterology. 
2014;49(10):1237-1244. 
18. Siiki A, Rinta-Kiikka I, Koivisto T, et al. Spyglass single-operator peroral cholangioscopy seems 
promising in the evaluation of primary sclerosing cholangitis-related biliary strictures. 
Scandinavian journal of gastroenterology. 2014;49(11):1385-1390. 
19. Bhandari S, Bathini R, Sharma A, et al. Usefulness of single-operator cholangioscopy-guided 
laser lithotripsy in patients with Mirizzi syndrome and cystic duct stones: Experience at a 
tertiary care center. Gastrointestinal Endoscopy. 2016;84(1):56-61. 
20. Thosani N, Zubarik RS, Kochar R, et al. Prospective evaluation of bacteremia rates and 
infectious complications among patients undergoing single-operator choledochoscopy during 
ERCP. Endoscopy. 2016;48(5):424-431. 
21. Tanaka R, Itoi T, Honjo M, et al. New digital cholangiopancreatoscopy for diagnosis and 
therapy of pancreaticobiliary diseases (with videos). Journal of Hepato-Biliary-Pancreatic 
Sciences. 2016;23(4):220-226. 
22. Kurihara T, Yasuda I, Isayama H, et al. Diagnostic and therapeutic single-operator 
cholangiopancreatoscopy in biliopancreatic diseases: Prospective multicenter study in Japan. 
World Journal of Gastroenterology. 2016;22(5):1891-1901. 
23. Laleman W, Verraes K, van Steenbergen W, et al. Usefulness of the single-operator 
cholangioscopy system SpyGlass in biliary disease: a single-center prospective cohort study and 
aggregated review. Surgical Endoscopy and Other Interventional Techniques. 2016:1-10. 
24. Arnelo U, Von Seth E, Bergquist A. Prospective evaluation of the clinical utility of single-
operator peroral cholangioscopy in patients with primary sclerosing cholangitis. Endoscopy. 
2015;47(8):696-702. 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT 
Confidential                                            
 
            Template 90702637 Rev/Ver AH 
                                                                                                                       Page 48 of 51 
  
25. Adler DG, Cox K, Milliken M, et al. A large multicenter study analysis of adverse events 
associated with single operator cholangiopancreatoscopy. Minerva Gastroenterologica e 
Dietologica. 2015;61(4):179-184. 
26. Aljebreen AM, Alharbi OR, Azzam N, et al. Efficacy of spyglass-guided electrohydraulic 
lithotripsy in difficult bile duct stones. Saudi Journal of Gastroenterology. 2014;20(6):366-370. 
27. Woo YS, Lee JK, Oh SH, et al. Role of SpyGlass Peroral Cholangioscopy in the Evaluation of 
Indeterminate Biliary Lesions. Digestive Diseases and Sciences. 2014;59(10):2565-2570. 
28. Maple JT, Ben-Menachem  T, Anderson AM, Appalaneni V, Banerjee S, Cash BD, Fisher L, 
Harrison ME, Fanelli R, Fukami N, Ikenberry SO, Jain R, Khan K, Krinsky ML, Strohmeyer L, 
Dominitz JA. Role of endoscopy in the evaluation of suspected choledocholithiais: American 
Society for Gastrointestinal Endoscopy (ASGE). Gastrointestinal Endoscopy 2010; Vol. 71, No. 
1, pp. 1-9 
 
22. Abbreviations and Definitions  
22.1. Abbreviations 
Abbreviations are shown in Table 22.1-1.   
Table 22.1-1: Abbreviations 
Abbreviation/Acronym 
Term 
ADE 
Adverse Device Effect 
AE 
BD 
Adverse Event 
Bile Duct 
BSC 
CBD 
CP 
Boston Scientific Corporation 
Common Bile Duct 
Chronic Pancreatitis 
CRF  
CRO 
CSEMS 
Case Report Form 
Contract Resource Organization 
Covered Self-Expanding Metal Stent 
CT 
Computed Tomography 
DFU 
DSC 
Directions for Use 
Direct Solitary Cholangioscopy 
eCRF 
EC 
Electronic Case Report Form 
Ethics Committee 
EDC 
EHL 
EPS 
Electronic Data Capture 
Electro-Hydraulic Lithotripsy 
Endoscopic Pancreatic Sphincterotomy 
ERC 
ERCP 
Endoscopic Retrograde Cholangiography 
Endoscopic Retrograde 
Cholangiopancreatography 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practices 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT 
Confidential                                            
 
            Template 90702637 Rev/Ver AH 
                                                                                                                       Page 49 of 51 
  
Table 22.1-1: Abbreviations 
Abbreviation/Acronym 
Term 
INR 
IRB 
International Normalized Ratio 
Institutional Review Board 
ISO 
ITT 
International Standards Organization 
Intent-to-Treat 
LL 
LFT 
MRCP 
PD 
Laser Lithotripsy 
Liver Function Test 
Magnetic Resonance Cholangiopancreatography 
Pancreatic Duct 
PI 
PP 
PT 
PTT 
Principal Investigator 
Per Protocol 
Prothrombin Time 
Partial Thromboplastin Time 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
22.2. Definitions 
Terms are defined in Table 22.2-1.  
Table 22.2-1: Definitions 
Term 
Definition 
Acute Pancreatitis 
 
 
 
 
Acute Cholecystitis 
 
 
Perforation 
 
 
Wound Infection 
 
 
Cholangitis 
 
 
 
Hemorrhage 
 
Abdominal pain and a serum concentration of pancreatic enzymes 
(lipase(required, amylase (optional)) three or more times the upper 
limit of normal, that required more than one night of 
hospitalization 
 
No suggestive clinical or radiographic signs of acute cholecystitis 
before the procedure and if emergency cholecystectomy is 
subsequently required 
 
Retroperitoneal or bowel-wall perforation documented by any 
radiographic technique or direc visual evidence. 
 
Requiring intervention otherwise considered as minor 
complication 
 
Elevation in termperature more than 38°C, thought to have a 
biliary cause, without concomitant evidence of acute cholecystitis, 
requiring intervention.  
 
Bleeding after the index procedure requiring transfusion of ≥4 
units of packed cells within a 24-hour period, or leading to 
relaparotomy/intervention 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT 
Confidential                                            
 
            Template 90702637 Rev/Ver AH 
                                                                                                                       Page 50 of 51 
  
Table 22.2-1: Definitions 
Term 
Definition 
 
 
(Emergency) 
(re)laparotomy 
 
Pneumonia 
 
 
Mortality 
 
Any (other) reason following either preoperative biliary drainage 
or another surgical procedure 
 
Pulmonary infection with radiological confirmation and requiring 
antibiotic treatment 
 
In-hospital death, due to protocol complications or any cause, 
including progression of disease, within the study period. 
Abbreviations are defined in Table 22.1-1. 
 
 
 
 
 
Probability of stones based on ASGE criteria are defined in Table 22.3-1. 
 
Table 22.23-2: Predictors of Choledocholithiasis 
Predictors of choledocholithiasis  
Very strong 
CBD stone on transabdominal US 
Clinical ascending cholangitis 
Bilirubin >4 mg/dL 
 
Strong 
Dilated CBD on US (>6 mm with gallbladder in situ) 
Bilirubin level 1.8mg/dL – 4 mg/dL 
 
Moderate 
Abnormal liver biochemical test other than bilirubin  
Age older than 55 y 
Clinical gallstone pancreatitis 
Assigning a likelihood of choledocholithiasis based on clinical predictors 
Presence of any very strong predictor                                           High 

E7131 
Non-Complex Biliary Stones DSC vs ERC RCT 
Confidential                                            
 
            Template 90702637 Rev/Ver AH 
                                                                                                                       Page 51 of 51 
  
Presence of both strong predictors                                                High 
No predictors present                                                                     Low 
All other patients                                                                           Intermediate 
Abbreviations are defined in Table 22.1-1.