Randomized Controlled Trial Comparing Covered and Uncovered Biliary Self Expanding Metal Stents (SEMS) for Pre-operative Drainage During Neoadjuvant Therapy in Patients With Pancreatic Cancer
Phase: NA
Conditions: Pancreatic Cancer
Sponsor: Boston Scientific Corporation

 
 
 
Pre-operative Biliary SEMS RCT During Neoadjuvant Therapy 
 
NCT02238847 
 
Clinical Protocol 
 
14 September 2015 

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CONSENT OF BOSTON SCIENTIFIC CORP. 
 
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Page 1 of 43 
 
 
 Randomized Controlled Trial Comparing Covered and Uncovered Biliary Self 
Expanding Metal Stents (SEMS) for Pre-operative Drainage During Neoadjuvant 
Therapy in Patients with Pancreatic Cancer 
 
Short Title 
Pre-operative Biliary SEMS RCT During Neoadjuvant Therapy 
 
 
CLINICAL PROTOCOL 
 
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Sponsored By 
Boston Scientific Corporation 
100 Boston Scientific Way 
Marlborough, MA 01752-1234 
USA 
 
 
 
 
 
This protocol contains confidential information for use by the Investigators and their 
designated representatives participating in this clinical investigation. It should be held 
confidential and maintained in a secure location. 
Do not copy or distribute without written permission from Boston Scientific Corporation. 

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Contact Information 
Role 
Contact  
Clinical Contact 
Nguyet Labenski 
Clinical Project Specialist 
Endoscopy 
Boston Scientific Corporation 
100 Boston Scientific Way 
Marlborough, MA 01752-1234 
Phone:  508-683-4065 
Email:   nguyet.labenski@bsci.com 
 
Lead Investigators 
Professor Hiroyuki Isayama, MD, PhD. 
Department of Gastroenterology, Graduate School of Medicine 
The University of Tokyo 
7-3-1 Hongo, Bunkyo-ku 
Tokyo 113-8655, Japan 
 
Professor Dong-Wan Seo, MD, PhD. 
Asan Medical Center 
88, Olympic-Ro 43-Gil, Songpa-Gu,  
Seoul 138-736, Korea 
 
 
Original Release: December 11, 2013 
Current Version:  September 14, 2015 

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Page 3 of 43 
 
Do not copy or distribute without written permission. 
 
Investigator’s Signature Page 
 
 
STUDY TITLE: 
Randomized Controlled Trial Comparing Covered and 
Uncovered Biliary Self Expanding Metal Stents (SEMS) for 
Pre-operative Drainage During Neoadjuvant Therapy in  
Patients with Pancreatic Cancer 
STUDY CENTER: 
_____________________________________________ 
(Print name of study center) 
 
PROTOCOL VERSION: 
AE 
 
 
We, the undersigned, have read and understand the protocol specified above and agree on its 
content.  We agree to perform and conduct the study as described in the protocol.  In addition, 
when applicable, we agree to enlist sub-investigators who also agree to perform and conduct the 
study as described in the protocol. 
 
 
 
 
Principal Investigator 
Print name: 
 
 
 
 
Co-Principal Investigator (if applicable) 
Print name: 
 
 
 
 
 
Date 
 
 
 
 
 
 
Date 
 

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Protocol Synopsis 
 
Full Title 
Randomized Controlled Trial Comparing Covered and Uncovered Biliary 
Self Expanding Metal Stents (SEMS) for Pre-operative Drainage During 
Neoadjuvant Therapy in  Patients with Pancreatic Cancer 
Abbreviated 
Title 
Pre-operative Biliary SEMS RCT During Neoadjuvant Therapy 
Primary 
Objective 
To demonstrate non-inferiority of Fully Covered biliary SEMS to 
Uncovered biliary SEMS in biliary drainage for the pre-operative 
management of biliary obstructive symptoms caused by pancreatic cancer 
in patients undergoing neoadjuvant therapy. 
Devices 
  Stent Type: 
FC Arm:  WallFlex Biliary RX Fully Covered Stent  
       UC Arm:  WallFlex Biliary RX Uncovered Stent 
Stent Diameter:  
8mm or 10mm 
Stent Length:  
40mm, 60mm, or 80mm 
The stent length will be selected to be such that the stent length should 
be long enough to cover the stricture completely but to leave sufficient 
length of normal bile duct for subsequent anastomosis. 
Device 
Indication 
The WallFlex Biliary RX Fully Covered Stent is indicated for use in the 
palliative treatment of biliary strictures produced by malignant neoplasms, 
relief of malignant biliary obstruction prior to surgery, and for treatment of 
benign biliary strictures. 
 
The WallFlex Biliary RX Uncovered Stent is indicated for use in the 
palliative treatment of biliary strictures produced by malignant neoplasms 
and relief of malignant biliary obstruction prior to surgery. 
Study Design 
Prospective, multi-center,  randomized, post-market 

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Primary 
Endpoint 
Successful pre-operative biliary drainage defined as absence of 
reinterventions for the management of biliary obstructive symptoms. 
• For patients undergoing surgery: from stent placement until surgery 
• For patients transitioning to palliative management: from stent 
placement until transition to palliation 
Secondary 
Endpoints 
 
 
 
 
 
 
 
 
 
 
 
 
1. 
Occurrence and severity of adverse events  related to the stent and/or 
stenting procedure  
2. 
Occurrence and severity of surgical complications  
3. 
Occurrence and severity of peri-surgical complications (up to 30 days 
after surgery)  
4. 
Ability to deploy the stent in a satisfactory position across the stricture 
(Stent Placement Success) 
5. 
Improvement of biliary obstructive symptoms during stent indwell at 
Week 1 and Monthly until surgery or transition to palliation as 
applicable, compared to Baseline 
6. 
Improvement of Laboratory Liver Function Tests (LFTs) until surgery 
for patients undergoing surgery, and at Week 1 and Monthly until 
transition to palliation, and at 1 year after stent placement for patients 
not undergoing surgery. 
7. 
Biliary Reintervention rate  
8. 
Ability to complete neoadjuvant therapy as intended without stent 
related interruptions of neoadjuvant therapy 
9. 
Stent migration rate 
10. Assessment by surgeon of interference, if any, of SEMS on time to 
surgery and/or success of pancreaticoduodenectomy  
11. For patients transitioning to palliative management:  Successful 
biliary drainage defined as absence of reinterventions for the 
management of biliary obstructive symptoms from stent placement to 
1 year after stent placement 
Hypothesis 
Statistical testing will be performed to determine if the rate of success when 
using the Fully Covered SEMS is non-inferior to the rate of success when 
using the Uncovered SEMS. The following hypothesis will be tested: 
Ho: πUC −πFC  ≥∆  (Inferior) 

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Ha: πUC −πFC  < ∆  (Non-inferior) 
where πFC  and πUC  are the probabilities of having success in the WallFlex 
Fully Covered Stent and WallFlex Uncovered Stent arms respectively, and 
∆ is defined as the non-inferiority margin. 
The sample size was calculated for the test using an exact non-inferiority 
test. The assumed success rates for both study arms and the non-inferiority 
margin are guided by the following analysis of literature: 
The success rate estimate is extracted from a full literature search which 
yielded nine articles (377 patients) 2, 7, 21, 24, 25, 27, 29-31 on the use of metal 
stents for pre-operative biliary drainage.  The nine articles yielded a success 
rate estimate of 84.6% with a 95% CI of (80.5% - 87.9%). 
Each arm is assumed to have a success rate of 80.5%.  The non-inferiority 
margin (Δ) is set at 20%.  Given these assumptions a sample size of 51 x 2 
= 102 patients provide 80% power to reject the null hypothesis. If the p-
value calculated for the test is below 0.05 it will be concluded that the test 
is significant, and that the WallFlex Fully Covered stent is non-inferior to 
the WallFlex Uncovered stent.   
An additional 20% of patients will be enrolled to compensate for possible 
loss of patients to follow-up, giving a total sample size of 122 patients. 
 
Planned 
Number of 
Patients 
122 
Planned 
Number of 
Sites 
6-12 
Key Inclusion 
Criteria 
1. 
Age 18 or older 
2. 
Patient indicated for biliary metal stent placement for the treatment of 
jaundice and/or cholestasis 
3. 
Willing and able to comply with the study procedures and provide 
written informed consent to participate in the study 
4. 
Suspicion of pancreatic adenocarcinoma 

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5. 
Likely indicated for neoadjuvant treatment 
6. 
Distal biliary obstruction consistent with pancreatic cancer 
7. 
Location of distal biliary obstruction such that it would allow the 
proximal end of a stent to be positioned at least 2 cm from the hilum 
8. 
Endoscopic and surgical treatment to be provided at the same 
institution 
Key Exclusion 
Criteria 
1. 
Benign biliary strictures 
2. 
Malignancy secondary to Intraductal Papillary Mucinous Neoplasm  
3. 
Surgically altered anatomy where ERCP is not possible  
4. 
Previous biliary drainage using a SEMS or multiple plastic stents 
5. 
Contraindications for endoscopic techniques 
6. 
Patients who are currently enrolled in another investigational trial that 
would directly interfere with the current study 
7. 
Pregnancy 
Visits 
• 
Screening 
• 
Baseline 
• 
Stent Placement Procedure Visit 
• 
Pre-Operative Follow-Up Visit (Week 1 and Monthly until Surgery or 
Transition to Palliation) 
• 
Biliary Reintervention Visit (as needed) 
• 
Curative Intent Surgery 
• 
Transition to Palliative Management Visit (as needed) 
• 
Post-Operative Follow-Up Visit (30 day Post-Surgery visit)  
• 
Long Term Follow-Up Visit (1 year after initial treatment for patients 
that have transitioned to palliation or 1 year post-stent placement for 
patients that have not undergone surgery or transitioned to palliation 
(with or without Neoadjuvant Therapy)) 
 

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TABLE OF CONTENTS 
TITLE PAGE  .................................................................................................................................................... 1 
1.  INTRODUCTION .................................................................................................................... 11 
2.  OBJECTIVES ......................................................................................................................... 13 
3.  DESIGN ................................................................................................................................. 13 
3.1. Scale and Duration ................................................................................................. 13 
3.2. Treatment Assignment........................................................................................... 13 
4.  ENDPOINTS ........................................................................................................................... 14 
4.1.  Primary Endpoint .................................................................................................... 14 
4.2.  Secondary Endpoints ............................................................................................... 14 
5.  PATIENT  SELECTION ........................................................................................................... 15 
5.1. Inclusion Criteria ................................................................................................... 15 
5.2. Exclusion Criteria .................................................................................................. 15 
6.  STUDY DEVICES ................................................................................................................... 16 
7.  STUDY VISITS ....................................................................................................................... 17 
7.1. Visit Schedule ......................................................................................................... 17 
7.2. Screening – Office Visit ......................................................................................... 20 
7.3. Baseline Visit – Office Visit ................................................................................... 20 
7.4. Tumor Diagnosis, Staging, and Characteristics – Office Visit .......................... 21 
7.5. Planned Neoadjuvant Therapy ............................................................................. 21 
7.6. Stent Placement Procedure Visit – Office Visit ................................................... 21 
7.7. Pre-Operative Follow-Up Visit – Phone and/or Office Visit .............................. 21 
7.8. Biliary Reintervention Visit (Arm 1 or 2) – as needed ....................................... 22 
7.9. Curative Intent Surgery – Office Visit ................................................................. 22 
7.10. Transition to Palliative Management Visit (as needed) – Phone and/or Office 
Visit .......................................................................................................................... 22 
7.11. Post-Operative Follow-Up Visit (30 days) – Phone and/or Office Visit ............ 23 

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7.12.   Long Term Follow-Up Visit (1 year after initial treatment for patients that have 
transitioned to palliation or 1 year post-stent placement for patients that have not 
undergone surgery or transitioned to palliation (with or without Neoadjuvant 
Therapy) – Phone and/or Office Visit .................................................................. 23 
7.13.    Study Completion ................................................................................................ 24 
8.  STATISTICAL CONSIDERATIONS .......................................................................................... 24 
8.1 
Hypotheses .............................................................................................................. 24 
8.2 
Sample Size ............................................................................................................. 24 
8.3 
Analysis Populations .............................................................................................. 25 
8.4 
Data Analysis .......................................................................................................... 25 
9.   POTENTIAL RISKS AND BENEFITS ...................................................................................... 27 
9.1.  Anticipated Adverse Device Effects ....................................................................... 27 
9.2.   Anticipated Surgical Adverse Events .................................................................... 27 
9.3.   Risk Minimization Actions ..................................................................................... 28 
9.4.  Anticipated Benefits ................................................................................................. 28 
9.5.  Risk to Benefit Rationale......................................................................................... 28 
10.  SAFETY REPORTING .......................................................................................................... 28 
10.1.  Definitions and Classification ............................................................................... 28 
10.2.  Relationship to Study Device(s) ............................................................................ 30 
10.3.  Investigator Reporting Requirements ................................................................. 31 
10.4.  Boston Scientific Device Deficiencies ................................................................... 31 
10.5.  Reporting to Regulatory Authorities / IRBs / Investigators .............................. 32 
11.  BIBLIOGRAPHY .................................................................................................................. 32 
APPENDIX B: SPONSOR REQUIRED PROTOCOL SECTIONS .................................. 34 
B.1.  DATA MANAGEMENT ....................................................................................................... 34 
B.2.  AMENDMENTS .................................................................................................................. 35 
B.3.   DEVICE/EQUIPMENT ACCOUNTABILITY ......................................................................... 35 
B.4.  DEVIATIONS ...................................................................................................................... 35 

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B.5.  COMPLIANCE .................................................................................................................... 36 
B.6.  INSTITUTIONAL REVIEW BOARD/ETHICS COMMITTEE .................................................. 38 
B.7.  MONITORING .................................................................................................................... 39 
B.8.  INSURANCE ....................................................................................................................... 39 
B.9.  INFORMED CONSENT ........................................................................................................ 39 
B.10.  PUBLICATION POLICY .................................................................................................... 40 
B.11.  DEFINITIONS OF COMPLICATION CRITERIA (PER VAN DER GAAG ARTICLE): .............. 41 
B.12.  ABBREVIATIONS AND DEFINITIONS ............................................................................... 42 

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1.  Introduction 
 
In the United States, pancreatic cancer is the second most common digestive cancer1  and the 
fourth leading cause of death with a 5-year survival rate of only 5%.2   Globally, there are an 
estimated 216,000 new cases of pancreatic cancer annually.3  Pancreatic cancer, which is the 
most prevalent peri-ampullary cancer, is located in the head of the pancreas in approximately 
two thirds of cases.4   Patients with pancreatic cancer presenting with biliary obstruction can be 
stratified into patients with unresectable tumors, with borderline resectable or locally advanced 
tumors, or with resectable tumors.  More than 70% of pancreatic cancer patients are poor 
candidates for surgery or are deemed unresectable5; the WallFlex Biliary SEMS are currently 
indicated for use in these patients. 
 
Some patients may be candidates for PD with curative intent, however, 25%-41% do not undergo 
PD as planned due to disease progression, evolving comorbidities, or decline in performance 
status during the time between diagnosis and scheduled PD.6-8  Pre-operative neoadjuvant chemo 
or chemoradiation therapy is increasingly considered in the treatment of patients with resectable 
or borderline resectable pancreatic cancer.  The aim is to downsize tumors and improve the 
likelihood of a margin-free (R0) resection, to provide early treatment of micrometastases, and 
ultimately to optimize post-operative survival.9-13 In a recent report, 32 of 84 (38%) patients with 
borderline resectable disease underwent a PD after neoadjuvant therapy, with R0 resection 
achieved in 94% of patients and resulting median survival of 40 months post PD.13   In another 
report on 132 patients with resectable pancreatic cancer, it was found that combined neoadjuvant 
chemoradiation and PD yielded a median survival of 21 months from the time of tissue 
diagnosis, and at a median follow-up of 14 months 42 of 132 patients (32%) survived with no 
clinical or radiographic evidence of disease.14   The duration of neoadjuvant chemoradiation 
typically ranges from 2 to 7 months6,14 and tends to require a subsequent pre-operative resting 
and restaging period which can last up to several months.7   
  
Periampullary cancer including cancer in the head of the pancreas is associated with biliary 
obstructive symptoms such as jaundice at initial patient presentation in approximately 50%-70% 
of patients.7  Biliary obstruction requires biliary decompression.6,15  Indeed, if left untreated, 
prolonged biliary obstruction leads to coagulopathy, malabsorption and consequent progressive 
malnutrition, pruritus, hepatic dysfunction, recurrent attacks of cholangitis and altered bile salt 
metabolism.16,17  Pre-operative biliary drainage provides relief of biliary obstructive symptoms 
during neoadjuvant therapy18,19 and improves post PD tissue healing in response to reduced 
bilirubin levels.20  Without such pre-operative drainage patients may lose their resectable or 
potentially resectable status due to interruption of the neoadjuvant therapy and/or delayed 
scheduling of the intended PD.  In addition, for patients receiving 3 to 4 months of neoadjuvant 
therapy, biliary drainage may be beneficial since some chemotherapeutic agents require adequate 
liver function and pre-operative immunosuppression can increase susceptibility to the risks of 
cholangitis if bile duct drainage is inadequate.21  If severely jaundiced patients do undergo PD, 
they may be at risk of significant post-operative complications36 such as renal failure and 

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sepsis.22,23  It is therefore important that pre-operative biliary drainage be provided during 
neoadjuvant therapy and the subsequent restaging and resting period.  
 
Pre-operative biliary drainage has traditionally been achieved with plastic stents.  However, these 
stents have been associated with high complication rates and relatively low success rates in pre-
operative management of biliary obstruction.6,21,24-27  Plastic stents used for pre-operative 
drainage can occlude within a few weeks which in turn may necessitate additional pre-operative 
ERCPs21.  The use of SEMS provides a viable alternative that has been shown to be superior to 
plastic stents for pre-operative biliary drainage due to lower rates of occlusion, fewer episodes of 
cholangitis/cholestasis, fewer additional ERCPs before surgery, and longer stent patency 
resulting in most patients completing  uninterrupted neoadjuvant chemoradiation therapy and 
preventing delays of surgery.1,24,27 
 
A literature review was conducted of clinical success of pre-operative biliary drainage using 
plastic or metal biliary stenting including all SEMS types used.  Two associated meta-analyses 
were generated based on published reports of ratios of the number of patients experiencing 
clinical success in pre-operative biliary drainage without stent related complications over the 
total number of stented patients.  A meta-analysis representing a total of 429 patients in six 
publications using plastic biliary stents  yielded a biliary drainage success rate estimate of 45.9% 
[95% CI, 34.7% - 57.5%].2,6, ,24-27  A meta-analysis representing a total of 377 patients in nine 
publications using SEMS yielded a biliary drainage success rate estimate of  84.6% [95% CI, 
80.5% - 87.9%].2, 7, 21, 24, 25, 27, 29-31 In patients who do ultimately undergo PD with curative intent, 
the SEMS is removed en-bloc inside the surgical specimen.  Six of the 9 publications reporting 
on the use of pre-operative biliary drainage using SEMS state explicitly on the fact that SEMS do 
not interfere with successful PD and could be easily removed intra-operatively without 
complications. 7,21,24,25,27,31  Some studies have reported an increased risk of post-operative wound 
infection13,33-35, but there were no other reported increases in  intra-operative or post-operative 
complications related to the use of SEMS.  In addition, SEMS could be easily removed intra-
operatively without complications.20, 27-30 
 
Pre-operative biliary drainage (PBD) prior to Pancreaticoduodenectomy (PD) continues to be 
routine in many centers despite retrospective data showing that PBD increases post-operative 
wound infection.13,33-35  It was shown that these post-operative wound infections were classified 
on a grading scale of 1-5, with all reported occurrences rated as either 1 (oral medication and 
bedside intervention) or 2 (IV medication, TPN, enteral nutrition, or blood), and managed non-
invasively.33  Other studies have also reported an increase in post-operative wound infection in 
the PBD group, but have indicated that although there is an increase in length of hospitalization, 
the length of time under anesthesia, amount of blood loss, and transfusion requirements were 
unaffected.32,34 
 
In line with the findings summarized above, SEMS have emerged as an alternative to using 
plastic stents for pre-operative biliary drainage.  Several opinion-leading centers in this field 
have adopted SEMS drainage as their standard of practice in PD-bound patients undergoing 

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neoadjuvant therapy. Most recently leading cancer centers7, 21, 32  have published that the use of 
pre-operative biliary SEMS, and not plastic stents, in patients with resectable or potentially 
resectable pancreatic or periampullary cancer receiving neoadjuvant therapy is effective and safe.  
Boston Scientific is proposing a multi-center, randomized, prospective, post-market trial on the 
use of SEMS for biliary drainage in patients with pancreatic cancer undergoing neoadjuvant 
therapy.   
2.  Objectives 
 
The purpose of this clinical trial is to demonstrate non-inferiority of Fully Covered biliary SEMS 
to Uncovered biliary SEMS in biliary drainage for the pre-operative management of biliary 
obstructive symptoms caused by pancreatic cancer in patients undergoing neoadjuvant therapy. 
3.  Design 
 
This is a post-market, prospective, multi-center, randomized study evaluating covered and 
uncovered SEMS for pre-operative management of patients with pancreatic cancer undergoing 
neoadjuvant therapy. 
3.1. Scale and Duration 
Patients that have gone to surgery will be followed for 30 days post-surgery.  For patients that 
have transitioned to palliation, the Long Term Follow-Up Visit will occur one (1) year after 
initial treatment.  Patients that have not gone to surgery and have not transitioned to palliation 
(with or without Neoadjuvant Therapy) will be followed up to 1 year post-stent placement.  
There will be 6-12 participating centers with anticipated enrollment of 122 patients. 
 
At each investigational center, there will be one principal investigator (PI) who will be an 
endoscopist.  Where possible at least one co-investigator should be a pancreaticobiliary surgeon.   
3.2. Treatment Assignment 
Patients will be randomized at Screening in equal proportions of 1:1 ratio between Arm 1 and 
Arm 2 as follows: 
• Arm 1: WallFlex Biliary RX Fully Covered Stent 
 
• Arm 2: WallFlex Biliary RX Uncovered Stent 
 
Block randomization through an online database system will be used.  Randomization will be 
stratified by study center. 

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4.  Endpoints  
4.1.  Primary Endpoint 
Successful pre-operative biliary drainage defined as absence of reinterventions for the 
management of biliary obstructive symptoms. 
• For patients undergoing surgery: from stent placement until surgery 
• For patients transitioning to palliative management: from stent placement until transition 
to palliation 
4.2.  Secondary Endpoints 
1. Occurrence and severity of adverse events related to the stent and/or stenting procedure  
2. Occurrence and severity of surgical complications  
3. Occurrence and severity of peri-surgical complications (up to 30 days after surgery)  
4. Ability to deploy the stent in satisfactory position across the stricture (Stent Placement 
Success) 
5. Improvement of biliary obstructive symptoms  during stent indwell at Week 1 and 
Monthly until surgery or transition to palliation as applicable, compared to Baseline 
6. Improvement of Laboratory Liver Function Tests (LFTs) until surgery for patients 
undergoing surgery, and at Week 1 and Monthly until transition to palliation, and at 1 
year after stent placement for patients not undergoing surgery  
7. Biliary Reintervention rate 
8. Ability to complete neoadjuvant therapy as intended without stent related interruptions of 
neoadjuvant therapy 
9. Stent migration rate  
10. Assessment by surgeon of interference, if any, of SEMS on time to surgery and/or 
success of pancreaticoduodenectomy 
11. For patients transitioning to palliative management:  Successful biliary drainage defined 
as absence of reinterventions for the management of biliary obstructive symptoms from 
stent placement to 1 year after stent placement 

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5.  Patient  Selection  
5.1. Inclusion Criteria 
Patients who meet all of the criteria listed below (see Table 1) may be given consideration for 
inclusion in this clinical investigation, provided no exclusion criterion (see Table 2) is met. 
Table 1: Inclusion Criteria 
Clinical 
Inclusion 
Criteria 
1. Age 18 or older 
2. Patient indicated for biliary metal stent placement for the treatment of 
jaundice and/or cholestasis 
3. Willing and able to comply with the study procedures and provide written 
informed consent to participate in the study 
4. Suspicion of pancreatic adenocarcinoma 
5. Likely indicated for neoadjuvant treatment 
6. Distal biliary obstruction consistent with pancreatic cancer 
7. Location of distal biliary obstruction such that it would allow the proximal 
end of a stent to be positioned at least 2 cm from the hilum 
8. Endoscopic and surgical treatment to be provided at the same institution 
 
 
5.2. Exclusion Criteria 
Patients who meet any one of the following criteria (See Table 2) will be excluded from this 
clinical study. 
Table 2: Exclusion Criteria 
Clinical 
Exclusion 
Criteria 
1. Benign biliary strictures 
2. Malignancy secondary to Intraductal Papillary Mucinous Neoplasm  
3. Surgically altered anatomy where ERCP is not possible  
4. Previous biliary drainage using a SEMS or multiple plastic stents 
5. Contraindications for endoscopic techniques  
6. Patients who are currently enrolled in another investigational trial that 
would directly interfere with the current study 
7. Pregnancy 
 

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6.  Study Devices 
 
The WallFlex Biliary RX Fully Covered stent and the WallFlex Biliary RX Uncovered stent will 
be used for the treatment of patients.   
The WallFlex Biliary RX Fully Covered and the WallFlex Biliary RX Uncovered Stent Systems 
are indicated for use in the palliative treatment of biliary strictures produced by malignant 
neoplasms and relief of malignant biliary obstruction prior to surgery; the WallFlex Biliary RX 
Fully Covered Stent System is also indicated for use in the palliative treatment of biliary 
strictures produced by malignant neoplasms and treatment of benign biliary strictures, per CE 
Mark. For a detailed description of the WallFlex Biliary Stent Systems, please reference the 
Directions for Use (DFU) included in each device package.  
Investigators should use the WallFlex Biliary RX Fully Covered and Uncovered Stent Systems 
in accordance with the DFUs. 
Study devices are labeled on the box and inner pouch and contain information including but not 
limited to:  device name and dimensions, lot number, expiration date, name of legal 
manufacturer, and investigational use statement. Device labeling will be provided in local 
language(s) as per national regulations. 
Study devices will be available in the following dimensions: 
 
WallFlex Biliary 
RX Stent 
Diameter 
Length 
Delivery System 
Diameter 
Guidewire 
Diameter 
Uncovered 
8 mm 
10 mm 
40, 60, 80mm 
40, 60, 80mm 
8 Fr 
.035” 
Fully Covered 
8 mm 
10 mm 
60, 80mm 
40, 60, 80mm 
8.5 Fr 
.035” 
 
Stent placement should be such that the proximal end of the stent is minimum 2 cm from the 
hilum.  Performing a biliary or pancreatic sphincterotomy or enlarging a prior sphincterotomy 
will be done at the discretion of the endoscopist.  Per literature, it is recommended that the 
shortest length of stent required to bridge the stricture21 is used so as to leave enough of the 
normal bile duct above the stent available for subsequent anastomosis7, 21,24,25,29.  It is hence 
anticipated that SEMS of 80 mm length will rarely or never be selected in this trial.   
 
In case of a failed stent placement due to a device event, a new attempt to place a stent will be 
made.  If a stent placement is not possible due to non-device related reasons (such as inability to 
cannulate the CBD or reach the papilla, extensive tumor growth at site of papilla, etc.), 
interventional radiologic (IR) access is allowed and, where possible, should be associated with 
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procedure.  Percutaneous transhepatic cholangiography (PTC) and a subsequent internal drainage 
with a stent placement may be done at the same time (one-stage procedure), or PTC with 
external drainage may be performed 2-3 days before stent insertion (two-stage procedure) per 
standard of practice.  If access to the biliary tree or endoscopic placement of the study stent 
through a “rendez-vous” procedure fails and patient requires percutaneous transhepatic biliary 
drainage (PTBD), then the patient will exit the study.  In case of failure of SEMS functionality 
during the neoadjuvant therapy, a new investigational SEMS may be placed, covered or 
uncovered at the discretion of the investigator.  In case of failure of SEMS functionality after 
transition to palliation, no new investigational SEMS will be provided and patient should be 
treated per standard of practice.   
7.  Study Visits 
7.1. Visit Schedule 
The schedule of observations and assessments to take place during the study is shown in Table 3 
below. 
 
 
 

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Table 3.  Study Event Schedule 
 
Procedure/Assessment 
 
 
 
 
Screening 
Baseline 
Stent 
Placement 
Procedure 
Visit 
Pre-Operative Follow-Up 
Visits 
 
 
 
Biliary 
Reintervention 
 
 
 
Curative 
Intent 
Surgery 
 
 
 
Transition to 
Palliative 
Management 
Visit 
 
 
 
Post-
Operative 
Follow-Up 
Visit - 
30 days 
from 
surgery  
(±15 Days) 
Office 
Visit 
 
 
 
*Long Term 
Follow-Up Visit  
(± 30 Days) 
 
 
Week 1 
(± 2 Days) 
Office 
Visit/ 
Telephone 
Interview 
 
 
 
 
Monthly 
(±15 Days) 
Office 
Visit/ 
Telephone 
Interview 
 
ICF 
X 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
 
X 
 
 
 
 
 
 
 
 
 
 
Medical history 
 
X 
 
 
 
 
 
 
 
 
 
 
Collection of Weight 
 
X 
 
 
X 
 
X 
 
 
 
 
 
Assessment of Biliary 
Obstructive Symptoms 
 
X 
 
 
X 
 
X 
 
X 
 
 
X 
X 
 
 
X (if applicable) 
Laboratory Liver Function Test 
(LFTs)  
 
X 
 
 
X 
 
X 
 
 
 
X 
 
 
X (if applicable) 
Imaginga  
 
X 
 
 
 
 
 
 
 
 
 
 
Tumor Diagnosis, Staging, and 
Characteristics 
X 
 
 
 
 
 
 
 
 
 
Randomization 
X 
 
 
 
 
 
 
 
 
 
 
 
Stent Details 
 
 
X 
 
 
 
 
X (if applicable) 
X 
 
 
 
Procedure Details 
 
 
X 
 
 
 
 
X (if applicable) 
 
 
 
 
Operative Details 
 
 
 
 
 
 
 
 
X 
 
 
 
Specimen Pathology 
 
 
 
 
 
 
 
 
X 
 
 
 
Planned Neoadjuvant therapy  
X 
 
 
 
 
 
 
 
 
 
Administered Neoadjuvant 
therapy (if applicable) 
 
 
 
 
X 
 
X 
 
X 
 
 
 

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Procedure/Assessment 
 
 
 
 
Screening 
Baseline 
Stent 
Placement 
Procedure 
Visit 
Pre-Operative Follow-Up 
Visits 
 
 
 
Biliary 
Reintervention 
 
 
 
Curative 
Intent 
Surgery 
 
 
 
Transition to 
Palliative 
Management 
Visit 
 
 
 
Post-
Operative 
Follow-Up 
Visit - 
30 days 
from 
surgery  
(±15 Days) 
Office 
Visit 
 
 
 
*Long Term 
Follow-Up Visit  
(± 30 Days) 
 
 
Week 1 
(± 2 Days) 
Office 
Visit/ 
Telephone 
Interview 
 
 
 
 
Monthly 
(±15 Days) 
Office 
Visit/ 
Telephone 
Interview 
 
Surgical assessment of tumor 
invasion 
 
 
 
 
 
 
 
 
X 
 
 
 
Patient’s overall health status  
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
Adverse events and 
reinterventions 
              X (as applicable) 
Device Events 
                                                                                                                        X (as applicable) 
Protocol Deviation 
              X (as applicable) 
 
 
a ERCP, CT and/or MRI 
 
*Long Term Follow-Up Visit: 1 year after initial treatment for patients that have transitioned to palliation or 1 year post-stent placement for patients that have not undergone 
surgery or transitioned to palliation (with or without Neoadjuvant Therapy)

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7.2. Screening – Office Visit 
• Informed Consent  
• Eligibility Criteria Assessment 
• Randomization 
 
No study-specific testing will be conducted until after the patient has signed an Informed 
Consent Form. A Screen Failure/Enrolled Log will be maintained in EDC by the center to 
document select information about candidates who signed consent.  
Written Informed Consent must be obtained for all patients who are potential study 
candidates.  Patients will be asked to sign the Informed Consent Form before any study-
specific tests or procedures are performed.  The Informed Consent Form is study-specific and 
must be approved by the study Institutional Review Board (IRB).  Study personnel should 
explain that even if a patient agrees to participate in the study and signs an Informed Consent 
Form, the inclusion/exclusion criteria may demonstrate that the patient is not a suitable 
candidate for the study. Screening and enrollment information will be collected in the 
database for all patients who sign a consent form.  
  
7.3. Baseline Visit – Office Visit 
• Demographics 
• Medical history  
• Collection of Weight 
• Patient’s overall health status 
• Assessment of Biliary Obstructive Symptoms 
o Right Upper Quadrant Pain 
o Fever/Chills 
o Jaundice 
o Itching 
o Dark urine 
o Pale stools 
o Nausea/Vomiting 
• Laboratory Liver Function Tests (LFTs)  
o Serum Albumin level 
o Total Bilirubin 
o Alkaline Phosphatase 
o SGPT (ALT) 
 

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• Imaging  
 
7.4. Tumor Diagnosis, Staging, and Characteristics – Office Visit 
• Tumor Diagnosis, Staging, and Characteristics can occur any time between the 
Screening Visit and the Stent Placement Procedure Visit 
7.5. Planned Neoadjuvant Therapy  
• Planned Neoadjuvant Therapy can occur any time between the Screening Visit 
and the Stent Placement Procedure Visit 
7.6. Stent Placement Procedure Visit – Office Visit 
• Placement of WallFlex Biliary RX stent(s) 
o During WallFlex Biliary RX placement the stent should be adjusted with 
the proximal end of the stent no more than 1-2cm beyond the proximal 
end of the stricture. This favors both stability and homogeneous 
development of tissue hyperplasia at the proximal uncovered part.  
• Procedure Details 
• Stent Details 
• Adverse Events (as applicable) 
• Device Events (as applicable) 
7.7. Pre-Operative Follow-Up Visit – Phone and/or Office Visit 
• Week 1 and Monthly until surgery or transition to palliation as applicable 
• Collection of Weight 
• Patient’s overall health status  
• Assessment of Biliary Obstructive Symptoms 
o Right Upper Quadrant Pain 
o Fever/Chills 
o Jaundice 
o Itching 
o Dark urine 
o Pale stools 
o Nausea/Vomiting 
• Laboratory Liver Function Tests (LFTs)  
o Serum Albumin level 
o Total Bilirubin 
o Alkaline Phosphatase 
o SGPT (ALT) 
 

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• Administered Neoadjuvant therapy 
• Adverse events and reinterventions (as applicable) 
• Device Events (as applicable) 
7.8. Biliary Reintervention Visit (Arm 1 or 2) – as needed 
• Timing 
• Reason for Biliary Reintervention 
• Type of Biliary Reintervention (including SEMS placement or removal) 
• Adverse Events (as applicable) 
• Device Events (as applicable) 
7.9. Curative Intent Surgery – Office Visit 
• Patient’s overall health status 
• Assessment of Biliary Obstructive Symptoms 
o Right Upper Quadrant Pain 
o Fever/Chills 
o Jaundice 
o Itching 
o Dark urine 
o Pale stools 
o Nausea/Vomiting 
• Operative Details 
• Stent Removal 
• Surgical Complications including intraoperative blood loss 
• Intra- and Post-Operative Transfusion 
• Post-Operative Course 
• Specimen Pathology 
• Administered Neoadjuvant therapy 
• Adverse events and reinterventions (as applicable) 
• Device Events (as applicable) 
7.10. Transition to Palliative Management Visit (as needed) – Phone and/or Office 
Visit 
• Assessment of Biliary Obstructive Symptoms 
o Right Upper Quadrant Pain 
o Fever/Chills 
o Jaundice 
o Itching 
o Dark urine 
o Pale stools 

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o Nausea/Vomiting 
• Laboratory Liver Function Tests (LFTs) 
o Serum Albumin level 
o Total Bilirubin 
o Alkaline Phosphatase 
o SGPT (ALT) 
• Adverse Events (as applicable) 
• Device Events (as applicable) 
7.11. Post-Operative Follow-Up Visit (30 days) – Phone and/or Office Visit 
• Day 30 Post-Surgery Visit  
• Patient’s overall  health status 
• Assessment of Biliary Obstructive Symptoms 
o Right Upper Quadrant Pain 
o Fever/Chills 
o Jaundice 
o Itching 
o Dark urine 
o Pale stools 
o Nausea/Vomiting 
• Adverse events and reinterventions (as applicable) 
• Device Events (as applicable) 
 
7.12.   Long Term Follow-Up Visit (1 year after initial treatment for patients that 
have transitioned to palliation or 1 year post-stent placement for patients that 
have not undergone surgery or transitioned to palliation (with or without 
Neoadjuvant Therapy) – Phone and/or Office Visit 
• For patients not undergoing surgery 
• Patient’s overall health status 
• Assessment of Biliary Obstructive Symptoms 
o Right Upper Quadrant Pain 
o Fever/Chills 
o Jaundice 
o Itching 
o Dark urine 
o Pale stools 
o Nausea/Vomiting 
• Laboratory Liver Function Tests (LFTs) 
o Serum Albumin level 
o Total Bilirubin 
o Alkaline Phosphatase 

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o SGPT (ALT) 
 
• Adverse events and reinterventions (as applicable) 
• Device Events (as applicable) 
 
  7.13.    Study Completion 
End of study will be reached at: 
• Up to 30 days post-surgery for those patients undergoing potential curative intent 
surgery 
• 1 year post stent placement for patients that have transitioned to palliation within 12 
months after stent placement 
• 1 year post stent placement for patients who do not undergo potential curative intent 
surgery and do not transition to palliation within 12 months after stent placement 
(with or without Neoadjuvant Therapy) 
End of study will be reached at study completion, at patient withdrawal from study, or at 
death, whichever comes first.   
8.  Statistical Considerations 
8.1  Hypotheses 
Compared to the use of an Uncovered SEMS, use of a Fully Covered SEMS may present a 
higher risk of migration, but offers the ability to remove the stent were this deemed indicated 
by the treating endoscopist.  Statistical testing will be performed to determine if the rate of 
success when using the Fully Covered SEMS is non-inferior to the rate of success when 
using the Uncovered SEMS. The following hypothesis will be tested: 
 
𝐻𝐻𝐻𝐻: 𝜋𝜋𝑈𝑈𝑈𝑈−𝜋𝜋𝐹𝐹𝐹𝐹 ≥∆  (Inferior) 
𝐻𝐻𝐻𝐻: 𝜋𝜋𝑈𝑈𝑈𝑈−𝜋𝜋𝐹𝐹𝐹𝐹 < ∆  (Non-inferior) 
 
where 𝜋𝜋𝐹𝐹𝐹𝐹  and 𝜋𝜋𝑈𝑈𝑈𝑈 are the probabilities of having success in the WallFlex Fully Covered 
Stent and WallFlex Uncovered Stent arms respectively, and ∆ is defined as the non-
inferiority margin. 
8.2 Sample Size  
The sample size was calculated for the test using an exact non-inferiority test in StatXact 9® 
software. The non-inferiority margin (Δ) is set at 20%. Each arm is assumed to have a 
success rate of 80.5%, which is the lower 95% CI boundary from the meta-analysis, which is 

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done below. Given these assumptions a sample size of 51 x 2 = 102 patients provides 80% 
power to reject the null hypothesis listed above. If the p-value calculated for the test is below 
0.05 it will be concluded that the test is significant and that the WallFlex Fully Covered stent 
is non-inferior to the WallFlex Uncovered stent.   
 
In order to compensate for possible loss of patients to follow-up or per Endoscopist’s 
decision to select the Uncovered stent based on ductal anatomy, namely stricture involving 
the low cystic duct confluence, an additional 20% of patients will be enrolled giving a total 
sample size of 122 patients. 
The success rate estimate is extracted from a full literature search which yielded nine articles 
(377 patients) 2, 7, 21, 24, 25, 27, 29-31 on the use metal stents for pre-operative biliary drainage.  
The nine articles yielded a success rate estimate of 84.6% with a 95% CI of (80.5%, 87.9%). 
8.3 Analysis Populations 
8.3.1   Enrolled Cohort 
A patient is considered “enrolled” after signing the study-specific ICF.  Patients who sign the 
ICF but subsequently do not meet one or more of the eligibility criteria provided in Section 
5.1 and Section 5.2 will be considered screen failures and excluded from the study. 
8.3.2. Intent-to-Treat Cohort 
This cohort consists of those “enrolled” patients who meet all inclusion/exclusion criteria and 
are subsequently randomized. 
8.3.3.   Per-Protocol Cohort 
The per-protocol cohort is a subset of the ITT patients who are treated per protocol and have 
no major protocol deviations (per ICH E9 definitions). 
8.4 Data Analysis 
All statistical analyses will be done using The SAS System software, version 8 or higher 
(Copyright © 2000 SAS Institute Inc., SAS Campus Drive, Cary, North Carolina 27513, 
USA. All rights reserved).  
 
The distribution of prognostic factors between patients with and without data will be 
examined. Statistical models that account for censored data will be employed in appropriate 
circumstances, e.g. for time-to-event outcomes. Sensitivity analyses will be conducted to 
assess the impact of missing data on the interpretation of the results, e.g. a tipping point 
analysis.  
 
8.4.1.  Baseline Data 
 

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Patient demographics, clinical history, risk factors, obstructive symptoms, LFTs, tumor 
diagnosis, patient overall health, neoadjuvant therapy, and assessment of tumor invasion will 
be summarized using descriptive statistics (e.g., mean, standard deviation, n, minimum, 
maximum) for continuous variables and frequency tables for discrete variables.   
 
8.4.2.  Post Procedure Data 
 
Post-procedure information will be collected at regularly scheduled follow-up examinations 
as detailed in the clinical study event schedule and will be summarized using descriptive 
statistics for continuous variables (e.g., mean, standard deviation, n, minimum, maximum) 
and frequency tables or proportions for discrete variables.  
 
8.4.3.  Interim Analyses 
 
No formal interim analyses are planned for this study. 
 
8.4.4.  Subgroup Analyses 
 
Stratified analyses will include tabulating the primary endpoint and select secondary 
endpoints by patients that undergo potentially curative surgery versus transition to palliation, 
by bilirubin level above or below 3 mg/dL, and gender.  
 
8.4.5.  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.  
 
8.4.6.  Multivariable Analyses 
 
Univariate and multivariate analyses may be performed to assess the effect of potential 
predictors on the primary endpoint using logistic regression or Cox Proportional Hazards 
regression.  
Variables from the following categories will be considered as possible predictors: 
demographics, tumor diagnosis, baseline LFTs, neoadjuvant therapy protocol, obstructive 
symptoms, baseline health status, and medical history. Factors from the univariate model 
with p≤0.20 will also be modeled multivariately using a stepwise procedure in a generalized 
linear model or Cox Proportional Hazards regression model. The significance thresholds for 
entry and exit into the model will be set to p≤0.10. 
 
8.4.7.  Changes to Planned Analyses 
 

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Any changes to the planned statistical analyses made prior will be documented in an 
amended Statistical Analysis Plan.  
9.   Potential Risks and Benefits 
 
9.1.  Anticipated Adverse Device Effects 
 
The following anticipated adverse device effects (ADE) should be reported only if they are 
related to the stent and/or stenting procedure.  They have been identified for the WallFlex 
Biliary FC and UC Stent, as indicated in the commercial Directions for Use (DFU) and may 
include, but are not limited to:   
• Pain 
• Bleeding 
• Fever 
• Nausea 
• Vomiting 
• Infection 
• Inflammation 
• Recurrent obstructive jaundice 
• Stent occlusion 
• Tumor overgrowth around ends of stent 
• Tumor ingrowth through the stent 
• Mucosal hyperplasia 
• Cholangitis 
• Cholecystitis 
• Pancreatitis 
• Ulceration of duodenum or bile duct 
• Perforation of duodenum or bile duct 
• Stent migration 
• Death (other than that due to normal disease progression) 
• Stent misplacement 
• Perforation of the gallbladder due to the stent covering the cystic duct 
• Stent Fracture 
• Hepatic abscess 
 
9.2.   Anticipated Surgical Adverse Events  
• Pancreaticojejunostomy leakage 
• Hepaticojejunostomy leakage  

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• Gastro-duodenojejunostomy leakage  
• Delayed gastric emptying   
• Biliary leakage  
• Intra-abdominal abscess formation  
• Wound infection  
• Portal Vein Thrombosis  
• Cholangitis   
• Hemorrhage  
• (Emergency) (re)laparotomy   
• Pneumonia 
• Myocardial infarction  
• Mortality  
9.3.   Risk Minimization Actions 
Additional risks may exist. Risks can be minimized by performing procedures in the 
appropriate hospital environment, adhering to patient selection criteria, and close monitoring 
the patient's physiologic status during research procedures and/or follow-up visits.  Promptly 
supplying BSC with all pertinent information required by this protocol may facilitate inter-
center communications regarding serious AEs. 
9.4.  Anticipated Benefits 
Patients may not receive any benefit from participating in this study but this study may 
provide a future benefit to medical science and other patients.  To date there is no broadly 
accepted standard of practice pertaining to the use of SEMS for Pre-operative management of 
patients with pancreatic cancer undergoing neoadjuvant therapy. 
9.5.  Risk to Benefit Rationale 
Based on prior BSC’s clinical studies and collected reports in literature to-date, the risk-to-
benefit ratio is within reason for foreseeable risks. However, literature reports do not always 
capture all side effects. Observation and follow up of patients is required as outlined in the 
protocol. 
10.  Safety Reporting 
 
10.1.  Definitions and Classification 
Adverse event definitions are provided in Table 4.  
 

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Table 4: Adverse Event Definitions 
Term 
Definition 
Adverse Event (AE) 
 
Ref: ISO 14155-2011 
 
 
 
Any untoward medical occurrence, unintended disease or injury, or any 
untoward clinical signs (including an abnormal laboratory finding) in 
patients, users or other persons, whether or not related to the 
investigational medical device. This includes events related to: 
• 
The investigational medical device or comparator 
• 
The procedures involved (study-required) 
 
For users/other persons, this definition is restricted to events related to the 
investigational device 
  
Adverse Device Effect (ADE) 
 
Ref: ISO 14155-2011 
 
 
Adverse event related to the use of an investigational medical device: 
• 
This includes adverse events resulting from insufficient or 
inadequate instructions for the use, deployment, implantation, 
installation or operation, or any malfunction of the investigational 
medical device. 
• 
This includes any event resulting from use error or from 
intentional misuse of the investigational medical device. 
 
Serious Adverse Event (SAE) 
 
Ref: ISO 14155-2011 
 
 
Adverse event that: 
• Led to death, 
• Led to  serious deterioration in the health of the patient, that either 
resulted in: 
o a life-threatening illness or injury, or 
o a permanent impairment of a body structure or a body function, or 
o in-patient hospitalization  or prolonged hospitalization (of existing 
hospitalization), or 
o medical or surgical intervention to prevent life-threatening illness or 
injury or permanent impairment to a body structure or a body 
function 
• Led to fetal distress, fetal death, or a congenital abnormality or birth 
defect. 
Note : Planned hospitalization for a pre-existing condition, or a procedure 
required by the protocol, without serious deterioration in health, is not 
considered a serious adverse event.  
Note:  For SAE reporting requirements see the information below for 
SADE. 
Serious Adverse Device Effect 
(SADE) 
 
Ref: ISO 14155-2011 
 
 
Adverse device effect that has resulted in any of the consequences 
characteristic of a serious adverse event. 
Note:  All SAEs that could have led to a SADE if suitable action had not 
been taken or if circumstances had been less fortunate shall be reported as 
required by the local IRB/EC, national regulations, or the protocol.  If 

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Table 4: Adverse Event Definitions 
Term 
Definition 
applicable, see MEDDEV 2.7/3 12/2010 for reporting timeline 
requirements. 
Unanticipated Adverse Device 
Effect (UADE) 
 
Ref: 21 CFR Part 812 
 
Any serious adverse effect on health or safety or any life-threatening 
problem or death caused by, or associated with, a device, if that effect, 
problem, or death was not previously identified in nature, severity, or 
degree of incidence in the investigational plan or application (including a 
supplementary plan or application), or any other unanticipated serious 
problem associated with a device that relates to the rights, safety, or 
welfare of subjects.   
Unanticipated Serious Adverse 
Device Effect (USADE) 
 
Ref: ISO 14155-2011 
 
 
 
Serious adverse device effect which by its nature, incidence, severity, or 
outcome has not been identified in the current version of the risk analysis 
report. 
Note: Anticipated serious adverse device effect (ASADE) is an effect 
which by its nature, incidence, severity or outcome has been identified in 
the risk analysis report. 
Device Deficiency 
 
Ref: ISO 14155-2011 
 
Ref: MEDDEV 2.7/3 12/2010 
A device deficiency is any inadequacy of a medical device with respect to 
its identity, quality, durability, reliability, safety or performance. 
Note: Device deficiencies include malfunctions, misuse or use errors, and 
inadequate labeling. 
Note: All device deficiencies that could have led to a SADE if suitable 
action had not been taken or if circumstances had been less fortunate shall 
be reported as required by the local IRB/EC, national regulations, or the 
protocol.  If applicable, see MEDDEV 2.7/3 12/2010 for reporting 
timeline requirements. 
Abbreviations: EC=Ethics Committee; IRB=Institutional Review Board 
 
Underlying diseases are not reported as AEs unless there is an increase in severity or 
frequency during the course of the investigation. Death should not be recorded as an AE, but 
should only be reflected as an outcome of a specific SAE (see Table 4 for AE definitions).  
All device-related events and all surgery related events experienced by the study patient after 
informed consent, whether during or subsequent to the procedure, must be recorded in the 
eCRF. 
10.2.  Relationship to Study Device(s) 
The Investigator must assess the relationship of the AE to the study device as related or 
unrelated. Unrelated AEs will not be reported.  Per protocol, only complications related to 
stent and/or stenting procedures will be reported.  See criteria in Table 5.   

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Table 5: Criteria for Assessing Relationship of Study Device to Adverse Event 
Classification 
Description 
Unrelated 
The adverse event is determined to be due to a concurrent illness or effect of 
another device and is not related to the investigational product. 
Related 
• The adverse event is determined to be potentially related to the investigational 
product, and an alternative etiology is equally or less likely compared to the 
potential relationship to investigational product. 
• There is a strong relationship to investigational product, or recurs on re-
challenge, and another etiology is unlikely. 
• There is no other reasonable medical explanation for the event. 
10.3.  Investigator Reporting Requirements 
Investigators will be required to report all SAEs and ADEs. 
10.3.1.  Serious Adverse Events 
 
These events should be reported to the Sponsor within 2 business days of first becoming 
aware of the event.  Events should be documented in the eCRF and all relevant source 
documentation for the event should be provided to the Safety Trial Manager, as applicable. 
10.3.2.  Adverse Events 
 
Device-related events should be reported to the Sponsor within 10 business days of first 
becoming aware of the event.  Unrelated AEs will not be collected. 
10.3.3.  Device Failures, Malfunctions, and Product Nonconformities 
 
These events should be reported to the Sponsor within 1 business day of first becoming 
aware of the event.  Events should be documented in the eCRF. 
10.4.  Boston Scientific Device Deficiencies 
All device deficiencies (including but not limited to failures, malfunctions, use errors, 
product nonconformities, and labeling errors) will be documented and reported to BSC. If 
possible, the device(s) should be returned to BSC for analysis. Instructions for returning the 
investigational device(s) will be provided. If it is not possible to return the device, the 
investigator should document why the device was not returned and the final disposition of the 
device. Device failures and malfunctions should also be documented in the patient’s medical 
record. 
Device deficiencies, failures, malfunctions, and product nonconformities are not to be 
reported as adverse events. However, if there is an adverse event that results from a device 
failure or malfunction, that specific event would be recorded on the appropriate eCRF. 

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10.5.  Reporting to Regulatory Authorities / IRBs / Investigators 
BSC is responsible for reporting adverse event information to all participating investigators 
and regulatory authorities, as applicable.  
The Principal Investigator is responsible for informing the IRB and regulatory authorities of 
SAEs as required by local procedure.   
11.  Bibliography 
 
1. Bonin E, Baron T.  Preoperative biliary stents in pancreatic cancer.  J Hepaticobiliary 
Pancreat Sci 2011;18:621-629 
2. Adams M, Anderson M, Myles J, et al.  Self-expanding metal stents (SEMS) provide superior 
outcomes compared to plastic stents for pancreatic cancer patients undergoing neoadjuvant 
therapy.  J Gastrointest Oncol 2012;3(4):309-313. 
3. The World Health Organization.  “Global cancer rates could increase by 50% to 15 million 
by 2020”.  3 Apr. 2003.  http://www.who.int/mediacentre/news/releases/2003/pr27/en/ 
4. Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ.  Cancer statistics, 2007. CA Cancer J 
Clin 2007;57:43-66. 
5. Dumonceau J, Devière J.  Self-expandable metal stents. Baillière’s Clinical Gastroenterology. 
1999; 1:109-130. 
6. Boulay BR, Gardner TB, Gordon SR.  Occlusion rate and complications of plastic biliary 
stent placement in patients undergoing neoadjuvant chemoradiotherapy for pancreatic 
cancer with malignant biliary obstruction.  J Clin Gastroenterol 2010 Jul;44(6):452-5 
7. Singal AK, Ross WA, Guturu P, et al.  Self-Expanding Metal Stents for Biliary Drainage in 
Patients with Resectable Pancreatic Cancer: Single-Center Experience with 79 Cases.  Dig 
Dis Sci 2011 Jul 13. [Epub ahead of print] 
8. Katz MH, Want H, Fleming JB, et al. Long-term survival after multidisciplinary management 
of resected pancreatic adenocarcinoma. Ann Surg Oncol 2009 Apr;16(4):836-47. 
9. Lowy AM. Neoadjuvant therapy for pancreatic cancer. J Gastrointest Surg. 2008;12:1600–
1608. 
10. Evans DB, Wolff RA, Crane CH. Neoadjuvant strategies for pancreatic cancer. Oncology 
(Williston Park). 2001;15:727–737. 
11. Greer SE, Pipas JM, Sutton JE, et al. Effect of neoadjuvant therapy on local recurrence after 
resection of pancreatic adenocarcinoma. J Am Coll Surg. 2008;206:451–457. 
12. NCCN, Guideline: Pancreatic Adenocarcinoma, 2012 
13. Wolff R.  Neoadjuvant Therapy for Resectable and Borderline Resectable Adenocarcinoma 
of the Pancreas. Curr Drug Targets. 2012 Jun;13(6):781-8 

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14. Breslin T, Hess K, Harbison D, et al.  Neoadjuvant chemoradiotherapy for adenocarcinoma 
of the pancreas: treatment variables and survival duration.  Ann Surg Oncol. 2001 Mar;8(2): 
123-32 
15. Hidalgo M. Pancreatic cancer. N Engl J Med. 2010;362:1605–1617. 
16. Feig BW, Berger DH, Fuhrman GM.  The M.D. Anderson surgical oncology handbook.    
Lippincott Williams & Wilkins, 2006 
17. Das A, Sivak MV.   Endoscopic palliation for inoperable pancreatic cancer.  Cancer Control 
2000 Sep/Oct; 7(5): 452-457 
18. Garcea G, Chee W, Ong SL, et al. Preoperative biliary drainage for distal obstruction the 
case against revisited. Pancreas 2010;39:119–126.  
19. Coates JM, Beal SH, Russo JE, et al. Negligible effect of selective preoperative biliary 
drainage on perioperative resuscitation, morbidity, and mortality in patients undergoing 
pancreaticoduodenectomy. Arch Surg 2009;144:841–847.  
20. Jaganmohan S, Lee J.  Self-expandable metal stents in malignant biliary obstruction.  Expert 
Rev.  Gastroenterol Hepatol 2012. 6(1), 105-114 
21. Aadam AA, Evans DB, Khan A, et al.  Efficacy and safety of self-expandable metal stents for 
biliary decompression in patients receiving neoadjuvant therapy for pancreatic cancer: a 
prospective study, Gastrointest Endosc 2012 Jul;76 (1) :67-75.  Epub 2012 Apr 5. 
22. Lacaine F, Fourtanier G, Fingerut A, et al. Surgical mortality and morbidity in malignant 
obstructive jaundice: a review of 373 patients. Eur J Surg 1995;161:729–734.  
23. Armstrong CP, Dixon JM, Taylor V, et al. Surgical experience of deeply jaundiced patients 
with bile duct obstruction. Br J Surg 1984;71:234–238.  
24. Wasan SM, Ross WA, Staerkel GA, Lee GH.  Use of Expandable Metallic Biliary Stents in 
Resectable Pancreatic Cancer. Am J Gastroenterol. 2005;100:2056–2061 
25. Mullen JT, Lee JH, Gomez HF, Ross WA, et al.  Pancreaticoduodenectomy After Placement 
of Endobiliary Metal Stents.  J Gastrointest Surg 2005;9:1094–1105 
26. van der Gaag NA, Rauws EAJ, van Eijck CHJ, et al. Preoperative Biliary Drainage for 
Cancer of the Head of the Pancreas.  N Engl J Med 2010;362:129-37 
27. Decker C, Christein JD, Phadnis MA et al.   Biliary metal stents are superior to plastic stents 
for preoperative biliary decompression in pancreatic cancer.  Surg Endosc 2011 
Jul;25(7):2364-7. Epub 2011 Mar 4 
28. Sanders Mk, El Hajj II, Slivka A, et al.  Placement of Self Expanding Metal Biliary   
Stents (SEMS) in Patients with Resectable Pancreatic Cancer [Abstract].  
Gastrointest Endosc 2009; 69 (5) 
29. Kahaleh M, Brock A, Conaway MR, et al. Covered self−expandable metal stents in 
pancreatic malignancy regardless of resectability: a new concept validated by a decision 
analysis.  Endoscopy 2007 Apr;39(4):319-24 
30. Pop GH, Richter JA, Sauer B, et al. Bridge to surgery using partially covered self-expandable 
metal stents (PCMS) in malignant biliary stricture: an acceptable paradigm?  Surg Endosc 
2011 Feb;25(2):613-8 

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31. Lawrence C, Howell DA, Conklin DE, et al. Delayed pancreaticoduodenectomy for cancer 
patients with prior ERCP-placed, nonforeshortening, self-expanding metal stents: a positive 
outcome, Gastrointest Endosc 2006 May;63 (6): 804-807 
32. Cavell L, Allen P, Vinoya C, et al.  Biliary Self-Expandable Metal Stents Do Not Adversely 
Affect Pancreaticoduodenectomy.  Am J Gastroenterol 2013 April; doi: 10.1038/ajg.2013.93  
33. Mezhir, J., et al.  A matched case-control study of preoperative biliary drainage in patients 
with pancreatic adenocarcinoma: routine drainage is not justified.  J Gastrointest Surg, 2009. 
13(12):p. 2163-9 
34. Heslin, M., et al.  A preoperative biliary stent is associated with increased complications 
after pancreaticoduodenectomy.  Arch Surg, 1998. 133(2): p. 149-54. 
35. Povoski, S., et al.  Preoperative biliary drainage: impact on intraoperative bile cultures and 
infectious morbidity and mortality after pancreaticoduodenectomy.  J Gastrointest Surg, 
1999. 3(5): p. 496-505.  
36. Son, J., et al.  The optimal duration of preoperative biliary drainage for periampullary 
tumors that cause severe obstructive jaundice.  AM J Surg, 2013.  206, 40-46 
APPENDIX B: SPONSOR REQUIRED PROTOCOL SECTIONS 
B.1.  Data Management 
 
B.1.1.  Data Collection, Processing, and Review 
 
Patient data will be recorded in a limited access secure electronic data capture (EDC) system.  
The clinical database will reside on a production server. 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 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 all 
queries in the database. 

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B.1.2.  Data Retention 
 
The Investigator will maintain, at the investigative site, in original format all essential study 
documents and source documentation that support the data collected on the study patients 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 local 
regulations. It is BSC’s responsibility to inform the Investigator when these documents no 
longer need to be maintained. The Investigator will take measures to ensure that these 
essential documents are not accidentally damaged or destroyed. If for any reason the 
Investigator 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.  
B.2.  Amendments 
 
If a protocol revision is necessary which affects the rights, safety or welfare of the patient 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. 
B.3.   Device/Equipment Accountability 
 
There are no investigational devices used in this study. The WallFlex Biliary Fully Covered 
and Uncovered Stent Systems are available for commercial use in the geographic areas in 
which this clinical study is taking place; therefore, there is no requirement for device 
accountability for the purposes of this study. Device lot information must be maintained in 
the subject’s medical record and recorded on the appropriate case report form.  
 
Any individual country/region requirements that depart from the aforementioned will be 
implemented on a case-by-case basis. 
B.4.  Deviations 
 
An Investigator must not make any changes or deviate from this protocol, except to protect 
the life and physical well-being of a patient 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 patient in an emergency, and those deviations which affect 
the scientific integrity of the clinical investigation. Such notice shall be given as soon as 

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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 and the date of 
occurrence, must be documented and reported to the sponsor using the Protocol Deviation 
EDC CRF. 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 notification, center re-training, or 
discontinuation) will be put into place by the sponsor. 
B.5.  Compliance 
 
B.5.1.  Statement of Compliance 
 
This study will be conducted in accordance with FDA regulations, ISO 14155: Clinical 
Investigation of Medical Devices for Human Subjects – Good Clinical Practices, the relevant 
parts of the ICH Guidelines for Good Clinical Practices, 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 shall be followed, if appropriate. 
 
B.5.2.  Investigator Responsibilities 
 
The Principal Investigator of an investigational center is responsible for ensuring that the 
study is conducted in accordance with the Clinical Study Agreement, the investigational 
plan/protocol, ISO 14155, 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 
patient. 
The Principal Investigator’s responsibilities include, but are not limited to, the following.  
• Prior to beginning the study, sign the Investigator Agreement and Protocol Signature 
page documenting his/her agreement to conduct the study in accordance with the 
protocol. 
• Provide his/her qualifications and experience to assume responsibility for the proper 
conduct of the study and that of key members of the center 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 
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• Make no changes in or deviate from this protocol, except to protect the life and physical 
well-being of a patient 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. 
• 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 and observed device deficiency. 
• Report to BSC, per the protocol requirements, all SAEs and device deficiencies that 
could have led to a SADE. 
• Report to the IRB/EC and regulatory authorities any SAEs and device deficiencies that 
could have led to a SADE, if required by the national regulations or this protocol or by 
the IRB/EC, and supply BSC with any additional requested information related to the 
safety reporting of a particular event. 
• Maintain the device accountability records and control of the device, ensuring that the 
investigational 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 
monitor and respond to questions during monitoring visits. 
• Allow and support regulatory authorities and the IRB/EC when performing auditing 
activities. 
• Ensure that informed consent is obtained in accordance with this protocol and local 
IRB/EC requirements. 
• Provide adequate medical care to a patient during and after a patient’s participation in a 
clinical study in the case of adverse events, as described in the Informed Consent Form 
(ICF). 
• Inform the patient of the nature and possible cause of any adverse events experienced. 
• As applicable, provide the patient with necessary instructions on proper use, handling, 
storage, and return of the investigational device when it is used/operated by the patient. 
• Inform the patient of any new significant findings occurring during the clinical 
investigation, including the need for additional medical care that may be required. 
• Provide the patient with well-defined procedures for possible emergency situations 
related to the clinical study, and make the necessary arrangements for emergency 

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treatment, including decoding procedures for blinded/masked clinical investigations, as 
needed. 
• Ensure that clinical medical records are clearly marked to indicate that the patient is 
enrolled in this clinical study. 
• Ensure that, if appropriate, patients 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 patient’s approval or when required by national regulations, the patient’s 
personal physician about the patient’s participation in the clinical investigation. 
• Make all reasonable efforts to ascertain the reason(s) for a patient’s premature withdrawal 
from clinical investigation while fully respecting the patient’s rights. 
• Ensure that an adequate investigation site team and facilities exist and are maintained and 
documented during the clinical investigation. 
• Ensure that maintenance and calibration of the equipment relevant for the assessment of 
the clinical investigation is appropriately performed and documented, where applicable. 
 
B.5.3.  Delegation of Responsibility 
 
When specific tasks are delegated by an investigator, including but not limited to conducting 
the informed consent process, the 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.  
B.6.  Institutional Review Board/Ethics Committee 
 
Prior to gaining Approval-to-Enroll status, the investigational center will provide to the 
sponsor documentation verifying that their IRB 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 patients into the study and shipment of investigational 
product/equipment. Prior approval must also be obtained for other materials related to patient 
recruitment or which will be provided to the patient. 

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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.  
B.7.  Monitoring 
 
Monitoring will be performed during the study to assess continued compliance with the 
protocol and applicable regulations. In addition, the 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 Investigator continues to have sufficient 
staff and facilities to conduct the study safely and effectively. The 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 Investigator and 
relevant study personnel are available during on-site monitoring visits or audits and that 
sufficient time is devoted to the process. 
B.8.  Insurance 
 
Where required by local/country regulation, proof, and type of insurance coverage, by BSC 
for patients in the study will be obtained. 
B.9.  Informed Consent 
 
Patient participation in this clinical study is voluntary.  Informed Consent is required from all 
patients or their 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, any applicable national regulations, and 
local Ethics Committee and/or Regulatory authority body, as applicable. The ICF must be 
approved by the center’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 center’s IRB/EC.  Any modification requires approval from BSC prior to use of 
the form.  The ICF must be in a language understandable to the patient and if needed, BSC 
will assist the center in obtaining a written consent translation. Translated consent forms 

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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: 
• 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 patient’s 
decision to participate throughout the clinical study, 
• avoid any coercion of or undue influence of patients to participate, 
• not waive or appear to waive patient’s legal rights, 
• use native language that is non-technical and understandable to the patient or his/her legal 
representative, 
• provide ample time for the patient to consider participation and ask questions if 
necessary, 
• ensure important new information is provided to new and existing patients throughout the 
clinical study. 
The ICF shall always be signed and personally dated by the patient or legal representative 
and by the investigator or an authorized designee responsible for conducting the informed 
consent process. If a legal representative signs, the patient 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 center 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 patient 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 
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 patient's future health 
and medical care, that information shall be provided to the affected patient(s) in written form 
via a revised ICF or, in some situations, enrolled patients 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 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. 
Boston Scientific approval is required if changes to the revised ICF are requested by the 
center’s IRB/EC. The IRB/EC will determine the patient population to be re-consented. 
B.10.  Publication Policy 
 

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In accordance with the Corporate Policy on the Conduct of Human Subject Research, 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. In accordance with the Corporate Policy 
for the Conduct of Human Subject Research, 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. 
• The First and Senior authors are the primary drivers of decisions regarding publication 
content, review, approval, and submission.  
B.11.  Definitions of complication criteria (per van der Gaag article): 
 
Specific PBD (ERCP, PTC) related: 
 
• 
Acute pancreatitis:  Abdominal pain and a serum concentration of pancreatic enzymes 
(amylase or lipase) three or more times the upper limit of normal, that required more than 
one night of hospitalization 
• 
Acute cholecystitis:  No suggestive clinical or radiographic signs of acute cholecystitis 
before the procedure and if emergency cholecystectomy is subsequently required 
• 
Perforation:  Retroperitoneal or bowel-wall perforation documented by any radiographic 
technique or direct visual evidence  
• 
Stent Occlusion:  Recurring obstructive jaundice with necessary stent replacement  
Specific surgery related:  
 
• 
Pancreaticojejunostomy leakage:  Drain output of any measurable volume of fluid on 
or after postoperative day 3 with an amylase content greater than 3 times the serum 
amylase activity, graded according to clinical course (ISGPS grade A, B, C), or direct 
visual evidence of defect at anastomosis  
• 
Delayed gastric emptying:  Gastric stasis requiring nasogastric intubation for 10 days or 
more, or the inability to tolerate a regular (solid) diet on or before the fourteenth 

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postoperative day, not due to sequelae of intra-abdominal complications (i.e. abscess, 
anastomotic leakage)  
• 
Biliary leakage:  Bilirubin in abdominal drain or dehiscence found at laparotomy  
• 
Gastro/-duodenojejunostomy leakage:  Conclusive radiographic or direct visual 
evidence of a defect of the anastomosis  
• 
Intra-abdominal abscess formation:  Intra-abdominal fluid collection with positive 
cultures identified by ultrasonography or computed tomography, associated with 
persistent fever and elevations of white blood cells  
• 
Wound infection:  Requiring intervention otherwise considered as minor complication  
• 
Portal Vein Thrombosis:  Conclusive radiologic evidence of thrombosis  
 
Following either procedure:  
 
• 
Cholangitis:  Elevation in temperature more than 38°C, thought to have a biliary cause, 
without concomitant evidence of acute cholecystitis, requiring intervention  
• 
Hemorrhage:  Bleeding after the index procedure requiring transfusion of ≥4 units of 
packed cells within a 24-hour period, or leading to relaparotomy/intervention  
• 
(Emergency) (re)laparotomy:  Any (other) reason following either preoperative biliary 
drainage or another surgical procedure  
• 
Pneumonia:  Pulmonary infection with radiological confirmation and requiring antibiotic 
treatment  
• 
Mortality:  In-hospital death, due to protocol complications or any cause, including 
progression of disease, within the study period  
B.12.  Abbreviations and Definitions  
 
B.12.1. Abbreviations 
Abbreviations are shown in Table 7.   
Table 7: Abbreviations 
Abbreviation/Acronym 
Term 
 
ADE 
AE 
BSC 
BTS 
CBD 
CI 
CRF 
CRO 
CT 
DFU 
eCRF 
 
Adverse Device Effect 
Adverse Event 
Boston Scientific Corporation 
Bridge to Surgery 
Common Bile Duct 
Confidence Interval 
Case Report Form 
Clinical Research Organization 
Computed Tomography 
Directions for Use 
Electronic Case Report Form 

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Table 7: Abbreviations 
EDC 
ERCP 
EC 
FDA 
GCP 
ICF 
ICH 
ICMJE 
IDE 
IDR 
IRB 
ISO 
IVRS 
LFT 
MEDDEV 
MRI 
OUS 
PAL 
PD 
SADE 
SAE 
SEMS 
SUB-I 
UADE 
USA 
Electronic Data Capture 
Endoscopic retrograde cholangiopancreatography 
Ethics Committee 
Food and Drug Administration 
Good Clinical Practices 
Informed Consent Form 
International Conference on Harmonization 
International Committee of Medical Journal Editors 
Investigational Device Exemption 
Independent Data Review Board 
Institutional Review Board 
International Organization for Standardization 
Interactive Voice Response System 
Liver Function Tests 
Medical Devices Directives 
Magnetic Resonance Imaging 
Outside of the United States 
Palliative 
Pancreaticoduodenectomy 
Serious Adverse Device Effect 
Serious Adverse Event 
Self-Expanding Metal Stent 
Sub-Investigator 
Unanticipated Adverse Device Effect 
  United States of America