Fully Covered Self Expanding Metal Stents (FCSEMS) for Pancreatic Duct Strictures in Patients With Chronic Pancreatitis
Phase: NA
Conditions: Chronic Pancreatitis
Sponsor: Boston Scientific Corporation

THESE DOCUMENTS ARE THE PROPERTY OF BOSTON SCIENTIFIC CORP. AND SHALL NOT BE REPRODUCED, 
DISTRIBUTED, DISCLOSED OR USED FOR MANUFACTURE OR SALE OF APPARATUS WITHOUT THE EXPRESS WRITTEN 
CONSENT OF BOSTON SCIENTIFIC CORP. 
 
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Fully Covered Self Expanding Metal Stents (FCSEMS) for Pancreatic Duct 
Strictures in Patients with Chronic Pancreatitis 
 
WallFlex Pancreatic Pivotal 
 
CLINICAL PROTOCOL 
 
PDM # 91067616 
Project # E7104 
 
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 
Brian Vatcher 
Associate Clinical Project Manager 
Boston Scientific Corporation 
100 Boston Scientific Way 
Marlborough, MA 01752 
USA 
Coordinating Principal 
Investigator 
Professor Jacques Devière, MD, PhD 
Chairman, Department of Gastroenterology, Hepatopancreatology 
and Digestive Oncology 
Erasme Hospital 
Université Libre de Bruxelles 
808 route de Lennik B 1070 Brussels 
 
Original Release: July 28, 2015 
Current Version: August 28, 2017 
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Protocol Synopsis 
 
Full Title 
Fully Covered Self Expanding Metal Stents (FCSEMS) for Pancreatic Duct 
Strictures in Patients with Chronic Pancreatitis 
Short Title 
WallFlex Pancreatic Pivotal 
Objective 
To prospectively document the performance of a FCSEMS for treatment 
of pancreatic duct strictures in patients with painful chronic pancreatitis.   
Indication(s) for 
Use  
Intended to facilitate drainage of the pancreatic duct to reduce pain in 
patients with painful chronic pancreatitis   
Test Device 
Fully Covered WallFlex Pancreatic Stent 
Device Selection Stents selected for use in this study: 
• Diameter: 6 mm, 8 mm 
• Length: 4cm, 5cm, 6cm  
• Type: Soft 
• Delivery system: Rapid Exchange  
Study Design 
• Prospective, single arm, multi-center  
• Intended WallFlex Pancreatic stent indwell duration for 6 months 
• Follow-up to 6 months post-stent removal or 6 months post-
observation of complete distal migration 
Number of 
Patients 
Up to 92 patients  
Number of 
Centers 
Up to 15 centers globally, including up to 8 centers in the U.S. 
Primary 
Endpoint 
Primary Effectiveness Endpoint: 
Pain Reduction  
Pain reduction will be assessed at 6 months post-stent removal or 6 
months post-observation of complete or partial stent migration compared 
to pain collected at baseline. Baseline for patients without a plastic 
pancreatic stent immediately prior to study stent placement will be at the 
time of enrollment. Baseline for patients with a plastic pancreatic stent 
immediately prior to study stent placement will be at the time of study 
stent placement. 
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Pain will be scored between 0 and 100 as the mean of the VAS Pain 
Score and Frequency of Pain sectors of the Izbicki pain scale. 
Complete pain relief is defined as pain score ≤ 10, and partial pain relief 
is defined as pain score ˃ 10 and reduced by at least 50% compared to 
baseline.  
Complete or partial pain relief in the setting of a 50% higher average 
daily narcotic dose will be considered a primary effectiveness endpoint 
failure. Average daily narcotic dosage for prior month will be assessed at 
baseline visit prior to plastic or study stent placement, whichever is 
implanted first, and at 6 months post-stent removal/observation of 
complete distal migration. 
Patients who experience stent migration in setting of recurring pain (VAS 
Pain Score of ≥ 20) will be considered as having failed the primary 
effectiveness endpoint. 
Patients who are restented in the setting of recurring pain will be 
considered as having failed both the primary effectiveness endpoint and 
the secondary endpoint for stricture resolution and may only be restented 
with a non-study stent. 
Restenting with a new study stent may only occur during the initial stent 
placement procedure for such situations as stent misplacement, improper 
stent size choice, or other conditions, as necessary and will not be 
considered a primary effectiveness endpoint failure or a secondary 
endpoint failure for stricture resolution. 
Primary Safety Endpoint: 
Rate of related Serious Adverse Events (SAEs) from WallFlex Pancreatic 
stent placement to end of study. 
Relatedness will be determined by the PI, reporting if the SAE is related 
to the study stenting procedure, to the indwelling study stent, to study 
stent removal and/or to study stent migration. 
Pain thought to be caused by WallFlex Pancreatic stent expansion will be 
reported, but will not count towards the endpoint if all three of the 
following conditions apply:5  
1. Pain can be managed by medication, with the exception of 
injectable narcotic use for more than 24 hours. 
2. Pain does not cause WallFlex Pancreatic stent removal. 
3. Pain resolves by 72 hours after WallFlex Pancreatic stent 
placement.     
Secondary 
Endpoints 
Effectiveness 
1. Stricture Resolution 
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Stricture resolution will be assessed at the time of stent removal or 
observation of complete or partial stent migration.  
Stricture resolution is defined as maintained pain relief without need 
for restenting or, if pain recurs, confirmation of stent patency 
adequate for providing drainage of the pancreatic duct.    
Restenting with a non-study stent will take place if there is no 
improvement of clinical status (see definition in secondary endpoint 
2 below) and associated persistence of the stricture based on 
imaging. Imaging will be conducted per standard of practice and may 
be prompted by lack of improved clinical status and may consist of 
non-invasive imaging or pancreatogram. A pancreatogram will only 
be performed if an ERCP is necessitated for a reintervention with or 
without restenting.      
NOTE:  Patients who are restented for recurring pain (VAS Pain 
Score of ≥ 20) will be considered a failure for stricture resolution 
and the primary endpoint and may only be restented with a non-
study stent.  
Restenting with a new study stent may only occur during the initial 
stent placement procedure for such situations as stent misplacement, 
improper stent size choice, or other conditions, as necessary and will 
not be considered a secondary effectiveness stricture resolution 
endpoint failure or a primary endpoint failure. 
2. Improved clinical status compared to baseline assessed at each  study 
visit. 
Improved clinical status is defined as improvement in at least one 
and deterioration in none of the following: Pain, Weight and Quality 
of Life (QOL) 
• Pain: Scored between 0 and 100 as the mean of the VAS Pain 
Score and Frequency of Pain sectors of the Izbicki pain scale. 
• Weight  
• Quality of life: Recorded using SF12 
3. Recurrence of Stricture 
Stricture recurrence will be assessed in the subset of patients who 
had stricture resolution at stent removal or observation of complete 
or partial stent migration.  
Recurrence of stricture is defined as recurrence of pain with loss of 
adequate pancreatic duct drainage requiring restenting. Restenting 
will take place if there is deterioration of clinical status (see 
definition in secondary endpoint 2 above) and documented recurrent 
stricture based on imaging. Imaging may be prompted by 
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deterioration of clinical status and may consist of non-invasive 
imaging or of a pancreatogram. A pancreatogram will only be 
performed if an ERCP is necessitated for a reintervention with or 
without restenting.   
4. Stent Functionality 
Stent functionality will be assessed from stent placement until stent 
removal or observation of complete or partial stent migration. 
Stent functionality is defined as adequate pancreatic duct drainage 
reflected by reduction of pain and lack of restenting. 
5. Izbicki pain scale assessed at each study visit 
The Izbicki pain scale (see appendix in section 22.1) has four sectors 
related to severity of pain, frequency of pain, analgesic medication, 
and disease-related inability to work.   
6. Average daily narcotic dose for prior month assessed at each study 
visit 
 
7. Maintenance of the VAS Pain Score and Frequency of Pain Score 
recorded at 6 months post-stent removal compared with that recorded 
at the time of plastic stent removal, for patients with plastic 
pancreatic stent indwelling immediately prior to study stent 
placement 
Technical Success 
8. Ability to deploy the stent in satisfactory position (Stent Placement 
Success). Ease of placement will also be assessed.on a 5 point Likert 
scale. 
Satisfactory position is defined as the stent being across the stricture, 
without visible occluding impaction at the genu of the pancreatic 
duct and with distal end of the stent visible in the duodenum.  
9. Successful endoscopic stent removal (Endoscopic Stent Removal 
Success). 
Endoscopic stent removal success is defined as ability to remove 
stent endoscopically (forceps, snare) without serious stent removal-
related adverse events. Ease of removal will also be assessed.on a 5 
point Likert scale. Use of stent-in-stent removal technique will be 
considered a removal failure. For patients who experience complete 
distal migration of the study stent, this endpoint will not be 
evaluated.  
Safety and Device Events   
10. Device Events, including findings not associated with adverse 
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events, such as but not limited to asymptomatic stent migration. 
Study Visits and 
Follow-Up 
Schedule 
• Baseline Visit: Demographics, Medical History, Symptom 
Assessment including Pain Score, Concomitant Medications 
(including injectable narcotics), Average Daily Narcotic Dose, 
Weight, Quality of Life Score, EPS History, Adverse Events, Imaging 
(if applicable). If ESWL is deemed necessary at Baseline visit, patient 
may receive a plastic pancreatic stent placed for 30 to 90 days before 
study stent placement at the discretion of the Investigator, for 
example, if there is concern about stone fragments of stone sludge in 
side branches of the pancreatic duct. 
• WallFlex Pancreatic Stenting Procedure: Pre-stenting pancreatic stone 
clearance (if applicable), Pancreatic Duct Imaging or other imaging, 
WallFlex Pancreatic Stent Placement, EPS (if required), Pain Score 
(prior to stent procedures), Weight, Concomitant Medications 
(including injectable narcotics), Average Daily Narcotic Dose, 
Quality of Life, Adverse Events, Plastic Stent Removal prior to study 
stent placement, as applicable 
• Indwell Follow-up via Telephone or in Person on Month 1 and Month 
3: Pain Score, Concomitant Medications (including injectable 
narcotics), Average Daily Narcotic Dose, Weight, Quality of Life 
Score, Adverse Events  
• Study Stent Removal(s) intended after 6 months of stent indwell: Pain 
Score prior to Stent Removal, Concomitant Medications (including 
injectable narcotics), Average Daily Narcotic Dose, Stent Removal 
Procedure(s), Weight, Quality of Life Score, Adverse Events, 
Pancreatic Duct imaging or other imaging to assess stricture 
resolution 
• Post-Removal Follow-up via Telephone or in Person 3 months after 
stent removal or observation of complete distal migraton: Pain Score, 
Concomitant Medications (including injectable narcotics), Average 
Daily Narcotic Dose, Weight, Quality of Life Score, Adverse Events 
• Post-Removal Follow-up via Telephone or in Person 6 months after 
stent removal or observation of complete distal migraton: Pancreatic 
Duct Imaging or other Imaging, Pain Score, Concomitant Medications 
(including injectable narcotics), Average Daily Narcotic Dose, 
Weight, Quality of Life Score, Adverse Events 
• OPTIONAL: If a naso-pancreatic drain is placed after stent removal, 
then repeated pancreatographic assessment of stricture resolution at 
24 to 72 hours post stent removal.   
• Additional visits as needed 
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Key Inclusion 
Criteria 
1. Age 18 or older 
2. Willing and able to comply with study procedures and follow-up 
schedule and provide written informed consent to participate in study 
3. Chronic pancreatitis induced stricture of Cremer Type IV, namely 
distal dominant stricture with upstream ductal dilation. 
4. For patients with a prior plastic pancreatic stent: VAS Pain Score and 
Frequency of Pain sectors of the Izbicki pain scale at the time of 
placement of the plastic stent. 
5. Availability of narcotic dosage for at least one month prior to baseline 
visit for patients who do not have a prior plastic pancreatic stent or 
availability for one month prior to placement of prior plastic 
pancreatic stent, where applicable. 
6. VAS Pain Score of ≥ 20 before study stent placement for patients 
without a prior plastic pancreatic stent. VAS Pain Score of ≥ 20 
before initial plastic pancreatic stent placement for patients with a 
prior plastic pancreatic stent indwelling for 90 days or less before 
study stent placement. VAS Pain Score is captured via Izbicki pain 
scale. 
7. Pain occurring weekly or more frequently (assessed by Frequency of 
Pain sector of the Izbicki pain scale) as reported before study stent 
placement for patients without a prior plastic pancreatic stent, or 
before placement of initial plastic pancreatic stent for patients with a 
prior plastic pancreatic stent indwelling for 90 days or less before 
study stent placement. 
8. Minimum 5 mm diameter of dilated duct immediately upstream of 
pancreatic duct stricture  
9. Prior clearance of pancreatic stones where needed   
• If pancreatic duct stone clearance prior to placement of the 
study stent includes ESWL, then a plastic pancreatic stent may 
be placed immediately after the ESWL procedure at the 
discretion of the Investigator, for example, if there is concern 
about stone fragments of stone sludge in side branches of the 
pancreatic duct, and may be left indwelling for 30-90 days. 
• If new pancreatic duct stones requiring ESWL have formed by 
the time of intended study stent placement, then the patient 
will not receive the study stent and be excluded from the 
study. Further treatment of the patient will be provided per 
standard of practice outside of the study. In case the study 
stent is not placed during the same session in which the plastic 
stent is removed, the pain score needs to be collected again 
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prior to study stent placement.  
10. Prior endoscopic pancreatic sphincterotomy (EPS), historically or to 
be provided at time of SEMS placement as applicable.   
Key Exclusion 
Criteria 
1. Pancreatic or peri-ampullary cancer with or without pancreatic duct 
strictures caused by malignancy  
2. Biliary strictures caused by chronic pancreatitis that are symptomatic 
and/or in need of therapeutic intervention 
3. Perforated duct 
4. Ansa pancreatica 
5. Presence of pancreatic cysts suspected to be cystic tumor or requiring 
transmural drainage 
6. Duodenal/groove pancreatitis 
7. Autoimmune pancreatitis 
8. Pancreatic duct stenoses not located in the head of the pancreas 
9. Failed access during an attempted ERCP on a prior date at the 
investigational center 
10. Duration of indwell of one single plastic pancreatic stent or 
cumulative duration of consecutive single plastic pancreatic stents 
immediately prior to study stent placement exceeding 90 days 
11. History of prior single pancreatic plastic stent(s) followed by a stent-
free period shorter than 1 year before enrollment into the study  
12. History of prior side-by-side multiple pancreatic plastic stents up to 
one year prior to enrollment 
13. History of prior pancreatic metal stent(s) 
14. Reported recent history of acute relapsing pancreatitis in the absence 
of chronic pancreatitis 
15. Patients for whom endoscopic techniques are contraindicated. 
16. Patients who are currently enrolled in another investigational study 
that would directly interfere with the current study, without prior 
written approval from the sponsor 
17. Inability or refusal to comply with the follow-up schedule including 
patients living at such a distance from the investigational center that 
attending follow-up visits would be unusually difficult or burdensome 
Statistical Methods  
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Primary 
Statistical 
Hypotheses 
A literature search was performed on plastic pancreatic stenting in CP. 
Ten (10) articles that represent 392 evaluable patients2-11 were found.  
Primary Effectiveness Endpoint: 
A meta-analysis of “pain reduction” reported in these articles yielded a 
point estimate of 66% with a 95% Confidence Interval (CI) of 53% to 
76%, using a random effects model.  
Statistical testing will be conducted to determine if “pain reduction” 
using the WallFlex Pancreatic Stent is greater than 53%, assuming an 
observed “pain reduction” rate of 75% and using an exact test with a 
one-sided alpha of 0.025 and power of 80%, 43 patients will be required.  
Primary Safety Endpoint: 
The same literature search as above was used; however, one article, Seza 
et al. did not report on “related serious adverse events.” Therefore, nine 
(9) articles representing 386 evaluable patients were found. A meta-
analysis of “related serious adverse events” reported in these articles 
yielded a point estimate of 25% with a 95% CI of 19% to 32%, using a 
random effects model.  
Statistical testing will be conducted to determine if “related serious 
adverse events” is less than 32%, assuming an observed “related serious 
adverse event” rate of 15% and using an exact test with a one-sided 
alpha of 0.025 and power of 80%, 57 patients will be required. 
Taking the larger of the two hypotheses and compensating for possible 
loss of patients after enrollment, an additional 10% of patients will be 
required, for a total of 64 patients.  
The percentage of patients who do not meet the inclusion criteria levels 
of the VAS pain score (≥ 20) and frequency of pain score (50, 75, or 
100) at the time of study stent placement, due to a prior single plastic 
pancreatic stent, is anticipated to range from 20-30%.  Therefore, we 
propose to enroll up to 92 patients so as to have 64 patients who met the 
inclusion criteria levels of the VAS pain score (≥ 20) and frequency of 
pain score (50, 75, or 100) at the time of study stent placement. 
 
 
 
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Table of Contents 
1 
Introduction ..................................................................................................................... 15 
1.1 
Literature Review ..................................................................................................... 15 
1.2 
Prior Clinical Trials .................................................................................................. 17 
1.3 
Conclusion ............................................................................................................... 18 
2 
Device Use and Description ............................................................................................ 18 
2.1 
Device Description ................................................................................................... 18 
2.2 
Device Use ............................................................................................................... 19 
3 
Primary Objective ........................................................................................................... 19 
4 
Endpoints and Study Design ........................................................................................... 19 
4.1 
Primary Effectiveness Endpoint ............................................................................... 19 
4.2 
Primary Safety Endpoint .......................................................................................... 20 
4.3 
Secondary Endpoints ................................................................................................ 20 
4.4 
Study Design ............................................................................................................ 22 
4.5 
Stent Removal .......................................................................................................... 22 
4.6 
Restenting ................................................................................................................. 22 
5 
Patient Selection ............................................................................................................... 23 
5.1 
Inclusion Criteria ...................................................................................................... 23 
5.2 
Exclusion Criteria..................................................................................................... 24 
6 
Patient Accountability ..................................................................................................... 25 
6.1 
Patient Status and Classification .............................................................................. 25 
6.2 
Enrollment Controls ................................................................................................. 25 
6.3 
Withdrawal ............................................................................................................... 25 
6.4 
End of Study Action Plan ......................................................................................... 26 
7 
Study Methods ................................................................................................................. 27 
7.1 
Data Collection ........................................................................................................ 27 
7.2 
Study Candidate Screening ...................................................................................... 28 
7.3 
Informed Consent ..................................................................................................... 28 
7.4 
Scoring System ........................................................................................................ 28 
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7.5 
Screening/Baseline – Office/Hospital Visit ............................................................. 29 
7.6 
WallFlex Pancreatic Study Stent Placement – Office/Hospital Visit ...................... 29 
7.7 
Stent Indwell Follow-Up: Month 1 (30 days ± 5 days) and Month 3 (90 days ± 10 
days) – Telephone or Office/Hospital Visit ............................................................. 30 
7.8 
Study Stent Removal Visit: Month 6 (180 days ± 15 days) – Office/Hospital Visit30 
7.9 
Post-Stent Removal Follow-Up: Month 3 (90 days±15 days post-removal) – 
Telephone or Office/Hospital Visit .......................................................................... 30 
7.10 Post-Stent Removal Follow-Up: Month 6 (180 days±15 days post-removal) – 
Telephone or Office/Hospital Visit .......................................................................... 30 
7.11 Additional Visits as Required .................................................................................. 31 
7.12 Study Completion .................................................................................................... 31 
7.13 Source Documents ................................................................................................... 31 
8 
Statistical Considerations ............................................................................................... 32 
8.1 
Endpoints ................................................................................................................. 32 
8.2 
Statistical Methods ................................................................................................... 36 
9 
Data Management ........................................................................................................... 38 
9.1 
Data Collection, Processing, and Review ................................................................ 38 
9.2 
Data Retention .......................................................................................................... 38 
10 Amendments .................................................................................................................... 39 
11 Deviations ......................................................................................................................... 39 
12 Device/Equipment Accountability ................................................................................. 39 
13 Compliance ....................................................................................................................... 40 
13.1 Statement of Compliance ......................................................................................... 40 
13.2 Investigator Responsibilities .................................................................................... 40 
13.3 Institutional Review Board/ Ethics Committee........................................................ 42 
13.4 Sponsor Responsibilities .......................................................................................... 42 
13.5 Insurance .................................................................................................................. 42 
14 Monitoring ........................................................................................................................ 43 
15 Potential Risks and Benefits ........................................................................................... 43 
15.1 Anticipated Adverse Device Effects ........................................................................ 43 
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15.2 Risks Associated with Clinical Trial Participation .................................................. 44 
15.3 Risk Minimization Actions ...................................................................................... 44 
15.4 Anticipated Benefits ................................................................................................. 44 
15.5 Risk to Benefit Rationale ......................................................................................... 44 
16 Safety Reporting .............................................................................................................. 44 
16.1 Definitions and Classification .................................................................................. 44 
16.2 Relationship to Study Device(s) .............................................................................. 46 
16.3 Investigator Reporting Requirements ...................................................................... 47 
16.4 Boston Scientific Device Deficiencies ..................................................................... 49 
16.5 Reporting to Regulatory Authorities / IRBs / ECs / Investigators ........................... 49 
16.6 Adverse Event Coding ............................................................................................. 50 
17 Informed Consent ............................................................................................................ 50 
18 Suspension or Termination ............................................................................................. 51 
18.1 Premature Termination of the Study ........................................................................ 51 
18.2 Termination of Study Participation by the Investigator or Withdrawal of IRB/ EC 
Approval ................................................................................................................... 51 
18.3 Requirements for Documentation and Patient Follow-up ........................................ 52 
18.4 Criteria for Suspending/Terminating a Study Center .............................................. 52 
19 Publication Policy ............................................................................................................ 52 
20 Bibliography ..................................................................................................................... 54 
21 Abbreviations and Definitions ........................................................................................ 56 
22 Appendices ....................................................................................................................... 57 
22.1 Izbicki Pain Scale ..................................................................................................... 57 
22.2 SF12 ......................................................................................................................... 58 
22.3 Cremer Classification of Chronic Pancreatitis ......................................................... 61 
22.4 Morphine Milligram Equivalent (MME) Narcotic Conversion Guidance ............... 63 
22.5 Guidance on Collecting VAS Pain Score and Frequency of Pain Attacks 
Information ............................................................................................................... 64 
 
 
 
 
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Table of Tables 
 
Table 1.1-1: Plastic Stent Literature Values ....................................................................... 16 
Table 2.1-1: Clinical UPN (RX, Soft) .................................................................................... 19 
Table 7.133-1: Source Documentation Requirements ............................................................ 31 
Table 8.1.2-1: Pain Reduction and Related SAE Rates by Publication ........................... 33 
Table 16.1-1: Safety Definitions ............................................................................................. 44 
Table 16.2-1: Criteria for Assessing Relationship of Study Device or Procedure to Adverse 
Event .................................................................................................................... 46 
Table 16.3-1: Investigator Reporting Requirements ......................................................... 47 
 
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1 Introduction  
1.1 
Literature Review 
Chronic pancreatitis (CP) is a debilitating disease. Pain is the principal symptom associated 
with CP. The cause of pain may be multi-factorial. Correlation between morphological 
aspects of CP and phenotypical patient presentations including frequency and severity of pain 
is ill understood.  Response to various treatment modalities for the pain – medical 
management, endotherapy, or surgery – is also poorly predicted. However, it is well 
recognized that in some patients the pancreatic type pain seems associated with pancreatic 
duct (PD) obstruction and associated PD dilation. Endotherapy using pancreatic stents may 
have a beneficial effect in such cases by calibrating the PD strictures, reducing upstream 
ductal dilation and reducing pain. However, calibaration of PD strictures may not alleviate 
pain if the origin of the pain has causes other than PD hypertension and dilation. Thus, 
success of endotherapy using any type of PD stents should combine assessment of pain and 
calibration of the PD stricture without clinically significant stent-induced ductal changes.   
In the treatment of benign PD strictures often in the presence of PD stones caused by CP, the 
ultimate clinical objective is acceptable quality of life including durable pain control without 
major complications, preferably stent-free. The gold standard of treatment in this indication 
remains surgery1,2; however, the morbidity associated with these major surgical procedures 
has made endoscopic, less invasive alternatives a first-line approach for simple benign main 
PD strictures associated with CP at several expert centers. Endotherapy in this indication 
mostly consists of single or multiple pancreatic plastic stents2-11. The most frequently quoted 
publication5 on long-term resolution of refractory PD strictures after temporary indwell of 
multiple plastic stents in patients with severe CP reports effectiveness comparable to surgical 
outcomes. A meta-analysis of publications of pancreatic plastic stenting in CP patients2-11 
was used as a basis to generate the hypothesis of the current trial.  
Use of self-expanding metal stents (SEMS) in benign main PD strictures associated with 
painful chronic pancreatitis (CP) was first described in the 1990s, culminating in a 
recommendation12 that use of uncovered SEMSs in the PD should be avoided and that use of 
covered SEMSs (CSEMSs) in the PD holds promise in this indication. Compared to resective 
or bypass surgery, the use of SEMS is less invasive. Compared to MPS, the use of SEMS is 
anticipated to result in similar long-term stent-free pain relief, however requiring a shorter 
duration of stent therapy and fewer ERCPs. Literature-based values are summarized below.  
 
 
 
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Table 1.1-1: Plastic Stent Literature Values 
Study 
Number of ERCPs 
Total PS indwell duration 
Eleftheriadis 20052 
Median 3  
Range 1-18 
Median 23 months  
Range 2-134 months 
Vitale 20043 
Mean 4.1 
Range 3-12 months  
Topazian 20054 
Mean 3.2 
Intended 6 months, actual 
duration not reported 
Costamagna 20065 
Not reported 
Mean 7 months 
Range 5-11 months 
Farnbacher 20066 
Not reported 
Mean 10 months±10 months 
Ishiara 20067 
Not reported 
Mean 335±31 days 
Cahen 20078 
Median 5 
Range 1-11 
Mean 27 weeks 
Range 6-67 
Weber 20079 
Not reported 
Mean 5.6 months  
Range 1-1- months 
Seza 201110 
Not reported 
Mean 15.2±3.1 months 
Gabrielli 200511 
Not reported 
Not reported 
 
A literature review of 2000-2012 yielded 5 publications with series of 5 or more cases 
totaling 72 cases13-17 pertaining to benign PD stricture resolution after treatment using 
CSEMS. After stent indwell ranging from 2 to 9 months, CSEMS removal was attempted in 
71 patients and was achieved without difficulty in 97% (69/71). In 3% (2/71) CSEMS were 
embedded and required a stent-in-stent technique for subsequent removal. Overall clinical 
success after post stent removal follow-up ranging from 4 to 20 months averaged 83% 
(59/71) (range 40%-100%). The overall reintervention rate was 18% (13/72) (range 8%-
45%).  There were 22 reported stent-related complications in 72 patients, including 
immediate post FCSEMS placement pain that may require stent removal in some patients.  
Of note are publications by the American Society of Gastroenterological Endoscopy (ASGE) 
and the European Society of Gastroenterological Endoscopy (ESGE) on endotherapy in 
patients with painful CP: 
• In an ASGE Status Evaluation Report in 201318, the ASGE states: “Pancreatic duct 
stenting can resolve or improve symptoms in chronic pancreatitis patients with 
pancreatic duct strictures. With pain relief as the endpoint, placement of plastic stents 
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across pancreatic strictures has 70% to 94% short-term and 52% to 80% long-term 
effectiveness.58-63 Stenting is usually required for multiple months with frequent stent 
changes. Fully-covered SEMSs have been used to treat chronic pancreatitis strictures 
in small uncontrolled studies.64,65 After placement for 2 to 3 months, the SEMSs were 
removed with resolution of strictures in all patients and with some improvement in 
pain. Frequent adverse events of stent migration and stent-induced strictures were 
reported. In very small case series, plastic or metal stents were placed in the 
pancreatic duct across a malignant stricture to relieve pain thought to be caused by 
ductal obstruction. Pain was decreased in 75% to 90% of patients.66,67”and “The 
main adverse events of pancreatic stents include migration, stent occlusion, and 
stent-induced pancreatic ductal changes. Undesired stent migration occurs in 5.2% 
(proximal) and 7.5% (distal) of cases.108 Because of the generally smaller diameter 
stents used in the pancreas, approximately 50% will be occluded by 4 weeks, with the 
majority occluded by 3 months.45,46,109,110 Pancreatic ductal changes can occur in as 
many as 36% to 83% of ducts after stenting for as briefly as 2 to 3 weeks.111,112 
Ductal changes occur more frequently in patients with a normal pancreatogram 
before stenting and may be permanent in one third of cases. Pancreatitis was 
reported in 3% with removal of prophylactic pancreatic duct stents even without 
ERCP.113” 
• In an ESGE Guideline in 201219, the ESGE states: “Pancreatic stenting is technically 
successful in 85–98% of attempted cases58–60, 64; it is immediately followed by pain 
relief in 65–95% of patients58–61,63–65, 68; during follow-up (14–58 months), pain relief 
reported in 32%–68% of patients25, 37,59–61, 63, 64, 68.” and  “The ESGE recommends 
treating dominant MPD stricture by inserting a single 10-Fr plastic stent, with stent 
exchange planned within 1 year even in asymptomatic patients to prevent 
complications related to long-standing pancreatic stent occlusion (Recommendation 
grade C). Simultaneous placement of multiple, side-by-side, pancreatic stents could 
be applied more extensively, particularly in patients with MPD strictures persisting 
after 12 months of single plastic stenting. At this time point, the ESGE recommends 
that available options (e. g., endoscopic placement of multiple simultaneous MPD 
stents, surgery) be discussed by a multidisciplinary team (Recommendation grade 
D).” and “Patency of pancreatic SEMSs is short with regard to life expectancy of 
patients with chronic pancreatitis (Evidence level 2–). Preliminary studies suggest 
that temporary placement of fully covered SEMS is safe and allows resolution of 
MPD strictures plus pain relief in a majority of patients but no follow-up longer than 
1 year is available (Evidence level 2+).” and “Uncovered SEMSs should not be 
inserted in MPD strictures (Recommendation grade D); temporary placement of fully 
covered SEMSs holds promise but it should be performed only in setting of trials with 
approval of the institutional review board (Recommendation grade C).” 
1.2 
Prior Clinical Trials 
In addition to the above publications, preliminary data is available from a small 10 patient 
trial conducted with the Fully Covered WallFlex Pancreatic Stent. Patients with painful 
chronic pancreatitis of Cremer Type IV were enrolled between June and September 2014. 
Intended indwell was 3 months in 5 patients and 6 months in 5 patients. In total 14 stents 
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were placed, with 2 patients having immediate removal and replacement of the initial stent 
due to deployment in unsatisfactory position and 2 patients needing a second stent placement 
after premature complete distal migration of the first indwelling stent. Stent migration 
without symptoms, thought to be a reflection of adequate calibration of the benign stricture, 
occurred in 6 stent placements, not requiring restenting. Clinically meaningful complete 
distal migration (CDM) with symptoms occurred in 25% (3/12) of stent placements with 
intended stent indwell. There were no proximal stent migrations. Endoscopic stent removal 
was performed per-protocol easily in one patient after a 3 month indwell and in 2 patients 
after a 6 month indwell without stent removal-related adverse events (AEs). After a median 
follow-up of 196 days (range 175 - 373) after stent removal or observation of CDM of the 
stent, 80% (8/10) of patients remained stent-free. Longer term follow-up is ongoing. One 
patient had premature CDM followed by placement of plastic stents. One patient had no pain 
relief after SEMS placement and had subsequent pancreatic diversion surgery which did not 
provide pain relief either. Serious Adverse events (SAEs) occurred in 50% (5/10) of patients, 
with 7 SAEs (2 pain associated with premature CDM, 2 transient pain related to stent 
expansion immediately following stent placement, 1 pain unresolved by stenting or 
subsequent pancreatic diversion surgery, 1 bacterial infection and 1 mild acute pancreatitis). 
No SEMS needed to be removed due to intolerable pain after SEMS placement. There were 
no stent-induced ductal changes.  
1.3 
Conclusion 
These publications and published expert opinions conclude that the use of fully covered 
SEMSs (FCSEMSs) is feasible and can be safe and effective for treatment of Cremer type IV 
benign PD strictures caused by CP.  
2 Device Use and Description 
2.1 
Device Description 
Study devices are manufactured by Boston Scientific Corporation. The WallFlex™ 
Pancreatic RX Fully Covered Soft Stent System consists of a flexible delivery system 
preloaded with a self-expanding pancreatic metal stent. The stent is made from a metallic 
radiopaque material that is formed into a cylindrical mesh. The stent is offered fully covered 
with Permalume™ Coating, a translucent silicone polymer, to reduce the potential for 
ingrowth through the stent. The stent has a retrieval loop for removal during the initial stent 
placement procedure. The retrieval loop may be  used in the event of incorrect placement 
and/or removal from benign strictures. The stent has a flare on the duodenal end to prevent 
migration into the pancreas. The WallFlex™ Pancreatic RX Fully Covered Soft Stent System 
is provided sterile using ethylene oxide and is a single use device. 
The study device is not approved for commercial use. However, the clinical study will be 
conducted only in countries where the WallFlex Pancreatic Stent is approved for the clinical 
trial indication for use by the Competent Authority (CA). Local EC (Ethics Committee)/IRB 
(Institutional Review Board) approval will be obtained at each participating center.   
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Study devices are labeled on the box and inner pouch and include information not limited to 
name of legal manufacturer, device name and dimensions, lot number, expiration date and 
investigational use statement. Device labeling will be provided in local language(s) as per 
national regulations. Devices will be available in the following matrix:  
Table 2.1-1: Clinical UPN (RX, Soft) 
Rapid 
Exchange 
Length 
Width 
6mm 
8mm 
40 mm 
M00577420 
M00577480 
50 mm 
M00577430 
M00577490 
60mm 
M00577440 
M00577500 
 
For a detailed description of the WallFlex™ Pancreatic RX Fully Covered Soft Stent System, 
please reference the Investigator’s Brochure.   
2.2 
Device Use 
• The WallFlex Pancreatic Stent is intended to facilitate drainage of the pancreatic duct 
to reduce pain in patients with painful chronic pancreatitis.  
• Prior to WallFlex Pancreatic  stent placement, the patient must receive/have received 
an endoscopic pancreatic sphincterotomy (EPS). The EPS can be administered at the 
time of the stent placement procedure or can have been administered during a prior 
endoscopic procedure.  
• Investigators in this trial should be experienced with pancreatic endotherapy.  
3 Primary Objective 
To prospectively document the performance of a FCSEMS for treatment of pancreatic duct 
strictures in patients with painful chronic pancreatitis.   
4 Endpoints and Study Design 
4.1 
Primary Effectiveness Endpoint 
Pain Reduction  
Pain reduction will be assessed at 6 months post-stent removal or 6 months post-observation 
of complete or partial stent migration compared to pain collected at baseline. Baseline for 
patients without a plastic pancreatic stent immediately prior to study stent placement will be 
at the time of enrollment. Baseline for patients with a plastic pancreatic stent immediately 
prior to study stent placement will be at the time of study stent placement. 
Pain will be scored between 0 and 100 as the mean of the VAS Pain Score and Frequency of 
Pain sectors of the Izbicki pain scale. 
Complete pain relief is defined as pain score ≤ 10, and partial pain relief is defined as pain 
score ˃ 10 and reduced by at least 50% compared to baseline.  
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Complete or partial pain relief in the setting of a 50% higher average daily narcotic dose will 
be considered a primary effectiveness endpoint failure. Average daily narcotic dosage for 
prior month will be assessed at baseline visit prior to plastic or study stent placement, 
whichever is implanted first, and at 6 months post-stent removal/observation of complete 
distal migration. 
Patients who experience stent migration in setting of recurring pain (VAS Pain Score of ≥ 
20) will be considered as having failed the primary effectiveness endpoint. 
Patients who are restented in the setting of recurring pain will be considered as having failed 
both the primary effectiveness endpoint and the secondary endpoint for stricture resolution 
and may only be restented with a non-study stent. 
 
Restenting with a new study stent may only occur during the initial stent placement 
procedure for such situations as stent misplacement, improper stent size choice, or other 
conditions, as necessary and will not be considered a primary effectiveness endpoint failure 
or a secondary effectiveness stricture resolution endpoint failure. 
4.2 
Primary Safety Endpoint 
Primary Safety Endpoint: 
Rate of related SAEs from WallFlex Pancreatic stent placement to end of study. 
Relatedness will be determined by the PI, reporting if the SAE is related to the study stenting 
procedure, to the indwelling study stent, to study stent removal and/or to study stent 
migration. 
Pain thought to be caused by WallFlex Pancreatic stent expansion will be reported, but will 
not count towards the endpoint if all three of the following conditions apply:  
1. Pain can be managed by medication, with the exception of injectable narcotic use for 
more than 24 hours. 
2. Pain does not cause WallFlex Pancreatic stent removal. 
3. Pain resolves by 72 hours after WallFlex Pancreatic stent placement.     
4.3 
Secondary Endpoints 
Effectiveness 
1. Stricture Resolution 
Stricture resolution will be assessed at the time of stent removal or observation of 
complete or partial stent migration.  
Stricture resolution is defined as maintained pain relief without need for restenting or, if 
pain recurs, confirmation of stent patency adequate for providing drainage of the 
pancreatic duct.    
Restenting with a non-study stent will take place if there is no improvement of clinical 
status (see definition in secondary endpoint 2 below) and associated persistence of the 
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stricture based on imaging. Imaging will be conducted per standard of practice and may 
be prompted by lack of improved clinical status and may consist of non-invasive 
imaging or pancreatogram. A pancreatogram will only be performed if an ERCP is 
necessitated for a reintervention with or without restenting.  
NOTE:  Patients who are restented for recurring pain (VAS Pain Score of ≥ 20) will be 
considered a failure for stricture resolution and the primary endpoint and may only be 
restented with a non-study stent. 
Restenting with a new study stent may only occur during the initial stent placement 
procedure for such situations as stent misplacement, improper stent size choice, or other 
conditions, as necessary and will not be considered a secondary effectiveness stricture 
resolution endpoint failure or a primary effectiveness endpoint failure. 
2. Improved clinical status compared to baseline assessed at each study visit. 
Improved clinical status is defined as improvement in at least one and deterioration in 
none of the following: Pain, Weight and Quality of Life (QOL) 
• Pain: Scored between 0 and 100 as the mean of the VAS Pain Score and Frequency 
of Pain sectors of the Izbicki pain scale. 
• Weight is measured  
• Quality of life: Recorded using SF12 
3. Recurrence of Stricture documented by recurrence of pain with loss of adequate 
pancreatic duct drainage. 
Recurrence of stricture is defined as need for restenting. Restenting will take place if 
there is deterioration of clinical status (see definition in secondary endpoint 2 above) and 
documented recurrent stricture based on imaging. Imaging may be prompted by 
deterioration of clinical status and may consist of non-invasive imaging or of a 
pancreatogram. A pancreatogram will only be performed if an ERCP is necessitated for 
a reintervention with or without restenting.   
4. Stent Functionality 
Stent functionality will be assessed from stent placement until stent removal or 
observation of complete or partial stent migration. 
Stent functionality is defined as adequate pancreatic duct drainage reflected by reduction 
of pain and lack of restenting. 
5. Izbicki pain scale assesed at each study visit 
The Izbicki pain scale (see appendix in section 22.1) has four sectors related to severity 
of pain, frequency of pain, analgesic medication, and disease-related inability to work.  
6. Average daily narcotic dose for prior month assessed at each study visit  
7. Maintenance of the VAS Pain Score and Frequency of Pain Score recorded at 6 months 
post-stent removal compared with that recorded at the time of plastic stent removal, for 
patients with plastic pancreatic stent indwelling immediately prior to study stent 
placement 
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Technical Success 
8. Ability to deploy the stent in satisfactory position (Stent Placement Success).  
Satisfactory position is defined as the stent being across the stricture, without visible 
occluding impaction at the genu of the pancreatic duct and with distal end of the stent 
visible in the duodenum. Ease of placement will also be assessed.on a 5 point Likert 
scale. 
9. Successful endoscopic stent removal (Endoscopic Stent Removal Success). 
Endoscopic stent removal success is defined as ability to remove stent endoscopically 
(forceps, snare) without serious stent removal-related adverse events. Ease of removal 
will also be assessed.on a 5 point Likert scale. Use of stent-in-stent removal technique 
will be considered a removal failure. If stent migration is noted at time of study stent 
removal, the patient will be excluded from this endpoint’s analysis. 
Safety and Device Events   
10. Device Events, including findings not associated with adverse events, such as but not 
limited to asymptomatic stent migration. 
4.4 
Study Design 
This study is a prospective, single arm, pre-approval study. Treatment of up to 92 patients 
will take place at up to 15 clinical centers. Patient who meet all eligibility criteria will receive 
the WallFlex Pancreatic stent for up to 6 months stent indwell and 6 months follow-up after 
stent removal.  
4.5 
Stent Removal 
Stent removal will be performed using a rat-tooth forceps to grasp the retrieval loop on the 
end of the stent. The stent is gently pulled back with the scope to remove. Forceps, grasper, 
snare or stent-in-stent technique may be utilized for removal.   
Stent removal will be planned after 6 months of stent indwell. Early stent removal may be 
prompted by increased pain that the investigator deems not to be adequately managed with 
medication.  
4.6 
Restenting 
Restenting with a non-study stent will take place if there is no improvement of clinical status 
(see definition in secondary endpoint 2) and associated persistence of the stricture based on 
imaging. Imaging will be conducted per standard of practice. Such may be prompted by lack 
of improved clinical status and may consist of non-invasive imaging or of a pancreatogram.  
A pancreatogram will only be performed if an ERCP is necessitated for a reintervention with 
or without restenting. 
Restenting with a new study stent may only occur during the initial stent placement 
procedure for conditions such as stent misplacement, improper stent size choice, and other 
conditions, as necessary.      
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5 Patient Selection  
5.1 
Inclusion Criteria 
Patients who meet all of the following criteria may be given consideration for inclusion in 
this clinical investigation, provided no exclusion criterion is met. 
1. Age 18 or older 
2. Willing and able to comply with study procedures and follow-up schedule and provide 
written informed consent to participate in study 
3. Chronic pancreatitis induced stricture of Cremer Type IV, namely distal dominant 
stricture with upstream ductal dilation. 
4. For patients with a prior plastic pancreatic stent: VAS Pain Score and Frequency of Pain 
sectors of the Izbicki pain scale at the time of placement of the plastic stent. 
5. Availability of narcotic dosage for at least one month prior to baseline visit for patients 
who do not have a prior plastic pancreatic stent or availability for one month prior to 
placement of prior plastic pancreatic stent, where applicable. 
6. VAS Pain Score of ≥ 20 before study stent placement for patients without a prior plastic 
pancreatic stent. VAS Pain Score of ≥ 20 before initial plastic pancreatic stent placement 
for patients with a prior plastic pancreatic stent indwelling for 90 days or less before 
study stent placement. VAS Pain Score is captured via Izbicki pain scale. 
7. Pain occurring weekly or more frequently (assessed by Frequency of Pain sector of the 
Izbicki pain scale) as reported before study stent placement for patients without a prior 
plastic pancreatic stent, or before placement of initial plastic pancreatic stent for patients 
with a prior plastic pancreatic stent indwelling for 90 days or less before study stent 
placement. 
8. Minimum 5 mm diameter of dilated duct immediately upstream of pancreatic duct 
stricture  
9. Prior clearance of pancreatic stones where needed   
• If pancreatic duct stone clearance prior to placement of the study stent includes 
ESWL, then a plastic pancreatic stent may be placed immediately after the ESWL 
procedure at the discretion of the Investigator, for example, if there is concern 
about stone fragments of stone sludge in side branches of the pancreatic duct, and 
may be left indwelling for 30-90 days.  
• If new pancreatic duct stones requiring ESWL have formed by the time of 
intended study stent placement, then the patient will not receive the study stent 
and be excluded from the study. Further treatment of the patient will be provided 
per standard of practice outside of the study. In case the study stent is not placed 
during the same session in which the plastic stent is removed, the pain score needs 
to be collected again prior to study stent placement.  
10. Prior endoscopic pancreatic sphincterotomy (EPS), historically or to be provided at time 
of SEMS placement as applicable 
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5.2 
Exclusion Criteria 
Patients who meet any one of the following criteria will be excluded from this clinical study. 
1. Pancreatic or peri-ampullary cancer with or without pancreatic duct strictures caused by 
malignancy  
2. Biliary strictures caused by chronic pancreatitis that are symptomatic and/or in need of 
therapeutic intervention 
3. Perforated duct 
4. Ansa pancreatica 
5. Presence of pancreatic cysts suspected to be cystic tumor or requiring transmural 
drainage 
6. Duodenal/groove pancreatitis 
7. Autoimmune pancreatitis 
8. Pancreatic duct stenoses not located in the head of the pancreas 
9. Failed access during an attempted ERCP on a prior date at the investigational center 
10. Duration of indwell of one single plastic pancreatic stent or cumulative duration of 
consecutive single plastic pancreatic stents immediately prior to study stent placement 
exceeding 90 days 
11. History of prior single pancreatic plastic stent(s) followed by a stent-free period shorter 
than 1 year before enrollment into the study 
12. History of prior side-by-side multiple pancreatic plastic stents up to one year prior to 
enrollment 
13. History of prior pancreatic metal stent(s) 
14. Reported recent history of acute relapsing pancreatitis in the absence of chronic 
pancreatitis 
15. Patients for whom endoscopic techniques are contraindicated. 
16. Patients who are currently enrolled in another investigational study that would directly 
interfere with the current study, without prior written approval from the sponsor 
17. Inability or refusal to comply with the follow-up schedule including patient living at such 
a distance from the investigational center that attending follow-up visits would be 
unusually difficult or burdensome 
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6 Patient Accountability 
6.1 
Patient Status and Classification 
6.1.1 Enrolled Cohort 
A patient 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 excluded from the study. 
6.1.2 Intent-to-Treat Cohort 
This cohort (ITT) consists of those “enrolled” patients who meet all inclusion/exclusion 
criteria. Any adverse events occurring or resulting from a treatment attempt will be collected. 
Protocol deviations will be collected as necessary. Patients in this cohort will be counted 
towards the enrollment ceiling, and this cohort will be considered the primary analysis 
cohort.  
6.1.3 Per-Protocol Cohort 
The per-protocol cohort is a subset of the ITT patients who receive a study stent(s) and who 
do not experience major protocol deviations (ICH E9 definitions).  
6.2 
Enrollment Controls 
The risk of over-enrollment is minimized by utilizing a limited number of clinical centers and 
maintaining close communication with study centers.  
6.3 
Withdrawal 
All patients enrolled in the clinical study (including those withdrawn from the clinical study 
or lost to follow-up) shall be accounted for and documented. If a patient withdraws from the 
clinical investigation, the reason(s) shall be reported. If such withdrawal is due to problems 
related to investigational device safety or performance, the investigator shall ask for the 
patients permission to follow his/her status/condition outside of the clinical study.   
Reasons for withdrawal include physician discretion, patient choice to withdraw consent, loss 
to follow-up and death. While study withdrawal is discouraged, patients may withdraw from 
the study at any time, with or without reason, and without prejudice to further treatment. All 
applicable case report forms up to the point of patient withdrawal must be completed. 
Additional data may no longer be collected after the point at which a patient has been 
withdrawn from the study or withdraws his/her consent, for whatever reason. All open 
adverse events should be closed or include resolution status. Data collected up to the point of 
patient withdrawal may be used. Withdrawn patients will not be replaced. Patients who 
withdraw from the study with the study stent in place will be followed per standard of care at 
the local institution. 
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6.4 
End of Study Action Plan 
Patients will have the study device, the WallFlex Pancreatic Stent, implanted temporarily for 
up to six months. Per section 7.11, a patient will be considered lost to follow-up if the patient 
remains unresponsive to communication after three documented attempts by study staff. 
However, for those patients who remain unresponsive to communication while the stent 
remains in place, additional attempts will be made to request the patient’s return for study 
stent removal. These additional attempts may include increased telephone and written 
communications and contact with the patient’s primary care physician (if this communication 
is consented to in the Informed Consent Form).  
 
 
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7 Study Methods 
7.1 
Data Collection 
Procedure/Assessment 
Screening/ 
Baseline 
Study Stent 
Placement**** 
Month 1 
 (30 ± 5 
Days) 
Month 3 
(90 ± 10 
Days) 
Month 6 
Study Stent 
Removal 
(180 ± 15 Days) 
Month 3 
 Post-Removal 
Follow-up Visit 
 (90± 15 Days) 
Month 6 
 Post-Removal 
Follow-Up Visit 
(180 days ± 15 days) 
Informed consent form, 
including informed consent 
signature date 
X 
 
 
 
 
 
 
Demographics and  Medical 
and EPS History 
X 
 
 
 
 
 
 
Weight* 
X 
X 
X 
X 
X 
X 
X 
EPS 
 
X (if required) 
 
 
 
 
 
Pre-stenting pancreatic stone 
clearance (as applicable) 
X*** 
X 
 
 
 
 
 
Study Stent Placement  
 
X 
 
 
 
 
 
Study Stent Removal 
 
 
 
 
X 
 
 
Pancreatic Duct Imaging 
(may be non-invasive) 
 
X*** 
X 
Pre- and Post-
Stent Placement 
 
 
X**  
Post-Stent 
Removal 
 
X 
Pain Score, Average Daily 
Narcotic Dose, and QOL 
Score* 
X 
X (prior to all 
stent procedures) 
X 
X 
X (prior to stent 
removal) 
X 
X 
Adverse Event Assessment 
X*** 
X 
X 
X 
X 
X 
X 
Concomitant Medications, 
including injectable narcotics 
X 
X 
X 
X 
X 
X 
X 
* Weight Pain Score and QOL must be assessed at all visits, including any unscheduled visits. 
**Window for imaging is ±4 weeks.  
***Applicable at Baseline visit for patients who undergo plastic stent placement for ESWL per inclusion criteria 9.  
****Study Stent Placement visit may take place on the same day as Screening/Baseline, if deemed appropriate by the treating physician
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7.2 
Study Candidate Screening 
No study-specific testing will be conducted until after the patient has signed an ICF. A 
Screen Failure/Enrolled Log will be maintained in Electronic Data Capture (EDC) by the 
center to document select information about candidates who signed consent.   
7.3 
Informed 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)/Ethics Committee (EC) and 
Competent Authority, as applicable. Study personnel should explain that even if a patient 
agrees to participate in the study and signs the ICF, the ERCP procedure may demonstrate 
that the patient is not a suitable candidate for the study.  
7.4 
Scoring System 
7.4.1 Izbicki Scoring System 
The Izbicki Pain Scale incorporates four elements: 1) patient self-estimation of intensity of 
pain using a visual analog scale (VAS), 2) the frequency of pain attacks, 3) analgesic 
medication usage and 4) the time periods of inability to work. The sum of the rank values 
divided by four gives the final value of the pain score. See Appendix 22.1 for the Pain Scale. 
 
Patients will be asked to report on the average pain experienced since the prior visit when 
reporting pain via VAS for the first element of the Izbicki Pain Scale. Patients will be asked 
to report the average frequency of pain attacks experienced since the prior visit for the 
second element of the Izbicki Pain Scale. Please see Appendix 22.5 for further guidance on 
collecting the VAS and frequency of pain attacks information. 
 
Note: For centers with medication types that do not align with section 3 of the Izbicki Pain 
scale, relevant corresponding medication types may be made available for scoring.   
7.4.2 SF-12 
The SF-12 (Short Form 12 Item Survey), see Appendix 22.2, is a twelve question survey 
based off the larger SF-36 scoring system that assesses overall health-related quality of life. 
The SF-12 is weighted and summed to provide scales for physical and mental health.  
 
7.4.3 Average Daily Narcotic Dosage 
Average Daily Narcotic Dose for the previous month will be calculated for all study patients 
at all study visits. The value for this data point will be expressed in units of morphine 
milligram equivalents (MME). 
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Site personnel will collect narcotic use information as part of concomitant medication data 
collection at each visit.  Documentation of all narcotic dosage increases and/or decreases 
throughout the patient’s participation will be very important for the accurate calculation of 
Average Daily Narcotic Dose. 
Site personnel will convert all daily narcotic dosages for the previous month to MME. The 
daily MME values obtained will be added together and divided by the number of days in the 
previous month to obtain the Average Daily Narcotic Dose. The Average Daily Narcotic 
Dose value will be rounded to the nearest whole number, if necessary. 
Please see Appendix 22.4 for examples of Average Daily Narcotic Dosage calculations. 
7.5 
Screening/Baseline – Office/Hospital Visit 
• Informed Consent  
• Eligibility Criteria Assessment 
• Demographics 
• Medical and EPS History 
• Pain Score 
• Concomitant Medications (including injectable narcotics) 
• Average Daily Narcotic Dose for Prior Month 
• Weight 
• Quality of Life 
• EPS History 
• Plastic Stent Placement, as applicable per inclusion criteria 9 
• Imaging, as applicable 
• Adverse Event/Device Event Assessment, as applicable 
7.6 
WallFlex Pancreatic Study Stent Placement – Office/Hospital Visit 
• May be performed on the same day as Screening/Baseline visit, if deemed 
appropriate by the treating physician 
7.6.1 Stent Size Selection 
• If the upstream dilated pancreatic duct is ≤ 6 mm, a 6 mm diameter WallFlex 
Pancreatic stent should be placed. 
• If the upstream dilated pancreatic duct is > 6 mm, an 8 mm diameter WallFlex 
Pancreatic stent should be placed.  
7.6.2 Assessments 
• Pain Score (prior to stent procedures) 
• Weight 
• Concomitant Medications (including injectable narcotics) 
• Average Daily Narcotic Dose for Prior Month  
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• Quality of Life 
• Pancreatic Duct Imaging (pre-and post-procedure) 
• EPS (if required, per section 2.2) 
• Plastic Stent Removal prior to study stent placement, as applicable 
• Study Stent Placement Procedure 
• Adverse Event/Device Event Assessment 
7.7 
Stent Indwell Follow-Up: Month 1 (30 days ± 5 days) and Month 3 (90 days ± 10 
days) – Telephone or Office/Hospital Visit 
• Pain Score 
• Concomitant Medications (including injectable narcotics) 
• Average Daily Narcotic Dose for Prior Month 
• Weight 
• Quality of Life 
• Adverse Event/Device Event Assessment 
7.8 
Study Stent Removal Visit: Month 6 (180 days ± 15 days) – Office/Hospital Visit 
• Pain Score (prior to stent removal) 
• Concomitant Medications (including injectable narcotics) 
• Average Daily Narcotic Dose for Prior Month 
• Weight 
• Quality of Life 
• Study Stent Removal 
• Adverse Event/Device Event Assessment 
• Pancreatic Duct Imaging 
• OPTIONAL: Pancreatogram 24-72 hours post-stent removal, in case a naso-
pancreatic drain was left in place after stent removal.  
7.9 
Post-Stent Removal Follow-Up: Month 3 (90 days±15 days post-removal) – 
Telephone or Office/Hospital Visit 
• Pain Score 
• Concomitant Medications (including injectable narcotics) 
• Average Daily Narcotic Dose for Prior Month 
• Weight 
• Quality of Life 
• Adverse Event/Device Event Assessment 
7.10 Post-Stent Removal Follow-Up: Month 6 (180 days±15 days post-removal) – 
Telephone or Office/Hospital Visit 
• Pain Score 
• Concomitant Medications (including injectable narcotics) 
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• Average Daily Narcotic Dose for Prior Month 
• Weight 
• Quality of Life 
• Adverse Event/Device Event Assessment 
• Pancreatic Duct Imaging 
7.11 Additional Visits as Required 
• Pain Score 
• Concomitant Medications (including injectable narcotics) 
• Average Daily Narcotic Dose for Prior Month 
• Weight 
• Quality of life 
• Adverse Event/Device Event Assessment 
• Pancreatic Duct Imaging, as applicable 
7.12 Study Completion 
Patients who receive the WallFlex Pancreatic stent will be followed for 6 months after initial 
stent removal or 6 months after observation of complete distal migration. See Section 4.3 
(secondary endpoint bullet #3) for directions regarding restenting of recurrent strictures.  
Additional visits may be conducted at the Investigator’s discretion in accordance with 
Adverse Event or Device Event data collection. A patient will be considered lost to follow-up 
if the patient remains unresponsive to communication after three documented attempts by 
study staff. 
7.13 Source Documents 
Table 7.133-1: Source Documentation Requirements 
Requirement 
Disposition 
Imaging before and after study stent placement  
Retain at center 
Imaging after study stent removal 
Retain at center 
Imaging 6 months after stent removal/observation of 
complete distal migration 
Retain at center 
 
The Investigator/institution guarantees direct access to original source documents, including 
cholangiogram and/or imaging documentation, by BSC personnel, their designees, and 
appropriate regulatory authorities. In the event that the original medical records cannot be 
obtained for a patient that is seen by a non-study physician at a non-study institution, 
photocopies of the original source documents must be made available for review. 
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8 Statistical Considerations 
8.1 
Endpoints 
8.1.1 Primary Endpoint 
Primary Effectiveness Endpoint: 
Pain Reduction  
Pain reduction will be assessed at 6 months post-stent removal or 6 months post-observation 
of complete or partial stent migration compared to pain collected at baseline. Baseline for 
patients without a plastic pancreatic stent immediately prior to study stent placement will be 
at the time of enrollment. Baseline for patients with a plastic pancreatic stent immediately 
prior to study stent placement will be at the time of study stent placement. 
Pain will be scored between 0 and 100 as the mean of the VAS Pain Score and Frequency of 
Pain sectors of the Izbicki pain scale. 
Complete pain relief is defined as pain score ≤ 10, and partial pain relief is defined as pain 
score ˃ 10 and reduced by at least 50% compared to baseline.  
Complete or partial pain relief in the setting of a 50% higher average daily narcotic dose will 
be considered a primary effectiveness endpoint failure. Average daily narcotic dosage for 
prior month will be assessed at baseline visit prior to plastic or study stent placement, 
whichever is implanted first, and at 6 months post-stent removal/observation of complete 
distal migration. 
Patients who experience stent migration in setting of recurring pain (VAS Pain Score of ≥ 
20) will be considered as having failed the primary effectiveness endpoint. 
Patients who are restented in the setting of recurring pain will be considered as having failed 
both the primary effectiveness endpoint and the secondary stricture resolution endpoint and 
may only be restented with a non-study stent. 
Restenting with a new study stent may only occur during the initial stent placement 
procedure for such situations as stent misplacement, improper stent size choice, or other 
conditions, as necessary and will not be considered a primary effectiveness endpoint failure 
or a secondary effectiveness stricture resolution endpoint failure. 
For the patients who have a single plastic stent in place for up to 90 days before receiving the 
study stent, inclusion criteria #6 and #7 will be reassessed immediately prior to the plastic to 
study stent exchange. Patients who do not meet the inclusion criteria levels of the VAS pain 
score (≥20) and frequency of pain score (50, 75, or 100) at the time of stent exchange will be 
excluded from the primary effectiveness endpoint analyses but will be included in the 
primary safety endpoint analysis and all secondary endpoint analyses. For the patients who 
meet the inclusion criteria levels, we will use the scores (VAS Pain Score and Frequency of 
Pain Score) collected immediately prior to the plastic to study stent exchange as their 
baseline and include them in the primary effectiveness endpoint analyses. 
Primary Safety Endpoint: 
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Rate of related Serious Adverse Events (SAEs) from WallFlex Pancreatic stent placement to 
end of study. 
Relatedness will be determined by the PI, reporting if the SAE is related to the study stenting 
procedure, to the indwelling study stent, to study stent removal and/or to study stent 
migration. 
Pain thought to be caused by WallFlex Pancreatic stent expansion will be reported, but will 
not count towards the endpoint if all three of the following conditions apply:5  
1. Pain can be managed by medication, with the exception of injectable narcotic use for 
more than 24 hours. 
2. Pain does not cause WallFlex Pancreatic stent removal. 
3. Pain resolves by 72 hours after WallFlex Pancreatic stent placement. 
8.1.2 Hypotheses/Sample Size  
Ten (10) articles2-11 were identified to be reporting on “pain reduction,” representing 392 
evaluable patients. One of these articles10 did not report on “related SAE rate”; thus, for this 
endpoint we used 9 articles2-9,11, representing 386 evaluable patients. The table below 
provides by-publication “pain reduction” and “related SAE” rate used to conduct respective 
meta-analyses.   
Meta-analyses were conducted using a random effects model.  The sample sizes were 
calculated using SAS version 9.4. 
Table 8.1.2-1: Pain Reduction and Related SAE Rates by Publication 
Study 
“Pain Reduction” 
“Related SAEs” 
Eleftheriadis 20052 
62% (62/100) 
25% (25/100) 
Vitale 20043 
83% (62/75) 
19% (17/89) 
Topazian 20054 
60% (9/15) 
47% (7/15) 
Costamagna 20065 
84% (16/19) 
0% (0/19) 
Farnbacher 20066 
55% (53/96) 
28% (27/96) 
Ishiara 20067 
78% (7/9) 
0% (0/9) 
Cahen 20078 
32% (6/19) 
26% (5/19) 
Weber 20079 
82% (14/17) 
12% (2/17) 
Seza 201110 
85% (17/20) 
N/A 
Gabrielli 200511 
32% (7/22) 
32% (7/22) 
 
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Pain reduction 
For “pain reduction” the meta-analysis yielded a point estimate of 66% with a 95% 
Confidence Interval (CI) from 53% to 76%. 
Statistical testing will be performed to determine if the probability of “pain reduction” when 
using the WallFlex Pancreatic Stent is greater than the performance goal (PG) set at 53%, the 
lower bound of the 95% CI from the meta-analysis above. Hence, the following hypothesis 
will be tested: 
Ho: π1  ≤53% 
Ha: π1 > 53% 
where π1 is the probability of observing “pain reduction”. 
Assuming that the observed probability is 75%, 43 patients will be required for the above 
hypothesis, with a one-sided alpha of 0.025 and power of 80%.   
The observed probability of pain reduction was set to 75% given that 8 out of 10 patients in a 
10 patient pilot study remained stent free at 6 months post-removal. The primary 
effectiveness endpoint will be assessed in two ways, namely one using last observation 
carried forward for patients that are missing 6 month pain data and one counting patients 
with 6 month pain data as failures. A tipping point analysis will be performed to assess the 
validity of the associated conclusions. 
Related SAEs 
For “related SAE rate” the meta-analysis yielded a point estimate of 25% with a 95% CI 
from 19% to 32%.  
Statistical testing will be performed to determine if the probability of “related SAE rate” is 
lower than 32%, the upper bound of the 95% CI of the meta-analysis. Hence, the following 
hypothesis will be tested: 
Ho: π2  ≥32% 
Ha: π2 < 32% 
where π2 is the probability of observing “related SAE rate”. 
Assuming that the observed probability is 15%, 57 patients will be required for the above 
hypothesis, with a one-sided alpha of 0.025 and power of 80%.   
The observed probability of the related SAE rate was set to 15% given what was observed in 
a 10 patient pilot study and the resulting mitigation measures put in place to reduce the risk 
of observed related SAEs per definition of the Primary Safety Endpoint. 
The primary safety endpoint will be assessed in two ways, namely one using all related SAEs 
(excluding pain thought to be caused by stent expansion per Section 4.2) and one using all 
related SAEs except those termed as pain by the site. 
 Sample size 
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Taking the largest of the two sample sizes, namely 43 and 57, and compensating for possible 
loss of patients after enrollment, an additional 10% of patients will be required, for a total of 
64 Intent-to-Treat patients. 
The percentage of patients who do not meet the inclusion criteria levels of the VAS pain 
score (≥ 20) and frequency of pain score (50, 75, or 100) at the time of study stent placement, 
due to a prior single plastic pancreatic stent, is anticipated to range from 20-30%.  Therefore, 
we propose to enroll up to 92 patients so as to have 64 patients who met the inclusion criteria 
levels of the VAS pain score (≥ 20) and frequency of pain score (50, 75, or 100) at the time 
of study stent placement. No more than 28 subjects who do not meet these inclusion criteria 
at the time of study stent placement will be enrolled into the study. 
Forest plots illustrating the two meta-analyses and marking the selected PG and assumed 
observed probability are provided below. 
 
Meta-Analysis of Pain  
 
 
 
Meta-Analysis of SAE 
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NOTE: A literature search was performed on metal pancreatic stenting, and 4 articles that 
represented 61 patients13-16 were found. The meta-analyses yielded a point estimate of 84% 
with a 95% CI of (72%, 92 %) and 19% with a 95% CI of (8%, 38%) for “pain reduction” 
and “related serious adverse events,” respectively. These are similar to the findings of the 
meta-analyses for plastic pancreatic stenting.   
8.1.3 Sensitivity Analyses 
Sensitivity analyses, specifically a tipping-point analysis for the primary endpoint, may be 
conducted to assess the impact of missing data on interpretation of the results. Missing equals 
failure method will be used, such that missing data will be added into the primary analyses as 
failures until the null hypotheses are not rejected any longer. Multiple imputation methods 
will not be used. 
8.2 
Statistical Methods 
8.2.1 Baseline Data 
Patient demographics, medical history, risk factors, pain score, QOL, pancreatic duct 
imaging, EPS history, and ESWL history will be summarized using descriptive statistics 
(e.g., mean, standard deviation, n, minimum, maximum) for continuous variables and 
frequency statistics for discrete variables.  
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8.2.2 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.  
8.2.3 Subgroup Analyses 
The subgroup analyses will include tabulating the primary endpoints and select secondary 
endpoints by gender. The primary efficacy endpoint will be stratified by narcotic use. 
(Stratification levels for narcotic use will be based on the data and will not be pre-specified.) 
Finally, a stratified analysis will be performed to detect potential differences between 
patients with and without a history of prior side-by-side multiple plastic pancreatic stents. It 
is not expected that this analysis will be statistically powered to make claims of potential 
differences between the groups.  
8.2.4 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 logistic regression models with site 
as the factor of interest and the primary endpoint as outcomes. Certain baseline variables may 
also be explored for pooling. 
 
If the P value for the site or baseline variable coefficient is ≥0.15, it will be concluded that 
the treatment effect is not different across sites, and the data can be pooled. If the P value for 
the site coefficient is <0.15, site differences will be explored.  
8.2.5 Mulitvariate Analyses 
Univariate and multivariate analyses may be performed to assess the effect of potential 
predictors on the primary endpoint using logistic regression.  
Variables from the following categories will be considered as possible predictors: 
demographics and medical history. Factors will be modeled multivariately using a stepwise 
procedure in a logistic regression model. The significance thresholds for entry and exit into 
the model will be set to p≤0.10. 
8.2.6 Interim Analyses 
 
No formal interim analyses are planned for this study. 
8.2.7 Statistical Software  
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). 
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8.2.8 Changes to Planned Analyses 
Any changes to the planned statistical analyses made prior will be documented in an 
amended Statistical Analysis Plan.  
9 Data Management 
9.1 
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 hosted by Medidata. 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 all 
queries in the database. 
9.2 
Data Retention 
The Investigator or Investigational site 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.  
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10 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. 
11 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 
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 must be documented and reported to the sponsor 
using entry onto the eCRF. 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. 
12 Device/Equipment Accountability 
The investigational devices/equipment shall be securely maintained, controlled, and used 
only in this clinical study.  
The sponsor shall keep records to document the physical location of all investigational 
devices from shipment of investigational devices to the investigation sites until return or 
disposal. Records shall also be kept by study personnel to document the physical location and 
conditions of storage of all investigational devices/equipment.  
The principal investigator or an authorized designee shall keep records documenting the 
receipt, use, return and disposal of the investigational devices/equipment, which shall include 
the following 
• Date of receipt 
• Identification of each investigational device (batch number or unique code) 
• Expiry date, as applicable 
• Date or dates of use 
• Patient identification 
• Date on which the investigational device was returned/explanted from patient, if 
applicable 
• Date of return of unused, expired, or malfunctioning investigational devices, if 
applicable. 
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Written procedures may be required by national regulations. 
13 Compliance 
13.1 Statement of Compliance 
This study will be conducted in accordance with relevant sections of the International 
Standard (ISO) 14155: Clinical Investigation of Medical devices for Human Subjects – Good 
Clinical Practice, 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 or regulatory authority shall be followed, if 
appropriate. 
13.2 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 
interpretation of results. 
• 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. 
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• Record, report, and assess (seriousness and relationship to the device/procedure, 
including stent removal and complete distal migration) every adverse event and observed 
device deficiency. 
• Report to BSC per the protocol requirements and the IRB/EC, as applicable, all SAEs and 
device deficiencies that could have led to a Serious Adverse Device Event (SADE). 
• 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. 
• 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 
treatment. 
• 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. 
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13.2.1 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.  
13.3 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/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 patients into the study and shipment of investigational 
product/equipment. Prior approval must also be obtained for other materials related to 
patients recruitment or which will be provided to the patient. 
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.  
13.4 Sponsor Responsibilities 
All information and data sent to BSC concerning patients or their participation in this study 
will be considered confidential by BSC. Only authorized BSC personnel or a BSC 
representative including 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 patient name. 
Boston Scientific will keep patient’s health information confidential in accordance with all 
applicable laws and regulations.  Boston Scientific may use patient’s 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 patients; patient names will not be placed on any 
mailing lists or sold to anyone for marketing purposes.  
13.5 Insurance  
Where required by local/country regulation, proof and type of insurance coverage, by BSC 
for patients in the study will be obtained. 
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14 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 patient 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. 
15 Potential Risks and Benefits 
15.1 Anticipated Adverse Device Effects  
The following anticipated adverse events (AE) have been identified for this study associated 
with the placement and removal of the study device. 
• Pain 
• Cholestasis 
• Cholangitis 
• Pancreatitis 
• Secondary stricture formation 
• Obstructive Jaundice 
• Vomiting 
• Bleeding 
• Infection 
• Sepsis 
• Abscess Formation 
• Hyperplastic Tissue Reaction 
• Tissue trauma (including events such as duct injury, rupture, edema, inflammation, 
impaction, laceration and necrosis)  
• Pancreatic Duct Rupture 
• Allergic Reaction 
• Pseudocyst development 
• Fever 
• Death (excluding disease progression) 
• Impaction to pancreatic duct wall 
• 
Perforation with or without pneumoperitoneum  
• Pseudoaneurysm 
 
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Please refer to the Investigator Brochure for a list of anticipated adverse device effects.  
15.2 Risks Associated with Clinical Trial Participation 
Participation in the trial may be demanding and time consuming,  
15.3 Risk Minimization Actions 
Additional risks may exist. Risks can be minimized through compliance with this protocol, 
performing procedures in the appropriate hospital environment, adherence to patient 
selection criteria, close monitoring of the patient’s physiologic status during research 
procedures and/or follow-ups and by promptly supplying BSC with all pertinent information 
required by this protocol. 
15.4 Anticipated Benefits 
Patients may not receive any benefit from participating in this study. However, medical 
science and future patients may benefit from this study.  
15.5 Risk to Benefit Rationale 
Based on collected reports in literature to-date, the risk-to-benefit ratio is within reason for 
foreseeable risks. However, literature reports do not always capture all side effects. 
Observation and follow-up of patients is required as outlined in the protocol. 
16 Safety Reporting 
16.1 Definitions and Classification 
Adverse event definitions are provided in Table 16.1-1. Administrative edits were made to 
combine definitions from ISO 14155-2011 and MEDDEV 2.7/3 (2015). 
 
Table 16.1-1: Safety Definitions 
Term 
Definition 
Adverse Event (AE) 
 
Ref: ISO 14155-2011 
 
Ref: MEDDEV 2.7/3 (2015) 
 
 
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 14155-2011 
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 
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Table 16.1-1: Safety Definitions 
Term 
Definition 
 
Ref: MEDDEV 2.7/3 (2015) 
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 14155-2011 
 
Ref: MEDDEV 2.7/3 (2015) 
Adverse event that: 
• Led to death, 
• Led to  serious deterioration in the health of the subject, as defined by 
either: 
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 prolongation  of existing hospitalization, 
or 
o medical or surgical intervention to prevent life-threatening illness  
o 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 1: Planned hospitalization for a pre-existing condition, or a 
procedure required by the clinical investigational plan, without serious 
deterioration in health, is not considered a serious adverse event.  
Serious Adverse Device Effect 
(SADE) 
 
Ref: ISO 14155-2011 
 
Ref: MEDDEV 2.7/3 (2015) 
Adverse device effect that has resulted in any of the consequences 
characteristic of a serious adverse event. 
 
Unanticipated Adverse Device 
Effect (UADE) 
 
Ref: 21 CFR Part 812 
 
 
Any serious adverse effect on health or safety or any life-threatening 
problem or death caused by, or associated with, a device, if that effect, 
problem, or death was not previously identified in nature, severity, or degree 
of incidence in the investigational plan or application (including a 
supplementary plan or application), or any other unanticipated serious 
problem associated with a device that relates to the rights, safety, or welfare 
of subjects.   
Unanticipated Serious Adverse 
Device Effect (USADE) 
 
Ref: ISO 14155-2011 
 
Ref: MEDDEV 2.7/3 (2015) 
 
 
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 1: 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 (2015) 
A device deficiency is any inadequacy of a 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. 
 
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Table 16.1-1: Safety Definitions 
Term 
Definition 
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 16.1-1 for AE 
definitions).  
Any related AE experienced by the study patient after informed consent, whether during or 
subsequent to the procedure, must be recorded in the eCRF. Unrelated AEs will not be 
collected for this study. 
Refer to Section 15 for the known risks associated with the study device(s). 
16.2 Relationship to Study Device(s) 
The Investigator must assess the relationship of any SAE  or AE to the study device, study 
stent placement procedure, study sent removal and complete distal stent migration. See 
criteria in Table 16.2-1:  
Table 16.2-1: Criteria for Assessing Relationship of Study Device or Procedure 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 
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. 
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Table 16.2-1: Criteria for Assessing Relationship of Study Device or Procedure to 
Adverse Event 
Classification 
Description 
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 
where 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 
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. 
16.3 Investigator Reporting Requirements 
The communication requirements for reporting to BSC are as shown in Table 16.3-1. 
Table 16.3-1: Investigator Reporting Requirements 
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Event Classification 
Communication 
Method  
Communication Timeline (Pre-Market Studies) 
(MEDDEV 2.7/3 (2015):  
CLINICAL INVESTIGATIONS: SERIOUS ADVERSE EVENT 
REPORTING UNDER DIRECTIVES 90/385/EEC AND 93/42/EEC) 
Unanticipated Adverse 
Device Effect / 
Unanticipated Serious 
Adverse Device Effect  
Complete AE eCRF 
page with all available 
new and updated 
information.  
• Within 1 business day of first becoming aware of the 
event. 
• Terminating at the end of the study 
Serious Adverse Event  
Complete AE eCRF 
page with all available 
new and updated 
information.  
• Within 3 calendar days of first becoming aware of the 
event or as per local/regional regulations.  
• Reporting required through the end of the study 
Provide all relevant 
source documentation 
(unidentified) for 
reported event upon 
request of the sponsor 
• At request of sponsor 
Serious Adverse Device 
Effects 
Complete AE eCRF 
page with all available 
new and updated 
information. 
• Within 3 calendar days of first becoming aware of the 
event or as per local/regional regulations.  
• Reporting required through the end of the study 
Provide all relevant 
source documentation 
(unidentified) for 
reported event 
• 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 eCRF page 
with all available new 
and updated 
information.  
• Within 3 calendar days of first becoming aware of the 
event.  
• Reporting required through the end of the study 
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Table 16.3-1: Investigator Reporting Requirements 
Event Classification 
Communication 
Method  
Communication Timeline (Pre-Market Studies) 
(MEDDEV 2.7/3 (2015):  
CLINICAL INVESTIGATIONS: SERIOUS ADVERSE EVENT 
REPORTING UNDER DIRECTIVES 90/385/EEC AND 93/42/EEC) 
Adverse Event 
including Adverse 
Device Effects 
Complete AE eCRF 
page, which contains 
such information as date 
of AE, treatment of AE 
resolution, assessment 
of seriousness and 
relationship to the 
device.  
• In a timely manner  (e.g. Recommend within 10 
business days) after becoming aware of the 
information 
• Reporting required through end of study 
Abbreviations: AE=adverse event; CRF=case report form; IDE=Investigational Device Exemption; 
UADE=unanticipated adverse device effect 
* Please note that pre-market studies are clinical studies with investigational devices or with medical devices 
that bear the regulatory approval and are not being used for the same approved indications. 
16.4 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 on the 
eCRF. 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 (including but not limited to 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. 
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. 
16.5 Reporting to Regulatory Authorities / IRBs / ECs / 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/EC, and regulatory 
authorities of any UADE/USADE and SAE as required by local/regional regulations. 
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16.6 Adverse Event Coding 
MedDRA version 17.1 or higher will be utilized to map verbatim AE terms to medical 
dictionary-derived terms.  
17 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 
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.  
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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. 
18 Suspension or Termination 
18.1 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 patients.  Investigators, associated IRBs/ECs, and regulatory 
authorities, as applicable, will be notified in writing in the event of study termination. 
18.1.1 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 patients 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. 
18.2 Termination of Study Participation by the Investigator or Withdrawal of IRB/ EC 
Approval 
Any investigator, or IRB/ EC in the study 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. 
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18.3 Requirements for Documentation and Patient 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 centers by Boston Scientific. 
The IRB/EC and regulatory authorities, as applicable, will be notified. Detailed information 
on how enrolled patient 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 patients will be managed thereafter will be provided by 
Boston Scientific. 
In the event an investigator terminates participation in the study, study responsibility will be 
transferred to a co-investigator, if possible. In the event there are no opportunities to transfer 
investigator responsibility; detailed information on how enrolled patients will be managed 
thereafter will be provided by Boston Scientific. 
The investigator must return all documents and investigational product to Boston Scientific, 
unless this action would jeopardize the rights, safety, or welfare of the patients. 
18.4 Criteria for Suspending/Terminating a Study Center 
Boston Scientific Corporation reserves the right to stop the inclusion of patients at a study 
center at any time after the study initiation visit if no patients have been enrolled for a period 
beyond 12 months after center initiation, or if the center has multiple or severe protocol 
violations/noncompliance without justification and/or fails to follow remedial actions. 
In the event of termination of investigator 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 patients. The IRB/EC and regulatory authorities, as 
applicable, should be notified. All patients enrolled in the study at the center will continue to 
be followed for the protocol follow-up period after study termination. The Principal 
Investigator at the center must make provision for these follow-up visits unless BSC notifies 
the investigational center otherwise. 
19 Publication Policy 
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. 
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• 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.  
 
 
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20 Bibliography 
1. Cremer, M., Deviere, J., Delhaye, M., Baize, Vandermeeren, A., Stenting in severe 
chronic pancreatitis: Results of medium-term follow-up in seventy-six patients. 
Endoscopy, 1991, 23, 171-6  
2. Eleftherladis N., Dinu F., Delhaye M. et al. Long-term outcome after pancreatic stenting 
in severe chronic pancreatitis. Endoscopy, 2005, 37, 223-30  
3. Vitale G, E Cothron and A Vitale, et al. Role of pancreatic duct stenting in the treatment 
of chronic pancreatitis. Surg Endosc 2004, 18, 1431–1434 
4. Topazian, M., H. Aslanian, and D. Andersen, Outcome following endoscopic stenting of 
pancreatic duct strictures in chronic pancreatitis. J Clin Gastroenterol, 2005, 39, 908-11 
5. Costamagna, G., et al., Multiple stenting for refractory pancreatic duct strictures in 
severe chronic pancreatitis: long-term results. Endoscopy, 2006, 38(3), 254-9  
6. Farnbacher, M., S. Muhldorfer, and M. Wehler, et al. Interventional endoscopic therapy 
in chronic pancreatitis including temporary stenting: A definitive treatment? 
Scandinavian Journal of Gastroenterology, 2006, 41, 111-117 
7. Ishihara, T, T Yamaguchi and K Seza, et al. Efficacy of s-type stents for the treatment of 
the main pancreatic duct stricture in patients with chronic pancreatitis. Scandinavian 
Journal of Gastroenterology, 2006, 41, 744-750 
8. Cahen, L, D Gouma, and Y Nio, et al. Endoscopic vesus Surgical Drainage of the 
Pancreatic Duct in Chronic Pancreatitis. N Engl J Med, 2007, 56, 676-84. 
9. Weber, A, J Schneider, and N Bruno, et al. Endoscopic Stent Therapy for Patients with 
Chronic Pancreatitis. Pancreas, 2007,  34 (3), 287-294 
10. Seza, K., et al., A long-term controlled trial of endoscopic pancreatic stenting for 
treatment of main pancreatic duct stricture in chronic pancreatitis. 
Hepatogastroenterology, 2011, 58, 2128-31 
11. Gabbrielli, A, M Pandolfi, and M Mutignani, et al. Efficacy of main pancreatic-duct 
endoscopic drainage in patients with chronic pancreatitis, continuous pain, and dilated 
duct. Gastrointest Endosc, 2005, 61(4), 576-581 
12. Eisendrath, P. and J. Deviere, Expandable metal stents for benign pancreatic duct 
obstruction. Gastrointestinal Endoscopy Clinics of North America, 1999, 9(3), 547-54 
13. Park do, H., et al., Feasibility and safety of placement of a newly designed, fully covered 
self-expandable metal stent for refractory benign pancreatic ductal strictures: a pilot 
study (with video). Gastrointest Endosc, 2008, 68(6), 1182-9 
14. Sauer, B., et al., Temporary placement of a fully covered self-expandable metal stent in 
the pancreatic duct for management of symptomatic refractory chronic pancreatitis: 
preliminary data (with videos). Gastrointest Endosc, 2008, 68(6), 1173-8 
15. Moon, S.H., et al., Modified fully covered self-expandable metal stents with antimigration 
features for benign pancreatic-duct strictures in advanced chronic pancreatitis, with a 
focus on the safety profile and reducing migration. Gastrointest Endosc, 2010, 72(1), 86-
91 
16. Giacino, C., P. Grandval, and R. Laugier, Fully covered self-expanding metal stents for 
refractory pancreatic duct strictures in chronic pancreatitis. Endoscopy, 2012, 44(9), 
874-7 
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17. Diehl, D.L., et al., Fully covered self-expanding metal stents for remodeling of refractory 
pancreatic duct strictures: A multicenter experience. Gastrointestinal Endoscopy, 2012, 
75(4), AB318-AB319 
18. Pfau, P.R., et al., ASGE Status Evaluation Report, Pancreatic and biliary stents. 
Gastrointest Endosc, 2013, 77(3), 319-27 
19. Dumonceau, J.M., et al., Endoscopic treatment of chronic pancreatitis: European Society 
of Gastrointestinal Endoscopy (ESGE) Clinical Guideline. Endoscopy, 2012, 44, 784-96  
 
 
 
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21 Abbreviations and Definitions  
Acronym 
Definition 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
BSC 
CP 
CI 
Boston Scientific Corporation 
Chronic Pancreatitis 
Confidence Interval 
CRF  
CRO 
CSEMS 
Case Report Form 
Contract Resource Organization 
Covered Self-Expanding Metal Stent 
CT 
Computed Tomography 
DFU 
Directions for Use 
eCRF 
EC 
Electronic Case Report Form 
Ethics Committee 
EDC 
EPS 
Electronic Data Capture 
Endoscopic Pancreatic Sphincterotomy 
ERCP 
ESWL 
FCSEMS 
Endoscopic Retrograde Cholangiopancreatography 
Extracorporeal Shock Wave Lithotripsy 
Fully Covered Self-Expanding Metal Stent 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practices 
IB 
Investigator Brochure 
ICF 
Informed Consent Form 
ICH 
IRB 
International Conference on Harmonization 
Institutional Review Board 
ISO 
ITT 
International Standards Organization 
Intent-to-Treat 
LFT 
MRCP 
MS 
PD 
Liver Function Test 
Magnetic Resonance Cholangiopancreatography 
Metal Stent 
Pancreatic Duct 
PG 
Performance Goal 
PI 
PS 
Principal Investigator 
Plastic Stent 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SEMS 
VAS 
Self-Expanding Metal Stent 
Visual Analog Scale 
 
 
 
 
 
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22 Appendices 
22.1 Izbicki Pain Scale 
 
 
 
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22.2 SF12 
 
 
 
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22.2  SF12 (continued) 
 
 
 
 
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22.2  SF12 (continued) 
 
 
 
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22.3 Cremer Classification of Chronic Pancreatitis 
 
 
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22.3  Cremer Classification of Chronic Pancreatitis (continued) 
 
 
 
 
 
 
 
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22.4 Morphine Milligram Equivalent (MME) Narcotic Conversion Guidance 
Average Daily Narcotic Dose for the previous month will be calculated for all study patients 
at all study visits. The value for this data point will be expressed in units of morphine 
milligram equivalents (MME). 
Please see the examples below and the guidance on the following pages for assistance with 
calculating Average Daily Narcotic Dose. 
 
Example 1: 
A patient reporting for a study visit on November 3rd reports to have taken 20 mg/day 
of Oxymorphone for the previous month.  
The MME conversion factor for Oxymorphone is 3. 
20 mg/day x 3 MME = 60 MME 
Since the patient’s daily narcotic dose was constant over the previous month, you can 
multiply the daily narcotic dose by the MME conversion factor to obtain the Average 
Daily Narcotic Dose. The Average Daily Narcotic Dose is 60 MME. 
 
Example 2: 
A patient reporting for a study visit on May 11th reports a reduction of Oxycodone from 
30 mg/day to 20 mg/day on April 18th of the previous month. 
The previous month (April 11th – May 10th) contained 30 days. The MME conversion 
factor for Oxycodone is 1.5. 
Since the patient had two different daily narcotic doses during the previous month, you 
will have to find the cumulative MME for each time period containing a unique daily 
narcotic dose then add the cumulative MMEs together and divide the total by the number 
of days in the previous month. This will provide the Average Daily Narcotic Dose. 
 
For 7 days (April 11th – April 17th), the patient took 30 mg/day of Oxycodone. 
7 days x (30 mg/day x 1.5 MME) = 7 days x 45 MME = 315 MME 
For 23 days (April 18th – May 10th), the patient took 20 mg/day of Oxycodone. 
23 days x (20 mg/day x 1.5 MME) = 23 days x 30 MME = 690 MME 
Add the cumulative MMEs together and divide by 30 days: 
(315 MME + 690 MME) ÷ 30 days = 1005 MME ÷ 30 days = 33.5 MME 
 
The Average Daily Narcotic Dosage value will be rounded to the nearest whole number, 
resulting in a final value of 34 MME. 
 
 
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22.5 
Guidance on Collecting VAS Pain Score and Frequency of Pain Attacks 
Information 
The Izbicki Pain Scale incorporates the following four elements in its measurement of pain:  
1) patient self-estimation of intensity of pain using a visual analog scale (VAS) 
2) the frequency of pain attacks 
3) analgesic medication usage 
4) the time of disease-related inability to work 
The sum of the rank values divided by four gives the final value of the pain score. Please see 
Appendix 22.1 for more information. The Izbicki Pain Scale will be collected at every study 
visit. The information below will serve as guidance when collecting information for the first 
two elements of the Izbicki Pain Scale. 
When reporting pain via VAS for the first element of the Izbicki Pain Scale, patients will be 
asked to report on the average pain experienced since the prior study visit. For the second 
element of the Izbicki Pain Scale, patients will be asked to report the average frequency of 
pain attacks experienced since the prior study visit. The manner in which these two questions 
are posed will depend upon the patient’s pain pattern. 
 
 
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