Randomized, Multi-Center, Comparative and Cost Effectiveness Study of a Lumen- Apposing, Covered, Self-Expanding Metal Stent (Axios™) Versus Multiple Double Pigtail Stents in the Management of Walled Off Pancreatic Necrosis
Phase: NA
Conditions: Pancreatic Necrosis
Sponsor: Dartmouth-Hitchcock Medical Center

 
CONFIDENTIAL 
CLINICAL RESEARCH PROTOCOL 
 
 
 
 
 
 
 
 
 
RANDOMIZED, MUTI-CENTER, COMPARATIVE AND COST 
EFFECTIVENESS STUDY OF A LUMEN-APPOSING, 
COVERED, SELF-EXPANDING METAL STENT (AXIOS™) 
VERSUS MULTIPLE DOUBLE PIGTAIL STENTS IN THE 
MANAGEMENT OFF WALLED OF PANCREATIC NECROSIS  
. 
 
 
Investigators: 
Timothy Gardner, MD 
Department of Gastroenterology and Hepatology 
Dartmouth-Hitchcock Medical Center 
One Medical Center Drive  
Lebanon, New Hampshire 
603-650-5261 
 
Stuart R. Gordon, MD 
Department of Gastroenterology and Hepatology 
Dartmouth-Hitchcock Medical Center 
One Medical Center Drive  
Lebanon, New Hampshire 
603-650-5261 
 
Jeffrey Adler, MD 
Department of Gastroenterology and Hepatology 
Dartmouth-Hitchcock Medical Center 
One Medical Center Drive  
Lebanon, New Hampshire 
603-650-5261 
 
 
 
Funding Sponsor: 
None 
 
Study Products: 
A Lumen Apposing, covered, self-expanding metal stent 
(AXIOS™) [The AXIOS™ lumen-apposing stent (Xlumena Inc., 
Mountain View, California, USA)], and Double Pigtail Stents 
[Solus® Double Pigtail Stent with Introducer (Cook, Ireland 
Ltd.)] 
Protocol Number: 
1-2015   NCT02673541 

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IND Number: 
NA 
 
 
 
 
 
 
 
 
 
 
Initial version: 9/3/15 
Amended: 
[date] 
Amended: 
[date] 

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Table of Contents 
 
STUDY SUMMARY ...................................................................................................................................... 1 
1 
INTRODUCTION .................................................................................................................................. 2 
1.1 
BACKGROUND ................................................................................................................................ 2 
1.2 
INVESTIGATIONAL AGENT ................................................................................................................ 3 
1.3 
PRECLINICAL DATA ........................................................................................................................ 4 
1.4 
CLINICAL DATA TO DATE................................................................................................................. 4 
1.5 
DOSE RATIONALE AND RISK/BENEFITS ............................................................................................ 5 
2 
STUDY OBJECTIVES ......................................................................................................................... 5 
3 
STUDY DESIGN ................................................................................................................................... 6 
3.1 
GENERAL DESIGN .......................................................................................................................... 6 
3.2 
PRIMARY STUDY ENDPOINTS .......................................................................................................... 8 
3.3 
SECONDARY STUDY ENDPOINTS ..................................................................................................... 8 
3.4 
PRIMARY SAFETY ENDPOINTS ......................................................................................................... 8 
4 
SUBJECT SELECTION AND WITHDRAWAL .................................................................................... 8 
4.1 
INCLUSION CRITERIA ...................................................................................................................... 8 
4.2 
EXCLUSION CRITERIA ..................................................................................................................... 8 
4.3 
SUBJECT RECRUITMENT AND SCREENING ....................................................................................... 9 
4.4 
EARLY WITHDRAWAL OF SUBJECTS................................................................................................. 9 
4.4.1 
When and How to Withdraw Subjects ..................................................................................... 9 
4.4.2 
Data Collection and Follow-up for Withdrawn Subjects .......................................................... 9 
5 
STUDY DRUG ...................................................................................................................................... 9 
5.1 
DESCRIPTION ................................................................................................................................. 9 
5.2 
TREATMENT REGIMEN .................................................................................................................... 9 
5.3 
METHOD FOR ASSIGNING SUBJECTS TO TREATMENT GROUPS ....................................................... 10 
5.4 
PREPARATION AND ADMINISTRATION OF STUDY DRUG ................................................................... 10 
5.5 
SUBJECT COMPLIANCE MONITORING ............................................................................................. 10 
5.6 
PRIOR AND CONCOMITANT THERAPY ............................................................................................. 10 
5.7 
PACKAGING ................................................................................................................................. 10 
5.8 
BLINDING OF STUDY DRUG ........................................................................................................... 10 
5.9 
RECEIVING, STORAGE, DISPENSING AND RETURN .......................................................................... 10 
5.9.1 
Receipt of Drug Supplies ....................................................................................................... 10 
5.9.2 
Storage .................................................................................................................................. 10 
5.9.3 
Dispensing of Study Drug ...................................................................................................... 10 
5.9.4 
Return or Destruction of Study Drug ..................................................................................... 10 
6 
STUDY PROCEDURES ..................................................................................................................... 10 
6.1 
VISIT 1 ........................................................................................................................................ 11 
6.2 
VISIT 2 ........................................................................................ ERROR! BOOKMARK NOT DEFINED. 
6.3 
ETC. ............................................................................................ ERROR! BOOKMARK NOT DEFINED. 
7 
STATISTICAL PLAN ......................................................................................................................... 12 
7.1 
SAMPLE SIZE DETERMINATION ...................................................................................................... 12 
7.2 
STATISTICAL METHODS ................................................................................................................ 12 
7.3 
SUBJECT POPULATION(S) FOR ANALYSIS ....................................................................................... 12 
8 
SAFETY AND ADVERSE EVENTS ................................................................................................... 13 
8.1 
DEFINITIONS ................................................................................................................................ 13 
8.2 
RECORDING OF ADVERSE EVENTS ................................................................................................ 14 

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8.3 
REPORTING OF SERIOUS ADVERSE EVENTS AND UNANTICIPATED PROBLEMS ................................. 15 
8.3.1 
Investigator reporting: notifying the study sponsor................................................................ 15 
8.3.2 
Investigator reporting: notifying the Dartmouth IRB .............................................................. 15 
8.3.3 
Investigator reporting: Notifying a non-Dartmouth IRB ......................................................... 17 
8.3.4 
Sponsor reporting: Notifying the FDA ..................................... Error! Bookmark not defined. 
8.3.5 
Sponsor reporting: Notifying participating investigators ........................................................ 17 
8.4 
UNBLINDING PROCEDURES ........................................................................................................... 17 
8.5 
STOPPING RULES ......................................................................................................................... 17 
8.6 
MEDICAL MONITORING ................................................................................................................. 17 
8.6.1 
Internal Data and Safety Monitoring Board ............................. Error! Bookmark not defined. 
8.6.2 
Independent Data and Safety Monitoring Board ................................................................... 17 
9 
DATA HANDLING AND RECORD KEEPING ................................................................................... 17 
9.1 
CONFIDENTIALITY ......................................................................................................................... 17 
9.2 
SOURCE DOCUMENTS .................................................................................................................. 18 
9.3 
CASE REPORT FORMS.................................................................................................................. 18 
9.4 
RECORDS RETENTION .................................................................................................................. 18 
10 
STUDY MONITORING, AUDITING, AND INSPECTING .................................................................. 18 
10.1 
STUDY MONITORING PLAN ............................................................................................................ 18 
10.2 
AUDITING AND INSPECTING ........................................................................................................... 18 
11 
ETHICAL CONSIDERATIONS .......................................................................................................... 19 
12 
STUDY FINANCES ............................................................................................................................ 19 
12.1 
FUNDING SOURCE ........................................................................................................................ 19 
12.2 
CONFLICT OF INTEREST ................................................................................................................ 19 
12.3 
SUBJECT STIPENDS OR PAYMENTS ............................................... ERROR! BOOKMARK NOT DEFINED. 
13 
PUBLICATION PLAN ........................................................................................................................ 19 
14 
REFERENCES ................................................................................................................................... 19 
15 
ATTACHMENTS ................................................................................................................................ 21 
 

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List of Abbreviations 
 
 
 
 
 
 
 
 
 

[Insert short name of protocol here] 
 
page 1 
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Study Summary 
Title 
RANDOMIZED, 
MUTI-CENTER, 
COMPARATIVE 
AND 
COST 
EFFECTIVENESS STUDY OF A LUMEN-APPOSING, COVERED, SELF-
EXPANDING METAL STENT (AXIOS™) VERSUS MULTIPLE DOUBLE 
PIGTAIL STENTS IN THE MANAGEMENT OFF WALLED OF PANCREATIC 
NECROSIS 
Short Title 
The AXIOS™ Stent Versus Solus® Double Pigtail Stents for WOPN 
Protocol Number 
TBD   
Phase 
Pilot – Phase NA 
Methodology 
Single Blind, Randomized, Active Control 
Study Duration 
2 year 
Study Center(s) 
Multi-center.  Number of centers - 3 
Objectives 
Objective 1: Compare costs between the two management strategies 
Objective 2: To evaluate the efficacy of the AXIOS™ stent (Xlumena Inc., 
Mountain View, California, USA) versus multiple double pigtail stents [Solus® 
Double Pigtail Stent with Introducer (Cook, Ireland Ltd.)] in the management of 
walled off pancreatic necrosis 
Number of Subjects 
20 patients 
Diagnosis and Main 
Inclusion Criteria 
Walled off pancreatic necrosis (WOPN) 
Study Product, Dose, 
Route, Regimen 
AXIOS™ lumen-apposing stent (Xlumena Inc., Mountain View, California, 
USA) 
Duration 
of 
administration 
The AXIOS™ stent implantation should not exceed 60 days according to the 
manufacturer.  The Double Pigtail Stents [Solus® Double Pigtail Stent with 
Introducer (Cook, Ireland Ltd.)] do not require removal 
Reference therapy 
Double Pigtail Stents [Solus® Double Pigtail Stent with Introducer (Cook, 
Ireland Ltd.)] 
Statistical 
Methodology 
Continuous data will be expressed as means with SDs or medians with 
interquartile ranges and compared using student’s t-test.  Catagoric data will 
be expressed as frequencies and percentages and be compared using 
Fisher’s Exact test. 
 

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1 Introduction 
 
This document is a clinical research protocol for a human research study. This study is to be 
conducted according to US and international standards of Good Clinical Practice (FDA Title 21 part 312 
and International Conference on Harmonization guidelines), applicable government regulations and 
Institutional research policies and procedures.  
1.1 Background 
 
Acute pancreatitis (AP) is responsible for nearly a quarter million hospital admissions annually 
and will affect around 40 per 100,000 persons per year (1).  The majority of patients experience a 
clinically mild course; however, as many as one in five patients develop a severe illness associated with a 
high mortality (2).  In early phases of the disease, there is an acute inflammatory process that may involve 
necrosis of the pancreatic or peri-pancreatic tissues (3).  There are also delayed complications that may 
develop locally, usually over a period of weeks, which include the formation of walled-off fluid collections.  
These are sometimes composed of simple fluid and termed pseudocysts, while in other cases they 
represent organization and encapsulation of sterile or infected necrosis and are termed walled-off 
pancreatic necrosis (WOPN) (4).  The indication to drain or debride these collections usually depends 
upon on a number of factors, but principally on whether they are symptomatic, infected, or responsible for 
other local or systemic complications.  
 
The contemporary management strategy for walled-off pancreatic fluid collections has shifted in 
recent years.  Surgery, and even percutaneous catheter drainage, should no longer be considered the 
initial mainstay of therapy in place of endoscopic drainage for simple pseudocysts (5) (6).  In addition 
there is good evidence to support an endoscopic approach for patients with infected necrosis (7).  There 
are now numerous publications reporting the success of direct endoscopic transmural drainage or 
necrosectomy (ETD/N) for a variety of indications including infected and sterile walled-off collections (8). 
 
The issue that now deserves attention is a matter of selecting the best technique to accomplish 
ETD/N.  The current process involves first creating a cystenterotomy to gain access to the walled-off 
collection, dilating the tract, and then inserting a drainage device.  However, there are a variety of 
available devices and methods in use for drainage, and to our knowledge, none to date have been 
directly compared in a randomized controlled trial.   
 
The conventional approach involves inserting either a pair or more of plastic double pigtail stents 
or a self-expanding metal stent (SEMS) through a cystenterotomy: both approaches have limitations, and 
may require multiple endoscopic sessions before definitive resolution (9).  One, the pigtail stents have a 
narrow lumen (7F-10F) and often migrate or become occluded (10).  Two, the SEMS also have a 
tendency occlude, cause local trauma with bleeding and infection, and migrate, which has led some to 
also use double pigtails to help anchor the SEMS in place (11) (12).   
 
These challenges have led to the innovation of large caliber covered stents with flanges on either 
end to facilitate apposition of the cyst wall and enteral tissues, preventing migration, and allowing for 
necrosectomy through their wide lumen.  To our knowledge there are at least two designs in production; 
the AXIOS™ stent and the Nagi stent (13) (14).  There is now a fair amount of experience, particularly 
using the AXIOS™ stent (with or without a novel NAVIX access system) for both WOPN and 
pseudocysts, with the majority of reports showing it to be safe and effective (15) (16) (17) (18) (19) (20).  
The device has also been successfully used for novel indications including access and drainage of the 
gallbladder and an intrathoracic fluid collection (21) (22) (23).  The AXIOS™ stent is FDA approved for 
the indication of draining walled off pancreatic necrosis. 
 
The present study aims to compare the clinical efficacy and cost effectiveness of the AXIOS™ 
stent versus the “conventional” approach using double pigtail plastic stents in the treatment of patients 
with walled-off pancreatic necrosis. 
 
[For the remainder of this document, the AXIOS™ stent will be in reference the AXIOS™ Stent and 
Delivery System (Xlumena Inc., Mountain View, California, USA), and use of the terms “double pigtail 
stent(s)” will be in reference to the Solus® Double Pigtail Stent with Introducer (Cook, Ireland Ltd.)] 

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1.2 Investigational Agent 
 
The AXIOS™ Stent is a flexible, fully-covered, self-expanding Nitinol stent, which is preloaded 
within the catheter-based delivery system.  It is radiopaque and is fully covered with silicone.  The 
AXIOS™ stent has been labeled as MR conditional.   The stent permits passive drainage of material from 
within the accessed fluid collection to the gastrointestinal lumen, and serves as a conduit through which 
additional diagnostic or therapeutic endoscopic procedure can be performed. AXIOS™ is FDA-approved 
for treating WOPN. 
 
 
 

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AXIOS™ Stent Sizes 
 
AXS-10-10 
AXS-15-10 
Stent Lumen Diameter (mm) 
10 
15 
Stent Length (mm) 
10 
10 
 
1.3 Preclinical Data 
 
Device information from the manufacturer discusses performance testing in animals to assess 
chronic performance of the device (long-term patency, removability, and migration), adverse events, and 
histopathology.  Benchtop and animal testing in porcine models demonstrated ex-vivo durability, 
successful deployment across the stomach and gallbladder lumens of 4 animals, and stable positioning 
and patency.  There was no hyperplastic tissue ingrowth or overgrowth, or tissue injury reported (20).   
 
1.4 Clinical Data to Date 
 
Use of the AXIOS™ stent for the treatment of walled off pancreatic fluid collections has been 
examined in a number of studies.  A prospective study in 33 patients with either symptomatic pancreatic 
pseudocysts or walled off necrosis, reported successful placement in 91% of subjects, and resolution of 
the pancreatic fluid collection (PFC) in 93% of subjects.  Complications were reported in n=5 (15.2%) of 
the subjects, and included access-site infection, stent migration/dislodgment, back pain, and abdominal 
pain requiring endoscopy (15).  A study of 9 patients undergoing EUS-guided draining and AXIOS™ 
placement for a PFC (pancreatic pseudocysts and walled off necrosis included), reported a technical 
success rate of 88.8%.  All patients were reported to have achieved complete cyst resolution in a mean 
follow up of 50 weeks.  There was one fluid collection recurrence 4 weeks after stent removal, no 
migrations reported, and all stents were removed easily.  There was one tension pneumothorax that 
developed immediately after transesophageal drainage of a fluid collection (16).  A study of 33 patients 
reported successful placement of the AXIOS™ stent in 91% of subjects with pancreatic pseudocysts.  
Cyst resolution was achieved in 93% of the patients.  Complications were observed in a total of 4 patients 
and included abdominal pain, spontaneous stent migration and back/shoulder pain, and access site 
infection and stent dislodgement (18).  Technical success was reported in the case of one patient with 
more than one pancreatic fluid collection, one of which was drained using the AXIOS™ stent (19).  A 
retrospective case series that included patients who received the AXIOS™ stent for drainage of 

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symptomatic pancreatic pseudocysts (n=15) (or acute cholecystitis (n=5)), reported successfully 
placement and resolution of the pseudocysts in all patients.  There were no pseudocyst recurrences 
during 11.4 months of follow up.  All stents were later removed without procedure-related complications.  
Stent migration was reported in one case (21).  A case report of transesophageal EUS-guided draining of 
a mediastinal pancreatic fluid collection reported technical success with placement and removal, and 
complete resolution of the collection at 6 weeks of follow up (23)    
 
1.5 Dose Rationale and Risk/Benefits 
 
Endoscopic transmural drainage and/or necrosectomy of either sterile of infected walled off 
pancreatic necrosis is an established management option.  There are a variety of techniques currently 
used in practice; however, the optimal technique has not been established.  The AXIOS™ stent and 
delivery system is one available method that has not been compared directly in any randomized trial to 
any other method.  The duration of AXIOS™ stent insertion should not exceed 60 days based upon the 
manufactures recommendations.  Patients selected for this study will be those who already have an 
indication for endoscopic drainage of their pancreatic necrosis.  The general risks of not pursuing therapy 
in these cases include, but are not limited to, ongoing pain, gastrointestinal obstruction, infection, sepsis, 
and death.  The typical risks of endoscopic cystogastrostomy/enterostomy and necrosectomy include 
uncontained visceral perforation, bleeding, infection, emergency surgery, and death.  There is also the 
risk of needing repeat endoscopic procedures, and unintended reactions to sedation.  There is a risk of 
stent migration with both the conventional double-pigtail stents and the AXIOS™ stent.  The benefit of 
endoscopic cystogastrostomy/enterostomy and necrosectomy include resolution of the pancreatic fluid 
collection and its related complications (e.g., pain, infections, intestinal obstruction). 
Specifically, the risks to subjects in the study are reasonable because subjects are not being 
exposed to risk beyond what they would ordinarily be exposed to for the treatment of their underlying 
condition.  These are patients who have been referred for established therapy using devices that currently 
used in practice. 
 
2 Study Objectives 
 
Primary Objectives 
 
1. To compare the cost differences of the AXIOS™ stent vs. multiple double pigtail stents in 
the management of walled-off pancreatic necrosis. 
 
Secondary Objectives 
 
1. To compare the relative efficacy in terms of definitive resolution of walled off pancreatic 
necrosis using the AXIOS™ stent vs. multiple double pigtail stents. 
2. To compare the number of endoscopic sessions required to achieve definitive resolution of 
walled-off pancreatic fluid necrosis using the AXIOS™ stent vs. multiple double pigtail stents. 
3. To compare the number of additional procedures (surgical, percutaneous, or nasocystic) 
required to achieve definitive resolution of walled-off pancreatic necrosis using the AXIOS™ 
stent vs. multiple double pigtail stents. 
4. To compare the frequency of stent migration using the AXIOS™ stent vs. multiple double 
pigtail stents in the management of walled-off pancreatic necrosis. 
5. To compare the safety and tolerability of the AXIOS™ stent vs. multiple double pigtail 
stents in the management of walled-off pancreatic necrosis. 
 

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3 Study Design 
3.1 General Design 
 
1. Multi-center, single blind, randomized controlled trial 
2. Inclusion Criteria. 
a. Male or female between 18-80 years old (including patients aged 18 and 80) 
b. Subjects capable of giving informed consent 
c. Patients carrying the diagnosis or symptomatic sterile or infected walled-off pancreatic 
necrosis (WOPN) based upon Atlanta Classification (4) >4cm in largest diameter, 
deemed to require and amenable to endoscopic transmural drainage and/or 
necrosectomy by attending gastroenterologist 
d. Fluid collection size ≥ 4cm in largest diameter (based on CT, MRI, transabdominal or 
endoscopic ultrasound within 30days) 
e. Fluid collection that is adherent to the stomach/bowel wall allowing for fistula tract 
creation 
f. 
Fluid collection containing significant amount of necrotic material (defined as >30% of 
echogenic material by ultrasound/EUS, or necrotic debris by CT/MRI)  
 
3. Exclusion Criteria:  
a. Inability to provide written informed consent  
b. Contraindications to endoscopic treatment as determined by the gastroenterologist 
attending 
c. Pregnant or nursing mothers 
d. Bleeding or coagulation disorder 
e. Previous surgical or endoscopic cystogastrostomy/enterostomy or necrosectomy 
f. 
Shock 
g. Cystic neoplasms or pancreatic malignancy 
h. Pseudocysts  
i. 
Subjects cannot be homeless or incarcerated 
j. 
Age younger than 18 or older than 80 
k. More than one pancreatic/peri-pancreatic fluid collection 
 
All eligible participants will be randomized to one of two arms:  
1. Arm 1: EUS-guided cystogastrostomy/enterostomy and placement of the AXIOS™ stent  
2. Arm 2: EUS-guided cystogastrostomy/enterostomy and placement of multiple double pigtail 
stents 
The procedure will be performed under monitored or general anesthesia using a therapeutic linear 
array echoendoscop.  Antibiotic will be administered at the start of the procedure (ciprofloxacin 
500mg or acceptable alternative), and continued for 3 days.  EUS will be performed to localize, 
confirm the size and features, and evaluate for bowel adherence of the target collection.  Color 
Doppler will be performed to identify the presence of vascular structures within the planned drainage 
tract.  The collection will be accessed by needle puncture.  The fluid will be aspirated and sent for 
microscopic analysis and culture.  A guidewire will then be threaded into the collection cavity and 
confirmed by fluoroscopy.  The needle will then be withdrawn and the tract serially dilated using 
balloons passed over the guidewire through the tract, and expanded stepwise to 15-20mm at the 
discretion of the treating gastroenterologist. 

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1. Arm 1 will have an AXIOS™ stent 10-15mm (saddled diameter; choice at the discretion 
of the treating gastroenterologist) deployed though the tract into the cavity, and correct 
positioning of the inner flange confirmed by EUS prior to deploying within the stomach or 
duodenum. 
2. Arm 2 will have multiple double pigtail (i.e. ≥2) stents placed through the tract into the 
collection cavity 
Necrosectomy will be performed at the discretion of the treating gastroenterologist in all cases.  The 
pancreatic fluid collections will be re-assessed at 30 days (all patients) and 60 days (at the discretion of 
the treating gastroenterologist) after the procedure by abdominal/pelvic CT or MRI – or sooner should the 
need arise. Repeat endoscopies for necrosectomy will be permitted in all patients at the discretion of the 
attending gastroenterologist. Patients who receive the AXIOS™ stent will routinely undergo a second 
endoscopy no later than 60 days after insertion of the stent for removal. Overall expected duration of 
study participation is 60 days. 
 
 
 
Patients Presenting to Gastrointestinal Endoscopy Suite for EUS-Guided 
cystgastrostomy/enterostomy
+/- Necrosectomy for sterile or infected walled off pancreatic necrosis 
(WOPN)
Patients excluded if 1. not meeting inclusion criteria, 2. meeting 
exclusion criteria
Arm 1: EUS-guided cystenterostomy and 
placement of the AXIOS stent +/-
Necrosectomy
Arm 2: EUS-guided cystenterostomy and 
placement of multiple double pigtail stents 
+/- Necrosectomy
Abdominal/Pelvic cross -sectional  imaging 
at 30 days
Abdominal/Pelvic cross -sectional  imaging 
at 30 days
Subsequent endoscopic necrosectomy at the 
discretion of the treating gastroenterologist
Subsequent endoscopic necrosectomy at the 
discretion of the treating gastroenterologist
Randomized
Abdominal/Pelvic cross -sectional  imaging 
at 60 days at the discretion of the treating 
gastroenterologist
Abdominal/Pelvic cross -sectional  imaging 
at 60 days at the discretion of the treating 
gastroenterologist
 
 
        

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3.2 Primary Study Endpoints 
 
1. Cost of therapy using AXIOS™ stent versus double-pigtail stents; billing from individual 
center departments 
 
3.3 Secondary Study Endpoints 
 
1. Rate of recurrence of pancreatic fluid collection/definitive resolution  
2. Complete or partial resolution of walled-off necrosis - (defined as >90% resolution on cross-
sectional imaging) 
3. Number of endoscopic sessions required to achieve complete or partial resolution of 
pancreatic necrosis 
4. Requirement for surgical, percutaneous, or nasocystic intervention to facilitate resolution of 
walled-off pancreatic necrosis 
5. Frequency of stent migration prior to resolution of walled-off pancreatic necrosis 
 
3.4 Primary Safety Endpoints 
 
1. Frequency of death, bleeding, infection, uncontained perforation, or need for urgent or 
emergent surgical or radiology guided procedure at any time during the study period 
4 Subject Selection and Withdrawal 
4.1 Inclusion Criteria 
1. Male or female between 18-80 years old (including ages 18 and 80) 
2. Subjects capable of giving informed consent 
3. Patients carrying the diagnosis or symptomatic sterile or infected walled-off pancreatic 
necrosis (WOPN) based upon Atlanta Classification (4) >4cm in largest diameter, deemed to 
require and amenable to endoscopic transmural drainage and/or necrosectomy by attending 
gastroenterologist 
4. Fluid collection size ≥ 4cm in largest diameter (based on CT, MRI, transabdominal or 
endoscopic ultrasound within 30days) 
5. Fluid collection that is adherent to the stomach/bowel wall allowing for fistula tract creation 
6. Fluid collection containing significant amount of necrotic material (defined as >30% of 
echogenic material by ultrasound/EUS, or necrotic debris by CT/MRI)  
4.2 Exclusion Criteria 
1. Inability to provide written informed consent  
2. Contraindications to endoscopic treatment as determined by the gastroenterologist attending 
3. Pregnant or nursing mothers 
4. Bleeding or coagulation disorder 
5. Previous surgical or endoscopic cystogastrostomy/enterostomy or necrosectomy 
6. Shock 
7. Cystic neoplasms or pancreatic malignancy 
8. Pseudocysts  

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9. Subjects cannot be homeless or incarcerated 
10. Age younger than 18 or older than 80 
11. More than one pancreatic/peri-pancreatic fluid collection 
4.3 Subject Recruitment and Screening 
 
Patients diagnosed with sterile or infected walled off pancreatic necrosis already referred for endoscopic 
treatment will be offered enrollment at the time they present to the endoscopy suite for their procedure.  
Patients will be informed that the techniques used for endoscopic transmural drainage and necrosectomy 
are operator and case dependent, and ordinarily may involve the use of multiple double pigtail stents or 
the AXIOS™ stent; however their relative efficacy and safety have not been directly compared and is the 
subject of investigation.  Patient will be informed that should they consent to participating in the study, 
they will be randomly allocated to one of the two methodologies without knowing which technique they 
receive.  Patients will need to have lab work within 14 days of the procedure that included a complete 
blood cell count, basic metabolic panel, liver function tests, and coagulation tests.  Patients will be 
informed that they have the option to opt-out of the study, and will receive therapy at the discretion of the 
treating gastroenterologist.         
4.4 Early Withdrawal of Subjects 
4.4.1 When and How to Withdraw Subjects 
 
Patients will have the option to withdraw at any time during the study period for any reason.  Patients who 
fail to comply with follow up imaging will be reported as such in the final analysis.     
4.4.2 Data Collection and Follow-up for Withdrawn Subjects 
 
Patients may prematurely withdraw from the study.  Because survival and delayed complications are a 
subject of this study, efforts will be made to collect, at a minimum, survival data on all patients who elect 
to enroll.  Before being considered truly lost to follow up, a minimum of three phone calls will be made to 
the patient and/or next of kin, and if contact is not established, a certified letter will be mailed.  Contact 
information will be collected at enrollment.      
5 Study Drug  
5.1 Description 
AXIOS™ Stent is a flexible, fully-covered, self-expanding Nitinol stent, which is preloaded within the 
catheter-based delivery system.   
5.2 Treatment Regimen 
1. Arm 1 will undergo EUS-guided cystogastrostomy/enterostomy and placement of the 
AXIOS™ stent 10-15mm (saddled diameter; choice at the discretion of the treating 
gastroenterologist) though the tract into the collection cavity, and correct positioning of 
the inner flange confirmed by EUS prior to deploying within the stomach or duodenum.  
Necrosecomy will be performed at the discretion of the attending gastroenterologist.  
Repeat endoscopy will be performed for stent removal at or before 60 days at the 
discretion of the attending gastroenterologist 
2. Arm 2 will undergo EUS-guided cystogastrostomy/enterostomy and placement of multiple 
double pigtail stents (i.e. ≥2) through the tract into the collection cavity. Necrosectomy will 
be performed at the discretion of the attending gastroenterologist.  Routine repeat 

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treating gastroenterologist for stent removal will not be necessary, but left to the 
discretion of the attending gastroenterologist. 
.  
5.3 Method for Assigning Subjects to Treatment Groups 
Patients will be randomly assigned to either of the two treatment arms by a sequentially numbered card 
box that will be opened by the attending gastroenterologist in the procedure room  
5.4 Preparation and Administration of Study Drug 
The study devices are prepackaged by the manufacturer 
5.5 Subject Compliance Monitoring 
 
All participating centers will notify the study coordinator of any newly enrolled patient.  All consent 
materials and the patient’s chart will remain at the site of enrollment.  A central and secure databank will 
be maintained by the study coordinator that includes the patient’s basic information and a copy of the 
consent form.  All patients enrolled will be provided a means of contacting the study coordinator during 
routine business hours for questions or concerns.  They will be advised to go through the on-call system 
of their treating institution for off hour emergencies.  All scheduled follow up imaging will ordered by the 
attending gastroenterologist overseeing the patients care, and arranged though the usual mechanisms 
unique to their institution.  Scheduled imaging will be tracked by the study coordinator and updated 
weekly until completion of the study.  Patients who do not show up for their scheduled imaging will be 
contacted (and/or next of kin) by phone with a minimum of 3 attempts, and if contact is not established, a 
certified letter will be mailed.  Contact information will be collected at enrollment.   
5.6 Prior and Concomitant Therapy 
Patients will receive a short course of antibiotics around the time of their procedure, for a total of 
3-5 days based on the discretion of the attending gastroenterologist per standard of care. 
5.7 Packaging 
All devices in use are pre-packaged by the manufacturer 
5.8 Blinding of Study Drug 
Patients will be blinded to which of the two devices they receive until the end of the follow up 
period 
5.9 Receiving, Storage, Dispensing and Return 
5.9.1 Receipt of Drug Supplies 
An inventory is routinely performed by the endoscopy suite for all supplies and devises being 
used in this study. 
5.9.2 Storage 
All devices are stored in the Endoscopy suite 
5.9.3 Dispensing of Study Drug 
Not applicable 
5.9.4 Return or Destruction of Study Drug 
Not applicable 

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6 Study Procedures 
 
Visit 1: Endoscopy Suite: patients scheduled and presenting to the gastrointestinal endoscopy suite 
for EUS-Guided cystogastrostomy/enterostomy  +/- Necrosectomy for sterile or infected walled off 
pancreatic necrosis (WOPN) will be offered the option to participate in the study.  Patients interested will 
be screening for eligibility using the Case Report Form (See Attachment 1).  Eligible patients will asked if 
they consent to 1. The endoscopic procedure and anesthesia plan as outlined by the treating 
gastroenterologist and participating anesthesiologist according to their routine pre-procedure consent 
practice, and 2. Participation in the research study as indicated, after review, by signature of a copy of the 
CPHS approved and stamped consent form (See Attachment 2).  The Principal Investigator is responsible 
for ensuring all participants enrolling in this study have provided informed consent.  The PI (Dr. Timothy 
Gardner) may authorize other appropriately trained individuals to obtain informed consent and sign as 
'designee.'  These designees include: Dr. Stuart Gordon, Dr. John Levenick, Dr. Jason Ferreira, Dr. 
Jeffrey Adler, Dr. David Rahni.  Those consenting, will be brought into the procedure room, and assigned 
to either of the two treatment arms by a sequentially numbered card box that will be opened by the 
attending gastroenterologist in the procedure room.  Following endoscopic intervention patients will 
recover in the endoscopy recovery area or PACU and will either be discharged home or admitted at the 
discretion of the treating gastroenterologist.   
Visit 2: Subsequent endoscopic necrosectomy.  This is variable and will be left to the discretion of 
the treating gastroenterologist (some patients will require additional routine endoscopic procedure(s) for 
necrosectomy after the initial intervention which will have to be decided on a case-by-case basis by the 
treating gastroenterologist) 
Visit 3: All patients will be asked to return for abdominal/pelvic cross-sectional imaging (CT or MRI) 
at 30 days from the initial intervention; the modality will be left to the discretion of the treating 
gastroenterologist 
Visit 4: Patients may be asked to undergo additional follow up imaging (up to 60 days after the initial 
procedure), which will be left to the discretion of the treating gastroenterologist.  
  
 

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Patients Presenting to Gastrointestinal Endoscopy Suite for EUS-Guided 
cystgastrostomy/enterostomy
+/- Necrosectomy for sterile or infected walled off pancreatic necrosis 
(WOPN)
Patients will be offered option to participate in the study
Patients interested are screened for eligibility using Case Report Form (CRF) available for 
use by the gastroenterologist
Eligible patients will be asked if they consent to: 
1. The endoscopic procedure and anesthesia plan as outlined by the treating 
gastroenterologist and participating anesthesiologist according to their routine 
pre-procedure consent practice
2. Participation in the research study as indicated, after review, by signature of a 
copy of the CPHS approved and stamped consent form (included in 
Attachments section)
Patients will be brought into the procedure room and assigned to either of the two 
treatment arms by a sequentially numbered card box that will be opened by the attending 
gastroenterologist in the procedure room
Following endoscopic intervention patients will recover in the endoscopy recovery area or 
PACU and will either be discharged home or admitted at the discretion of the treating 
gastroenterologist
Patients may require subsequent routine endoscopic procedures for necrosectomy, which 
will be determined on a case-by-base basis by the treating gastroenterologist
All patients will be asked to return for abdominal/pelvic cross-sectional imaging (CT or 
MRI) at 30 days from the initial intervention; the modality will be left to the discretion of the 
treating gastroenterologist
Patients may be asked to undergo additional follow up imaging (up to 60 days after the 
initial procedure), which will be left to the discretion of the treating gastroenterologist. 
 
 
7 Statistical Plan 
7.1 Sample Size Determination 
As this represents a pilot study, we plan on enrolling only 10 patients in each study arm. This number is 
based on previous studies of endoscopic intervention – most notably the landmark PENGUIN trial from 
the Netherlands which compared endoscopic vs surgical treatment for WOPN (7).  We feel confident that 
using 10 patients in each arm will allow us to complete the study, and likely see a difference in cost 
between the two procedures.  
7.2 Statistical Methods 
The statistical model will be very simple.  For the primary outcome – cost – we will compare the overall 
mean costs (procedure, hospitalization, complication) for each type of stent using a student’s t test.  For 
secondary outcomes using continuous data, we will use the student’s t-test and for categorical data we 
will use the Fisher’s Exact test.  Given the small number of subjects in each arm, regression models will 
not be built. 
7.3 Subject Population(s) for Analysis 
We will use an All-treated population:  Any subject randomized into the study that received at least one 
dose of study drug. 

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8 Safety and Adverse Events 
8.1 Definitions 
Unanticipated Problems Involving Risk to Subjects or Others 
Any incident, experience, or outcome that meets all of the following criteria:  
 Unexpected in nature, severity, or frequency  (i.e. not described in study-related documents such 
as the IRB-approved protocol or consent form, the investigators brochure, etc) 
 Related or possibly related to participation in the research (i.e. possibly related means there is a 
reasonable possibility that the incident experience, or outcome may have been caused by the 
procedures involved in the research) 
 Suggests that the research places subjects or others at greater risk of harm (including physical, 
psychological, economic, or social harm). 
 
Adverse Event 
An adverse event (AE) is any symptom, sign, illness or experience that develops or worsens in severity 
during the course of the study.  Intercurrent illnesses or injuries should be regarded as adverse events.  
Abnormal results of diagnostic procedures are considered to be adverse events if the abnormality: 
 results in study withdrawal 
 is associated with a serious adverse event 
 is associated with clinical signs or symptoms 
 leads to additional treatment or to further diagnostic tests 
 is considered by the investigator to be of clinical significance 
 
Serious Adverse Event 
Adverse events are classified as serious or non-serious.  A serious adverse event is any AE that is:  
 fatal 
 life-threatening 
 requires or prolongs hospital stay 
 results in persistent or significant disability or incapacity 
 a congenital anomaly or birth defect 
 an important medical event 
 
Important medical events are those that may not be immediately life threatening, but are clearly of major 
clinical significance.   They may jeopardize the subject, and may require intervention to prevent one of the 
other serious outcomes noted above.  For example, drug overdose or abuse, a seizure that did not result 
in in-patient hospitalization, or intensive treatment of bronchospasm in an emergency department would 
typically be considered serious.  
 
All adverse events that do not meet any of the criteria for serious should be regarded as non-serious 
adverse events.  
 
Adverse Event Reporting Period 
The study period during which adverse events must be reported will include the period from the initiation 
of the study procedure to the end of the study treatment follow-up.  For this study, the study treatment 
follow-up is defined as 60 days following the last administration of study treatment.  
 
Preexisting Condition 
A preexisting condition is one that is present at the start of the study.  A preexisting condition will be 
recorded as an adverse event if the frequency, intensity, or the character of the condition worsens during 
the study period. 
 
General Physical Examination Findings 

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At screening, any clinically significant abnormality should be recorded as a preexisting condition.  At the 
end of the study, any new clinically significant findings/abnormalities that meet the definition of an 
adverse event must also be recorded and documented as an adverse event.  
 
Post-study Adverse Event 
All unresolved adverse events will be followed by the investigator until the events are resolved, the 
subject is lost to follow-up, or the adverse event is otherwise explained.  At the last scheduled visit, the 
investigator will instruct each subject to report any subsequent event(s) that the subject, or the subject’s 
personal physician, believes might reasonably be related to participation in this study.  The investigator 
will notify the study sponsor of any death or adverse event occurring at any time after a subject has 
discontinued or terminated study participation that may reasonably be related to this study.  The sponsor 
will also be notified if the investigator should become aware of the development of cancer or of a 
congenital anomaly in a subsequently conceived offspring of a subject that has participated in this study.  
 
Abnormal Laboratory Values 
A clinical laboratory abnormality will be documented as an adverse event if any one of the following 
conditions is met:  
 The laboratory abnormality is not otherwise refuted by a repeat test to confirm the abnormality 
 The abnormality suggests a disease and/or organ toxicity 
 The abnormality is of a degree that requires active management; e.g. change of dose, 
discontinuation of the drug, more frequent follow-up assessments, further diagnostic investigation, 
etc. 
 
Hospitalization, Prolonged Hospitalization or Surgery 
Any adverse event that results in hospitalization or prolonged hospitalization will be documented and 
reported as a serious adverse event unless specifically instructed otherwise in this protocol.  Any 
condition responsible for surgery should be documented as an adverse event if the condition meets the 
criteria for and adverse event.  
 
Neither the condition, hospitalization, prolonged hospitalization, nor surgery are reported as an adverse 
event in the following circumstances: 
 Hospitalization or prolonged hospitalization for diagnostic or elective surgical procedures for a 
preexisting condition.  Surgery should not be reported as an outcome of an adverse event if the 
purpose of the surgery was elective or diagnostic and the outcome was uneventful. 
 Hospitalization or prolonged hospitalization required to allow efficacy measurement for the study. 
 Hospitalization or prolonged hospitalization for therapy of the target disease of the study, unless it 
is a worsening or increase in frequency of hospital admissions as judged by the clinical 
investigator. 
8.2 Recording of Adverse Events 
At each contact with the subject, the investigator will seek information on adverse events by specific 
questioning and, as appropriate, by examination.  Information on all adverse events will be recorded 
immediately in the source document, and also in the appropriate adverse event module of the case report 
form (CRF).  All clearly related signs, symptoms, and abnormal diagnostic procedures results will 
recorded in the source document, though will be grouped under one diagnosis. 
 
All adverse events occurring during the study period must be recorded.  The clinical course of each event 
will be followed until resolution, stabilization, or until it has been determined that the study treatment or 
participation is not the cause.  Serious adverse events that are still ongoing at the end of the study period 
will be followed up to determine the final outcome.  Any serious adverse event that occurs after the study 
period and is considered to be possibly related to the study treatment or study participation will be 
recorded and reported immediately. 

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8.3 Reporting of Serious Adverse Events and Unanticipated Problems 
 
Investigators and the protocol sponsor will conform to the adverse event reporting timelines, formats and 
requirements of the various entities to which they are responsible, but at a minimum those events that 
must be reported are those that are: 
 related to study participation, 
 unexpected, and  
 serious or involve risks to subjects or others  
(see definitions, section 8.1).   
If the report is supplied as a narrative, the minimum necessary information to be provided at the time of 
the initial report includes: 
 
Study identifier 
 
Study Center 
 
Subject number 
 
A description of the event 
 
Date of onset 
 
Current status 
 
Whether study treatment was discontinued 
 
The reason why the event is classified as serious 
 
Investigator 
assessment 
of 
the 
association 
between the event and study treatment 
 
8.3.1 Investigator reporting: notifying the study sponsor 
Any study-related unanticipated problem posing risk of harm to subjects or others, and any type of 
serious adverse event, will be reported to the study sponsor by telephone within 24 hours of the event.  
To report such events, a Serious Adverse Event (SAE) form will be completed by the investigator and 
faxed to the study sponsor within 24 hours.  The investigator will keep a copy of this SAE form on file at 
the study site.  Report serious adverse events by phone and facsimile to: Timothy Gardner, phone 603-
650-5206, fax 603-650-5225 
 
Within the following 48 hours, the investigator will provide further information on the serious adverse 
event or the unanticipated problem in the form of a written narrative.  This will include a copy of the 
completed Serious Adverse Event form, and any other diagnostic information that will assist the 
understanding of the event.  Significant new information on ongoing serious adverse events should be 
provided promptly to the study sponsor 
8.3.2 Investigator reporting: notifying the Dartmouth IRB 
This section describes the requirements for safety reporting by investigators who are Dartmouth faculty, 
affiliated with a Dartmouth research site, or otherwise responsible for safety reporting to the Dartmouth 
IRB. The Dartmouth College IRB (CPHS) requires expedited reporting of those events related to study 
participation that are unforeseen and indicate that participants or others are at increased risk of harm.  
The Dartmouth IRB will not acknowledge safety reports or bulk adverse event submissions that do not 
meet the criteria outlined below.  The Dartmouth IRB requires researchers to submit reports of the 
following problems within 10 working days from the time the investigator becomes aware of the event: 
 Any adverse event (regardless of whether the event is serious or non-serious, on-site or off-site) 
that occurs any time during or after the research study, which in the opinion of the principal 
investigator is: 
Unexpected (An event is “unexpected” when its specificity and severity are not accurately reflected 
in the protocol-related documents, such as the IRB-approved research protocol, any applicable 
investigator brochure, and the current IRB-approved informed consent document and other 
relevant sources of information, such as product labeling and package inserts.) 
AND 
Related to the research procedures (An event is “related to the research procedures” if in the 
opinion of the principal investigator or sponsor, the event was more likely than not to be caused by 
the research procedures.) 
 

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Reporting Process 
Unanticipated problems posing risks to subjects or others as noted above will be reported to the 
Dartmouth IRB using the form: “Unanticipated Problems Posing Risks to Subjects or Others Including 
Reportable Adverse Events” or as a written report of the event (including a description of the event with 
information regarding its fulfillment of the above criteria, follow-up/resolution and need for revision to 
consent form and/or other study documentation). 
 
Copies of each report and documentation of IRB notification and receipt will be kept in the Clinical 
Investigator’s study file. 
 
Reporting Deaths:  more rapid reporting requirements 
Concerning deaths that occur during the course of a research study, the following describes the more 
rapid reporting requirement of the Dartmouth IRB for specific situations: 
 Report the event within 24 hours when the death is unforeseen (unexpected) and indicates 
participants or others are at increased risk of harm. 
 Report the event within 72 hours, for all other deaths, regardless of whether the death is related to 
study participation. 
 
For reportable deaths, the initial submission to the Dartmouth IRB may be made by contacting the IRB 
Director or Associate Director. The AE/Unanticipated Problem Form is required as a follow up to the initial 
submission. 
 
Other Reportable events: 
For clinical drug trials, the following events are also reportable to the Dartmouth IRB: 
 Any adverse experience that, even without detailed analysis, represents a serious unexpected 
adverse event that is rare in the absence of drug exposure (such as agranulocytosis, hepatic 
necrosis, Stevens-Johnson syndrome). 
 Any adverse event that would cause the sponsor to modify the investigators brochure, protocol or 
informed consent form, or would prompt other action by the IRB to assure protection of human 
subjects. 
 Information that indicates a change to the risks or potential benefits of the research, in terms of 
severity or frequency. For example:  
– An interim analysis indicates that participants have a lower rate of response to treatment than 
initially expected. 
– Safety monitoring indicates that a particular side effect is more severe, or more frequent than 
initially expected. 
– A paper is published from another study that shows that an arm of your research study is of no 
therapeutic value. 
 Change in FDA safety labeling or withdrawal from marketing of a drug, device, or biologic used in 
a research protocol. 
 Breach of confidentiality 
 Change to the protocol taken without prior IRB review to eliminate apparent immediate hazard to a 
research participant. 
 Incarceration of a participant when the research was not previously approved under Subpart C 
and the investigator believes it is in the best interest of the subject to remain on the study. 
 Complaint of a participant when the complaint indicates unexpected risks or the complaint cannot 
be resolved by the research team. 
 Protocol violation (meaning an accidental or unintentional deviation from the IRB approved 
protocol) that in the opinion of the investigator placed one or more participants at increased risk, or 
affects the rights or welfare of subjects. 

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8.3.3 Investigator reporting: Notifying another IRB 
Investigators who are not Dartmouth faculty or affiliated with a Dartmouth research site are responsible 
for safety reporting to their local IRB.  Investigators are responsible for complying with their local IRB’s 
reporting requirements, though must submit the required reports to their IRB no later than 10 working 
days.  Copies of each report and documentation of IRB notification and receipt will be kept in the 
investigator’s study file. 
 
8.3.4 Sponsor reporting: Notifying participating investigators 
 
It is the responsibility of the study sponsor to notify all participating investigators, in a written IND safety 
report, of any adverse event associated with the use of the drug that is both serious and unexpected, as 
well as any finding from tests in laboratory animals that suggest a significant risk for human subjects.  
Additionally, sponsors are also required to identify in IND safety reports all previous reports concerning 
similar adverse events and to analyze the significance of the current event in light of the previous reports. 
8.4 Unblinding Procedures 
Study participants will be un-blinded in the event of a Serious Adverse Event (SAE) as outline in the 
preceding sections, and will be reported along with the report of the SAE.  Patients will otherwise be un-
blinded at the end of the study period.  The investigator must inform the sponsor of all subjects whose 
treatment was un-blinded within 48 hours of un-blinding.   
8.5 Stopping Rules  
Complication rates associated with endoscopic necrosectomy approach 30%, and are mostly procedure 
related (89%).  The mortality rate may be close to 5% (9).  The study will be stopped early for 
complication and mortality rates that significantly exceed these rates and we will evaluate the outcomes 
after 10 patients have been enrolled for an interim analysis. 
8.6 Medical Monitoring 
It is the responsibility of the Principal Investigator to oversee the safety of the study at his/her site.  This 
safety monitoring will include careful assessment and appropriate reporting of adverse events as noted 
above, as well as the construction and implementation of a site data and safety-monitoring plan (see 
section 9 Auditing, Monitoring and Inspecting).  Medical monitoring will include a regular assessment of 
the number and type of serious adverse events. 
8.6.1 Independent Data and Safety Monitoring Board 
Dr. Steven Bensen in the section of Gastroenterology and Hepatology at DHMC will serve as the internal 
DSMB.  After 10 patients have been enrolled, he will be given access to all of the primary and secondary 
clinic outcomes in an unblinded fashion – including all adverse events.  If there is a statistically significant 
difference in any of the appropriate outcomes or AEs, CPHS will be contacted and that their discretion the 
study will continue or be terminated. 
 
9 Data Handling and Record Keeping 
9.1 Confidentiality 
Information about study subjects will be kept confidential and managed according to the requirements of 
the Health Insurance Portability and Accountability Act of 1996 (HIPAA).  Those regulations require a 
signed subject authorization informing the subject of the following:  
 What protected health information (PHI) will be collected from subjects in this study 
 Who will have access to that information and why 
 Who will use or disclose that information 

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 The rights of a research subject to revoke their authorization for use of their PHI.  
 
In the event that a subject revokes authorization to collect or use PHI, the investigator, by regulation, 
retains the ability to use all information collected prior to the revocation of subject authorization.  For 
subjects that have revoked authorization to collect or use PHI, attempts should be made to obtain 
permission to collect at least vital status (i.e. that the subject is alive) at the end of their scheduled study 
period. 
9.2 Source Documents 
Source data is all information, original records of clinical findings, observations, or other activities in a 
clinical trial necessary for the reconstruction and evaluation of the trial.  Source data are contained in 
source documents.  Examples of these original documents, and data records include: hospital records, 
clinical and office charts, laboratory notes, memoranda, subjects’ diaries or evaluation checklists, 
pharmacy dispensing records, recorded data from automated instruments, copies or transcriptions 
certified after verification as being accurate and complete, microfiches, photographic negatives, microfilm 
or magnetic media, x-rays, subject files, and records kept at the pharmacy, at the laboratories, and at 
medico-technical departments involved in the clinical trial. 
9.3 Case Report Forms 
The study case report form (CRF) is the primary data collection instrument for the study.  All data 
requested on the CRF must be recorded.  All missing data must be explained.  If a space on the CRF is 
left blank because the procedure was not done or the question was not asked, write “N/D”.  If the item is 
not applicable to the individual case, write “N/A”.  All entries should be printed legibly in black ink.  If any 
entry error has been made, to correct such an error, draw a single straight line through the incorrect entry 
and enter the correct data above it.  All such changes must be initialed and dated.  DO NOT ERASE OR 
WHITE OUT ERRORS.  For clarification of illegible or uncertain entries, print the clarification above the 
item, then initial and date it. 
9.4 Records Retention 
It is the investigator’s responsibility to retain study essential documents for at least 1 year after 
enrollment.  
 
10 Study Monitoring, Auditing, and Inspecting 
10.1 Study Monitoring Plan 
This study will be monitored according to the monitoring plan by the CTO.  The investigator will allocate 
adequate time for such monitoring activities.  The Investigator will also ensure that the monitor or other 
compliance or quality assurance reviewer is given access to all the above noted study-related documents 
and study related facilities (e.g. pharmacy, diagnostic laboratory, etc.), and has adequate space to 
conduct the monitoring visit. 
10.2 Auditing and Inspecting 
The investigator will permit study-related monitoring, audits, and inspections by the EC/IRB, the sponsor, 
government regulatory bodies, and Dartmouth compliance and quality assurance groups of all study 
related documents (e.g. source documents, regulatory documents, data collection instruments, study data 
etc.).  The investigator will ensure the capability for inspections of applicable study-related facilities (e.g. 
pharmacy, diagnostic laboratory, etc.). 
 
Participation as an investigator in this study implies acceptance of potential inspection by government 
regulatory authorities and applicable Dartmouth compliance and quality assurance offices. 

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11 Ethical Considerations 
This study is to be conducted according to US and international standards of Good Clinical Practice (FDA 
Title 21 part 312 and International Conference on Harmonization guidelines), applicable government 
regulations and Institutional research policies and procedures. 
 
This protocol and any amendments will be submitted to a properly constituted independent Ethics 
Committee (EC) or Institutional Review Board (IRB), in agreement with local legal prescriptions, for formal 
approval of the study conduct.  The decision of the EC/IRB concerning the conduct of the study will be 
made in writing to the investigator and a copy of this decision will be provided to the sponsor before 
commencement of this study.  The investigator should provide a list of EC/IRB members and their affiliate 
to the sponsor. 
 
All subjects for this study will be provided a consent form describing this study and providing sufficient 
information for subjects to make an informed decision about their participation in this study.  See 
Attachment 2 for a copy of the Subject Informed Consent Form.  This consent form will be submitted with 
the protocol for review and approval by the EC/IRB for the study.  The formal consent of a subject, using 
the EC/IRB-approved consent form, must be obtained before that subject undergoes any study 
procedure.  The consent form must be signed by the subject or legally acceptable surrogate, and the 
investigator-designated research professional obtaining the consent.  
12 Study Finances 
12.1 Funding Source 
This study will not require dedicated funding. 
12.2 Conflict of Interest 
Any investigator who has a conflict of interest with this study (patent ownership, royalties, or financial gain 
greater than the minimum allowable by their institution, etc.) must have the conflict reviewed by a properly 
constituted Conflict of Interest Committee with a Committee-sanctioned conflict management plan that 
has been reviewed and approved by the study sponsor prior to participation in this study.  All Dartmouth 
investigators will follow the Dartmouth conflict of interest policy. 
13 Publication Plan 
 
Neither the complete nor any part of the results of the study carried out under this protocol, nor any of the 
information provided by the sponsor for the purposes of performing the study, will be published or passed 
on to any third party without the consent of the study sponsor.  Any investigator involved with this study is 
obligated to provide the sponsor with complete test results and all data derived from the study. 
14 References 
1. The epidemiology of pancreatitis and pancreatic cancer. Yadav D1, Lowenfels AB. s.l. : 
Gastroenterology. 2013 Jun;144(6):1252-61. 
2. Clinical practice. Acute pancreatitis. DC1., Whitcomb. N Engl J Med. 2006 May 18;354(20):2142-50. 
3. Validation of the determinant-based classification and revision of the Atlanta classification systems for 
acute pancreatitis. Acevedo-Piedra NG1, Moya-Hoyo N1, Rey-Riveiro M1, Gil S2, Sempere L1, 
Martínez J1, Lluís F1, Sánchez-Payá J3, de-Madaria E4. s.l. : Clin Gastroenterol Hepatol. 
2014;12(2):311. 
4. Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by 
international consensus. Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, 
Tsiotos GG, Vege SS and Group., Acute Pancreatitis Classification Working. s.l. : Gut. 2013 
Jan;62(1):102-11. 

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5. Equal efficacy of endoscopic and surgical cystogastrostomy for pancreatic pseudocyst drainage in a 
randomized trial. Varadarajulu S1, Bang JY, Sutton BS, Trevino JM, Christein JD, Wilcox CM. s.l. : 
Gastroenterology. 2013 Sep;145(3):583-90. 
6. Surgical versus nonsurgical management of pancreatic pseudocysts. Johnson MD1, Walsh RM, 
Henderson JM, Brown N, Ponsky J, Dumot J, Zuccaro G, Vargo J. s.l. : J Clin Gastroenterol. 2009 
Jul;43(6):586-90. 
7. Endoscopic transgastric vs surgical necrosectomy for infected necrotizing pancreatitis: a randomized 
trial. Bakker OJ1, van Santvoort HC, van Brunschot S, Geskus RB, Besselink MG, Bollen TL, van 
Eijck CH, Fockens P, Hazebroek EJ, Nijmeijer RM, Poley JW, van Ramshorst B, Vleggaar FP, 
Boermeester MA, Gooszen HG, Weusten BL, Timmer R and Grou, Dutch Pancreatitis Study. s.l. : 
JAMA. 2012 Mar 14;307(10):1053-61. 
8. Paradigm shift away from open surgical necrosectomy toward endoscopic interventions for necrotizing 
pancreatitis. Jae Hee Cho, Yoon Jae Kim, and Yeon Suk Kim. s.l. : Gastrointestinal Intervention 2014; 
3(2): 84-88. 
9. Endoscopic necrosectomy of pancreatic necrosis: a systematic review. Haghshenasskashani A1, 
Laurence JM, Kwan V, Johnston E, Hollands MJ, Richardson AJ, Pleass HC, Lam VW. s.l. : Surg 
Endosc. 2011 Dec;25(12):3724-30. 
10. Endoscopic-ultrasound-guided endoscopic transmural drainage of pancreatic pseudocysts and 
abscesses. Lopes CV1, Pesenti C, Bories E, Caillol F, Giovannini M. s.l. : J Clin Gastroenterol. 2009 
Jul;43(6):586-90. . 
11. Transenteric drainage of pancreatic-fluid collections with fully covered self-expanding metallic stents 
(with video). Talreja JP1, Shami VM, Ku J, Morris TD, Ellen K, Kahaleh M. s.l. : Gastrointest Endosc. 
2008 Dec;68(6):1199-203. 
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[Stents and WOPN] 
 
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15 Attachments 
 
#1 CPHS Protocol Plus 
#2 Case Report Form (separate document) 
#3 Consent to take part in research (separate document)