A Multicenter, Prospective Study of EUS-Guided Transluminal Gallbladder Drainage in Patients With Acute Cholecystitis as an Alternative to Percutaneous Gallbladder Drainage
Phase: NA
Conditions: Cholecystitis, Acute
Sponsor: Boston Scientific Corporation

 
AXIOS™ for Gallbladder Drainage as an Alternative to Percutaneous Drainage IDE 
NCT03767881 
Clinical Protocol 
06 June 2020 

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A Multicenter, Prospective Study of EUS-Guided Transluminal 
Gallbladder Drainage in Patients with Acute Cholecystitis as an 
Alternative to Percutaneous Gallbladder Drainage  
AXIOSTM for Gallbladder Drainage as an Alternative to Percutaneous Drainage IDE 
 
Clinical Investigation Plan 
 
Project # E7108 
 
IDE# G170190 
 
 
National Clinical Trial (NCT) Identified Number: NCT03767881 
Sponsored By 
Boston Scientific Corporation 
300 Boston Scientific Way 
Marlborough, MA 01752-1234 
USA 
 
Boston Scientific International S.A. 
Parc Val Saint-Quentin, Bâtiment H 
2 Rue René Caudron 
78960 Voisins le Bretonneux 
France 
 
 
 
 
 
 
 
 
 
 
 
This protocol contains confidential information for use by the Investigators and their 
designated representatives participating in this clinical investigation. The protocol should be 
held confidential and maintained in a secure location. 
Do not copy or distribute without written permission from Boston Scientific Corporation.

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Contact Information 
Role 
Contact  
Clinical Contact 
Lina Ginnetti 
Clinical Director 
Boston Scientific Corporation 
200 Boston Scientific Way 
Marlborough, MA 01752-1234 
USA 
Coordinating Principal 
Investigator 
Shayan Irani, MD  
Virginia Mason Medical Center 
1100 Ninth Avenue 
Seattle, WA 98101 
USA  
 
 
 

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Original Release: July 21, 2017 
Current Version: June 06, 2020 
Revision History 
 
Revision 
Number 
Release 
Date 
Template 
number 
and 
version 
Section 
Change 
Reason 
for 
Change 
92147168, 
Rev/Ver 
B 
 
December 
20, 2017 
 
Template 
90702637 
Rev/Ver  
AH 
Synopsis, 2, 
3, 4, 5, 6, 7, 
8, 15, 16, 17 
 
Wording modifications including: 
Study title, device description, 
study objective, endpoints, 
inclusion criterion, exclusion 
criterion, subject status and 
classification, additional 
procedural notices, study methods, 
statistical considerations and 
general statistical methods, 
committees, risk management 
strategy, and safety reporting 
Per FDA 
review 
and 
feedback 
92147168, 
Rev/Ver 
C 
 
May 17, 
2018 
 
Template 
90702637 
Rev/Ver  
AH 
Study 
Objective, 
Synopsis, 
Exclusion 
Criteria 5, 6, 
7, 8, 16, 5.2 
Added statement to Study 
Objective, Changed Exclusion 
Criteria # 9; add collection of 
current medications at baseline 
and follow-up visits and exclude 
patients with any prior 
interventions; change follow-up of 
patients who do not have an 
AXIOS stent implanted; change 
primary analysis cohort and 
enrollment cohort to ITT; specify 
the evaluation of the primary 
effectiveness endpoint; minor edits 
to section 7.4 to match synopsis; 
added exclusion criterion. Added 
windows for end of study visit and 
72hr post stent removal visit; 
raised the number of participating 
centers 
Per FDA 
review 
and 
feedback 
92147168, 
Rev/Ver 
D 
August 15, 
2018 
Template 
90702637 
Rev/Ver 
AJ 
Synopsis, 
Section 7, 
17, 18, 20, 21  
Updated language to reflect 
updated protocol template 
Updated 
protocol 
template 

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Revision 
Number 
Release 
Date 
Template 
number 
and 
version 
Section 
Change 
Reason 
for 
Change 
92147168, 
Rev/Ver 
E 
September 
05, 2018 
Template 
90702637 
Rev/Ver 
AJ 
Synopsis, 
Section 5.1, 
Figure 4.3-1, 
8.1 
Updated inclusion criteria #2 in 
Synopsis and Section 5.1; updated 
flowchart in Figure 4.3-1; added 
that patient not receiving an Axios 
stent will be censored in the KM 
analysis at 60 days.  Added a 
sensitivity analysis for the KM 
analysis; updated number of 
centers in synopsis 
Per FDA 
review 
and 
feedback  
92147168,
Rev/Ver 
F 
October 
18, 2018 
Template 
90702637 
Rev/Ver 
AJ 
Synopsis, 
Section 4.1; 
Contact 
information 
Updated primary effectiveness 
endpoint in synopsis and section 
8.1; Changed sample size to 24 
patients; Updated coordinating 
lead investigator 
Per FDA 
review 
and 
feedback 
92147168, 
Rev/Ver 
G 
November 
6, 2018 
Template 
90702637 
Rev/Ver 
AJ 
Synopsis, 
Section 4.1;  
Updated primary effectiveness 
endpoint in synopsis and section 
8.1; Changed sample size to 30 
patients; updated number of 
centers in the synopsis 
Per FDA 
review 
and 
feedback 
92147168, 
Rev/Ver 
H 
December 
19, 2018 
Template 
90702637 
Rev/Ver 
AJ 
Additional 
Endpoints, 
Section 8.1, 
Section 16.1 
Updated Additional Endpoints and 
section 8.1; Changed performance 
goal to 3.5 days. Section 16.1 edited 
to reflect coverage of Adverse 
Events and Adverse Device Effects  
Per FDA 
review 
and 
feedback 
92147168, 
Rev/Ver I 
February 
20, 2020 
Template 
90702637 
Rev/Ver 
AL 
Synopsis, 
section 5.2, 
section 4.4, 
section 6.5, 
section 7.4 
Updated exclusion criteria #5 in 
synopsis and section 5.2, increased   
number of centers in section 4.4; 
study design, added definition of 
end of study in section 6.5 end of 
study, moved clinical symptom 
assessment to stent removal visit in 
section 7.4 
Updated 
protocol 
template; 
improve 
study 
enrollme
nt 
92147168, 
Rev/Ver 
J 
June 06, 
2020 
Template 
90702637 
Rev/Ver 
AL 
Synopsis, 
section 5.2, 
section 7.4 
Updated exclusion criteria #9 in 
synopsis and section 5.2, updated 
imaging window flowchart; added 
repeat imaging procedure in case 
of patient’s deteriorating clinical 
status in section 7.4 
Per FDA 
feedback 

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Protocol Synopsis  
 
Full Title 
A Multicenter, Prospective Study of EUS-Guided Transluminal 
Gallbladder Drainage in Patients with Acute Cholecystitis as an 
Alternative to Percutaneous Gallbladder Drainage 
Short Title 
AXIOSTM for Gallbladder Drainage as an Alternative to Percutaneous 
Drainage IDE 
Background 
The established treatment for acute cholecystitis in patients who are 
unsuitable or at high risk for surgery is percutaneous transhepatic 
gallbladder drainage (PT-GBD) also known as percutaneous 
cholecystostomy (PC).   However, external drainage provided by 
percutaneous tubes is associated with high rate of complications, 
including peritonitis, bleeding, pneumothorax, recurrent cholecystitis, 
and secondary infections. In addition, percutaneous cholecystostomy 
tubes can be uncomfortable, have a negative effect on the patient’s 
quality of life, [1] and may result in inadvertent dislodgement or 
intentional removal requiring numerous reinterventions.  
 
An alternative to PT-GBD is Endoscopic Ultrasound-guided Transmural 
Gallbladder Drainage (EUS-GBD) which is an internal drainage method 
having the potential to eliminate many of the shortcomings of PT-GBD 
[2].  The literature contains clinical results of the successful use of the 
AXIOS™ stent in EUS-GBD.  The AXIOSTM transluminal stent system 
can be used to bridge two lumens or organs to create an internal drain.  
It is cleared in the U.S. to drain pancreatic pseudocysts into the stomach 
or the duodenum while outside the U.S. its indication includes EUS-
GBD.    
 
The purpose of this IDE clinical trial is to evaluate the use of the 
AXIOS™ stent in the EUS-GBD procedure for gallbladder drainage into 
the stomach or duodenum.   
Study Objective To evaluate the safety and effectiveness of the AXIOSTM Stent with 
Electrocautery Enhanced Delivery System in the management of 
symptoms of acute cholecystitis as an alternative to percutaneous 
gallbladder drainage. It is anticipated that a transluminal EUS drainage 
approach with the AXIOS™ stent will provided benefits in time to 
resolution of acute cholecystitis as well as a lower the fraction of 
patients whom would require additional interventions compared to those 
treated with percutaneous cholecystostomy; study endpoints will be used 
to further evaluate.  

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Indication(s) for 
Use  
Current cleared indication for use:  The AXIOSTM Stent and 
Electrocautery Enhanced Delivery System is cleared in the U.S. “for use 
to facilitate transgastric or transduodenal endoscopic drainage of 
symptomatic pancreatic pseudocysts ≥ 6cm in size and walled-off 
necrosis ≥ 6cm in size with ≥ 70% fluid content that are adherent to the 
gastric or bowel wall.  Once placed, the AXIOSTM Stent functions as an 
access port allowing passage of standard and therapeutic endoscopes to 
facilitate debridement, irrigation and cystoscopy.  The stent is intended 
for implantation up to 60 days and should be removed upon 
confirmation of pseudocyst or walled-off necrosis resolution” Outside 
the U.S., the AXIOSTM Stent and Electrocautery Enhanced Delivery 
System are indicated for use to facilitate transgastric or transduodenal 
endoscopic drainage of a pancreatic pseudocyst or walled-off necrosis 
with ≥ 70% fluid content or to facilitate drainage of the biliary tract.  
 
Proposed expanded indication in the U.S. for this IDE study:  The 
AXIOSTM Stent and Electrocautery Enhanced Delivery System is 
intended for endoscopic ultrasound-guided transluminal gallbladder 
drainage in patients with acute cholecystitis who are at high risk or 
unsuitable for surgery. 
Test Device 
AXIOSTM Stent and Electrocautery Enhanced Delivery System 
Test Device 
Sizes 
• Diameter: 10 mm, 15 mm 
• Length: 10mm  
Study Design 
Prospective, multi-center, single arm, consecutive series study 
Number of 
Subjects 
30 subjects 
Number of 
Centers 
Up to 9 sites (US and OUS) 
Primary 
Effectiveness 
Endpoint 
Time to resolution of acute cholecystitis measured in days.  
Note: Resolution is defined as either a fever of less than 100.5°F, or at 
least a 4-point decrease in the pain score, or WBC count less than 
12,000/cc, with improvement in at least two of these categories without 
the deterioration of the third category.   
Secondary 
Effectiveness 
Endpoint 
Rate of re-interventions including but not limited to stent migration, 
stent occlusion by GB stones, and luminal debridement 
Additional 
Endpoints 
1. Stent patency (ability to facilitate gallbladder drainage) defined 
indirectly as resolution of acute cholecystitis or, in the absence of 

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resolution of acute cholecystitis, endoscopic observation of 
unobstructed AXIOSTM stent lumen  
2. Technical stent placement success: Successful stent placement, 
defined as transmural placement of the AXIOSTM stent with 
confirmed stent patency via (i) drainage visualized through the stent 
or fluoroscopically, or (ii) ability to endoscopically observe the 
inner walls of the gallbladder through the AXIOSTM stent  
3. Technical stent removal success:  Successful stent removal, defined 
as ability to remove the AXIOSTM stent endoscopically without 
stent removal related serious adverse events 
4. Rate of recurrence of acute cholecystitis and its management 
5. Number of cumulative hospital and ICU days from initial stent 
placement to resolution of symptoms of acute cholecystitis 
Method of 
Assigning 
Subjects to 
Treatment 
All subjects with acute cholecystitis at high risk or unsuitable for 
cholecystectomy and indicated for gallbladder drainage will be 
approached for participation. 
Study Visits and 
Follow-Up 
Schedule 
• Screening/ Baseline Visit (Office/Hospital Visit): informed consent, 
eligibility criteria assessment, pre-procedure transabdominal 
ultrasound or CT scan (within 5 days of drainage procedure), 
demographics, medical history, pre-procedural patient management 
including labs and clinical symptom assessment, laboratory markers 
of inflammation or cholestasis (including WBC), current 
medication(s) 
• Stent Placement Procedure (Office/Hospital Visit): stent 
placement procedure per DFU/ IB, adverse event/device event 
assessment, stent patency assessment, current medication(s)                
Additional Procedural Notices: 
o Procedure should be done with CO2 insufflation. 
o Choice of placement of stent between the duodenum and the 
gallbladder or between the stomach and the gallbladder is left at 
discretion of treating physician.   
o Physicians will select the site of the AXIOS stent placement 
under EUS guidance and choose an access location where there 
is  
o adequate stone-free space within the gallbladder to 
deploy the flange 
o distance between the gallbladder and the stomach or 
duodenal lumen that does not exceed 10mm, the saddle 
length of the AXIOSTM stent 

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o no intervening ascites, bowel, or fat, as identified by EUS  
o If a patient’s gallbladder has minimal stone burden and is free of 
large stones per baseline imaging, a 10mm lumen diameter 
AXIOSTM stent is recommended 
o If a patient’s gallbladder is packed with stones or large stones 
(1cm or larger in diameter) are present per baseline imaging, a 
15mm lumen diameter AXIOSTM stent is recommended 
o Stones and/or sludge will be cleared using gentle basketing and 
irrigation through the stent if necessary, at the discretion of 
investigator 
o Placement of double pigtail plastic stent(s) through AXIOSTM 
will not be allowed in the study. 
o If placement of the AXIOSTM stent is attempted but no stent 
placement occurs, patient will be followed until 30 days after 
resolution of the cholecystitis, or 60 days after the index 
procedure, whichever comes first. The patient’s treatment will be 
at the discretion of the physician. 
• Daily Acute Cholecystitis Assessment Visits (Office/Hospital 
Visit): until discharge/resolution: clinical symptom assessment 
(including pain score, and fever), laboratory markers of 
inflammation, or cholestasis (including WBC), imaging (as 
applicable), adverse event / device event assessment, documentation 
of any re-intervention, including luminal debridement (as 
applicable), current medication(s) 
o If discharged less than 72 hours post stent placement, patient 
may have a follow-up phone call instead: clinical symptom 
assessment, adverse/ device event assessment, documentation of 
any re-intervention (as applicable) 
o If acute cholecystitis is not resolving or not improving, a CT with 
contrast (unless contraindicated) will be required to rule out 
possible stent migration, perforation, cholangitis, sepsis or 
portal vein thrombosis. 
• Reintervention Visit (if applicable): Documentation of any re-
intervention (including luminal debridement), imaging (as 
applicable), labs (as applicable), clinical symptom assessment, stent 
placement (as applicable), stent removal (as applicable), stent 
patency assessment (as applicable), adverse event/device event 
assessment, current medication(s) 
• Stent Removal Procedure (Office/Hospital Visit): at 30-60 days 
after stent placement in the setting of resolved acute cholecystitis 
(unless medically recommended otherwise, i.e. the stent remain 

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indwelling indefinitely): stent removal, adverse event/device event 
assessment, documentation of any re-intervention (as applicable), 
stent patency assessment, clinical symptom assessment, current 
medication(s) 
Note: After stent removal, the physician will continue to treat the 
patient per standard of practice  
• 72 Hour Post-Stent Removal Visit (+24 hours) (Telephone): 
adverse event assessment, documentation of any re-intervention (as 
applicable), current medication(s) 
• End of Study Visit (Office/Hospital Visit):  at 30 days (+/- 7 days) 
post stent removal or 90 days (+/- 14 days) post stent placement 
(whichever comes first) for patients with an AXIOSTM stent 
implanted; 30 days post-resolution of cholecystitis or 60 days post-
index procedure (whichever comes first) for patients without an 
AXIOSTM stent implanted: clinical symptom assessment, laboratory 
markers of inflammation or cholestasis, adverse event assessment, 
documentation of any re-intervention (as applicable), current 
medications 
• Additional visits as needed: Adverse events assessment / device 
event assessment, imaging (as applicable), labs (as applicable), 
documentation of any re-intervention (as applicable), current 
medication 
Study Duration Subjects will be on study for up to 15 weeks 
Key Inclusion 
Criteria 
1. Patient requiring intervention for the management of symptoms 
associated with acute cholecystitis 
2. Patients referred for percutaneous drainage of the gallbladder who 
are not surgical candidates because of advanced age, anesthetic risk, 
significant co-morbidities and/or overall health 
3. Eligible for endoscopic intervention 
4. Acute Cholecystitis (AC) Grade I (mild) or II (moderate) per Tokyo 
guidelines [3]: 
• AC Grade I (mild) defined as acute cholecystitis in an otherwise 
healthy patient with mild local inflammatory changes and 
without organ dysfunction. Criteria for grade II or III not met. 
• AC Grade II (moderate) defined by any one of the following 
characteristics 
o Leukocytosis (>18,000 cells per mm3)  
o Palpable, tender mass in right upper quadrant 
o Symptom duration >72 hours 

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o Marked local inflammation (gangrenous or emphysematous 
cholecystitis, pericholecystic or hepatic abscess, biliary 
peritonitis)  
5. Pre-drainage imaging confirms sufficient stone-free space to allow 
AXIOSTM stent deployment and complete flange expansion 
6. 18 years of age or older 
7. Willing and able to comply with the study procedures and patient or 
legally authorized representative (LAR) must provide written 
informed consent form (ICF) to participate in the study 
Key Exclusion 
Criteria 
1. AC Grade III (severe) per Tokyo guidelines [3] defined by organ 
dysfunction in any one of the following systems: 
• Cardiovascular - Hypotension requiring administration of 
≥5μg/kg/min of dopamine or any dose of norepinephrine 
• Neurologic - Decreased level of consciousness 
• Respiratory - PaO2/FiO2 <300 
• Renal - Oliguria and Creatinine >2.0 mg/dl (>177 μmol/liter) 
• Hepatic - International normalized ratio >1.5 
• Hematologic - Platelet count <100,000/mm3 
2. Obvious signs on diagnostic imaging of perforated, extensive 
gangrenous or ischemic gallbladder [44, 45].   
3. Hepatic abscess 
4. Ascites 
5. Patients with abnormal coagulation or who require ongoing 
complete anticoagulation 
6. Bleeding diathesis 
7. History of surgical treatment of acute cholecystitis (e.g. 
cholecystectomy) 
8. Patients with a current percutaneous drainage 
9. Patients with a history of percutaneous gallbladder drainage without 
AC free period following percutaneous drainage removal   
10. Distance between gallbladder wall and duodenal or gastric wall 
>1cm by US (ultrasound) at the time of drainage 
11. Patients with intervening gastric varices or vessels within a one 
centimeter radius of the device insertion location 
12. Patients that have allergies or are sensitive to any of the device 
materials 
13. Patients with contraindications to use of electrical devices 

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14. Pregnancy 
15. Prisoners and other vulnerable populations 
Statistical Methods  
Statistical Test 
Method for the 
Primary 
Effectiveness 
Endpoint 
The analysis of the primary effectiveness endpoint is to compare the 
days to clinical resolution using an AXIOSTM Stent to a performance 
goal (PG). 
The null and alternative hypotheses for the primary effectiveness 
endpoint analysis are as follows: 
H0: μdays ≥ PG 
H1: μdays < PG 
where μdays is the mean days to clinical resolution for patients in the 
AXIOSTM Gallbladder Drainage Study and PG is a performance goal of 
3.5 days based on a literature review of percutaneous drainage studies. 
Sample Size 
Parameters 
This analysis of the primary effectiveness endpoint is to compare the 
observed days to clinical resolution for AXIOSTM stents from this study 
to a PG. 
• Expected AXIOSTM stent (test) mean days to clinical resolution 
= 2.35 days with standard deviation 2 days (point estimate of 
days to clinical resolution based on rates reported in literature 
[4] with median days to clinical response of 1 day, range 0 to 3 
days) 
• PG = 3.5 days (mean days to resolution for percutaneous GB 
drainage based on historical rates reported in literature [5]) 
• Test significance level (α) = 0.022 (1-sided) 
• Power (1-β) = 80.4% 
• Evaluable number of patients needed = 27 
• Expected rate of attrition = 10% 
• Enrolled number of patients = 30 
Success 
Criteria for the 
Primary 
Effectiveness 
Endpoint 
For the primary effectiveness endpoint of days to clinical resolution, 
testing will be performed as described below. The mean time to 
resolution and standard error of the mean will be estimated from a 
Kaplan-Meier analysis so that subjects for whom resolution is not 
obtained can be included in the analysis. 

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The estimated mean and standard error from the Kaplan-Meier analysis 
will be used to construct a one-sided 97.8% upper confidence bound of 
the mean.  If the upper 97.8% confidence bound of the mean days to 
clinical resolution for the AXIOS™ group is less than the performance 
goal of 3.5 days, the null hypothesis will be rejected in favor of the 
alternative hypothesis and the mean days to resolution for the AXIOS™ 
group will be considered to be significantly less than the performance 
goal of 3.5 days. 
Secondary 
Effectiveness 
Endpoint 
The null and alternative hypotheses for the secondary effectiveness 
endpoint are as follows: 
H0: πreint ≥ PG 
H1: πreint < PG 
where πreint is the rate of reintervention for patients in the AXIOSTM 
Gallbladder Drainage Study and PG is a performance goal of 46.2% 
based on reintervention rates associated with percutaneous drainage 
reported in literature [19, 41]. 
Sample Size 
Parameters 
This analysis of the secondary effectiveness endpoint is to compare the 
observed rate of reintervention for AXIOSTM stents from this study to a 
PG. 
• Expected AXIOSTM stent (test) rate of reintervention = 8.0%  
(point estimate of rate of reintervention based on historical rates 
reported in literature [19, 41]) 
• PG = 46.2% (rate of reintervention for percutaneous GB 
drainage based on historical rates reported in literature [19, 41]) 
• Test significance level (α) = 0.003 (1-sided) 
• Power (1-β) = 99% 
• Evaluable number of patients needed = 27 
• Expected rate of attrition = 10% 
• Enrolled number of patients = 30 
Success 
Criteria for the 
Secondary 
Effectiveness 
Endpoint 
For the secondary effectiveness endpoint of rate of reintervention, 
testing will be performed as described below. 
If the P value from the one-group binomial test comparing the rate of 
reintervention from the AXIOSTM stent to the performance goal is 
<0.003, the rate of reintervention for the AXIOSTM group will be 
concluded to be significantly less than the performance goal for the 
analysis set being tested.  This corresponds to the one-sided Clopper-
Pearson upper 99.7% confidence bound on the rate of reintervention for 
the AXIOSTM group being less than the performance goal of 46.2%. 

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Table of Contents 
1 
Introduction ....................................................................................................................16 
1.1 
Background .............................................................................................................16 
1.2 
Rationale for Study .................................................................................................20 
2 
Device Description ..........................................................................................................21 
2.1 
Device Use ..............................................................................................................21 
3 
Study Objective ...............................................................................................................22 
4 
Endpoints and Study Design ..........................................................................................22 
4.1 
Primary Effectiveness Endpoint ..............................................................................22 
4.2 
Secondary Effectiveness Endpoint ..........................................................................22 
4.3 
Additional Endpoints ..............................................................................................22 
4.4 
Study Design ...........................................................................................................23 
5 
Subject Selection .............................................................................................................25 
5.1 
Inclusion Criteria .....................................................................................................25 
5.2 
Exclusion Criteria....................................................................................................25 
6 
Subject Accountability ...................................................................................................26 
6.1 
Point of Enrollment .................................................................................................26 
6.2 
Withdrawal ..............................................................................................................26 
6.3 
Lost to Follow-Up ...................................................................................................27 
6.4 
Subject Status and Classification ............................................................................27 
6.5 
End of Study Definition ..........................................................................................28 
7 
Study Methods ................................................................................................................29 
7.1 
Data Collection .......................................................................................................29 
7.2 
Study Candidate Screening .....................................................................................30 
7.3 
Informed Consent ....................................................................................................30 
7.4 
Visit Schedule .........................................................................................................30 
7.5 
Scoring System .......................................................................................................34 
7.6 
Study Completion ...................................................................................................34 

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7.7 
Source Documents ..................................................................................................34 
8 
Statistical Considerations ..............................................................................................35 
8.1 
Primary Effectiveness Endpoint ..............................................................................35 
8.2 
Secondary Effectiveness Endpoint ..........................................................................36 
8.3 
Study Success Criteria.............................................................................................38 
8.4 
General Statistical Methods ....................................................................................38 
9 
Data Management ..........................................................................................................39 
9.1 
Data Collection, Processing, and Review ...............................................................39 
9.2 
Data Retention .........................................................................................................39 
10 Amendments ...................................................................................................................40 
11 Deviations ........................................................................................................................40 
12 Device/Equipment Accountability ................................................................................40 
13 Compliance ......................................................................................................................41 
13.1 Statement of Compliance ........................................................................................41 
13.2 Investigator Responsibilities ...................................................................................41 
13.3 Institutional Review Board/ Ethics Committee.......................................................43 
13.4 Sponsor Responsibilities .........................................................................................43 
13.5 Insurance .................................................................................................................44 
14 Monitoring .......................................................................................................................44 
15 Committees ......................................................................................................................44 
16 Potential Risks and Benefits ..........................................................................................45 
16.1 Anticipated Adverse Events and Anticipated Adverse Device Effects ..................45 
16.2 Risk Minimization Actions .....................................................................................45 
16.3 Anticipated Benefits ................................................................................................46 
16.4 Risk to Benefit Rationale ........................................................................................46 
17 Safety Reporting .............................................................................................................46 
17.1 Reportable Events by Investigational Site to Boston Scientific ..............................46 
17.2 Definitions and Classification .................................................................................47 

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17.3 Relationship to Study Device(s) .............................................................................48 
17.4 Investigator Reporting Requirements .....................................................................50 
17.5 Boston Scientific Device Deficiencies ....................................................................52 
17.6 Reporting to Regulatory Authorities / IRBs / ECs / Investigators ..........................52 
18 Informed Consent ...........................................................................................................52 
19 Suspension or Termination ............................................................................................54 
19.1 Premature Termination of the Study .......................................................................54 
19.2 Termination of Study Participation by the Investigator or Withdrawal of IRB/ EC 
Approval ..................................................................................................................54 
20 Requirements for Documentation and Subject Follow-up .........................................54 
20.1 Criteria for Suspending/Terminating a Study Center .............................................55 
21 Publication Policy ...........................................................................................................55 
22 Bibliography ....................................................................................................................56 
23 Abbreviations and Definitions .......................................................................................59 
24 Appendices ......................................................................................................................60 
24.1 AXIOSTM EUS-GBD with Comparison to PC (Windbladh et al 2009) .................60 
24.2 EUS-GBD VS. PTGBD ..........................................................................................61 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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1 Introduction  
1.1 
Background  
Acute cholecystitis is one of the most common complications of gallstone disease [7,8]. In 
patients affected by acute cholecystitis, percutaneous transhepatic drainage of the gallbladder 
(PT-GBD) using a thin plastic tube (catheter), that allows the bile to drain into a collection 
bag outside the body, is considered the standard of care when the patients are at high risk for 
cholecystectomy [9]. In these patients percutaneous cholecystostomy (PC) can act either as a 
bridging procedure to cholecystectomy or as a definitive treatment in those who are 
permanently medically unfit for surgery [10].  However, this procedure is associated with 
catheter migration, or dislodgement including inadvertent or intentional removal by patients, 
requiring numerous re-interventions [11-13] in order to reach clinical resolution of acute 
cholecystitis (average of 5.4 days) [5,46,47].  Additionally, percutaneous cholecystostomy is 
associated with a high rate of complications.  Bile leaks that could result in peritonitis, 
bleeding, pneumothorax, recurrent cholecystitis, and secondary infection are among the most 
common complications of percutaneous gallbladder drainage [4,14,15].  
The issues associated with percutaneous drainage, as described above, led physicians to 
develop an alternative procedure called endoscopic ultrasound-guided transmural gallbladder 
drainage (EUS-GBD).  EUS-GBD is non-surgical, endoscopic procedure, whereby a stent is 
placed in the gallbladder to allow bile to directly drain into the gastrointestinal tract. EUS-
GBD has the potential to eliminate some of the shortcomings of PC [2], and possibly 
ameliorate the quality of life in these high-risk, non-surgical patients by excluding the need 
for an external drain and reducing the number of procedural re-interventions.   
Historically EUS-GBD was first performed with small diameter plastic stents, and later with 
self-expanding metal stents (SEMS) that were designed for use in other indications and were 
not developed specifically for transmural placement.  Although such EUS-GBD methods 
provided many advantages associated with an internal drain, the complication rates were not 
optimal.     
More recently, lumen apposing metal stents (LAMS), such as the AXIOSTM Stent with 
Electrocautery Enhanced Delivery System, which was specifically designed for transmural 
placement and internal drainage between two organs, have started to be used for GB drainage 
in patients with acute cholecystitis.  The AXIOSTM system includes a silicone-covered, 
bilaterally flanged nitinol stent and an electrocautery enabled delivery system that allows 
one-step placement of the device without a need for ancillary procedures.  Nine (9) 
publications [4,16-23] representing 264 patients suggest that AXIOSTM has a low risk of 
procedure related mortality (3.0%) while offering the advantages of internal gallbladder 
drainage in the setting of acute cholecystitis (Appendix 24.1).   
Complications of PC, especially in critically ill, high-risk surgical patients, may contribute to 
higher morbidity than in patients treated with EUS-GBD; especially due to the high rate of 
re-interventions required.  This is documented in three head to head studies comparing the 
outcome of EUS-GBD using LAMS with that of PT-GBD (Appendix 24.2).  One of these 3 
publications does not explicitly state that AXIOSTM LAMS was used, although the figures in 

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this publication are suggestive thereof.  The overall complication rate is 24.7% for EUS-
GBD, versus 37.8% for PT-GBD (P-value 0.16) with procedure related mortality rates of 
2.9% for both procedures and clinical success rate of 93.2% for EUS-GBD, versus 89.4% for 
PT-GBD (P-value 0.50).  In addition to these studies, a large systematic review on PC, 
Winbladh et al, reports a 30-day mortality of 15.4% [6] compared to a rate of 16.9% in 
AXIOSTM.  The procedure related mortality of PC is 4.0% [6] versus 3.0% in AXIOSTM. 
These mortality rates are not statistically significant (exact P-value 0.57 and 0.37 for 30-day 
and procedure-related mortality, respectively).  It is critical to note that Winbladh et al 
separately reported biliary deaths, which also fall under ‘procedure mortality’ [6].  
Our proposed study aims to prospectively document the safety and effectiveness of the use of 
the AXIOSTM stent for EUS-GBD.  We anticipate it will demonstrate that transmural 
drainage with AXIOSTM, compared to historical percutaneous drainage, will result in faster 
resolution of acute cholecystitis, and possibly lower complication rates, thus possibly 
reducing the length of post procedural hospital stay.  The goal is to document that EUS-GBD 
using AXIOSTM may be a suitable treatment alternative for patients with acute cholecystitis 
who are at high risk or unsuitable for cholecystectomy. 
Acute Cholecystitis 
Acute cholecystitis, or inflammation of the gallbladder, is a common surgical condition 
[24,25].   This condition often develops over a period of hours, with symptoms that include 
right upper quadrant pain and tenderness, fever, chills, nausea, and vomiting. Cholecystitis is 
a well-recognized complication of cholelithiasis (gall stones).  When a stone becomes 
impacted in the cystic duct, blocking normal bile flow, it often causes inflammation of the 
gallbladder.  The inflammatory processes resulting from bile stasis then perpetuates mucosal 
damage within the gallbladder, which leads to fluid secretion and further inflammation.  If 
left untreated, bacterial infection, necrosis, and perforation of the gallbladder can occur.  
Thus, timely treatment with antibiotics and often cholecystectomy (removal of the 
gallbladder) is required.   
Cholecystectomy 
Currently, laparoscopic cholecystectomy is the gold standard of treatment for otherwise 
healthy patients with acute cholecystitis, and in these patients, this procedure is associated 
with a very low risk of morbidity and mortality [25,26].  However, there is an increased 
incidence of cholelithiasis with increasing age.  In the United States, the overall incidence of 
cholelithiasis is reported to be 7.9% for men and 16.6% in women.  However, the prevalence 
of gallbladder disease increases with age, beginning at 1.3% for men and 6.5% for women 
aged 20-29 and increasing to 25.3% of men and 33.1% of women between the ages of 60-74 
[25].  Incidence rates in other Western countries are similar (for example, in Italy, the 
incidence rate of gallbladder disease in men aged 20-29 is 2.3% while in women in the same 
age group the incidence is 7.4%, and these incidence rates rise to 19.4% for men and 31.6% 
for women over the age of 60) [25]. Additionally, in the indigenous populations in the 
Americas the incidence of gallstone disease is especially high, particularly in the Malpuche 
Indian population in Chile.  In this population, the incidence of gallbladder disease 
approaches 50% in women over 50 years of age [25]. This presents a dilemma for the 
treating physician, because for elderly patients or patients with other serious underlying 

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comorbidities, laparoscopic cholecystectomy can be associated with significant risk of 
morbidity (up to 41%) [27-29] and mortality (up to 19%) [6]. Thus, these patients are usually 
not considered for cholecystectomy.  In such patients, surgery is either delayed (which can 
increase the risk of eventual sepsis and death) or avoided altogether through the use of non-
surgical options for gallbladder drainage.  These non-surgical techniques can be used as 
either a bridge to surgery or as definitive treatment in patients who remain unfit for surgery. 
Percutaneous Cholecystostomy 
Percutaneous cholecystostomy is the most common and most studied non-surgical, second-
line procedure used to drain the gallbladder and relieve symptoms of cholecystitis.   
However, percutaneous cholecystostomy is associated with significant morbidity as well (up 
to 25%) [6], and mortality (up to 60%) [32]. Adverse events associated with an external 
gallbladder drainage tube can occur and may include post-procedure pain and discomfort, 
infection, and catheter dislodgement and migration [6,25]. Catheter migration, for example, 
has been shown to occur in up to 12% of percutaneous cholecystostomy cases [30-33], and 
other adverse events, including bile leaks, bleeding, and pneumothorax have been reported to 
occur in about 10% of patients [19,32,33].   
Endoscopic Gallbladder Drainage 
Recently, endoscopic techniques for managing acute cholecystitis in high-risk patients have 
gained popularity. Endoscopic techniques are thought to be advantageous because they allow 
avoidance of both surgery and the need to place an external drainage catheter and therefore 
may present fewer risks to the patient [34]. Endoscopic drainage techniques include the 
placement of nasogallbladder catheters and transpapillary gallbladder stenting [34,35]. In 
addition, EUS-guided transmural gallbladder drainage procedures have been developed as 
another alternative option for managing cholecystitis in patients who are not surgical 
candidates. Transmural drainage techniques have been performed with plastic stents, self-
expanding metal stents, and most recently, with novel lumen-apposing metal stents (LAMS) 
such as the AXIOSTM Stent with Electrocautery Enhanced Delivery System [4,34,36,37]. The 
AXIOSTM stent system includes a silicone-covered, bilaterally flanged nitinol stent and an 
electrocautery enabled delivery system that allows one-step placement of the stent.   
Historically when EUS-guided drainage of the gallbladder was first attempted, there was a 
concern over air or bile leakage into the peritoneal cavity as a complication of the procedure 
since insertion of a drain or plastic stent requires a fistula tract with a diameter larger than the 
diameter of the inserted drain or stent [16,38]. In the beginning, when plastic stents were 
used for drainage, their small diameter were associated with increased risk of clogging, 
leading physicians to use self-expanding metal stents (SEMS) [39] which tend to occlude less 
frequently; however, fully covered versions of SEMS showed a higher propensity to migrate 
[39]. Consequently improvement in stent technology continued and eventually led to the 
development of a lumen apposing metal stent (LAMS). LAMS were developed to overcome 
the risk of bile or enteric content leakage and stent migration, more specifically a large- 
caliber lumen apposing metal stent would be ideal for transmural cholecystostomy [38,40]. 
This type of stent reduces the risk of bile and gas leakage when adherence to the gallbladder 
wall is lacking or indeterminate [39], eliminating the restriction of LAMS for use only in 

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certain complications such as gallbladder empyema whereby the gallbladder wall is attached 
to the GI tract.  
Theoretically, the advantages to using LAMS such as AXIOSTM for transmural drainage of 
the gallbladder rather than other stents include the LAMS’ ability to oppose the gallbladder 
wall to the gastric or intestinal lumen, which can prevent possible bile leaks and also prevent 
migration of the stent.  The silicone covering of AXIOSTM may also prevent tissue ingrowth 
into the stent, which allows the stent to be removed more easily when needed.  Finally, the 
large lumen diameter of the AXIOSTM stent could allow passage of an endoscope into the 
gallbladder, which can then be used to perform lithotripsy to break up and remove remaining 
large gallstones residing in the gallbladder.   
AXIOSTM Stents for EUS-GBD, and Comparisons with PT-GBD 
In 9 published studies consisting of a total of 264 patients, gallbladder drainage was 
performed using a lumen apposing metal stent, AXIOSTM, to treat patients with acute 
cholecystitis [4,15-22].  In these 264 patients, there were two (0.76%) cases of peritonitis 
[17,19].  These studies have demonstrated that there is no longer a significant risk of 
developing peritonitis when treating patients with acute cholecystitis, nor gallbladder 
empyema, by EUS-GBD with LAMS.  In addition, these studies document that in cases in 
which the AXIOSTM stent was removed after resolution of acute cholecystitis, there were no 
serious late complications in patients with a follow-up period of up to 19 months [22]. 
However, in most cases the LAMS are left in place in order to reduce the number of 
interventions primarily due to the poor clinical condition of these patients.  A prospective 
study reports a mean indwell time of 364 days using AXIOSTM with no device related 
adverse events reported [16].   
Published evidence suggests that EUS-GBD, using lumen apposing metal stents, is a feasible 
and safe alternative to percutaneous gallbladder drainage (PT-GBD) choice for patients 
unsuitable for cholecystectomy.  Technical success (correct and successful placement of 
stent), clinical success (resolution of acute cholecystitis), post-procedural pain, the number of 
additional interventions needed to reach clinical success, and post-procedural hospital stay, 
are among some of the variables analyzed in studies comparing EUS-GBD with percutaneous 
gallbladder drainage [17,18,41].  None of these variables have shown to be unfavorable 
towards EUS-GBD.  An analysis of the data yields no statistical difference in the technical 
success and clinical success rate of EUS-GBD versus PC (96.6% vs 99.5%) and (93.2% vs 
89.4%) respectively, (p value 0.85 and 0.50), [Appendix 24.2].  However, there is a trend 
towards lower complications for EUS-GB vs. PC (24.7% vs. 37.8%).  Among all variables, 
the most prominent difference between the two procedures is in the average number of 
subjects that require additional interventions to resolve acute cholecystitis.  In the 
aforementioned studies only an overall average of 8.0% of EUS-GBD patients required 
additional interventions, such as additional endoscopic sessions or surgery, in comparison to 
an average of 46.2% of patients who were required to undergo further procedures post initial 
PT-GBD.  
To date there are 3 medical device reporting (MDR) submissions related either to the 
AXIOSTM stent or to the placement procedure that had fatal outcomes (1 Netherlands, 1 
China, 1 USA). The fatalities were due to aspiration pneumonia, bile peritonitis, and one 

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death that was possibly related to either pancreatic cancer or infection. Of these, two are 
included in the literature rates mentioned previously, namely bile peritonitis and aspiration 
pneumonia [15].  Death due to aspiration pneumonia, infection, and bile peritonitis have all 
been reported in PC literature [9,11,42,43], and bile leaks that could result in peritonitis are 
among the most common complications of percutaneous gallbladder drainage [4,14,15]; 
however they seem to occur less frequently with AXIOSTM (only two cases in literature 
report a patient developing bile peritonitis, one of which was successfully resolved) [17, 19]. 
Two studies [19,23] provide safety and efficacy data for AXIOSTM as well as parameters that 
are not recorded in most studies with AXIOSTM such as pain, and post procedural hospital 
stay.  Irani et al., a large retrospective study, examines outcomes of 45 subjects that 
underwent EUS-GBD using AXIOSTM and 45 subjects that underwent PT-GBD for acute 
cholecystitis in patients who were not surgical candidates [19].  Kaheleh et al classified their 
subjects as poor surgical candidates, based on either a diagnosis of unresectable cancer, or 
multiple co-morbities that precluded surgery [23].  Irani et al’s retrospective chart review 
included only patients who were deemed non-surgical candidates [19].  Their patient 
population was so critically ill, that 47% of their overall patient population passed away at 
follow up due to co-morbidities.  Malignancy was seen to be the most common co-morbidity 
in these two studies.  Both average pain scores and average number of patients hospitalized 
after the procedure were lower among AXIOSTM recipients versus those subjects who 
underwent PT-GBD.  On average the pain scores were 2.5 vs 6.5 (P<.05) and 9.9% of 
patients were hospitalized after receiving AXIOSTM vs 40.1% of patients were hospitalized 
after having a PC procedure [19].  Additionally, the number of repeat interventions per 
patient was lower at an average of 0.2 ± 0.4 in the EUS-GBD with AXIOSTM group vs 2.5 ± 
2.8 (P<.05), in the PT-GBD group.  This study concludes on an overall lower pain score, 
shorter hospital stay, and fewer repeat interventions for unsuitable surgical candidates 
undergoing EUS-GBD using AXIOSTM in comparison to those undergoing PT-GBD.  
Kahaleh et. al. reports on an international collaborative study of 35 patients who underwent 
EUS-GBD, 15 of which received the AXIOSTM stent [23].  An overall EUS-GBD technical 
success rate of 97.2%, clinical success rate of 92%, and a low re-intervention rate of 9.4%, 
suggest that EUS-GBD using LAMS might be a suitable alternative to PT-GBD in critically 
ill, non-surgical candidates suffering from multiple co-morbidities and/or advanced 
malignancies.   
1.2 
Rationale for Study  
In conclusion, data suggests that treatment of critically ill, non-surgical candidates with EUS-
GBD using the AXIOSTM stent results in clinical resolution of their acute cholecystitis 
coupled with a better quality of life resulting from shorter post-procedural hospital stay, 
lower post-procedural pain scores, and most notably – fewer post-procedural interventions.  
We propose a multi-center single arm prospective study in 30 patients to confirm the safety 
and efficacy of AXIOSTM for EUS-GBD in patients referred to percutaneous drainage of the 
gallbladder due to advanced age, anesthetic risk, significant co-morbidities and/or overall 
health. 

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2 Device Description 
Study devices are manufactured by Boston Scientific Corporation. The AXIOSTM Stent is a 
flexible, fully-covered self-expanding metal stent that is preloaded within the Electrocautery-
Enhanced Delivery System. The stent is made of nitinol and fully-covered with silicone. The 
AXIOSTM Stent and Electrocautery-Enhanced Delivery System is compatible with 
therapeutic echoendoscopes having a working channel of 3.7mm diameter or larger. The 
AXIOSTM Stent and Electrocautery-Enhanced Delivery System is intended for single use and 
is provided sterile using ethylene oxide. 
The study device is indicated for use to facilitate drainage of the biliary tract (which includes 
the gallbladder) outside of the U.S.  The study device is not approved for gallbladder 
drainage in the U.S. and will be considered investigational for this indication. Local Ethics 
Committee (EC)/Institutional Review Board (IRB)/Research Ethics Board (REB) approval 
will be obtained at each participating center. 
Study devices are labeled on the box and inner pouch and include information not limited to 
name of legal manufacturer, device name and dimensions, lot number and expiration date. 
Device labeling will be provided in local language(s) as per national regulations. Devices 
will be available in the following matrix: 
Table 2.0-1: Device Matrix 
Description 
Stent Size 
Delivery 
System 
Outer Diam. 
Lumen 
Diameter 
Saddle 
Length 
Overall 
Stent 
Length 
Flange 
Diameter 
Electrocautery 
Enhanced AXIOSTM 
System with 10x10 
Stent 
10 mm 
10 mm 
20 mm 
21 mm 
10.8Fr 
Electrocautery 
Enhanced AXIOSTM 
System with 15x10 
Stent 
15 mm 
10 mm 
20 mm 
24 mm 
10.8Fr 
 
For a detailed description of the AXIOSTM Stent and Electrocautery-Enhanced Delivery 
System, please reference the Investigator’s Brochure. 
2.1 
Device Use  
Current cleared indication for use:  The AXIOSTM Stent and Electrocautery Enhanced 
Delivery System is cleared in the US “for use to facilitate transgastric or transduodenal 
endoscopic drainage of symptomatic pancreatic pseudocysts ≥ 6cm in size and walled-off 
necrosis ≥ 6cm in size with ≥ 70% fluid content that are adherent to the gastric or bowel wall.  
Once placed, the AXIOSTM Stent functions as an access port allowing passage of standard 
and therapeutic endoscopes to facilitate debridement, irrigation and cystoscopy.  The stent is 
intended for implantation up to 60 days and should be removed upon confirmation of 

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pseudocyst or walled-off necrosis resolution” Outside the U.S., the AXIOSTM Stent and 
Electrocautery Enhanced Delivery System are indicated for use to facilitate transgastric or 
transduodenal endoscopic drainage of a pancreatic pseudocyst or walled-off necrosis with ≥ 
70% fluid content or to facilitate drainage of the biliary tract. 
Proposed expanded indication in the U.S. for this IDE study:  The AXIOSTM Stent and 
Electrocautery Enhanced Delivery System is intended for endoscopic ultrasound-guided 
transluminal gallbladder drainage in patients with acute cholecystitis who are at high risk or 
unsuitable for surgery. 
3 Study Objective 
To evaluate the safety and effectiveness of the AXIOSTM Stent with Electrocautery Enhanced 
Delivery System in the management of symptoms of acute cholecystitis as an alternative to 
percutaneous gallbladder drainage. 
4 Endpoints and Study Design 
4.1 
Primary Effectiveness Endpoint 
The primary effectiveness endpoint is time to resolution of acute cholecystitis which will be 
measured in days.  Resolution is defined as either a fever of less than 100.5°F, or at least a 4-
point decrease in the pain score, or WBC count less than 12,000/cc, with improvement in at 
least two of these categories without the deterioration of the third category.   
4.2 
Secondary Effectiveness Endpoint 
The secondary effectiveness endpoint is the rate of re-interventions including but not limited 
to stent migration, stent occlusion by GB stones, and luminal debridement. 
4.3 
Additional Endpoints 
1. Stent patency (ability to facilitate gallbladder drainage) defined indirectly as resolution of 
acute cholecystitis or, in the absence of resolution of acute cholecystitis, endoscopic 
observation of unobstructed AXIOSTM stent lumen 
2. Technical stent placement success: Successful stent placement, defined as transmural 
placement of the AXIOSTM stent with confirmed stent patency via (i) drainage visualized 
through the stent or fluoroscopically, or (ii) ability to endoscopically observe the inner 
walls of the gallbladder through the AXIOSTM stent  
3. Technical stent removal success: Successful stent removal, defined as ability to remove 
the AXIOSTM stent endoscopically without stent removal related serious adverse events 
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5. Number of cumulative hospital and ICU days from initial stent placement to resolution of 
symptoms of acute cholecystitis. 
4.4 
Study Design 
This study is a prospective, multi-center, single arm, consecutive series study. Treatment of 
up to 30 subjects will take place at up to 9 clinical centers. Subjects who meet all eligibility 
criteria will receive the AXIOSTM stent for up to 8 weeks stent indwell (unless medically 
recommended otherwise, i.e. the stent remain indwelling indefinitely) and 30-day follow-up 
after stent removal. 
 
 
 

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Figure 4.4-1: AXIOSTM for GB Drainage IDE Study Design 
 

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5 Subject Selection  
5.1 
Inclusion Criteria 
Subjects who meet all of the following criteria may be given consideration for inclusion in 
this clinical investigation, provided no exclusion criterion is met. 
1. Patients requiring intervention for the management of symptoms associated with acute 
cholecystitis 
2. Patients referred to percutaneous drainage of the gallbladder who are not surgical 
candidates because of advanced age, anesthetic risk, significant co-morbidities and/or 
overall health 
3. Eligible for endoscopic intervention 
4. Acute Cholecystitis, Grade I (mild) or II (moderate) per Tokyo guidelines [3]: 
• 
AC Grade I (mild) defined as acute cholecystitis in an otherwise healthy patient with 
mild local inflammatory changes and without organ dysfunction. Criteria for grade II 
or III not met. 
• 
AC Grade II (moderate) defined by any one of the following characteristics 
o Leukocytosis (>18,000 cells per mm3) 
o Palpable, tender mass in right upper quadrant 
o Symptom duration >72 hours 
o Marked local inflammation (gangrenous or emphysematous cholecystitis, 
pericholecystic or hepatic abscess, biliary peritonitis) 
5. Pre-drainage imaging confirms sufficient stone-free space to allow AXIOSTM stent 
deployment and complete flange expansion 
6. 18 years of age or older 
7. Willing and able to comply with the study procedures and patient or Legally authorized 
representative (LAR) must provide written informed consent form (ICF) to participate in 
the study 
5.2 
Exclusion Criteria 
Subjects who meet any one of the following criteria will be excluded from this clinical study. 
1. AC Grade III (severe) per Tokyo guidelines [3] defined by organ dysfunction in any one 
of the following systems: 
• Cardiovascular - Hypotension requiring administration of ≥5μg/kg/min of dopamine 
or any dose of norepinephrine 
• Neurologic - Decreased level of consciousness 
• Respiratory - PaO2/FiO2 <300 
• Renal - Oliguria and Creatinine >2.0 mg/dl (>177 μmol/liter) 
• Hepatic - International normalized ratio >1.5 
• Hematologic - Platelet count <100,000/mm3 

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2. Obvious signs on diagnostic imaging of perforated, extensive gangrenous or ischemic 
gallbladder [44, 45] 
3. Hepatic abscess 
4. Ascites 
5. Patients with abnormal coagulation or who require ongoing complete anticoagulation 
6. Bleeding diathesis 
7. History of surgical treatment of acute cholecystitis (e.g. cholecystectomy)  
8. Patients with a current percutaneous drainage 
9. Patients with a history of percutaneous gallbladder drainage without AC free period 
following percutaneous drainage removal   
10. Distance between gallbladder wall and duodenal or gastric wall > 1cm by US 
(ultrasound) at the time of drainage 
11. Patients with intervening gastric varices or vessels within a one centimeter radius of the 
device insertion location 
12. Patients that have allergies or are sensitive to any of the device materials 
13. Patients with contraindications to use of electrical devices 
14. Pregnancy 
15. Prisoners and other vulnerable populations 
6 Subject Accountability 
6.1 
Point of Enrollment 
A subject is considered “enrolled” after signing the study-specific Informed Consent Form 
(ICF). Subjects 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. 
6.2 
Withdrawal 
All subjects 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 subject 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 
subject’s permission to follow his/her status/condition outside of the clinical study. 
Reasons for withdrawal include physician discretion, subject choice to withdraw consent, 
loss to follow-up, and death. While study withdrawal is discouraged, subjects may withdraw 
from the study at any time, with or without reason, and without prejudice to further 
treatment. 

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All applicable case report forms up to the point of subject withdrawal must be completed. 
Additional data may no longer be collected after the point at which a subject 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 
subject withdrawal may be used. Withdrawn subjects will not be replaced. Subjects who 
withdraw from the study with the study stent in place will be followed per standard of care at 
the local institution. 
6.3 
Lost to Follow-Up 
A subject will be considered lost to follow-up if the subject remains unresponsive to 
communication after three documented attempts by study staff. (where possible, 3 telephone 
calls and, if necessary, a certified letter to the subject’s last known mailing address or local 
equivalent methods).  
However, for those subjects who remain unresponsive to communication while the stent 
remains in place, additional attempts will be made to request the subject’s return for study 
stent removal. These additional attempts may include increased telephone and written 
communications and contact with the subject’s primary care physician (if this 
communication is consented to in the Informed Consent Form). These contact attempts 
should be documented in the subject’s medical record or study file. 
Should the subject continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up. 
6.4 
Subject Status and Classification 
Enrolled Cohort 
A subject will be considered enrolled when the ICF is signed.   
Intent-to-treat Cohort 
The intent-to-treat (ITT) cohort is defined as all subjects who signed the ICF, were evaluated 
for inclusion/exclusion criteria, and in whom the endoscopic procedure was initiated.  
Subjects in the ITT cohort will be counted towards the enrollment ceiling and this cohort will 
be considered the primary analysis cohort. 
Treated Cohort 
The treated cohort is defined as all ITT subjects who have an AXIOSTM stent implanted for 
the purpose of gallbladder drainage.  
Per Protocol Cohort 
The per-protocol cohort is defined as all treated subjects for whom an AXIOSTM stent was 
implanted for the purpose of gallbladder drainage and met all eligibility criteria. 

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6.5 
End of Study Definition 
A clinical trial is considered completed when subjects are no longer being examined or the 
last subject’s last study visit has occurred.  

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7 Study Methods 
7.1 
Data Collection 
 
Procedure / 
Assessment 
Screening 
/ Baseline 
Visit 
Stent 
Placement 
Procedure 
Daily Acute 
Cholecystitis 
Assessment 
Visits (until 
discharge/  
resolution) 
Reintervention 
Visit  
(if applicable) 
Stent Removal 
Procedure:  
30 – 60 days post 
stent placement 
(prompted by 
resolved Acute 
Cholecystitis) 
 
72hr (+24hr) 
post Stent 
Removal 
Visit 
End of Study 
Visit* 
 
Informed 
Consent  
X 
 
 
 
 
 
 
Eligibility 
Criteria 
Assessment  
X 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
Imaging** 
X 
X (as 
applicable) 
X (as 
applicable) 
X (as 
applicable) 
 
 
 
Clinical 
Symptom 
Assessment 
X 
 
X 
X 
X 
 
X 
Pre-Procedure 
Subject 
Management 
X 
 
 
 
 
 
 
Stent Placement 
 
X 
 
X  
(as applicable) 
 
 
 
Documentation 
of any 
Reintervention 
 
 
X 
(as 
applicable) 
X  
X 
(as applicable) 
X(as 
applicable) 
X 
(as applicable) 
Labs 
X 
 
X 
X 
 (as applicable) 
 
 
X 
Current 
Medications*** 
X 
X 
X 
X 
X 
X 
X 
Stent Removal 
 
 
 
X 
 (as applicable) 
X 
 
 
Stent Patency 
Assessment 
 
X 
 
X 
 (as applicable) 
X 
 
 
Adverse Events 
Assessment 
 
X 
X  
X 
X  
X  
X 
Device Events 
Assessment 
 
X  
X 
X 
X 
 
 

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X – Required 
* 30 days (+/- 7 days) post stent removal or 90 days (+/- 14 days) post stent placement, whichever comes first, 
for patients with an AXIOS stent implanted; 30 days post-resolution of cholecystitis or 60 days post-index 
procedure, whichever comes first, for patients without an AXIOS stent implanted 
** Diagnostic imaging may include CT with contrast (unless contraindicated), transabdominal ultrasound, MRI, 
EUS, fluoroscopy with contrast, hepatobiliary scintigraphy (HIDA scan). 
*** all anticoagulants, antiplatelet agents, antibiotics, and pain medications 
7.2 
Study Candidate Screening 
No study-specific testing will be conducted until after the subject 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 subjects who are potential study 
candidates. Subjects 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 subject 
agrees to participate in the study and signs the ICF, the endoscopic ultrasound procedure may 
demonstrate that the subject is not a suitable candidate for the study.  
7.4 
Visit Schedule 
Screening / Baseline – Office/Hospital Visit: 
• Informed Consent 
• Eligibility Criteria Assessment 
• Demographics 
• Medical History 
• Pre-Procedure imaging within 5 days of drainage procedure (CT scan or transabdominal 
ultrasound) 
 
Note: If there has been a deterioration of the patient’s clinical status or worsening of the 
patients’ liver chemistry profile since the most recent pre-procedure imaging, then 
additional imaging is needed to evaluate if the patient is still a candidate for the 
intervention. 
 
• Current Medications 
• Pre-Procedure subject management including labs and clinical symptom assessment 
o Laboratory markers of inflammation or cholestasis 
 White Blood Cells (WBC)   
 
 Hemoglobin 
 
 
 
 Alanine aminotransferase  

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 Alkaline phosphatase 
 
 
 C reactive protein  
 
 Bilirubin  
 
 
Stent Placement Procedure – Office/Hospital Visit 
• Stent Placement 
• Imaging (as applicable) 
• Adverse Events Assessment / Device Event Assessment 
• Stent Patency Assessment  
• Current Medications 
 
Note: See DFU/ IB and Additional Procedural Notices below for procedure guidance. 
 
Additional Procedural Notices: 
o Procedure should be done with CO2 insufflation. 
o Choice of placement of stent between the duodenum and the gallbladder or between 
the stomach and the gallbladder is left at discretion of treating physician. 
o  Physicians will select the site of the AXIOSTM stent placement under EUS guidance 
and choose an access location where there is  
o adequate stone-free space within the gallbladder to deploy the flange 
o distance between the gallbladder and the stomach or duodenal lumen that 
does not exceed 10mm, the saddle length of the AXIOSTM stent 
o no intervening ascites, bowel, or fat, as identified by EUS   
o If a patient’s gallbladder has minimal stone burden and is free of large stones per 
baseline imaging, a 10mm lumen diameter AXIOSTM stent is recommended 
o If a patient’s gallbladder is packed with stones or large stones (1cm or larger in 
diameter) are present per baseline imaging, a 15mm lumen diameter AXIOSTM stent 
is recommended 
o Stones and/or sludge will be cleared using gentle basketing and irrigation through 
the stent if necessary, at the discretion of investigator 
o Placement of double pigtail plastic stent(s) through AXIOSTM will not be allowed in 
the study. 
o If placement of the AXIOSTM stent is attempted but no stent placement occurs, patient 
will be followed until 30 days after resolution of the cholecystitis, or 60 days after the 
index procedure, whichever comes first. The patient’s treatment will be at the 
discretion of the physician.  
Additional Notes:  
• In case of leakage of gallbladder contents resulting from inability to place the AXIOSTM 
stent after puncturing the gallbladder, a second attempt will be made by placing a needle 
through the original enteric puncture and re-accessing the gallbladder. Once a guidewire 
is placed, a new AXIOSTM stent would be placed. If a second attempt to place an 
AXIOSTM stent is not successful, transpapillary gallbladder drainage with a cystic duct 
stent or percutaneous drainage may also be considered. Endoscopic closure of the 

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puncture site in the duodenal wall or stomach wall using conventional endoscopic 
techniques is advised in case of complete misdeployment and loss of puncture site access.   
• 
In addition, percutaneous drainage of any fluid collection caused by the bile leak might 
be needed. If endoscopic and percutaneous approaches for the management of the 
gallbladder leak are unsuccessful, then surgery should be considered as soon as possible 
in order to avoid uncontrolled biliary peritonitis.Patients who receive an AXIOSTM stent 
and experience a procedural complication during stent placement will be followed until 
end of study, which is 30 days post stent removal or 90 days post stent placement 
(whichever comes first).   
• 
In case of leakage of gallbladder or GI tract contents causing inflammation or peritonitis 
after the AXIOSTM placement procedure, due to early stent migration or other causes the 
following complication management approaches should be considered in the following 
sequence: 
o Administration of antibiotics and monitoring of the patient 
o Endoscopic management (e.g. ERCP) 
o Percutaneous drainage  
o Surgical closure of the leak and gallbladder drainage  
• 
In case of AXIOSTM stent misplacement or migration, stent will be removed 
endoscopically.   
A CT scan with contrast (unless contraindicated) will be required in all of the above-mentioned 
circumstances.  
 
• The maximum stent indwell time of 30 to 60 days should be intended. This timeframe 
takes into consideration both the time needed for AC resolution as well as time 
needed for fistula formation, unless medically recommended.  
 
Daily Acute Cholecystitis Assessment Visit (until discharge/resolution) – Office/Hospital 
Visit 
• Clinical Symptom Assessment 
• Laboratory markers of inflammation or cholestasis 
o White Blood Cells (WBC)    
o Hemoglobin  
 
 
o Alanine aminotransferase 
 
o Alkaline phosphatase 
 
o C reactive protein 
 
 
o Bilirubin 
 
• Imaging (as applicable) 
Note: CT with contrast (unless contraindicated) required if acute cholecystitis is not 
resolving or not improving 
 
• Adverse Events Assessment / Device Event Assessment  

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• Documentation of any re-intervention, including luminal debridement (as applicable) 
• Current Medications 
Note: if discharged less than 72 hours post stent placement, a follow-up phone call may be 
done instead of an office visit and the following assessments will be made:  
• 
Clinical symptom assessment  
• 
Adverse Events Assessment / Device Event Assessment  
• 
Documentation of any re-intervention (as applicable)  
If acute cholecystitis is not resolving or not improving, a CT with contrast (unless 
contraindicated) will be required to rule out possible stent migration, perforation, 
cholangitis, sepsis or portal vein thrombosis. 
 
Re-intervention Visit (if applicable) 
• 
Documentation of any re-intervention, including luminal debridement 
• 
Imaging (as applicable) 
• 
Labs (as applicable) 
• 
Clinical Symptom Assessment 
• 
Stent Placement (as applicable) 
• 
Stent Removal (as applicable) 
• 
Stent Patency Assessment (as applicable) 
• 
Adverse Events Assessment/Device Event Assessment 
• 
Current Medications 
 
Stent Removal Procedure (30-60 days after stent placement in the setting of resolved 
acute cholecystitis unless medically recommended otherwise, i.e. the stent remain 
indwelling indefinitely) – Office/Hospital Visit 
• Stent Removal (prompted by resolution of acute cholecystitis) 
• Clinical Symptom Assessment  
• Adverse Events Assessment / Device Event Assessment  
• Documentation of any re-intervention (as applicable) 
• Stent Patency Assessment 
• Current Medications 
 
Note: After stent removal, the physician will continue to treat the patient per standard of 
practice. 
 
72 Hour (+24 hours) Post-Stent Removal Visit – Telephone Visit 
• Adverse Events Assessment  
• Documentation of any re-intervention (as applicable) 
• Current Medications 
 
End of Study Visit – Office/Hospital Visit  
30 days (+/- 7 days) post stent removal or 90 days (+/- 14 days) post stent placement 
(whichever comes first) for patients with an AXIOS stent implanted. 

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30 days post-resolution of the cholecystitis or 60 days post-index procedure (whichever 
comes first) for patients without an AXIOS stent implanted. 
 
• Clinical Symptom Assessment 
• Laboratory markers of inflammation or cholestasis 
o White Blood Cells (WBC)    
o Hemoglobin  
 
 
o Alanine aminotransferase 
 
o Alkaline phosphatase 
 
o C reactive protein 
 
 
o Bilirubin 
 
• Adverse Events Assessment  
• Documentation of any re-intervention (as applicable) 
• Current Medications 
 
Additional visits as needed 
• Adverse Event assessment / Device Event assessment 
• Labs (as applicable)  
• Imaging (as applicable) 
• Documentation of any re-intervention (as applicable) 
• Current Medications 
7.5 
Scoring System 
Patients will be asked to report on the average pain experienced since the prior visit when 
reporting pain via VAS (can be done verbally). 
7.6 
Study Completion 
Subjects will be followed for 30 days after stent removal. 
Additional visits may be conducted at the Investigator’s discretion in accordance with 
Adverse Event or Device Event data collection. A subject will be considered lost to follow-
up if the subject remains unresponsive to communication after three documented attempts by 
study staff. 
7.7 
Source Documents 
The Investigator/institution guarantees direct access to original source documents, including 
imaging documentation, by BSC personnel, their designees, and appropriate regulatory 
authorities. In lieu of original source documents, certified copies are required to be 
maintained.  A certified copy is a copy (irrespective of the type of media used) of the original 
record that has been verified (i.e., by a dated signature or by generation through a validated 
process) to have the same information, including data that describe the context, content, and 
structure, as the original.  

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8 Statistical Considerations 
8.1 
Primary Effectiveness Endpoint 
The primary effectiveness endpoint is the time to resolution of acute cholecystitis measured 
in days. 
Statistical Test Method: 
The analysis of the primary effectiveness endpoint is to compare the days to clinical 
resolution using an AXIOSTM stent to a performance goal (PG). 
The null and alternative hypotheses for the primary effectiveness endpoint analysis are as 
follows: 
H0: μdays ≥ PG 
H1: μdays < PG 
where μdays is the mean days to clinical resolution for patients in the AXIOSTM Gallbladder 
Drainage Study and PG is a performance goal of 3.5 days based on a literature review of 
percutaneous drainage studies. 
Sample Size Parameters: 
This analysis of the primary effectiveness endpoint is to compare the observed days to 
clinical resolution for AXIOSTM stents from this study to a PG. 
 
• Expected AXIOSTM stent (test) mean days to clinical resolution = 2.35 days with 
standard deviation 2 days (point estimate of days to clinical resolution based on 
historical rates reported in literature [4] with median days to clinical response of 1 
day, range 0 to 3 days) 
• PG = 3.5 days (mean days to resolution for percutaneous GB drainage based on 
historical rates reported in literature [5]) 
• Test significance level (α) = 0.022 (1-sided) 
• Power (1-β) = 80.4% 
• Evaluable number of patients needed = 27 
• Expected rate of attrition = 10% 
• Enrolled number of patients = 30 
 
The historical time to cholecystitis resolutions comes from 2 studies that report time to 
cholecystitis for EUS-GBD [4] and PC-GBD [5] (Table 8.1-1 and Appendix 24.2). 
 
Table 8.1-1. Time to Cholecystitis Resolution (in days) 
Reference 
EUS-GBD 
PC-GBD 
Irani (2015) [4] 
Median=1 (0-3) 
[N=15] 
N/A 
Kedia (2015) [5] 
N/A* 
Mean 4.6 
[N=43] 

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* Endoscopic drainage was not transmural and therefore was not included in the analysis 
 
Evaluation of the Primary Effectiveness Endpoint: 
The primary effectiveness endpoint will be evaluated for all ITT patients regardless of 
whether an AXIOSTM stent is implanted.  Patients for whom an AXIOSTM stent is implanted 
and cholecystitis is resolved will be considered a success for the endpoint and the days to 
resolution will be the date of resolution minus the date of the index procedure.  If a patient 
does not receive an AXIOSTM stent, the patient will be considered a failure for the endpoint 
with censoring at 60 days. If a subject receiving an AXIOSTM stent does not achieve 
resolution of cholecystitis for any reason, the patient will be treated as censored in the 
Kaplan-Meier analysis and the days to censoring will be the date of censoring minus the date 
of the index procedure.  The date of censoring will be the earliest of the following: 
• 
date of the patient receiving a cholecystectomy, 
• 
date of the patient dying, 
• 
date of last contact for patients who withdraw from the study or are lost to follow-up, or 
• 
date of the AXIOSTM stent removal. 
Success Criteria for the Primary Effectiveness Endpoint: 
For the primary effectiveness endpoint of days to clinical resolution, testing will be 
performed as described below. 
The mean time to resolution and standard error of the mean will be estimated from a Kaplan-
Meier analysis so that subjects for whom resolution is not obtained can be included in the 
analysis. 
 
The estimated mean and standard error from the Kaplan-Meier analysis will be used to construct 
a one-sided 97.8% upper confidence bound of the mean.  If the upper 97.8% confidence bound 
of the mean days to clinical resolution for the AXIOSTM group is less than the performance 
goal of 3.5 days, the null hypothesis will be rejected in favor of the alternative hypothesis and 
the mean days to resolution for the AXIOSTM group will be considered to be significantly 
less than the performance goal of 3.5 days. 
 
As a worst-case scenario sensitivity analysis, the Kaplan-Meier analysis for the primary 
effectiveness endpoint will be re-analyzed with 60 days as the time to censoring for all 
censored patients with time to censoring <60 days. 
8.2 
Secondary Effectiveness Endpoint 
The secondary effectiveness endpoint is the rate of re-interventions including but not limited 
to stent migration, stent occlusion by GB stones, and luminal debridement. 
 
Statistical Test Method: 
The analysis of the secondary effectiveness endpoint is to compare the rate of reintervention 
using an AXIOSTM stent to a PG. 

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The null and alternative hypotheses for the secondary effectiveness endpoint analysis are as 
follows: 
H0: πreint ≥ PG 
H1: πreint < PG 
where πreint is the rate of reintervention for patients in the AXIOSTM Gallbladder Drainage 
Study and PG is a performance goal of 46.2% based on reintervention rates associated with 
percutaneous drainage reported in literature [19, 41]. 
Sample Size Parameters: 
This analysis of the secondary effectiveness endpoint is to compare the observed rate of 
reintervention for AXIOSTM stents from this study to a PG. 
• Expected AXIOSTM stent (test) rate of reintervention = 8.0% (point estimate of rate of 
reintervention based on historical rates reported in literature [19, 41]) 
• PG = 46.2% (rate of reintervention for percutaneous GB drainage based on historical 
rates reported in literature [19, 41]) 
• Test significance level (α) = 0.003 (1-sided) 
• Power (1-β) = 99% 
• Evaluable number of patients needed = 27 
• Expected rate of attrition = 10% 
• Enrolled number of patients = 30 
 
The historical rates of reintervention come from 2 studies that compare the use of the 
AXIOSTM stent to percutaneous drainage [19, 41] (Table 8.2-1 and Appendix 24.2).  The 
combined rate of reintervention from the AXIOSTM arms is 8.0% (7/87) and for the 
percutaneous drainage arms is 46.2% (73/158). 
 
Table 8.2-1. Proportion of Patients With a Reintervention 
Reference 
EUS-GBD 
PC-GBD 
Irani (2017)* [19] 
3/45 (6.7%) 
45/45 (100.0%) 
Tyberg (2016)** [41] 
4/42 (9.5%) 
28/113 (24.8%) 
Total 
7/87 (8.0%) 
73/158 (46.2%) 
*Reintervention defined as any procedure required to replace, check, or remove the previously placed 
drain or stent 
**Reintervention defined as repeat procedure 
 
Success Criteria for the Secondary Effectiveness Endpoint: 
For the secondary effectiveness endpoint of rate of reintervention, testing will be performed 
as described below. 
If the P value from the one-group binomial test comparing the rate of reintervention from the 
AXIOSTM stent to the performance goal is <0.003, the rate of reintervention for the 
AXIOSTM group will be concluded to be significantly less than the performance goal for the 
analysis set being tested.  This corresponds to the one-sided Clopper-Pearson upper 99.7% 

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confidence bound on the rate of reintervention for the AXIOSTM group being less than the 
performance goal of 46.2%.  A sensitivity analysis (ie tipping point analysis) will be done to 
assess the robustness of results in the case where subjects do not have resolution of 
cholecystitis and no reintervention was required. 
8.3 
Study Success Criteria 
To declare overall study success, the null hypotheses for both the primary and secondary 
effectiveness endpoints must be rejected in favor of the alternative hypotheses.  Since the 
type I errors for the primary and secondary effectiveness endpoints are 2.2% and 0.3%, 
respectively, the type I error for the entire study is 2.5%. 
8.4 
General Statistical Methods 
Control of Systematic Error/Bias: 
All subjects who have met the inclusion/exclusion criteria and have signed the ICF will be 
eligible for enrollment in the study. 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. 
Data Analysis: 
Descriptive statistics will be presented for all ITT and Treated subjects.  The primary 
analysis for the primary and secondary effectiveness endpoints and the additional endpoints 
will be assessed for the ITT cohort. The primary and secondary effectiveness endpoints and 
the additional endpoints will also be assessed for the Treated cohort and for the PP cohort if 
the PP cohort is different from the Treated cohort. The mean, standard deviation, minimum, 
and maximum will be used to describe continuous variables; the median (and interquartile 
range) will be calculated where appropriate. Frequency tables will be used to summarize 
discrete variables. Proportions of subjects with adverse events and SAEs will be reported for 
the ITT cohort. 
Interim Analysis: 
No formal interim analyses are planned for this study. 
Subgroup Analysis: 
There are no planned subgroup analyses. 
Justification of Pooling: 
The analyses will be performed using data pooled across institutions. An assessment of the 
poolability of subjects across sites for the primary and secondary effectiveness endpoints will 
be made by fitting an analysis of variance (ANOVA) model and logistic regression model, 
respectively, with site as a factor and the primary endpoint as outcome. The following 
baseline variables will also be explored for pooling: region (US or outside US), 
acalculous/calculous cholecystitis, grade I or II cholecystitis, and prior sphincterotomy. 

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If the P value for the site from the pooling analysis is ≥0.15, it will be concluded that the 
primary endpoint is not different across sites, and the data can be pooled. If the P value for 
site from the ANOVA model is <0.15, site differences will be explored. 
 
Multivariable Analyses: 
No multivariable analyses are planned for this study. 
Changes to Planned Analyses: 
Any changes to the planned statistical analyses made prior to performing the analyses will be 
documented in an amended Statistical Analysis Plan. Changes from the planned statistical 
methods after performing the analysis will be documented in the clinical study report along 
with a reason for the deviation. 
9 Data Management 
9.1 
Data Collection, Processing, and Review 
Subject data will be recorded in a limited access secure electronic data capture (EDC) 
system. All changes made to the clinical data will be captured in an electronic audit trail and 
available for review by the sponsor or its representatives.  
The clinical database will reside on a production server hosted by Medidata EDC System. All 
changes made to the clinical data will be captured in an electronic audit trail and available for 
review by the sponsor or its representative. The associated RAVE software and database 
have been designed to meet regulatory compliance for deployment as part of a validated 
system compliant with laws and regulations applicable to the conduct of clinical studies 
pertaining to the use of electronic records and signatures. Database backups are performed 
regularly.  
The Investigator provides his/her electronic signature on the appropriate electronic case 
report forms (eCRFs) in compliance with local regulations. 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 Principal Investigator or his/her designee or Investigational site will maintain, at the 
investigative site, all essential study documents and source documentation that support the 
data collected on the study subjects in compliance with ICH/GCP guidelines.  Documents 
must be retained for at least 2 years after the last approval of a marketing application or until 

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at least 2 years have elapsed since the formal discontinuation of the clinical investigation of 
the product. These documents will be retained for a longer period of time by agreement with 
BSC or in compliance with other country/regional/local regulations. Sites are required to 
inform Boston Scientific in writing where paper or electronic files are maintained in case 
files are stored off site and are not readily available. 
10 Amendments  
If a protocol revision is necessary which affects the rights, safety or welfare of the subject or 
scientific integrity of the data, an amendment is required. Appropriate approvals (e.g., 
IRB/EC/FDA/CA) of the revised protocol must be obtained prior to implementation. 
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 subject. An investigator shall notify the sponsor and the 
reviewing IRB/EC of any deviation from the investigational plan to protect the life or 
physical well-being of a subject, and those deviations which affect the scientific integrity of 
the clinical investigation. Such notice shall be given as soon as possible, but no later than 5 
working days after the emergency occurred, or per prevailing local requirements, if sooner 
than 5 working days. 
All deviations from the investigational plan, with the reason for the deviation and the date of 
occurrence, 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, site re-training, or site 
discontinuation) will be put into place by the sponsor. 
12 Device/Equipment Accountability 
The investigational devices shall be securely maintained, controlled, and used only in this 
clinical study. Equipment shall be returned in the condition in which it was provided, 
reasonable wear and tear excepted. 
The sponsor shall keep records to document the physical location of all investigational 
devices from shipment of investigational devices from BSC equipment to the investigation 
sites until return or disposal. 
Records shall be kept by study personnel to document the physical location and conditions of 
storage of all investigational devices.  
The principal investigator or an authorized designee shall keep records documenting the 
receipt, use, return and disposal of the investigational devices, which shall include the 
following: 

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• Date of receipt 
• Identification of each investigational device (batch number or unique code) 
• Expiry date, as applicable 
• Date of use 
• Subject identification 
• Date on which the investigational device/piece of equipment was returned/explanted from 
subject, if applicable 
• Date of return (and number) of unused, expired, or malfunctioning investigational 
devices/equipment, if applicable. 
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, 21CFR 814.20 part 56, part 50 and part 812 or 813, 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. Also, the study shall 
not begin prior to issuance of the site Authorization to Enroll, as provided by the sponsor. 
Any additional requirements imposed by the IRB/EC/REB or regulatory authority shall be 
followed, if appropriate. 
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 clinical 
investigation plan, ISO 14155, ethical principles that have their origins in the Declaration of 
Helsinki, any conditions of approval imposed by the reviewing IRB/EC, and prevailing local 
and/or country laws and/or regulations, whichever affords the greater protection to the 
subject. 
The Principal Investigator’s responsibilities include, but are not limited to, the following:  
• Prior to beginning the study, sign the 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 

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interest, including financial, that may interfere with the conduct of the clinical study or 
interpretation of results. 
• Make no changes in or deviate from this protocol, except to protect the life and physical 
well-being of a subject in an emergency; document and explain any deviation from the 
approved protocol that occurred during the course of the clinical investigation. 
• Create and maintain source documents throughout the clinical study and ensure their 
availability with direct access during monitoring visits or audits; ensure that all clinical-
investigation-related records are retained per requirements. 
• Ensure the accuracy, completeness, legibility, and timeliness of the data reported to the 
sponsor in the CRFs and in all required reports. 
• Record, report, and assess (seriousness and relationship to the device/procedure, 
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) and 
potential Unanticipated Serious Adverse Device Event (USADE) or Unanticipated 
Adverse Event (UADE). 
• 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 
clinical research monitor or auditor and respond to questions during monitoring visits or 
audit(s). 
• Allow and support regulatory authorities and the IRB/EC when performing auditing 
activities. 
• Ensure that informed consent is obtained in accordance with this protocol and local 
IRB/EC requirements. 
• Provide adequate medical care to a subject during and after a subject’s participation in a 
clinical study in the case of adverse events, as described in the Informed Consent Form 
(ICF). 
• Inform the subject of the nature and possible cause of any adverse events experienced. 
• Inform the subject of any new significant findings occurring during the clinical 
investigation, including the need for additional medical care that may be required. 
• Provide the subject with well-defined procedures for possible emergency situations 
related to the clinical study, and make the necessary arrangements for emergency 
treatment. 
• Ensure that clinical medical records are clearly marked to indicate that the subject is 
enrolled in this clinical study. 

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• Ensure that, if appropriate, subjects enrolled in the clinical investigation are provided 
with some means of showing their participation in the clinical investigation, together with 
identification and compliance information for concomitant treatment measures (contact 
address and telephone numbers shall be provided). 
• Inform, with the subject’s approval or when required by national regulations, the 
subject’s personal physician about the subject’s participation in the clinical investigation. 
• Make all reasonable efforts to ascertain the reason(s) for a subject’s premature 
withdrawal from clinical investigation while fully respecting the subject’s rights. 
• Ensure that an adequate investigation site team and facilities exist and are maintained and 
documented during the clinical investigation. 
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 Principal Investigator is responsible for providing 
appropriate training, are competent to perform the tasks they have been delegated and 
adequate supervision of those to whom tasks are delegated. Where there is a sub investigator 
at a site, the sub investigator should not be delegated the primary supervisory responsibility 
for the site. The investigator is accountable for regulatory violations resulting from failure to 
adequately supervise the conduct of the clinical study.  
13.3 Institutional Review Board/ Ethics Committee 
The investigational site will obtain the written and dated approval/favorable opinion of the 
IRB/EC/REB for the clinical investigation before recruiting subjects and implementing all 
subsequent amendments, if required. 
A copy of the written IRB/EC/REB and/or competent authority (CA) approval of the 
protocol (or permission to conduct the study) and ICF, must be received by the sponsor 
before recruitment of subjects into the study and shipment of investigational 
product/equipment. Prior approval must also be obtained for other materials related to subject 
recruitment or which will be provided to the subject. 
Any amendment to the protocol will require review and approval by the IRB/EC/REB before 
the changes are implemented to the study.  All changes to the ICF will be IRB/EC/REB 
approved; a determination will be made regarding whether a new ICF needs to be obtained 
from subjects who provided consent, using a previously approved ICF. Annual IRB/EC/REB 
approval and renewals will be obtained throughout the duration of the study as required by 
applicable local/country laws or regulations or IRB/EC/REB requirements. Copies of the 
study reports and the IRB/EC/REB continuance of approval must be provided to the sponsor. 
13.4 Sponsor Responsibilities 
All information and data sent to BSC concerning subjects or their participation in this study 
will be considered confidential by BSC and will be kept confidential in accordance with all 

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applicable laws and regulations. Only authorized BSC personnel and/ or a BSC 
representative including, but not limited to Contract Research Organization (CRO), will have 
access to this information. Authorized regulatory personnel have the right to inspect and copy 
all records pertinent to this study. Study data collected during this study may be used by BSC 
for the purposes of this study, publication, and to support future research and/or other 
business purposes, such as overseeing and improving the performance of its device, new 
medical research and proposals for developing new medical products and procedures. All 
data used in the analysis and reporting of this study or shared with a third-party researcher 
will be without identifiable reference to specific subjects. 
Information received during the study will not be used to market to subjects; subject names 
will not be placed on any mailing lists or sold to anyone for marketing purposes. 
13.5 Insurance  
Where required by local/country regulation, proof and type of insurance coverage by BSC for 
subjects in the study will be obtained. 
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 Principal Investigator continues to have 
sufficient staff and facilities to conduct the study safely and effectively. The Principal 
Investigator/institution guarantees direct access to original source documents by BSC 
personnel, their designees, and appropriate regulatory authorities. 
The study may also be subject to a quality assurance audit by BSC or its designees, as well as 
inspection by appropriate regulatory authorities. It is important that the Principal Investigator 
and relevant study personnel are available during on-site monitoring visits or audits and that 
sufficient time is devoted to the process. 
15 Committees 
An independent data review (IDR) board comprised of physician experts in surgery, 
interventional radiology, and gastroenterological endoscopy not participating in the clinical 
study and with no affiliation with BSC, will provide external oversight and review for 
potential safety concerns.  
During the course of the clinical study, the IDR board will periodically review aggregate 
safety data to monitor for the incidence of major adverse events and other trends. They will 
assess the AEs that are reported as Serious AEs that are unrelated, unlikely related, possibly 
related, probably related or related to the AXIOSTM stent or the AXIOSTM stent placement or 
removal procedures. The IDR will also review the incidence of such AEs.   

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Any IDR recommendations for clinical study modification or termination because of 
concerns over subject safety or issues relating to data monitoring or quality control will be 
submitted in writing to BSC for consideration. 
16 Potential Risks and Benefits 
16.1 Anticipated Adverse Events and Anticipated Adverse Device Effects  
Possible Adverse Events associated with the use of the AXIOSTM Stent and Electrocautery- 
Enhanced Delivery System may include those often associated with any endoscopic 
procedure. These complications include: 
• Anesthesia complications 
• Improper AXIOS Stent placement; incomplete deployment; stent migration into the 
gallbladder or, GI tract; separation of coating material from stent; stent fracture; 
coating material wear; coating material failure; puncture of coating material 
• Tissue ingrowth or overgrowth leading to difficulty or a failure to remove stent 
• Stent dislodgement 
• Adverse reaction to implant materials and/or delivery system (e.g., abdominal or back 
pain, nausea, infection, fever, chronic inflammation or foreign body reaction) 
• Minor or excessive bleeding requiring intervention 
• Leakage of gallbladder or GI tract contents causing inflammation or peritonitis 
• Stent occlusion 
• Local infection at the implant site 
• Tissue damage during stent implantation and/or removal 
• Ulceration or erosion of mucosal or organ wall linings 
• Pneumoperitoneum 
• Sepsis (bacterial, endotoxin or fungal) 
• Perforation 
• Surgical intervention (endoscopy, transfusion or surgery) 
• Persistent connection to the gallbladder after removal (fistula) 
• Unintended electrical shock, muscle stimulation or burns 
• Cardiac arrhythmia or arrest 
• Death 
16.2 Risk Minimization Actions 
Additional risks may exist. Risks can be minimized through compliance with this protocol, 
performing procedures in the appropriate hospital environment, adherence to subject 
selection criteria, close monitoring of the subject's physiologic status during research 

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procedures and/or follow-ups and by promptly supplying BSC with all pertinent information 
required by this protocol. 
16.3 Anticipated Benefits 
Subjects may not receive any benefit from participating in this study. However, medical 
science and future subjects may benefit from this study.  
16.4 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 subjects is required as outlined in the protocol. 
17 Safety Reporting 
17.1 Reportable Events by Investigational Site to Boston Scientific 
It is the responsibility of the investigator to assess and report to BSC any event which occurs 
in any of following categories: 
• All Adverse Events 
• All Serious Adverse Events 
• All Investigational Device Deficiencies  
• Unanticipated Adverse Device Effects/ Unanticipated Serious Adverse Device 
Effects* 
• New findings/updates in relation to already reported events 
* BSC Medical Safety will be responsible for all UADE/USADE assessments.  
Unanticipated means the effect, problem, or death is not previously identified in nature, 
severity, or degree of incidence in the investigational plan or application, investigator’s 
brochure, DFU/IFU, informed consent or other risk documents. 
When possible, the medical diagnosis should be reported as the Event Term instead of 
individual symptoms. 
If it is unclear whether or not an event fits one of the above categories, or if the event cannot 
be isolated from the device or procedure, it should be submitted as an adverse event and/or 
device deficiency. 
Any AE event required by the protocol, experienced by the study subject after informed 
consent and once considered enrolled in the study (as defined in study subject classification 
section), whether during or subsequent to the procedure, must be recorded in the eCRF. 
Underlying diseases are not reported as AEs unless there is an increase in severity of 
frequency during the course of the investigation. Death should not be recorded as an AE, but 

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should only be reflected as an outcome of ONE (1) specific SAE (see Table 17.2-1 for AE 
definitions). 
Refer to Section 16 for the known risks associated with the study device(s). 
17.2 Definitions and Classification 
Adverse event definitions are provided in Table 17.2-1. Administrative edits were made on 
the definition of serious adverse event from ISO 14155 and MEDDEV 2.7/3 for clarification 
purposes. 
 
Table 17.2-1: Safety Definitions 
Term 
Definition 
Adverse Event (AE) 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
 
 
Any untoward medical occurrence, unintended disease or injury, or any 
untoward clinical signs (including an abnormal laboratory finding) in 
subjects, users or other persons, whether or not related to the 
investigational medical device.  
 
NOTE 1: This includes events related to the investigational medical 
device or comparator. 
NOTE 2: This definition includes events related to the procedures 
involved. 
NOTE 3: For users or other persons, this definition is restricted to events 
related to the investigational medical device.  
Adverse Device Effect (ADE) 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
Adverse event related to the use of an investigational medical device. 
 
NOTE 1: This includes any adverse event resulting from insufficiencies 
or inadequacies in the instructions for use, the deployment, the 
implantation, the installation, the operation, or any malfunction of the 
investigational medical device. 
NOTE 2: This definition includes any event resulting from use error or 
intentional abnormal use of the investigational medical device. 
Serious Adverse Event (SAE) 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
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. 
•  

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Table 17.2-1: Safety Definitions 
Term 
Definition 
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 
 
Ref: MEDDEV 2.7/3  
Adverse device effect that has resulted in any of the consequences 
characteristic of a serious adverse event. 
 
Unanticipated Adverse Device 
Effect (UADE) 
 
Ref: 21 CFR Part 812 
 
 
Any serious adverse effect on health or safety or any life-threatening 
problem or death caused by, or associated with, a device, if that effect, 
problem, or death was not previously identified in nature, severity, or 
degree of incidence in the investigational plan or application (including a 
supplementary plan or application), or any other unanticipated serious 
problem associated with a device that relates to the rights, safety, or 
welfare of subjects.   
Unanticipated Serious Adverse 
Device Effect (USADE) 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
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 
 
Ref: MEDDEV 2.7/3  
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. 
Abbreviations: EC=Ethics Committee; IRB=Institutional Review Board 
 
Refer to Section 16 for the known risks associated with the study device(s). 
17.3 Relationship to Study Device(s) 
The Investigator must assess the relationship of the AE to the study device, study stent 
placement procedure, and study stent removal procedure. See criteria in Table 17.3-1:  

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Table 17.3-1: 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 re-introduction 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. 
Possibly Related 
The relationship with the use of the investigational device is weak but cannot be 
ruled out completely. Alternative causes are also possible (e.g. an underlying or 
concurrent illness/ clinical condition or/and an effect of another device, drug or 
treatment). Cases were relatedness cannot be assessed or no information has been 
obtained should also be classified as possible. 
Probably Related 
 
 
The relationship with the use of the investigational device seems relevant and/or 
the event cannot be reasonably be 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 
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Table 17.3-1: Criteria for Assessing Relationship of Study Device or Procedure to 
Adverse Event 
Classification 
Description 
- the discontinuation of medical device application (or reduction of the level of 
activation/exposure) and re-introduction 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. 
17.4 Investigator Reporting Requirements 
The communication requirements for reporting to BSC are as shown in Table 17.4-1. 
Table 17.4-1: Investigator Reporting Requirements 
Event Classification 
Communication Method  
Communication Timeline (Pre-Market Studies) 
(MEDDEV 2.7/3):  
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 
Provide all relevant source 
documentation (de-
identified/pseudonymized) 
for reported event upon 
request of the sponsor 
• At request of sponsor 
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 (de-
identified/pseudonymized) 
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 

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Table 17.4-1: Investigator Reporting Requirements 
Event Classification 
Communication Method  
Communication Timeline (Pre-Market Studies) 
(MEDDEV 2.7/3):  
CLINICAL INVESTIGATIONS: SERIOUS ADVERSE EVENT 
REPORTING UNDER DIRECTIVES 90/385/EEC AND 
93/42/EEC) 
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 
Provide all relevant source 
documentation (de-
identified/pseudonymized) 
for reported event 
• At request of sponsor 
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 
• At sponsor request 
Provide all relevant source 
documentation (de-
identified/pseudonymized) 
for reported event 
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. 

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17.5 Boston Scientific Device Deficiencies 
All device deficiencies (including but not limited to failures, malfunctions, user 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 
subject’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 Device Deficiency that might have led to a serious adverse event if a) suitable action 
had not been taken or b) intervention had not been made or c) if circumstances had been less 
fortunate is considered a reportable event. 
17.6 Reporting to Regulatory Authorities / IRBs / ECs / Investigators 
BSC is responsible for reporting adverse event information to all participating 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. 
18 Informed Consent 
Subject participation in this clinical study is voluntary.  Informed Consent is required from 
each subject or his/her legally authorized representative. The Investigator is responsible for 
ensuring that Informed Consent is obtained prior to the use of any investigational devices, 
study-required procedures and/or testing, or data collection.  
The obtaining and documentation of Informed Consent must be in accordance with the 
principles of the Declaration of Helsinki, ISO 14155, any applicable national regulations, and 
local Ethics Committee and/or Regulatory authority, as applicable. The ICF must be accepted 
by BSC or its delegate (e.g. CRO), and approved by the site’s IRB/EC, or central IRB, if 
applicable. 
Boston Scientific will provide a study-specific template of the ICF to investigators 
participating in this study. The ICF template may be modified to meet the requirements of the 
investigative site’s IRB/EC.  Any modification requires acceptance from BSC prior to use of 
the form.  The ICF must be in a language understandable to the subject and if needed, BSC 
will assist the site in obtaining a written consent translation. Translated consent forms must 
also have IRB/EC approval prior to their use.  Privacy language shall be included in the body 
of the form or as a separate form as applicable.   

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The process of obtaining Informed Consent shall: at a minimum include the following steps, 
as well as any other steps required by applicable laws, rules, regulations and guidelines: 
• be conducted by the Principal Investigator or designee authorized to conduct the 
process,  
• include a description of all aspects of the clinical study that are relevant to the 
subject’s decision to participate throughout the clinical study, 
• avoid any coercion of or undue influence of subjects to participate, 
• not waive or appear to waive subject’s legal rights, 
• use native language that is non-technical and understandable to the subject or his/her 
legal representative, 
• provide ample time for the subject to consider participation and ask questions if 
necessary, 
• ensure important new information is provided to new and existing subjects 
throughout the clinical study.  
The ICF shall always be signed and personally dated by the subject or legal representative 
competent to sign the ICF under the applicable laws, rules, regulations and guidelines and by 
the investigator and/or an authorized designee responsible for conducting the informed 
consent process. If a legal representative signs, the subject shall be asked to provide informed 
consent for continued participation as soon as his/her medical condition allows. The original 
signed ICF will be retained by the site and a copy of the signed and dated document and any 
other written information must be given to the person signing the form.  
Failure to obtain subject consent will be reported by BSC to the applicable regulatory 
authority according to their requirements (e.g., FDA requirement is within 5 working days of 
learning of such an event). Any violations of the informed consent process must be reported 
as deviations to the sponsor and local regulatory authorities (e.g. IRB/EC), as appropriate. 
If new information becomes available that can significantly affect a subject's future health 
and medical care, that information shall be provided to the affected subject(s) in written form 
via a revised ICF or, in some situations, enrolled subjects may be requested to sign and date 
an addendum to the ICF. In addition to new significant information during the course of a 
study, other situations may necessitate revision of the ICF, such as if there are amendments 
to the applicable laws, protocol, a change in Principal Investigator, administrative changes, or 
following annual review by the IRB/EC. The new version of the ICF must be approved by 
the IRB/EC. Acceptance by Boston Scientific is required if changes to the revised ICF are 
requested by the site’s IRB/EC. The IRB/EC will determine the subject population to be re-
consented. 

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19 Suspension or Termination 
19.1 Premature Termination of the Study 
Boston Scientific reserves the right to terminate the study at any stage but intends to exercise 
this right only for valid scientific or administrative reasons and reasons related to protection 
of subjects.  Investigators, associated IRBs/ECs, and regulatory authorities, as applicable, 
will be notified in writing in the event of study termination. 
19.1.1 Criteria for Premature Termination of the Study 
Possible reasons for premature study termination include, but are not limited to, the 
following. 
• The occurrence of unanticipated adverse device effects that present a significant or 
unreasonable risk to subjects enrolled in the study. 
• An enrollment rate far below expectation that prejudices the conclusion of the study.  
• A decision on the part of Boston Scientific to suspend or discontinue development of the 
device. 
19.2 Termination of Study Participation by the Investigator or Withdrawal of IRB/ 
EC Approval 
Any investigator, or IRB/ EC/ REB or regulatory authority may discontinue participation in 
the study or withdraw approval of the study, respectively, with suitable written notice to 
Boston Scientific. Investigators, associated IRBs/ECs, and regulatory authorities, as 
applicable, will be notified in writing in the event of these occurrences. 
20 Requirements for Documentation and Subject Follow-up 
In the event of premature study termination a written statement as to why the premature 
termination has occurred will be provided to all participating centers by Boston Scientific. 
The IRB/EC/REB and regulatory authorities, as applicable, will be notified. Detailed 
information on how enrolled Subject will be managed thereafter will be provided.  
In the event an IRB/EC/REB terminates participation in the study, participating investigators, 
associated IRBs/ECs/REBs, and regulatory authorities, as applicable, will be notified in 
writing. Detailed information on how enrolled subjects 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 subjects will be managed 
thereafter will be provided by Boston Scientific. 

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The investigator must return all documents and investigational product to Boston Scientific, 
unless this action would jeopardize the rights, safety, or welfare of the subjects. 
20.1 Criteria for Suspending/Terminating a Study Center 
Boston Scientific reserves the right to stop the inclusion of subjects at a study center at any 
time after the study initiation visit if no subjects 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 subjects. The IRB/EC and regulatory authorities, as 
applicable, should be notified. All subjects 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. 
21 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 adheres to the Contributorship Criteria set forth in the Uniform Requirements of 
the International Committee of Medical Journal Editors (ICMJE; http://www.icmje.org). In 
order to ensure the public disclosure of study results in a timely manner, while maintaining 
an unbiased presentation of study outcomes, BSC personnel may assist authors and 
investigators in publication preparation provided the following guidelines are followed. 
• All authorship and contributorship requirements as described above must be followed. 
• BSC involvement in the publication preparation and the BSC Publication Policy should 
be discussed with the Coordinating Principal Investigator(s) and/or Executive/Steering 
Committee at the onset of the project. 
• The First and Senior authors are the primary drivers of decisions regarding publication 
content, review, approval, and submission.  
• The data, analytic methods, and study materials for this clinical trial may be made 
available to other researchers in accordance with the Boston Scientific Data Sharing 
Policy (https://www.bostonscientific.com/).  
 
 
 

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22 Bibliography 
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6. Winbladh A, Gullstrand P, Svanvik J, Sandstrom P. Systematic review of 
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13. Súbtil, José Carlos, María Teresa Betes, and Miguel Muñoz-Navas. "Gallbladder 
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15. Andrén-Sandberg, Åke, et al. "Complications and late outcome following percutaneous 
drainage of the gallbladder in acute calculous cholecystitis." Digestive surgery 18.5 
(2001): 393-398. 
16. Walter D, Teoh AY, Itoi T, Perez-Miranda M, Larghi A, Sanchez-Yague A, Siersema 
PD, Vleggaar FP. EUS-guided gall bladder drainage with a lumen-apposing metal stent: a 
prospective long-term evaluation. Gut 2016; 65: 6-8. 
17. Teoh, Anthony Yuen Bun, et al. "Endoscopic ultrasound-guided gallbladder drainage 
reduces adverse events compared with percutaneous cholecystostomy in patients who are 
unfit for cholecystectomy." Endoscopy 49.02 (2017): 130-138. 
18. de la Serna-Higuera C, Perez-Miranda M, Gil-Simon P, Ruiz-Zorrilla R, Diez-Redondo 
P, Alcaide N, Sancho-del Val L, Nunez-Rodriguez H. EUS-guided transenteric 
gallbladder drainage with a new fistula-forming, lumen-apposing metal stent. 
Gastrointest Endosc 2013; 77: 303-308. 
19. Irani, Shayan, et al. "Similar Efficacies of Endoscopic Ultrasound Gallbladder Drainage 
with a Lumen-Apposing Metal Stent vs Percutaneous Transhepatic Gallbladder Drainage 
for Acute Cholecystitis." Clinical Gastroenterology and Hepatology (2017). 
20. Dollhopf, M., Larghi, A., Will, U., et al. EUS-guided gallbladder drainage in patients 
with acute cholecystitis and high surgical risk using an electrocautery-enhanced lumen-
apposing metal stent device. Gastrointestinal Endoscopy. 2017. 
21. Law, Ryan, et al. "Conversion of Percutaneous Cholecystostomy to Internal Transmural 
Gallbladder Drainage Using an Endoscopic Ultrasound–Guided, Lumen-Apposing Metal 
Stent." Clinical Gastroenterology and Hepatology 14.3 (2016): 476-480. 
22. Itoi, Takao, et al. "Clinical evaluation of a novel lumen-apposing metal stent for 
endosonography-guided pancreatic pseudocyst and gallbladder drainage (with videos)." 
Gastrointestinal endoscopy 75.4 (2012): 870-876. 
23. Kahaleh, Michel, et al. "International collaborative study on EUS-guided gallbladder 
drainage: Are we ready for prime time?." Digestive and Liver Disease 48.9 (2016): 1054-
1057. 
24. Lee SS, Park DH, Hwang CY, Ahn CS, Lee TY, Seo DW, Lee SK, Kim MW. EUS-
guided transmural cholecystostomy as rescue management for acute cholecystitis in 
elderly or high-risk patients: a prospective feasibility study. Gastrointest Endosc 2007; 
66: 1008-1012. 
25. Shaffer EA.  Epidemiology and risk factors for gallstone disease:  has the paradigm 
changed in the 21st century?  Curr Gastro                                                                                                       
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26. Keus F, Gooszen HG, van Laarhoven CJ. Open, small-incision, or laparoscopic 
cholecyctomy for patients with symptomatic cholecystolithiasis. An overview of 
Cochrane Hepato-Biliary Group reviews. Cochrane Database Syst Rev 2010: CD008318. 
27. Decker G, Goergen M, Philippart P, Mendes da Costa P. Laparoscopic cholecystectomy 
for acute cholecystitis in geriatric patients. Acta Chir Belg 2001; 101: 294-299. 

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28. Kirshtein B, Bayme M, Bolotin A, Mizrahi S, Lantsberg L. Laparoscopic 
cholecystectomy for acute cholecystitis in the elderly: is it safe? Surg Laparosc Endosc 
Percutan Tech 2008; 18: 334-339.  
29. Kortram K, de Vries Reilingh TS, Wiezer MJ, van Ramshorst B, Boerma D. 
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30. Kalloo AN, Thuluvath PJ, Pasricha PJ. Treatment of high-risk patients with symptomatic 
cholelithiasis by endoscopic gallbladder stenting. Gastrointest Endosc 1994; 40: 608-610. 
31. Johlin FC, Jr., Neil GA. Drainage of the gallbladder in patients with acute acalculous 
cholecystitis by transpapillary endoscopic cholecystotomy. Gastrointest Endosc 1993; 39: 
645-651. 
32. England RE, McDermott VG, Smith TP, Suhocki PV, Payne CS, Newman GE. 
Percutaneous cholecystostomy: who responds? AJR Am J Roentgenol 1997; 168: 1247-
1251. 
33. McGahan JP, Lindfors KK. Percutaneous cholecystostomy: an alternative to surgical 
cholecystostomy for acute cholecystitis? Radiology 1989; 173: 481-485. 
34. Anderloni A, Buda A, Vieceli F, Khashab MA, Hassan C, Repici A. Endoscopic 
ultrasound-guided transmural stenting for gallbladder drainage in high-risk patients with 
acute cholecystitis: a systematic review and pooled analysis. Surg Endosc 2016. 
35. Patil R, Ona MA, Papafragkakis C, Anand S, Duddempudi S. Endoscopic ultrasound-
guided placement of the lumen-apposing self-expandable metallic stent for gallbladder 
drainage: a promising technique. Ann Gastroenterol 2016; 29: 162-167. 
36. Khashab MA, Van der Merwe S,  et al, Prospective international multicenter study on 
endoscopic ultrasound-guided biliary drainage for patients with malignant distal biliary 
obstruction after failed endoscopic retrograde cholangiopancreatography. Endosc Int 
Open 2016; 4: E487-496. 
37. Kunda R, Perez-Miranda M, Will U, Ullrich S, Brenke D, Dollhopf M, Meier M, Larghi 
A. EUS-guided choledochoduodenostomy for malignant distal biliary obstruction using a 
lumen-apposing fully covered metal stent after failed ERCP. Surg Endosc 2016. 
38. Yeung, Baldwin, and Anthony Yuen Bun Teoh. "Endoscopic Management of Gallbladder 
Stones: Can We Eliminate Cholecystectomy?" Current gastroenterology reports 18.8 
(2016): 1-6. 
39. Weilert, Frank, and Kenneth F. Binmoeller. "Specially designed stents for translumenal 
drainage." Gastrointestinal Intervention 4.1 (2015): 40-45. 
40. Xu Z, Wang L, Zhang N, et al. Chemical ablation of the gallbladder: clinical application 
and long-term observations. Surg Endosc. 2005;19:693–6 
41. Tyberg, Amy, et al. "EUS-guided Versus Percutaneous Gallbladder Drainage: Isn't It 
Time to Convert?." Journal of Clinical Gastroenterology (2017). 

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42. Gingrich, Richard A., et al. "Cholecystostomy in acute cholecystitis: Factors influencing 
morbidity and mortality." The American Journal of Surgery 116.2 (1968): 310-315. 
43. Atar, E., et al. "Percutaneous cholecystostomy in critically ill patients with acute 
cholecystitis: complications and late outcome." Clinical radiology 69.6 (2014): e247-
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44. Chang, Wei-Chou, et al. "CT findings for detecting the presence of gangrenous ischemia 
in cholecystitis." American Journal of Roentgenology 207.2 (2016): 302-309. 
45. Bennett, Genevieve L., et al. "CT findings in acute gangrenous cholecystitis." American 
Journal of Roentgenology 178.2 (2002): 275-281. 
46. Jang, Won Seok, et al. "Outcome of conservative percutaneous cholecystostomy in high-
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23 Abbreviations and Definitions  
Acronym          Definition 
AC 
Acute Cholecystitis 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
ASADE 
Anticipated Serious Adverse Device Effect 
CA 
Competent Authority 
CE 
Conformité Européene 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
CT 
Computerized Tomography 
EC 
Ethics Committee 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
ERCP 
Endoscopic Retrograde Cholangiopancreatography 
EUS 
Endoscopic Ultrasound 
EUS-GBD 
Endoscopic Ultrasound Gallbladder Drainage 
FDA 
Food and Drug Administration 
GB 
Gallbladder 
GCP 
Good Clinical Practice 
GI 
Gastrointestinal 
Hb 
Hemoglobin 
ICF 
Informed Consent Form 
 

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ICH 
International Conference on Harmonisation of Technical 
Requirements for Registration of Pharmaceuticals for 
Human Use 
ICMJE 
International Committee of Medical Journal Editors 
ICU 
Intensive Care Unit 
IDE 
Investigational Device Exemption 
IRB 
Institutional Review Board 
ISO 
International Organization for Standardization 
ITT 
Intent-To-Treat 
LAMS 
Lumen-Apposing Metal Stents 
PC 
Percutaneous Cholecystostomy 
PT-GBD 
Percutaneous Gallbladder Drainage 
PG 
Performance Goal 
PP 
Per-Protocol 
SADE 
Serious Adverse Device Event 
SAE 
Serious Adverse Events 
SEMS 
Self-Expanding Metal Stents 
UADE 
Unanticipated Adverse Device Effect 
USADE 
Unanticipated Serious Adverse Device Effect 
 
 
24 Appendices 
24.1 AXIOSTM EUS-GBD with Comparison to PC (Windbladh et al 2009) 
 
 
 
1st Author, Year
# of 
Patients
30 Day  
Mortality (%)
Biliary/ 
Procedure 
Mortality (%)
Technical 
Success
Clinical 
Success
Itoi et al 2012  [22]
5
0/5 (0%)
0/5 (0%)
5/5 (100%)
5/5 (100%)
de la Serna-Higuera et al 2013 [18]
13
0/13 (0%)
0/13 (0%)
11/13 (85%)
11/11 (100%)
Walter et al 2016 [16]
30
5/30 (17%)
4/30 (13.3%)
27/30 (90%)
26/27 (96%)
Irani et al 2015 [4]
15
2/15 (13%)
0/15 (0%)
14/15 (93%)
15/15 (100%)
Law et al 2016 [21]
7
3/7 (42%)
0/7 (0%)
7/7 (100%)
7/7 (100%)
Kahaleh et al 2016 [23]
15
0/15 (0%)
0/15 (0%)
13/15 (87%)
13/15 (87%)
Irani et al 2017 [19]
45
23/45 (51%)
1/45 (2.2%)
44/45 (96%)
43/45 (96%)
Dollhopf et al 2017 [20]
75
7/75 (9%)
0/75 (0%)
74/75 (98.7%)
71/74 (95.9%)
Teoh et al 2017** [17]
59
1/38 (1.7%)*
1/38 (1.7%)*
57/59 (96.6%)
53/59 (89.8%)
Axios Total
264
41/243
6/243
252/264
244/264
Axios Average
264
16.9%
3.0%
95.5%
92.4%
PC
Average PC Rates [6]
1870
15.4%
4.0%
98.9%
86.0%
 Axios vs PC
Axios vs PC Fisher' Exact p-value
0.57
0.37
0.0002
0.003
Axios

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** Of 59 patients in Teoh et al 2017, 21 were already reported in Walter et al 2015, 
procedure mortality and 30-day mortality represents the 38 cases of Teoh 2017 that were not 
reported in Walter 2015 
 
*Teoh et al 2017: Procedure Mortality – 2 cases (1 overlaps with Walter et al 2015; 1 
(Aspiration Pneumonia) 
 
24.2 EUS-GBD VS. PTGBD 
 
 
 
 
 
 
 
1st Author, Year
# subjects  
EUS-GBD
# subjects  
PCGBD
Technical 
Success       
EUS-GBD
Technical 
Success         
PCGBD
Clinical 
Success     
EUS-GBD
Clinical 
Success  
PCGBD
# AE's EUS-
GBD
# AE's PCGBD
Irani et al 2017 [19]
45
45
44/45 (97.8%) 45/45 (100.0%) 43/45 (95.6%) 41/45 (91.1%)
8/45 (17.8%)
14/45 (31.1%)
Teoh et al 2017 [17]
59
59
57/59 (96.6%) 59/59 (100.0%) 53/59 (89.8%) 56/59 (94.9%)
19/59 (32.2%)
44/59 (74.6%)
Tyberg et al 2016 [41]
42
113
40/42 (95.2%) 112/113 (99.1%) 40/42 (95.2%) 97/113 (85.8%)
9/42 (21.4%)
24/113 (21.2%)
Average
146
217
96.6%
99.5%
93.2%
89.4%
24.7%
37.8%
1st Author, Year
30 Day 
Mortality   
EUS-GBD
30 Day 
Mortality 
PCGBD
Procedure 
Mortality EUS-
GBD
Procedure 
Mortality 
PCGBD
No. of 
subjects 
w/add'l 
interventions 
EUS-GBD
No. of subjects 
w/add'l 
interventions 
PCGBD
Overall 
Complications 
EUS-GBD
Overall 
Complications 
PCGBD
Irani et al 2017 [19]
23/45 (51.1%) 20/45 (44.4%) 1/45 (2.2%)
3/45 (6.7%)
3/45 (6.7%)
45/45 (100.0%)
8/45 (17.8%)
14/45 (31.1%)
Teoh et al 2017 [17]
5/59 (8.5%)
1/59 (1.7%)
2/59 (5.1%)
0/59 (0.0%)
NR
NR
19/59 (32.2%)
44/59 (74.6%)
Tyberg et al 2016 [41]
0/42 (0.0%)
4/113 (3.5%)
NR
NR
4/42 (9.5%)
28/113 (24.8%)
9/42 (21.4%)
24/113 (21.1%)
Average
19.2%
11.5%
2.9%
2.9%
8.0%
46.2%
24.7%
37.8%