Pipeline Flex With SHield Technology Embolization - An International MulticEnter ObservationaL Post Market StuDy of Treated Intra Cranial Aneurysms (SHIELD)
Conditions: Intracranial Aneurysm
Sponsor: Medtronic Neurovascular Clinical Affairs

Cover Page – Clinical Study Protocol 
CLINICAL STUDY PROTOCOL  
Clinical Investigation Plan 
Title 
Pipeline Flex with SHield Technology Embolization - An International 
MulticEnter ObservationaL Post Market StuDy of treated Intra 
Cranial Aneurysms (SHIELD) 
Clinical Investigation Plan 
Identifier 
NV-PED-010 
CIP/Protocol number 
Rev. B, 24 June 2016 
ClinicalTrials.gov Identifier 
NCT02719522 
 

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SHIELD 
Pipeline Flex with SHield Technology Embolization- An 
International MulticEnter ObservationaL Post Market StuDy of 
treated Intra Cranial Aneurysms. 
  
CLINICAL PROTOCOL 
Protocol Number: NV-PED-010 
REVISION: B, 24-Jun-2016
 
Sponsor: 
Medtronic Neurovascular
9775 Toledo Way
Irvine, California, USA 92618
949/837-3700 (Main)
949/837-2044 (Fax)
Regional Sponsor 
Medtronic Bakken Research Center BV
Endepolsdomein 5, 6229 GW Maastricht
The Netherlands
Tel.: +31(0)43-3566566
Medtronic Australasia Pty Ltd
97 Waterloo Road, North Ryde
NSW 2113 Australia

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Sponsor Signatures: 
Signature:
___________________________________________
Date:
____________
 / Clinical Program Director, Aneurysm Therapies 
Signature:
___________________________________________
Date
____________
 / Clinical Research Director EMEA, Neurovascular
Signature:
___________________________________________
Date
____________
 / Senior Director Corporate Affairs Australia
Signature:
___________________________________________
Date:
____________
 / Medical Monitor 
Signature:
___________________________________________
Date:
____________
 / Senior Regulatory Product Specialist
Signature:
___________________________________________
Date:
____________
 / Legal Counsel II ANZ
Signature:
___________________________________________
Date:
____________
 / Principal Regulatory Affairs Specialist ANZ
Signature:
___________________________________________
Date:
____________
 /  Senior Clinical Quality Specialist APAC
Signature:
___________________________________________
Date:
____________
 / Legal compliance ANZ
 
 
 

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Clinical Protocol – Rev.B - SHIELD Study 
 
Pipeline Shield Aneurysm Study: A Global Prospective Multicenter 
Observational Trial  
 
Clinical Protocol Investigator Agreement 
I will conduct the clinical study in accordance with this agreement, all requirements of the
investigational plan, all applicable regulations, and any conditions of approval imposed by my
reviewing Institutional Review Board (IRB) / Ethics Committee (EC), if applicable. I agree to abide by
all of the responsibilities of Investigators and ICH Good Clinical Practice including but not limited to
the following:
• 
If applicable, I will obtain written approval from the authorized IRB/EC for the institution at
which this study will be conducted and I will submit the certification of IRB/EC approval and
any conditions of this approval to the Sponsor.
• 
I will ensure that Informed Consent or Data Release Form (DRF) is obtained from each
subject participating in this clinical study in accordance with the informed consent
regulation, if applicable, and that a signed copy of the informed consent or DRF is available
to the Sponsor and the Sponsor’s designated monitor.
• 
I will ensure the timely reporting of adverse events to the Sponsor, the IRB/EC as required,
and applicable regulatory agencies as required.
• 
I will ensure the accurate completion of protocol case report forms and, I will submit
completed protocol case report forms, progress reports, and a final report as specified by
the IRB/EC and/or regulations, if applicable.
• 
I will direct the retention of required records and documents related to the study according
to regulatory and study protocol requirements.
____________________________________
_____/_______/_____
Principal Investigator Signature  
 
  
   DD 
MMM    YYYY 
____________________________________
_____/_______/_____
Sub-Investigator Signature 
 
 
 
   DD 
MMM    YYYY 
____________________________________
_____/_______/_____
Sub-Investigator Signature 
 
 
 
   DD 
MMM    YYYY 
____________________________________
_____/_______/_____
Sub-Investigator Signature 
 
 
 
   DD 
MMM    YYYY 
 
 

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TABLE OF CONTENTS 
REVISION HISTORY .................................................................................................................. 11
1
INTRODUCTION ................................................................................................................. 13
1.1
Purpose ................................................................................................................................13
1.2
Background and Significance...............................................................................................13
1.2.1
Clinical Background .................................................................................................13
1.2.2
Treatment ................................................................................................................13
1.2.3
Clinical Study Experience .........................................................................................13
1.3
Rationale of the Clinical Study ...........................................................................................15
2
DEVICE DESCRIPTION ........................................................................................................ 16
2.1
Intended Use of Device........................................................................................................16
2.1.1
Device Name.............................................................................................................16
2.2
Indication for Use .................................................................................................................19
2.3
Contraindications.................................................................................................................19
2.4
Device Labeling....................................................................................................................19
2.5
Device Tracking....................................................................................................................19
2.6
Pre-Clinical Testing..............................................................................................................19
3
STUDY OBJECTIVE ............................................................................................................. 20
3.1
Data Analyses.......................................................................................................................20
4
STUDY DESIGN ................................................................................................................... 22
4.1
Expected Duration of the Study and Subject Participation. ...............................................22
4.2
Number of Sites and Subjects..............................................................................................22
4.3
Study Population..................................................................................................................22
4.3.1
Inclusion Criteria.......................................................................................................22
4.3.2
Exclusion Criteria......................................................................................................23
4.3.3
Point of Enrollment...................................................................................................23
5
STUDY PROCEDURES ......................................................................................................... 24
5.1
Patient information process ................................................................................................24
5.2
Informed Consent process..................................................................................................24
5.3
Data Release Form process .................................................................................................24
5.4
Procedure.............................................................................................................................25
5.5
Data Collection.....................................................................................................................25
5.6
Screen Failure.......................................................................................................................26
5.7
New Information ..................................................................................................................27

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5.8
Study Exit .............................................................................................................................27
5.9
Termination of Subject Participation ..................................................................................27
5.9.1
Subject Withdrawal...................................................................................................27
5.9.2
Subject Discontinuation by Investigator .................................................................27
5.9.3
Lost to Follow-up......................................................................................................27
5.10 Deviations to the Investigation ...........................................................................................27
5.11 Discontinuation by IRB/EC...................................................................................................28
5.12 Study Discontinuation by Sponsor......................................................................................28
6
ADVERSE EVENTS .............................................................................................................. 28
6.1
Adverse Event Definitions ...................................................................................................29
6.2
Event Reporting ...................................................................................................................33
7
DEVICE SPECIFIC EVENT .................................................................................................... 33
8
STUDY COMMITTEES ......................................................................................................... 34
8.1
Clinical Events Committee (CEC) ........................................................................................34
8.2
Imaging Core Laboratory.....................................................................................................34
8.2.1
Baseline Anatomy.....................................................................................................34
8.2.2
Aneurysm Occlusion.................................................................................................35
8.2.3
Parent Artery Stenosis .............................................................................................35
9
STATISTICAL METHODS AND DATA ANALYSIS ................................................................. 35
9.1
General Principles ................................................................................................................35
9.2
Study Sample Size Assumptions and Justification .............................................................36
9.3
Analysis Population..............................................................................................................36
9.4
Analysis of Baseline Demographics and Procedural Characteristics..................................36
9.5
Additional Analysis...............................................................................................................37
9.6
Handling of Missing Data......................................................................................................37
10 RISK/BENEFIT ..................................................................................................................... 37
10.1 Potential Benefits.................................................................................................................37
10.2 Potential Risks......................................................................................................................37
10.3 Justification..........................................................................................................................39
11 STUDY MONITORING ......................................................................................................... 40
11.1 Direct Access to Source Documents ..................................................................................40
11.2 Close-out Visit .....................................................................................................................41
12 ELECTRONIC CASE REPORT FORMS (eCRFs)...................................................................... 41
13 RESEARCH COMPLIANCE ................................................................................................... 41
13.1 Sponsor Compliance............................................................................................................41

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13.2 Investigator Compliance......................................................................................................42
13.3 Onsite Audits........................................................................................................................42
14 RESPONSIBILITIES AND RECORDS ..................................................................................... 43
14.1 Investigator Responsibilities ...............................................................................................43
14.2 Investigator Record Retention ............................................................................................43
14.3 Sponsor Record Retention...................................................................................................43
15 ETHICAL CONDUCT OF THE STUDY ................................................................................... 43
16 INSTITUTIONAL REVIEW BOARDS / ETHICS COMMITTEE ................................................. 44
17 QUALITY CONTROL AND QUALITY ASSURANCE ............................................................... 44
17.1 Data Control.........................................................................................................................44
17.2 Site Selection .......................................................................................................................44
17.3 Site Training .........................................................................................................................45
17.4 Site Initiation ........................................................................................................................46
17.5 Data Quality Assurance .......................................................................................................46
17.6 Data Handling.......................................................................................................................46
18 DATA OWNERSHIP ............................................................................................................. 46
19 CONFIDENTIALITY ............................................................................................................. 47
20 PUBLICATIONS ................................................................................................................... 47
21 DEFINITIONS ...................................................................................................................... 47
22 REFERENCES ...................................................................................................................... 51
Appendix A – Investigators list & Study Staff ............................................................................ 55 
LIST OF TABLES 
Table 5-1. Data Collection ..................................................................................................................26
Table 6-1. GUSTO Bleeding Criteria ...................................................................................................29
Table 6-2. Expedited Adverse Event Reporting Requirements .........................................................33
Table 8-1. Scoring System for Stenosis .............................................................................................35
LIST OF FIGURES 
Figure 2-1. Pipeline™Flex Embolization Device with Shield Technology™......................................16
Figure 8-1. Scale of Roy for Judging IA Endosaccular Embolization Success....................................35 

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Statistical Analysis: 
Descriptive statistics will be used to present the data and to summarize the study results.
For
continuous variables, statistics will include means, standard deviations, medians and ranges, as
appropriate. Categorical variables will be summarized in frequency distributions. The unit of analysis for
baseline demographics, study device usage and safety-related endpoints will be the subject. The unit
of analysis for the device-related outcome will be the device. The unit of analysis for occlusion will be
the aneurysm.

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• The development phase has been removed from the synopsis;
• The number of patients has been changed in 200 (protocol synopsis
and sections 4.1 and 4.2);
• The number of sites has been changed in up to 25 (protocol
synopsis and section 4.2);
• The enrollment duration and the total study duration have been
changed in approximately 2 years and approximately 3 years
respectively (protocol synopsis and section 4.1);
• Suggested FU windows have been added in the protocol synopsis
and in sections 5.5
• The maximum number of patient enrolled for site has been changed
in 30 in section 4.2;
• Visit windows have been removed from sections 3.1 and 9.4;
• The first sentence in section 5.12 has been changed from “The 
Sponsor may choose to discontinue the study should the Sponsor 
discover additional information during the study that may cause harm 
to subject safety.” to “The Sponsor may choose to discontinue the 
study if the Sponsor discovers additional information during the study 
that may cause harm to subject or negatively affect subject safety.” 
• The adverse events causality assessment has been changed
following the new regulations in section 6.1;
• The list of adverse events that can be adjudicate by the CEC in
section 8.1 has been removed since all events of interest will be
adjudicate;
• The characterization of major strokes has been added in section
9.4;
• EC and IRB have been added as authorities that can request to have
access to patient medical files in section 11.1;
• Previous section 11.2 “Monitoring report” has been removed;
• Experience Statement from Principal Investigators and Sub-
Investigators has been added in section 17.4;
• The possibility to conduct ORACLE training also through a website
has been added in section 17.5;
• The definition of stroke has been modified in section 21 while the
following
definitions
have
been
added:
Neurological
Death,
Transient Ischemic Attack (TIA), cerebral infarction, Intra-Cranial
Hemorrhage (ICH).

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1 
INTRODUCTION 
1.1 
Purpose 
The primary study objective is to assess the performance of the Pipeline™Flex Embolization
Device with Shield Technology™in a large real-world, post-market setting.
1.2 
Background and Significance 
1.2.1 Clinical Background 
Intracranial aneurysms (IAs) are common cerebrovascular abnormalities with a prevalence of 0.5-
6% in adults.1-4 Most IAs are asymptomatic until they rupture, which can occur suddenly and
without warning. Rupture of an IA may lead to cerebral bleeding or subarachnoid hemorrhage
(SAH), a devastating complication with a case-fatality rate of 51%.5,6 Nearly half of SAH survivors
are functionally incapacitated, with less than 5% having good outcomes.5,6 Aneurysm size
influences the likelihood of rupture and correlates with morbidity and mortality. Compared to
smaller aneurysms, large aneurysms have a 3-fold higher probability of rupture within 5 years of
diagnosis while giant aneurysms have a 9-fold higher probability of rupture within 1-2 years.7,8
The ultimate goal of treatment of an unruptured aneurysm is to prevent rupture, while treatment
of a ruptured aneurysm aims to prevent further hemorrhage.
1.2.2 Treatment 
Despite advances in microsurgical techniques, treatment of large, giant, and wide-necked
unruptured aneurysms with surgical clipping remains challenging and carries an associated
mortality of 15-21% and morbidity of 9-35%.9 Occlusion rates can be high for surgical clipping,
however, many aneurysms are not amenable to open surgery and the procedure carries
considerably higher overall risk.10-12 The rates of morbidity and mortality for coiling range between
2.3-13% and 1.3-6.7%, respectively. 13-19
 Coiling with balloons or stents has relatively low
procedural risk, but these interventions have diminished efficacy for large, complex aneurysms,
with occlusion rates as low as 40%.20 Consequently, these low occlusion rates lead to high (27-
50%) recurrence rates, may require retreatment, and ultimately place the patient at continuing risk
for rupture. 20-25 Flow diverters such as the Pipeline™Embolization Device (PED) have created a
paradigm shift in the endovascular treatment of unruptured IAs, and their safety and efficacy have
been demonstrated consistently.26-36 Several studies evaluating the use of PED for treatment of
unruptured small, large, and giant aneurysms have demonstrated achievement of high complete
occlusion rates of 68-94.4% that are maintained up to 2-3 years after the index procedure with
overall 0-13.9% associated morbidity/mortality rates. .27,31,37 These rates compare very favorably
to that reported in the literature with the use of conventional IA treatments of surgical clipping or
coiling.25,38
1.2.3 Clinical Study Experience 
The clinical benefits achieved with the use of use of Pipeline™Embolization Device have been
consistently demonstrated in multiple clinical trials.26-36
Pipeline™Embolization Device
demonstrates high efficacy and a good safety profile in treating aneurysms of diverse morphology,
ranging from small to more complex and difficult to treat aneurysms (e.g. large aneurysms, wide-

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neck aneurysms, or aneurysms with complex morphology).27,30,37,39-41 Clinical outcomes from 5 key
studies sponsored by Medtronic/Covidien have been summarized below:
Pipeline for Intracranial treatment of Aneurysms (PITA) 
The PITA study was the first prospective multicenter trial of a flow-diverting construct for the
treatment of complex large and giant IAs.27 Thirty-one subjects with wide-necked (>4 mm) and
unfavorable dome/neck ratios (<1.5 mm) and subjects with an IA that had failed previous
endovascular treatment were included. Of the 31 aneurysms, 65% were small (<10 mm) and the
remaining 35% were large and giant in size. In total, 46 of 47 Pipeline™device braids were placed
successfully (97.9%). In 30 out of 31 subjects, the entire neck of the targeted intracranial aneurysm
was covered by the Pipeline™device braid. Complete aneurysm occlusion was observed in 93.3%
(28/30) subjects at 180 days. Two subjects experienced a major periprocedural stroke and no
deaths occurred.
Pipeline™ Embolization Device for Uncoilable or Failed Aneurysms (PUFs) 
The PUFs study was a multicenter, prospective, single-arm trial to evaluate the safety and
effectiveness of the PED in complex large and giant IAs.28 One hundred seven subjects with large
and giant unruptured wide-necked aneurysms in the petrous to the superior hypophyseal segment
of the ICA were treated with the PED. The aneurysms measured ≥10 mm in diameter and had
either a neck ≥4 mm or no discernable neck. A total of 104 subjects with 106 aneurysms were
included in the primary effectiveness cohort. Of the 106 aneurysms, 78 demonstrated complete
occlusion without major stenosis at 180 days (73.6%; 95% posterior probability interval: 64.4%–
81.0%). At one year, 86.8% (79/91) of the target aneurysms were completely occluded. This rate
increased to 95.2% (59/62) complete occlusion at five years. There were no cases of aneurysm
recurrence. The primary safety endpoint was the occurrence of major ipsilateral stroke or
neurologic death at 180 days, which occurred in six of the 107 subjects (5.6%; 95% posterior
probability interval: 2.6%–11.7%). At five year follow-up, the rate of major ipsilateral stroke or
neurologic death remained 5.6%.
International Retrospective Study of the Pipeline Embolization Device (IntrePED) 
The IntrePED study was a retrospective global post market study of subjects treated with the PED
at 17 centers worldwide.29 A total of 793 subjects with 906 aneurysms of various sizes and
locations were included. The median follow-up period was 19.3 months with 89% subjects with
greater than 1 year follow-up. The overall neurological morbidity rate was 7.4% (59/793) and the
neurological mortality rate was 3.8% (30/793). The combined neurological morbidity and mortality
rate was 8.4% (67/793). The combined neurological morbidity and mortality for treated ruptured
aneurysms was higher at 18.4% (14/76). Data from the IntrePED study report the safety of the
PED in the treatment of various IAs in a real-world clinical setting.
Aneurysm Study of Pipeline in an Observational Registry (ASPIRe) 
ASPIRe was a prospective, multi-center, single arm, post-market registry of 191 IA patients with
207 aneurysms from 28 worldwide centers who underwent PED treatment. The 207 aneurysms in
the study had a median follow-up duration of 6.6 months. The majority of aneurysms treated were
saccular and overall average size of treated aneurysms was 14.5mm.

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Neurological morbidity was 6.8% (13/191) and the neurologic mortality rate was 1.6% (3/191). The
combined rate of neurological morbidity and mortality was 6.8% (13/191), with the most common
major adverse event of interest being intracerebral hemorrhage (3.7%, 7/191) followed by
ischemic stroke (1.6%, 3/191). Most of the major adverse events (6.3%, 12/191) occurred in the
early post-operative phase within the first 30 days following PED treatment.
Aneurysm occlusion was assessed according to the Scale of Roy at last visit for all subjects with
imaging follow-up of at least 6 months. The median follow-up duration was 7.8 months and
complete occlusion was reported in 75% of subjects (77/103). The use of embolic coils was the
most common adjunctive therapy and was employed in 17.3% (33/191) of subjects.
The ASPIRe registry, as a comprehensive evaluation of PED use in the real world, confirmed that
the PED is safe when used for the treatment of IAs in routine clinical practice, reporting a 6.8% rate
of associated major morbidity and neurological mortality.
1.3 
Rationale of the Clinical Study 
The Pipeline™Embolization Device demonstrates high efficacy and a good safety profile in treating
aneurysms of diverse morphology. Continued development of the PED delivery system resulted in
the Pipeline™Flex Embolization Device (PFED), which incorporates a resheathing mechanism,
allowing
the
physicians
to
reposition
and
redeploy
the
PED
braid.
Additionally,
polytetrafluoroethylene (PTFE) sleeves are used in place of the protective coil, resulting in the
elimination of the need to torque the delivery system to release the PED braid. The latest
developmental modification to the PED system is Shield Technology™. Shield Technology™
utilizes a phosphorylcholine (PC) surface treatment to the existing implant combined with the
PFED delivery system. The Shield Technology™surface treatment applied to the implant is an
inert, PC polymer material that is chemically bonded to the braid surface. The polymer is a
chemically derived material, created to mimic the outer membrane of a human red blood cell.
Shield Technology™reduces the material thrombogenicity of the braid surface compared to the
current bare metal PFED implant based on bench data with human platelets and plasma. The study
described herein will evaluate the performance of the Pipeline™Flex Embolization Device with
Shield Technology™in a broad real-world clinical setting.
Platelet inhibition with dual antiplatelet therapy (DAPT); consisting of aspirin and a thienopyridine,
is necessary for the prevention of acute or subacute thrombosis and related complications after
neurointerventional procedures.42 DAPT has been associated with a reduction in thromboembolic
events, but has also been implicated as a potential factor contributing to the rates of ischemic and
hemorrhagic complications associated with PED placement.42 Current DAPT protocols used in PED
patients are developed based on studies in the field of cardiology and interventional radiology. In
addition, there is no consensus on the optimal DAPT regimen, dose, and duration.43 This study
aims to collect data on platelet function testing, DAPT regimens, optimal dose, and post-PED
DAPT duration to identify their association with thrombotic and hemorrhagic adverse events in the
clinical setting and evaluate related clinical outcomes.

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2 
DEVICE DESCRIPTION 
2.1 
Intended Use of Device 
The latest developmental modification to the Pipeline™Flex Embolization Device (PFED) system is
Shield Technology™. Shield Technology™utilizes a phosphorylcholine (PC) surface treatment to
the implant combined with the PFED delivery system. The Shield Technology™surface treatment
applied to the implant is an inert, PC polymer material that is chemically bonded to the braid
surface. The polymer is a chemically derived material, created to mimic the outer membrane of a
human red blood cell. Shield Technology™reduces the material thrombogenicity of the braid
surface compared to the bare metal PFED implant based on bench data with human platelets and
plasma.
The Pipeline™Flex Embolization Device with Shield Technology™is intended for endovascular
embolization of cerebral aneurysms and is designed to be placed across the opening (or ‘neck’) of a
brain aneurysm and redirect blood flow away from the aneurysm, causing the blood within the
aneurysm to clot. The device is designed for use in the neurovasculature.
2.1.1 Device Name 
Name: Pipeline™Flex Embolization Device with Shield Technology™.
A photo and diagram of the Pipeline™Flex Embolization Device with Shield Technology™is shown
in Error! Reference source not found.Figure 2.1.
Left, photo of the braid. Right, diagram of the distal end of the Pipeline™Flex Embolization Device with Shield
Technology™delivery system loaded into the introducer sheath.
All the Pipeline™Flex Embolization Device with Shield Technology™models used in this trial are
commercially available, CE-Marked and used within intended use in all the involved countries,
including Australia. The table below reports all the available models’ numbers:
 
Figure 2-1. Pipeline™ Flex Embolization Device with Shield Technology™ 

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PED2-375-12
3,75
12
PED2-375-14
3,75
14
PED2-375-16
3,75
16
PED2-375-18
3,75
18
PED2-375-20
3,75
20
PED2-375-25
3,75
25
PED2-375-30
3,75
30
PED2-375-35
3,75
35
PED2-400-10
4,00
10
PED2-400-12
4,00
12
PED2-400-14
4,00
14
PED2-400-16
4,00
16
PED2-400-18
4,00
18
PED2-400-20
4,00
20
PED2-400-25
4,00
25
PED2-400-30
4,00
30
PED2-400-35
4,00
35
PED2-425-10
4,25
10
PED2-425-12
4,25
12
PED2-425-14
4,25
14
PED2-425-16
4,25
16
PED2-425-18
4,25
18
PED2-425-20
4,25
20
PED2-425-25
4,25
25
PED2-425-30
4,25
30
PED2-425-35
4,25
35
PED2-450-10
4,50
10
PED2-450-12
4,50
12
PED2-450-14
4,50
14
PED2-450-16
4,50
16
PED2-450-18
4,50
18
PED2-450-20
4,50
20
PED2-450-25
4,50
25
PED2-450-30
4,50
30
PED2-450-35
4,50
35
PED2-475-10
4,75
10
PED2-475-12
4,75
12
PED2-475-14
4,75
14
PED2-475-16
4,75
16
PED2-475-18
4,75
18
PED2-475-20
4,75
20
PED2-475-25
4,75
25
PED2-475-30
4,75
30

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PED2-475-35
4,75
35
PED2-500-10
5,00
10
PED2-500-12
5,00
12
PED2-500-14
5,00
14
PED2-500-16
5,00
16
PED2-500-18
5,00
18
PED2-500-20
5,00
20
PED2-500-25
5,00
25
PED2-500-30
5,00
30
PED2-500-35
5,00
35
2.2 
Indication for Use 
The Pipeline™Flex embolization device with Shield Technology™is intended for endovascular
embolization of cerebral aneurysms.
2.3 
Contraindications 
• 
Patients who have not received antiplatelet agents prior to the procedure.
• 
Patients with active bacterial infection.
• 
Patients in whom antiplatelet and/or anticoagulation therapy is contraindicated.
• 
The Pipeline™Flex embolization device with Shield Technology™should not be used alone
as sole therapy for acutely ruptured aneurysms.
2.4 
Device Labeling 
The
Pipeline™
Flex
Embolization
Device
with
Shield
Technology™
is
approved
for
commercialization in the countries that will be participating in this study and will be used within its
intended use as specified in the approved labeling. The Pipeline™Flex Embolization Device with
Shield Technology™will be labeled as commercially available and in accordance with applicable
language requirements.
2.5 
Device Tracking 
The Pipeline™Flex Embolization Device with Shield Technology™is traced by lot number. The lot
number of each Pipeline™Flex Embolization Device with Shield Technology™used in this study will
be captured on the case report forms. Due to commercial availability, shipments will not be tracked
for the study.
2.6 
Pre-Clinical Testing 
Biocompatibility Summary 
All biocompatibility tests for The Pipeline™Flex Embolization Device with Shield Technology™
were completed, and all test results passed the acceptance criteria (per ISO 10993-1:2009 and
FDA G95-1). 

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 Study Summary  
Overall Study Conclusion
 Study Summary  
Taken together, the results show that the Pipeline™Flex Embolization Device with Shield
Technology™is safe and efficacious in this animal model.
3 
STUDY OBJECTIVE 
The study objective is to assess the performance of the Pipeline™Flex Embolization Device with
Shield Technology™in a large real-world, post-market setting.
3.1 
Data Analyses 
The following data will be analyzed in this study:
• 
Antiplatelet therapy regimen
• 
Adverse events related to antiplatelet therapy
• 
Platelet reactivity testing results
• 
Moderate and Severe bleeding events utilizing GUSTO criteria
• 
All intracranial hemorrhages and delayed intracranial hemorrhages (>30 days post-
procedure)

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• 
Index procedure time
• 
Number of Pipeline™Flex Embolization Device with Shield Technology™utilized 
• 
Device deployment success rate at target site 
• 
Aneurysm occlusion at 6 months, 1 year and at last follow-up 
• 
Recurrence and retreatment rates at 1 year post-procedure and at last follow-up 
• 
The composite percentage of patients with modified Rankin Scale of 0-2 or no change from
baseline at 1 year and at last follow-up.
• 
Occurrence of major stroke in the territory supplied by the treated artery or neurological
death. Stroke events will be further characterized based on whether:
- 
Event was caused by thromboembolic events
- 
Event was caused by side-branch occlusion due to the study device
For the purposes of this study protocol, stroke is defined as a focal neurological deficit of
presumed vascular origin persisting more than 24 hours from symptom onset and a neuro-imaging
study or other quantitative study that does not indicate a different etiology. The 24-hour criterion
is excluded if the subject undergoes cerebrovascular surgery or dies during the first 24 hours of
symptom onset.
The definition includes:
• 
Subjects presenting with clinical signs and symptoms suggestive of subarachnoid
hemorrhage, intracerebral hemorrhage, or cerebral infarction.
• 
Sudden loss or worsening of visual acuity due to retinal artery occlusion or retinal
emboli.
The definition excludes:
• 
Slowly progressive cranial nerve palsies or progressive visual field deficits due to
continued aneurysm growth.
• 
Stroke events in cases of blood disorders such as leukemia or external events such as
trauma.
Stroke severity will be graded by the investigator as major or minor:
• 
Major Stroke: A stroke, which is present after seven days and increases the NIH Stroke
Scale of the subject by ≥4.
• 
Minor Stroke: A stroke, which resolves completely within seven days OR increases the NIH
Stroke Scale of the subject by ≤3.
Neurological death is any subject death due to an underlying neurologic cause.
The safety events noted for analysis will be adjudicated by an independent clinical events
committee (CEC) (Section 8.1).
Aneurysm occlusion and recurrence will be evaluated by an
independent core laboratory (Section 8.2).

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4 
STUDY DESIGN 
This is a prospective, single-arm, multi-center post-market observational study to assess the
performance of the Pipeline™Flex Embolization Device with Shield Technology™in subjects
undergoing treatment for intracranial aneurysms.
4.1 
Expected Duration of the Study and Subject Participation.  
Up to 200 subjects who meet the Inclusion/Exclusion Criteria may be enrolled over a period of
approximately 2 years to reach a target number of subjects. Study participation includes initial
screening and baseline evaluation, treatment using the Pipeline™Flex Embolization Device with
Shield Technology™, and follow-up visits at the discretion of the treating physician for 1 year
beyond the index procedure. The total study duration is expected to be approximately 3 years.
4.2 
Number of Sites and Subjects 
Up to 200 subjects at up to 25 sites worldwide may participate. Each participating investigational
site should attempt to enroll at least 1 subject and will be allowed to enroll up to 30 subjects who
meet all study eligibility criteria.
4.3 
Study Population 
The study population will consist of subjects who have an intracranial aneurysm and are enrolled in
the study. The treated aneurysm may be ruptured (with a Hunt and Hess grade of ≤3) provided that
the Pipeline™Flex Embolization Device with Shield Technology™is used according to its
Instructions for Use and its intended use during the treatment regimen.
For subjects with more than one aneurysm requiring treatment, the following guidance is to be
followed for subjects to be enrolled in the study.
• 
If more than one aneurysm can be covered by a single Pipeline device or two overlapped
devices, the multiple aneurysms treated by that device(s) may all be included in the
study. A maximum of two overlapped devices in consecutive arterial segments will be
permitted. The largest aneurysm meeting criteria will be designated the target
aneurysm. For equal sized aneurysms, the Core Lab will designate the target aneurysm.
• 
If the subject has more than one aneurysm and all aneurysms requiring treatment
cannot be covered by a single Pipeline device or two overlapped devices, the non-target
aneurysms should be treated first. After waiting at least 30 days per exclusion criterion
#1 below, the subject may return for Pipeline treatment of the target aneurysm.
4.3.1 Inclusion Criteria 
Subjects must meet all of the following general inclusion criteria:
1. Subject has provided written DRF or informed consent using the IRB/EC-approved consent
form and agrees to comply with protocol requirements.
2. At least 18 years of age.
3. Subject has already been selected for flow diversion therapy as the appropriate treatment.

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4. Subject has a target IA that has a parent vessel with diameter 1.5-5.0 mm distal/proximal to the
target IA.
4.3.2 Exclusion Criteria 
The subject must not meet any of the following general exclusion criteria:
1. Major surgery including endovascular procedures within the past 30 days.
2. Subject with target IA located in the basilar artery.
3. Subject with anatomy not appropriate for endovascular treatment due to severe intracranial
vessel tortuosity or stenosis determined from baseline or pre-procedure imaging, or a history
of intracranial vasospasm not responsive to medical therapy.
4. Stent is in place in the parent artery at the target IA location.
5. Subject with an acutely (within 30 days) ruptured aneurysm with a Hunt and Hess grade of 4 or
higher.
6. Any known contraindication to treatment with the Pipeline™Flex Embolization Device with
Shield Technology™per Instructions for Use.
7. The investigator determines that the health of the subject or the validity of the study
outcomes (e.g., high risk of neurologic events, conditions that may increase the chance of
stroke, worsening of clinical condition in the last 30 days) may be compromised by the subject’s
enrollment.
8. Pregnant or breast-feeding women or women who wish to become pregnant during the length
of study participation.
9. Subject is currently enrolled or planning to participate in a potentially confounding drug or
device trial during the course of this study. Co-enrollment in concurrent trials is only allowed
when documented pre-approval is obtained from Medtronic.
10. Legal incapacity or evidence that a subject cannot understand the purpose and risks of the
study or inability to comply fully with study procedures.
4.3.3 Point of Enrollment 
Given that the prospective study population consists of patients who are already selected for flow
diversion therapy and that the screening assessments consist of standard patient diagnostics for
this therapy, subjects are considered enrolled in the study once the subject has signed and dated
the Informed Consent or DRF and the Pipeline™Flex Embolization Device with Shield
Technology™is advanced into the micro catheter inside the subject.

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5 
STUDY PROCEDURES 
5.1 
Patient information process 
Patient informed consent will be obtained in accordance with local laws and regulations. Whether
to use an Informed Consent or Data Release Form (DRF) is dependent on local regulatory
requirements and local EC/IRB requirements, if applicable. The strictest requirement will be
applied. The Informed Consent or DRF must be approved by the sponsor and the Site’s EC/IRB, if
applicable.
Legally incompetent or unconscious subjects are not expected to be included in this study.
5.2 
Informed Consent process  
A thorough explanation will be provided to the subject (or legally authorized representative) as to
the nature and objectives of this study. Details of the study should include (but are not limited to)
the following terms:
• 
Purpose of the study
• 
Participation is voluntary, and there is no penalty for withdrawal
• 
Potential risks/benefits for participation
• 
Contact information to ask questions or voice concerns
The study investigator and/or staff are responsible for obtaining written informed consent from
each potential subject. Informed consent should be obtained in written format and using a form
approved by the local IRB/EC, if applicable. The form should contain standard language consistent
with local policies for ensuring privacy of confidential information. All subjects must sign the
informed consent prior to any procedures/tests that go beyond initial assessments associated
with the standard care for subjects with intracranial aneurysms and before any study related
treatment assessments are administered and subject-related health information can be entered
into the study database.
It is the responsibility of the investigator to give each subject (or subject’s legally authorized
representative) prior to inclusion in the study, full and adequate verbal and written information
regarding the objective of this study and the confidentiality of the data collected.
The Sponsor will inform the investigators whenever information becomes available that may be
relevant to the subject’s confirmed participation in the clinical study. The investigator or his/her
authorized designee should inform the subject in a timely manner. The Sponsor will revise the
written Informed Consent Form whenever new information becomes available that may be
relevant to the subject’s confirmed participation in the clinical study. The revised information will
be sent to the investigator for approval by the EC/IRB, if applicable, and a copy of this information
must be provided to the participating subjects.
After all persons have signed and dated the informed consent, the investigator must provide the
subject with a copy of the signed and dated informed consent.
5.3 
Data Release Form process 
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During the consent discussion the investigator or his/her designee must fully inform the subject of
the study in non-technical wording understandable for the subject.
The subject must have ample time and opportunity to inquire about details of the study, and to
decide whether or not to participate in the clinical study. All questions about the study should be
answered to the satisfaction of the subject.
When the subject decides to participate in the clinical study, the written DRF must be signed and
personally dated by the subject and the investigator.
After all persons have signed and dated the DRF the investigator must provide the subject with a
copy of the signed and dated DRF.
5.4 
Procedure  
The Pipeline™Flex Embolization Device with Shield Technology™placement procedure is
described in detail in the Instructions for Use (IFU) document. The investigator should review and
understand the complete IFU prior to performing any Pipeline™Flex Embolization Device with
Shield Technology™placement in this clinical study.
Recommendations: In addition to the Pipeline™Flex Embolization Device with Shield Technology™
(study device), the following devices and equipment are recommended during the study
procedure.
• 
A tri-axial system
• 
0.027 microcatheter
• 
Navien support catheter
• 
Long sheath (minimum of 90 cm)
No other devices or concomitant medications different from clinical practice have to be used
during the SHIELD Study, since this is a post-market non-interventional study.
5.5 
Data Collection 
Eligible subjects will be treated with the Pipeline™Flex Embolization Device with Shield
Technology™.
Subjects will undergo standard of care follow-up visits. Data generated per standard of care will be
collected for 1 year (±8 weeks) beyond the index procedure. All follow-up visits and telephone calls
during this time period will be recorded. A summary of the data to be collected is listed in Table 5-1.
In order to track compliance with antiplatelet therapy, subjects will be contacted at a minimum of
approximately (±14 days), 3 (±30 days), 6 (±6 weeks), and 12 (±8 weeks) months post-index
procedure and asked to confirm their current antiplatelet regimen and that all relevant adverse
events (Section 6) have been reported.
A survey will be administered to all centers to collect their standard antiplatelet therapy regimen at
the start of the study and annually.

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Table 5-1. Data Collection 
Time Period 
Data to be Collected  
Baseline
• Relevant medical history and demographics
• Aneurysm characteristics, symptoms and status (ruptured or unruptured)
• Hunt & Hess Grade and WFNS (if ruptured)
• Antiplatelet medication use within past 30 days
• Other relevant concomitant medications
• Platelet reactivity testing
• NIH Stroke Scale (NIHSS)
• Modified Rankin Scale (mRS)
Procedure
• Relevant medications including antiplatelet regimen
• Adverse events
• Platelet reactivity testing
• Procedure and fluoroscopy times
• Study device information including side branches covered
• Concomitant treatments
• Deployment success at target IA
• Imaging to be sent to the Core Lab*
• Aneurysm occlusion
• NIHSS
• mRS
Post-Implant
Follow-up
• Relevant medications including antiplatelet regimen
• Adverse events
• Platelet reactivity testing
• Imaging to be sent to the Core Lab*
• Aneurysm occlusion
• Retreatment
• NIHSS
• mRS
*All imaging taken (e.g., angiograms, CT, MR, rotational angiography with 3D reconstruction, cone-
beam CT, etc.) should be provided to the Core Lab.
5.6 
Screen Failure 
Subject will be considered a screen failure if:
• 
The subject signs the informed consent or DRF but fails to meet study inclusion/exclusion
criteria during the screening and baseline phase.
• 
The subject signs the informed consent or DRF, meets the study inclusion/exclusion
criteria but an attempt to implant the Pipeline™Flex Embolization Device with Shield
Technology™is not performed.

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Subjects that undergo consent but are screen failures will be exited from the study and will not be
required to undergo any additional follow-up. Only the reason for subject screen failure will be
recorded.
5.7 
New Information 
Study subjects will be informed of new information that becomes available during the course of this
study by their treating physician. Subjects will be notified, at a minimum, in accordance with the
IRB/EC’s procedure for providing updated information to clinical study subjects, if applicable.
5.8 
Study Exit 
The subject will be seen by the treating physician according to standard care following intracranial
aneurysm treatment. One year post-procedure, the subject will exit the study and be exempt from
further data collection.
5.9 
Termination of Subject Participation 
Subjects may withdraw from the study at any time without penalty or loss of medical care, or they
may be withdrawn at any time at the discretion of the principal investigator (PI) or Sponsor for
safety or administrative reasons.
5.9.1 Subject Withdrawal 
All enrolled subjects have the right to withdraw their consent at any time during this study. All data
collected until the time of subject withdrawal will remain in the study database and will be used for
analysis. Whenever possible, the site staff should obtain written documentation from the subject
who wishes to withdraw his/her consent for future follow-up visits. If the site staff is unable to
obtain written documentation, all information regarding the subject’s withdrawal must be recorded
in the subject’s medical record. In addition, the appropriate eCRFs must be completed for the
subject to ensure clear documentation of the subject’s withdrawal.
5.9.2 Subject Discontinuation by Investigator 
An investigator may discontinue a subject from the study, with or without the subject’s consent,
for any reason that may, in the investigator’s opinion, negatively affect the well-being of the
subject should they continue in the study. If a subject is withdrawn from the study, the investigator
will promptly inform the subject and Sponsor.
5.9.3 Lost to Follow-up 
A subject will be considered lost to follow-up if the subject cannot be reached after three (3)
attempts to contact the subject for a follow-up visit. The site must document a minimum of three
(3) attempts, and the final documented attempt should be made via registered letter.
5.10 Deviations to the Investigation 
A protocol deviation is defined as an event where the investigator or study personnel did not
conduct the study according to the clinical protocol. Deviations shall be reported to the Sponsor
regardless of whether medically justifiable actions are taken to protect the subject in an
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Except for a change that is intended to eliminate an immediate hazard to a subject, the protocol will
be followed as described. Subject specific deviations and non-subject specific deviations will be
reported. Investigators will also adhere to procedures for reporting study deviations to their
IRB/EC in accordance with their specific IRB/EC’s reporting policies and procedures, if applicable.
Sites with a high rate of protocol deviations will be closely evaluated and are expected to
implement corrective actions to prevent further deviations. If a site demonstrates persistent
deviations, as described above, the site may be terminated.
5.11 Discontinuation by IRB/EC 
Where applicable, the IRB/EC may choose to discontinue the study at any center(s) for which they
granted approval if:
• 
The research study is not conducted in accordance with the IRB/EC’s requirements.
• 
The research study indicates unexpected serious harm to subjects.
5.12 Study Discontinuation by Sponsor 
The Sponsor may choose to discontinue the study if the Sponsor discovers additional information
during the study that may cause harm to subject or negatively affect subject safety.
If the study is terminated prematurely or suspended, the Sponsor will promptly inform all clinical
investigators of the termination or suspension and the reason(s) for this. Where applicable, the
IRB/EC will also be informed, either by the Sponsor or investigator if a local IRB/EC is utilized,
promptly and provided with the reasons(s) for the termination. If applicable, regulatory authorities
will be informed. Enrolled subjects will be asked to complete all remaining study visits and the
subject will then be seen by the treating physician according to standard care following intracranial
aneurysm treatment.
6 
ADVERSE EVENTS 
The following Adverse events will be collected during the course of the study on the eCRFs.
• 
All Adverse Events (AE) with an underlying neurological cause (Neurological Adverse
Events)
• 
All Device Related Adverse Effects
• 
All Procedure Related Adverse Events
• 
All Bleeding Events
• 
All Serious Adverse Events (SAEs)
Adverse event status will be evaluated throughout the study. These will include events occurring
from the point of enrollment until a subject exits the study. If the subject is enrolled and the study
procedure is attempted, but the Pipeline™Flex Embolization Device with Shield Technology™is
not implanted for any reason, subjects will be followed to discharge and relevant safety events will
be collected. Investigators must obtain all information available to determine the causality and
outcome of the AE and to assess whether it meets the criteria for classification as a serious and/or

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unexpected event requiring notification to the Sponsor, and, where applicable, regulatory agency
and IRB/EC, within the specified reporting timeframe. AEs will be categorized using the definitions
in Section 6.1.
All study AEs, as well as the treatment and follow-up required, should be documented in the
subject’s medical records and in the eCRF. All study SAEs that occur during the 1 year follow-up
period will be followed by the investigator until resolution or until 30 days after the occurrence of
that event. A list of potential anticipated adverse events is provided in Section 10.2.
Bleeding events will be captured as Adverse Events by the sites and will be graded according to the
GUSTO44 bleeding criteria as seen in  
Table 6-1 by the Clinical Events Committee.
 
Table 6-1. GUSTO Bleeding Criteria 
GUSTO Bleeding Category 
Definition 
Severe or Life-Threatening
Intracerebral hemorrhage
Substantial hemodynamic compromise requiring treatment
Moderate
Requiring blood transfusion but not resulting in hemodynamic
compromise
Mild
Bleeding that does not meet the above criteria
6.1 
Adverse Event Definitions 
An Adverse Event (AE) is defined as any untoward medical occurrence, unintended disease or injury,
or untoward clinical signs (including abnormal laboratory findings) in subjects, users or other
persons, whether or not related to the investigational medical device. (ISO 14155:2011 3.2)
Note 1: This definition includes events related to the investigational medical device or the
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
investigational medical devices.
An Adverse Device Effect (ADE) is defined as an adverse event related to the use of an
investigational medical device. (ISO 14155:2011 3.1) The investigational medical device for this
study is the Pipeline™Flex Embolization Device with Shield Technology™used during the
procedure (Day 0).
Note 1: This definition includes adverse events resulting from insufficient or inadequate
instructions for use, deployment, implantation, installation, or operation, or any
malfunction of the investigational medical device.

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Note 2: This definition includes any event resulting from use error or from intentional
misuse of the investigational medical device.
A Serious Adverse Event (SAE) is defined as an adverse event that
a) Led to death,
b) Led to serious deterioration in the health of the subject, that either resulted in
a. A life-threatening illness or injury, or
b. A permanent impairment of a body structure or a body function, or
c. In-subject or prolonged hospitalization, or
d. Medical or surgical intervention to prevent life-threatening illness or injury or
permanent impairment to a body structure or a body function,
c) Led to fetal distress, fetal death or a congenital abnormality or birth defect (ISO
14155:2011 3.37)
Note: Planned hospitalization for a pre-existing condition, or a procedure required by the
Clinical Investigation Plan, without serious deterioration in health, is not considered a
serious adverse event.
A Serious Adverse Device Effect (SADE) is defined as an adverse device effect that has resulted in
any of the consequences characteristic of a serious adverse event. (ISO 14155:2011 3.36)
An Unanticipated Serious Adverse Device Effect (USADE) is defined as a 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. (ISO 14155:2011 3.42)
Note: Anticipated serious adverse device effect (ASADE) is an effect which by its nature,
incidence, severity or outcome has been identified in the risk analysis report.
Severity:
• 
Mild: No limitation of usual activities, no therapy or only symptomatic therapy required to
treat the injury or illness.
• 
Moderate: Some limitation of usual activities or specific therapy is required.
• 
Severe: Inability to carry out usual activities, hospitalization, emergency treatment, life
threatening events, or death.
Causality Assessment:
The relationship between the use of the:
• 
Medical device (Medical device investigated in the Investigation) and
• 
The medical -surgical procedure (Procedure related events refers to the procedure related
to the initial application of the investigational medical device only and therefore not to any
other procedures or treatments applied later throughout the clinical investigation, for
instance to treat (serious) adverse events.)

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The occurrence of each adverse event shall be assessed and categorized according to five different
levels of causality for which the following definitions shall be used to assess the relationship of the
adverse event to the investigational medical device or procedure:
1. Not Related:
Relationship to the device or procedures can be excluded when:
• 
the event is not a known side effect of the product category the device belongs
to or of similar devices and procedures;
• 
the event has no temporal relationship with the use of the investigational device
or the procedures;
• 
the serious event does not follow a known response pattern to the medical
device (if the response pattern is previously known) and is biologically
implausible;
• 
the discontinuation of medical device application or the reduction of the level of
activation/exposure - when clinically feasible – and reintroduction of its use (or
increase of the level of activation/exposure), do not impact on the serious
event;
• 
the event involves a body-site or an organ not expected to be affected by the
device or procedure;
• 
the serious event can be attributed to another cause (e.g. an underlying or
concurrent illness/ clinical condition, an effect of another device, drug,
treatment or other risk factors);
• 
the event does not depend on a false result given by the investigational device
used for diagnosis* , when applicable [*If an investigational device gives an
incorrect diagnosis, the patient might, for example, receive an unnecessary
treatment and incur all the risks that accompany that treatment, or might be
incorrectly diagnosed with a serious disease. In other cases, the patient might
not receive an effective treatment (thereby missing out on the benefits that
treatment would confer), or might not be diagnosed with the correct disease or
condition];
• 
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.
2. Unlikely:
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.
3. Possible:
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

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were relatedness cannot be assessed or no information has been obtained should also
be classified as possible.
4. Probable:
The relationship with the use of the investigational device seems relevant and/or the
event cannot reasonably explained by another cause, but additional information may be
obtained.
5. Causal relationship:
The adverse 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 adverse event follows a known response pattern to the medical
device (if the response pattern is previously known);
 
the discontinuation of medical device application (or reduction of
the level of activation/exposure) and reintroduction of its use (or
increase of the level of activation/exposure), impact on the serious
event (when clinically feasible);
 
other possible causes (e.g. an underlying or concurrent illness/
clinical condition or/and an effect of another device, drug or
treatment) have been adequately ruled out;
 
harm to the subject is due to error in use;
 
the event depends on a false result given by the investigational
device used for diagnosis*, when applicable;
 
In order to establish the relatedness, not all the criteria listed above
might be met at the same time, depending on the type of
device/procedures and the serious event.
The Investigators shall distinguish between the adverse events related to the investigational
device and those related to the procedures (any procedure specific to the clinical investigation).
An adverse event can be related both to procedures and the investigational device.
Complications of procedures are considered not related if the said procedures would have been
applied to the patients also in the absence of investigational device use/application.
In some particular cases the event may be not adequately assessed because information is
insufficient or contradictory and/or the data cannot be verified or supplemented. The Investigators
will make the maximum effort to define and categorize the event and avoid these situations. Where

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Malfunction is defined as failure of an investigational medical device to perform in accordance with
its intended purpose when used in accordance with the Instructions for Use or Clinical
Investigational Plan (ISO 14155:2011 3.27).
Devices/products (including regulatory approved components used in combination with an
investigational product) used in this study are market release and commercially available.
Therefore, Post Market Surveillance is applicable.
Device complaints are not within the scope of this study and will be handled according to standard
Sponsor procedures: all device specific events must be reported to the Sponsor, EC/IRB (if
applicable) and local authorities as required by governing law. If a device malfunction results in an
adverse event for the subject, this adverse event will be considered a reportable adverse event and
must be reported as an Adverse Event (AE).
It is the responsibility of the investigator and the clinical study teams to report all product
complaint(s) associated with a medical device distributed by Medtronic, regardless whether they
are related to intended use, misuse or abuse.
All Regional Reporting requirements shall be followed: details will be specified in the Safety
Management Plan.
8 
STUDY COMMITTEES  
To avoid and minimize bias, an independent Clinical Events Committee and Core Laboratory will be
in place to adjudicate safety events and assess aneurysm occlusion.
8.1 
Clinical Events Committee (CEC) 
A CEC will be in place for the study using a minimum of three (3) physicians knowledgeable in the
appropriate disciplines and medical specialties pertinent to the disease state being evaluated in
this clinical study. This committee will be responsible for the review and adjudication of all adverse
events reported in the study.
The CEC will adjudicate to specified events of interest definitions (where available), event term,
event start date, event relatedness, event severity, and event outcomes.
The CEC can request additional source documentation and any potential imaging obtained in
support of the adverse event to assist with adjudication.
8.2 
Imaging Core Laboratory 
An imaging protocol will be provided to the site. The imaging core laboratory will be responsible for
the qualitative image analysis to determine aneurysm characteristics, side branch coverage by the
Pipeline device, aneurysm occlusion, parent artery stenosis, and device migration.
8.2.1 Baseline Anatomy 
Imaging obtained immediately prior to the procedure will be reviewed to assess baseline aneurysm
and parent artery characteristics.

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listings. Statistical analyses will be conducted in SAS version 9.1 or above (SAS Institute, Cary, NC)
or other validated statistical software package.
For adverse event reporting, the primary analysis will be based on subject counts (e.g., the number
and percentage of subjects with event among the total number of subjects). The data will be
presented in the format of p% (x/N) [e], with p and x being the percentage and number of subjects
with events, respectively, N being the sample size of the analysis population, and e being the total
number of events occurred in the x subjects.
For device-related outcomes (e.g., device deployment success rate), the unit of analysis will be
device.
For occlusion outcomes, the unit of analysis will be the aneurysm.
9.2 
Study Sample Size Assumptions and Justification 
No formal statistical success criteria are proposed. Therefore, the sample size of the study is not
based on statistical formulas for hypothesis testing of the primary outcome. Descriptive statistics
will be provided for all analyses.
9.3 
Analysis Population 
The primary analysis sample will be based on the principle of intention-to-treat (ITT). All enrolled
subjects who underwent the study procedure and in whom an attempt to implant the device was
made will be included in the analysis population.
9.4 
Analysis of Baseline Demographics and Procedural Characteristics 
Descriptive
statistics
will
be
generated
for
pre-intervention
demographics,
aneurysm
characteristics and procedural characteristics, device usage and adverse events. Categorical
variables will be analyzed using frequency, incidence, and event rate. For continuous variables
collected in the study, analysis will include mean, median, standard deviation, and range.
The following data points will be analyzed in this study:
• 
Antiplatelet therapy regimen
• 
Adverse events related to antiplatelet therapy
• 
Platelet reactivity testing results
• 
Moderate and Severe bleeding events utilizing GUSTO criteria
• 
All intracranial hemorrhages and delayed intracranial hemorrhages (>30 days post-
procedure)
• 
Index procedure time
• 
Number of Pipeline™Flex Embolization Device with Shield Technology™utilized 
• 
Device deployment success rate at target site 
• 
Aneurysm occlusion at 6 months, 1 year and at last follow-up
• 
Recurrence and retreatment rates at 1 year post-procedure and at last follow-up

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• 
The composite percentage of patients with modified Rankin Scale of 0-2 or no change from
baseline at 1 year and at last follow-up.
• 
Occurrence of major stroke in the territory supplied by the treated artery or neurological
death.
Major Stroke events will be further characterized based on whether:
- Event was caused by thromboembolic events
- Event was caused by side-branch occlusion due to the study device
9.5 
Additional Analysis  
All additional analyses are exploratory in nature. No formal statistical hypothesis will be proposed.
Other additional analysis may be performed as requested by the investigators upon request.
9.6 
Handling of Missing Data  
All available data from enrolled subjects will be provided. Handling of dropouts and missing data will
depend on their frequency and the nature of the outcome measure. Adjustments for missing data
will be performed if deemed necessary. Every effort will be made to ensure study follow-up visit
compliance.
10 RISK/BENEFIT 
10.1 Potential Benefits 
Patients’ participation in this study may offer no additional benefit in respect to the same
treatments provided outside of the trial. However, the evidence collected in this study may help to
improve future care.
The greatest clinical benefit of the Pipeline™device includes restoration of original, natural blood
circulation while providing permanent long-term IA occlusion. Intermediate benefits include
stabilizing the aneurysm and providing symptomatic relief. The long-term complete occlusion rate
of coil embolization in large or giant aneurysms appears to be far less than 50%, so flow diverters
such as Pipeline™Flex Embolization Device with Shield Technology™would increase the likelihood
that the procedure will provide full benefits to the subjects, without leaving behind coil mass which
may cause significant symptoms following treatment.
10.2 Potential Risks 
There are no expected additional risks relative to participation in this study as device used are
commercially available and used in accordance with approved labeling. Therefore no risks other
than the risks typically associated with routine device implantation and follow-up are anticipated.
Patients are treated according to general clinical practice, therefore there are no additional risks
associated with the participation in this study.
Potential risks associated with Pipeline™Flex Embolization Device with Shield Technology™use
and diagnostic imaging for subjects with intracranial aneurysms undergoing an endovascular
procedure include but are not limited to:

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Risks associated with placement of the Pipeline™Flex Embolization Device with Shield
Technology™:
Possible
• Embolism
• Headache
• Hematoma
• Hemorrhage, intracranial
• Hemorrhage, non-intracranial
• In-stent stenosis
• Pain
• Parent artery stenosis
• Thromboembolic events
• Vision impairment
Infrequent
• Amaurosis fugax (temporary loss of vision in one eye)
• Aneurysm rupture
• Arrhythmia
• AV fistula
• Blindness
• Blood vessel perforation / rupture / occlusion
• Carotid cavernous fistula
• Cranial neuropathy
• Death
• Dizziness / tinnitus
• Groin injury (including bleeding, bruising, infection, pain)
• In-stent occlusion
• Infection
• Ischemia
• Mass effect
• Nausea / vomiting
• Neurological deficits
• Palsy / muscle weakness
• Pseudoaneurysm
• Ptosis
• Stroke, hemorrhagic
• Stroke, ischemic
• Transient ischemic attack
• Thrombosis / occlusion of the parent artery
• Vasospasm
Rare
• Allergic reaction to medications and/or dye
• Coma
• Device fracture
• Device migration or misplacement
• Hydrocephalus
• Seizure

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Risks associated with imaging required for flow diverter treatment:
• 
Reddening of the skin, blistering and even ulceration
• 
Developing a radiation-induced cancer later in life
• 
Renal injury associated with contrast
Risks associated with Clinical Research
All records and other information about subjects participating in this study will be treated as
confidential so there will not be additional risk for the patient’s privacy that will be guaranteed.
Risk Mitigation
Several safeguards are incorporated into the study to minimize subject risk. All preclinical device
testing for the implantable braid and the single use delivery system are performed in accordance
with regulations and recognized standards. All test results have passed the required specifications
supporting reasonable safety for this clinical product.
At each investigational site, the study will be conducted under the direction of a qualified physician
experienced with endovascular procedures including intracranial aneurysm repair and will have
completed at least 20 cases with a flow diverter of which at least 15 were with a Pipeline device
including a minimum of 5 Pipeline™Flex or Pipeline Flex with Shield Technology™cases. All
principal investigators have experience conducting clinical research and have adequate personnel
to assure compliance to the study protocol. All clinical investigators will have received training
specific to the Pipeline™Flex Embolization Device with Shield Technology™. The Instructions for
Use provide details on the proper use of the Pipeline™Flex Embolization Device with Shield
Technology™.
Subjects will be monitored closely as part of the study to allow for detection of adverse events,
should they be present. Thus, in turn, should allow for early treatment, if necessary. Personally
identifying subject information will not be collected on electronic Case Report Forms (eCRFs) or
other study-related documentation to be provided to the Sponsor. In the event the Sponsor
receives source documents or other information not yet redacted, the Sponsor will ensure
confidentiality is maintained and appropriate de-identification is completed prior to filing in the
study master file.
Study data will be monitored by individual site and combined sites. Clinical outcomes of all study
subjects will be routinely monitored by the Sponsor during the course of the study. Safety endpoint
related events will be reviewed and adjudicated by an independent CEC. In the event of unforeseen
or increased risks to subjects encountered during the course of the study, the study may be
suspended or terminated.
10.3 Justification 
The risks associated with use of the Pipeline™Flex Embolization Device with Shield Technology™
are expected to be similar in nature and rate to those of the PED. Existing clinical studies and
numerous independent publications with the PED provide clinical data to support the reasonable
safety of the device. Therefore, the Sponsor considers the benefits of using the Pipeline™Flex
Embolization Device with Shield Technology™to outweigh the risks in the defined subject
population.

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11 STUDY MONITORING 
Medtronic, as the Sponsor, will be responsible for ensuring that adequate monitoring at each site is
completed to ensure protection of the rights of subjects, the safety of subjects, and the quality and
integrity of the data collected and submitted in compliance with applicable regulations.
Appropriately qualified and trained personnel appointed by Sponsor will conduct monitoring at
each site per the Clinical Monitoring Plan. Monitors for the clinical study will consist of Sponsor
Clinical staff and/or qualified contract services (e.g., CRO) appointed by the Sponsor. The primary
contact for the clinical study will be the Clinical Project Leader.
Clinical Affairs Department
9775 Toledo Way
Irvine, CA 92618
Phone: 949-837-3700
Fax: 760-591-3295
Study Monitors will conduct site visits to ensure accuracy of data, timeliness of data submissions,
adequate subject enrollment, compliance with applicable laws and regulations, compliance with the
protocol, compliance with the signed investigator agreement, and compliance with IRB/EC
conditions and guidelines. Any non-compliance with these items that is not adequately addressed
by the principal investigator/site staff is cause for the Sponsor to put the investigator/site staff on
probation or withdraw the investigator/site staff from the study. Frequency of monitoring will be
based upon enrollment, study duration, compliance, and any suspected inconsistency in data that
requires investigation.
All subject treatments, follow-up visits and phone conversations/interviews will be fully
documented either in the subject’s medical records or any other source documentation.
Information entered into the eCRFs will be verified against the source documents and subject’s
medical records. Additional subject medical record review may be required for AE adjudication. De-
identified study-related source documents may be photocopied, if required. The study Monitor will
also check the Investigator Site File (ISF) to ensure that study-related documents are current.
A Medtronic representative or their agent may be present during the endovascular procedure.
11.1 Direct Access to Source Documents 
By participating in this research study, the investigator agrees to permit monitoring and auditing by
the Sponsor and/or its designee(s) and inspection by applicable regulatory authorities. The
investigator also agrees to allow the Sponsors CRAs/monitors/auditors/EC/IRB/regulatory
agencies to have direct access to his/her research-related study records (e.g. medical records,
source documentation, and billing information) for review. If an investigator is notified of a pending
investigation by a regulatory agency, IRB/EC, or other similar organization, he/she will inform the
Sponsor promptly.

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11.2 Close-out Visit 
Final close out visits at the sites will be conducted at the end of the study according to the Clinical
Monitoring Plan. The purpose of the final visit is collect all outstanding study data documents,
ensure that the principal investigator’s files are accurate and complete, review record retention
requirements with the principal investigator, provide for appropriate disposition of any remaining
supplies, and ensure that all applicable requirements are met for the study. Close-out visits may be
conducted via telephone under appropriate conditions.
12 ELECTRONIC CASE REPORT FORMS (eCRFs) 
Study data will be collected using electronic case report forms and a 21 CFR Part 11-compliant
electronic data capture system. The application provides the capability of data collection remotely
through the Internet so the participating site personnel may log on the system securely and enter
the data. All subjects’ data collected in the system will be extensively verified through data
validation programs, database integrity rules, and investigation-specific data entry conventions for
data accuracy and logical meaningfulness. Periodic review of all subjects’ collected data will be
performed in order to examine the expected distributions of data and to identify outliers for
possible data entry errors.
The investigator is responsible for reviewing all eCRF entries for completion and correctness.
Changes in case report forms will be made electronically and the system used will keep an audit trail
of changes. If necessary, an explanation for the change(s) may be provided. All study staff that will
enter data into eCRFs will undergo appropriate training for use of electronic CRFs.
Further information regarding eCRF navigation and use may be found in the eCRF Completion
Guidelines.
13 RESEARCH COMPLIANCE 
13.1 Sponsor Compliance 
The Sponsor is responsible for implementing and maintaining quality assurance and a quality
control system to ensure that the data generated are recorded and reported in accordance with
established procedures. The study will be organized, performed, and reported in compliance with
this research study protocol, Standard Operating Procedures, applicable regulations and
recognized standards and, if applicable, any additional requirements imposed by the IRB/EC or
regulatory authority.
The Sponsor is responsible for obtaining and maintaining appropriate insurance policies for the
clinical study, if requested by the local regulations.
The regional Sponsor Medtronic Australasia is a wholly owned subsidiary of Medtronic Inc., which
as the parent company of such entity maintains appropriate clinical study liability insurance
coverage as required under applicable laws and regulations and will comply with applicable law and

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custom
concerning
specific
insurance
coverage.
If
required,
a
Clinical
Trial
Insurance
statement/certificate will be provided to the EC/IRB.
The Sponsor will secure an agreement with all parties to allow direct access to all study-related
sites, source documents, and reports for the purpose of monitoring and auditing by the Sponsor
and/or its designee(s) and inspection by regulatory agencies.
The Sponsor will apply quality control measures to all stages of data collection and handling to
ensure reliability and accuracy. In addition, the Sponsor will confirm that the data are processed
correctly.
Data from eCRFs and other external data will be entered into a clinical database as specified in the
Data Management Plan. Quality control and data validation procedures will be applied to ensure the
validity and accuracy of the clinical database.
The clinical database will be reviewed and checked for omissions, apparent errors, and values
requiring further clarification in accordance with the Data Management Plan. Data queries requiring
clarification will be documented and returned to the study site for resolution. Only authorized
personnel will make corrections to the clinical database, and all corrections will be documented in
an audit trail.
During the course of the study, an amendment to the protocol may be necessary. Only the
Sponsor is allowed to amend this protocol. Where applicable, any amendments or modifications
must be approved by the research site’s IRB/EC prior to research-study staff implementation,
unless the modifications increase Subject safety. The research sites will receive the following for
their regulatory file and, if applicable, IRB/EC submission:
• An updated protocol
• Changes to informed consent or DRF templates (if necessary)
13.2 Investigator Compliance 
The site principal investigator assumes full responsibility for performance of the research study in
accordance with the Clinical Study Agreement, this protocol, GCP, all regulatory requirements
applicable to the jurisdictions in which the study is being conducted, and any additional
requirements imposed by the IRB/EC.
13.3 Onsite Audits 
Representatives of the Sponsor may visit the study site(s) to conduct an audit of the study in
compliance with regulatory guidelines and company policy. These audits will require access to all
study records, including source documents, for inspection and comparison with the eCRFs. Subject
privacy will be respected.
Similar auditing procedures may also be conducted by agents of any regulatory body reviewing the
results of the study in support of a regulatory submission. The investigator should immediately
notify the Sponsor if he/she has been contacted by a regulatory agency concerning an upcoming
inspection.

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14 RESPONSIBILITIES AND RECORDS 
14.1 Investigator Responsibilities 
The principal investigator shall be responsible for the day-to-day conduct of the clinical
investigation as well as for the safety and well-being of the human subjects involved in the clinical
investigation.
14.2 Investigator Record Retention 
The investigator shall maintain all study documentation in his/her possession and/or control and
institute measures to prevent accidental or premature destruction of any data and/or documents
related to the study.
The investigator shall retain study documentation during the study and for a period of at least 2
years or longer, if required by local laws, after the last approval of a marketing application in an
International Conference on Harmonization (ICH) region and until there are no pending or
contemplated marketing applications in an ICH region or at least 2 years have elapsed since the
formal discontinuation of clinical development of the investigational product.
For Australia, the Investigator shall retain and preserve a copy of all Study Materials, including
copies of signed consent forms, Case Report Forms, Clinical Investigation Plan, information
relating to the Investigational Product, correspondence and investigator files for at least 15 years
from Study Completion and must ensure that no Study related materials are destroyed before the
expiration of this time period without the written approval of Sponsor. The Institution agrees to
notify the Sponsor before destroying any Study Materials and agrees to retain the Study Materials
for such longer period as reasonably required by the Sponsor at the Sponsor’s expense.
14.3 Sponsor Record Retention 
The Sponsor will maintain all study documentation in its possession and/or contact and institute
measures to prevent accidental or premature destruction of any data and/or documents related to
the research study.
The Sponsor shall retain the study documentation during the study and for a period of at least 2
years after the last approval of a marketing application in an ICH region and until there are no
pending or contemplated marketing applications in an ICH region or at least 2 years have elapsed
since the formal discontinuation of clinical development of the investigational product.
15 ETHICAL CONDUCT OF THE STUDY 
This study is to be conducted in accordance with ethical principles based on the Declaration of
Helsinki concerning medical research in humans and applicable regulations. This study is to be
conducted in compliance with any additional laws and regulatory requirements of the country in
which the site resides, including data protection laws.

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The principles of the Declaration of Helsinki have all been implemented in this study by means of
the informed consent/DRF process, EC/IRB approval (where applicable), study training, clinical trial
registration, preclinical testing, risk benefit assessment, publication policy, etc.
The investigator agrees by participating in the conduct of this protocol to adhere to the
instructions and procedures described and to adhere to the principals of GCP.
16 INSTITUTIONAL REVIEW BOARDS / ETHICS COMMITTEE 
The requirement to obtain EC/IRB approval depends on local law/hospital requirements.
If approval by the EC/IRB is required, the Sponsor and/or investigator must submit this protocol to
the appropriate IRB/EC, and is required to forward to the Sponsor a copy of the written and dated
approval.
The study (study number, protocol title, and version), documents reviewed (e.g. protocol, informed
consent or DRF, etc.) and the date of the review should be clearly stated on the written IRB/EC
approval/favorable opinion.
The study will not start at a site and subjects will not be enrolled until a copy of written and dated
approval/favorable opinion has been received by the IRB/EC.
Any amendment or modification to the protocol should be sent to the IRB/EC. The IRB/EC should
also be informed of any event likely to affect the safety of subjects or the conduct of the study.
The informed consent or DRF used by the investigator for obtaining the subjects consent must be
reviewed and approved by the Sponsor prior to submission to the appropriate IRB/EC for
approval/favorable opinion.
17 QUALITY CONTROL AND QUALITY ASSURANCE 
17.1 Data Control 
Every effort will be taken to ensure the accuracy and reliability of data including the selection of
qualified investigators and appropriate study centers, review of protocol procedures with the
investigator and associated personnel before the study commences, and periodic onsite
monitoring visits by the Sponsor as deemed appropriate by the Sponsor. Guidance for eCRF
completion will be provided and reviewed with the study personnel. The Sponsor will review eCRFs
for accuracy and completeness and any discrepancies will be resolved with the investigator or
designee, as appropriate.
17.2 Site Selection 
The Sponsor or representative of the Sponsor will assess each potential site to ensure the principal
investigator and his/her staff has the facilities and expertise required for the study. Sites will be
selected based upon a site assessment, appropriate facilities, and the qualifications of the

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investigator(s). Individual investigators will be evaluated by the Sponsor based on experience with
the intended procedure(s) and ability to conduct the study according to the study protocol.
To participate, a site must have the following components:
• 
A physician trained in the use of the Pipeline™device with a history of completing at least
20 flow diversion cases of which a minimum of 15 are with a Pipeline device including a
minimum of 5 Pipeline™Flex or Pipeline Flex with Shield Technology™cases.
• 
An established antiplatelet regimen used in conjunction with Pipeline™device utilization.
• 
Commitment from the participating physician to pursue details of any safety outcomes.
• 
Commitment from the participating physician to enroll only subjects meeting the study
criteria.
• 
Be willing to enter data and respond to queries.
• 
Internet access (for electronic data capture) in the hospital or clinic setting.
• 
Be willing to perform necessary documentation (e.g., eCRF).
• 
Agree to sign and adhere to the Investigator Agreement
• 
Agree to participate in Investigator meetings as scheduled by Medtronic.
17.3 Site Training 
Each investigational site will be trained to the investigational plan. Investigator/Site Personnel will
undergo training prior to performing any study-related procedures. All training must be
documented. Study training requirements will include the following topics:
• 
Protocol review
• 
Delegation of authority for study-related tasks
• 
Informed Consent process, including any relevant IRB/EC requirements
• 
Electronic Case Report Forms and completion instructions
• 
Documentation of protocol deviations
• 
Adverse Event Reporting
• 
Device specific events reporting
• 
Instructions for Use of the Pipeline™Flex Embolization Device with Shield
Technology™
• 
Responsibilities and obligations of the investigator/staff
• 
General guidelines for good clinical practices
• 
Study documentation required (essential documents)
Existing study site personnel who have been delegated new tasks and new study site personnel will
undergo training to the investigational plan, as appropriate.

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17.4 Site Initiation 
The Sponsor or a representative of the Sponsor will conduct a training session with site staff to
review the protocol, eCRFs, the informed consent or DRF process, IRB/EC involvement (if
applicable) and guidelines, responsibilities and obligations, reporting requirements, and general
guidelines for good clinical practices.
Prior to enrolling subjects at an investigational site, the following documentation must be provided
to the Sponsor:
• 
IRB/EC approval for the Investigational Plan, if applicable
• 
IRB/EC and Sponsor approved Informed Consent or DRF for the study, if applicable
• 
Signed Confidentiality Agreement (CDA)
• 
Signed Clinical Study Agreement (CSA), Investigator Agreement and if applicable, Sub-
Investigator Agreement(s)
• 
Training log documentation to verify the appropriate study staff has been trained on the
protocol, eCRFs, and study conduct.
• 
Investigator(s’) curriculum vitae (CV)
• 
Experience Statement from Principal Investigators and Sub-Investigators
17.5 Data Quality Assurance 
ORACLE Clinical Remote Data Capture (OC/RDC) is the EDC system that will be deployed to
support data collection for this study. Documentation pertinent to the use of the EDC system will
be made available for use by appropriate site personnel. All individuals who will be expected to use
the EDC system will be given adequate training necessary to perform their assigned tasks as
described in (21 CFR 11.10(i)). Training will be conducted through a website or by qualified
individuals initially and on a continuing basis, as needed.
17.6 Data Handling 
The Sponsor is responsible for compilation and verification of the study data, retention of the
clinical study database, performance of statistical analysis, and preparation of the study reports.
The Sponsor will ensure that the performance of Data Management activities occur in accordance
with the study Data Management Plan.
18 DATA OWNERSHIP 
Rights, duties, and obligations regarding ownership of any ideas, concepts, inventions, or results,
whether patentable or not, shall be in accordance with the terms and conditions set forth in the
Clinical Study Agreement by and between the Institution and Sponsor. Unless otherwise expressly
set forth in the Clinical Study Agreement, the Sponsor retains exclusive ownership of all data,
results, reports, findings, discoveries and any other information collected during this study. The
Sponsor reserves the right to use the data from the database in the present study.

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22 REFERENCES 
1
Inagawa, T. & Hirano, A. Autopsy study of unruptured incidental intracranial aneurysms. Surg 
Neurol 34, 361-365 (1990).
2
Edlow, J. A., Malek, A. M. & Ogilvy, C. S. Aneurysmal subarachnoid hemorrhage: update for
emergency physicians. J Emerg Med 34, 237-251, doi:10.1016/j.jemermed.2007.10.003 (2008).
3
Agarwal, N. et al. Prevalence of Asymptomatic Incidental Aneurysms: A Review of 2685
Computed Tomographic Angiograms. World Neurosurg, doi:10.1016/j.wneu.2013.01.082
(2013).
4
Dodd RL, S. G. Intracranial aneurysms. In: Aminoff MJ, Daroff RB, eds. Encyclopedia of 
Neurological Sciences. St. Louis: Academic Press, Elsevier (2003).
5
Roy, D., Milot, G. & Raymond, J. Endovascular treatment of unruptured aneurysms. Stroke 32,
1998-2004 (2001).
6
Zuccarello, M. Treatment strategy for patients with unruptured intracranial aneurysms. Neurol 
Med Chir (Tokyo) 41, 571-575 (2001).
7
Wiebers, D. O. et al. Unruptured intracranial aneurysms: natural history, clinical outcome, and
risks of surgical and endovascular treatment. Lancet 362, 103-110 (2003).
8
Wermer, M. J. H., van der Schaaf, I. C., Algra, A. & Rinkel, G. J. E. Risk of Rupture of Unruptured
Intracranial Aneurysms in Relation to Patient and Aneurysm Characteristics: An Updated Meta-
Analysis. Stroke 38, 1404-1410, doi:10.1161/01.STR.0000260955.51401.cd (2007).
9
Fiorella, D. et al. Curative cerebrovascular reconstruction with the Pipeline embolization device:
the emergence of definitive endovascular therapy for intracranial aneurysms. Journal of 
neurointerventional surgery 1, 56-65, doi:10.1136/jnis.2009.000083 (2009).
10 Gruber, D. P. et al. A comparison between endovascular and surgical management of basilar
artery apex aneurysms. J. Neurosurg. 90, 868-874, doi:10.3171/jns.1999.90.5.0868 (1999).
11 Cognard, C. et al. Long-term angiographic follow-up of 169 intracranial berry aneurysms
occluded
with
detachable
coils.
Radiology
212,
348-356,
doi:10.1148/radiology.212.2.r99jl47348 (1999).
12 Molyneux, A. J. et al. International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping
versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a
randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups,
and aneurysm occlusion. Lancet 366, 809-817, doi:10.1016/S0140-6736(05)67214-5 (2005).
13 Cantore, G. et al. Surgical treatment of giant intracranial aneurysms: current viewpoint.
Neurosurgery 63, 279-289 (2008).
14 Hauck, E. F., Wohlfeld, B., Welch, B. G., White, J. A. & Samson, D. Clipping of very large or giant
unruptured intracranial aneurysms in the anterior circulation: an outcome study. J Neurosurg
109, 1012-1018 (2008).

FD3512 
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Page 52 of 55 
Study Protocol – Rev.B - SHIELD Study 
15 Sughrue, M. E., Saloner, D., Rayz, V. L. & Lawton, M. T. Giant intracranial aneurysms: evolution
of management in a contemporary surgical series. Neurosurgery 69, 1261-1270 (2011).
16 Jahromi, B. S. et al. Clinical and angiographic outcome after endovascular management of giant
intracranial
aneurysms.
Neurosurgery
63,
662-674;
discussion
674-665,
doi:10.1227/01.NEU.0000325497.79690.4C (2008).
17 Kato, Y. et al. Surgical strategies for treatment of giant or large intracranial aneurysms: our
experience with 139 cases. Minim Invasive Neurosurg 46, 339-343 (2003).
18 Nakase, H. et al. Long-term outcome of unruptured giant cerebral aneurysms. Neurol Med Chir
46, 379-384 (2006).
19 Sharma, B. S., Gupta, A., Ahmad, F. U., Suri, A. & Mehta, V. S. Surgical management of giant
intracranial aneurysms. Clin Neurol Neurosurg 110, 674-681 (2008).
20 Murayama, Y. et al. Guglielmi detachable coil embolization of cerebral aneurysms: 11 years'
experience. J Neurosurg 98, 959-966 (2003).
21 Gao, X., Liang, G., Li, Z., Wei, X. & Cao, P. A single-centre experience and follow-up of patients
with endovascular coiling of large and giant intracranial aneurysms with parent artery
preservation. Journal of clinical neuroscience : official journal of the Neurosurgical Society of 
Australasia 19, 364-369, doi:10.1016/j.jocn.2011.03.038 (2012).
22 Chalouhi, N. et al. Stent-assisted coiling versus balloon remodeling of wide-neck aneurysms:
comparison of angiographic outcomes. AJNR. American journal of neuroradiology 34, 1987-
1992, doi:10.3174/ajnr.A3538 (2013).
23 Zanaty, M. et al. Flow diversion versus conventional treatment for carotid cavernous
aneurysms. Stroke 45, 2656-2661, doi:10.1161/STROKEAHA.114.006247 (2014).
24 O'Kelly, C. J. et al. Canadian Experience with the Pipeline Embolization Device for Repair of
Unruptured Intracranial Aneurysms. AJNR Am J Neuroradiol 2, 2 (2012).
25 Raymond, J. et al. Long-term angiographic recurrences after selective endovascular treatment
of
aneurysms
with
detachable
coils.
Stroke
34,
1398-1403,
doi:10.1161/01.STR.0000073841.88563.E9 (2003).
26 Machi, P. et al. Endovascular therapeutic strategies in ruptured intracranial aneurysms.
European journal of radiology 82, 1646-1652, doi:10.1016/j.ejrad.2013.01.034 (2013).
27 Nelson, P. K. et al. The pipeline embolization device for the intracranial treatment of aneurysms
trial. AJNR. American journal of neuroradiology 32, 34-40 (2011).
28 Becske, T. et al. Pipeline for Uncoilable or Failed Aneurysms: Results from a Multicenter Clinical
Trial. Radiology 267, 858-868, doi:doi:10.1148/radiol.13120099 (2013).
29 Kallmes, D. F. et al. International Retrospective Study of the Pipeline Embolization Device: A
Multicenter
Aneurysm
Treatment
Study.
AJNR. American journal of neuroradiology,
doi:10.3174/ajnr.A4111 (2014).

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30 Lylyk, P. et al. Curative endovascular reconstruction of cerebral aneurysms with the pipeline
embolization device: the Buenos Aires experience. Neurosurgery 64, 632-642 (2009).
31 Chitale, R. et al. Single center experience with pipeline stent: feasibility, technique, and
complications. Neurosurgery 71, 679-691 (2012).
32 Colby, G. P. et al. Immediate procedural outcomes in 35 consecutive pipeline embolization
cases: a single-center, single-user experience. Journal of neurointerventional surgery 5, 237-
246, doi:10.1136/neurintsurg-2012-010299 (2013).
33 Saatci, I., Yavuz, K., Ozer, C., Geyik, S. & Cekirge, H. S. Treatment of Intracranial Aneurysms
Using the Pipeline Flow-Diverter Embolization Device: A Single-Center Experience with Long-
Term Follow-Up Results. AJNR. American journal of neuroradiology 33, 1436-1446 (2012).
34 O'Kelly, C. J. et al. Canadian Experience with the Pipeline Embolization Device for Repair of
Unruptured Intracranial Aneurysms. American Journal of Neuroradiology 34, 381-387,
doi:10.3174/ajnr.A3224 (2013).
35 Kan, P. et al. Early Postmarket Results After Treatment of Intracranial Aneurysms With the
Pipeline Embolization Device: A US Multicenter Experience. Neurosurgery 71, 1080-1088
1010.1227/NEU.1080b1013e31827060d31827069 (2012).
36 Yu, S. C.-H. et al. Intracranial Aneurysms: Midterm Outcome of Pipeline Embolization Device—
A Prospective Study in 143 Patients with 178 Aneurysms. Radiology 265, 893-901,
doi:10.1148/radiol.12120422 (2012).
37 Szikora, I. et al. Treatment of intracranial aneurysms by functional reconstruction of the parent
artery: the Budapest experience with the pipeline embolization device. AJNR. American journal 
of neuroradiology 31, 1139-1147, doi:10.3174/ajnr.A2023 (2010).
38 Kars, H. Z. & Gurelik, M. Clipping of large and giant aneurysms of anterior circulation. Turk 
Neurosurg 21, 53-58 (2011).
39 McAuliffe, W. et al. Immediate and midterm results following treatment of unruptured
intracranial aneurysms with the pipeline embolization device. AJNR. American journal of 
neuroradiology 33, 164-170 (2012).
40 Saatci, I., Yavuz, K., Ozer, C., Geyik, S. & Cekirge, H. S. Treatment of Intracranial Aneurysms
Using the Pipeline Flow-Diverter Embolization Device: A Single-Center Experience with Long-
Term Follow-Up Results. AJNR. American journal of neuroradiology 19, 19 (2012).
41 Chalouhi, N. et al. Extending the Indications of Flow Diversion to Small, Unruptured, Saccular
Aneurysms of the Anterior Circulation. Stroke 45, 54-58, doi:10.1161/strokeaha.113.003038
(2014).
42 Lee, D. H. et al. Dual antiplatelet therapy monitoring for neurointerventional procedures using a
point-of-care platelet function test: a single-center experience. AJNR Am. J. Neuroradiol. 29,
1389-1394, doi:10.3174/ajnr.A1070 (2008).
43 Skukalek, S. L. et al. Effect of antiplatelet therapy and platelet function testing on hemorrhagic
and thrombotic complications in patients with cerebral aneurysms treated with the pipeline

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Page 54 of 55 
Study Protocol – Rev.B - SHIELD Study 
embolization device: a review and meta-analysis. Journal of neurointerventional surgery,
doi:10.1136/neurintsurg-2014-011145 (2014).
44 Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J et al. Standardized bleeding
definitions for cardiovascular clinical trials: a consensus report from the bleeding academic
research
consortium.".
Circulation
123
(23):
2736-47.
doi:10.1161/CIRCULATIONAHA.110.009449 (2011).

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Appendix A – Investigators list & Study Staff 
A list of investigation sites including Name and title of the investigator(s) who is (are) responsible
for conducting the trial, and the address and telephone number(s) of the trial site(s). is maintained
separately and regularly updated. 
A list of Study Contacts, including Name, title, address, and telephone number(s) of Sponsor SAE
Hotline contact information, Sponsor Global Project Manager, Local Monitors and Sponsor Medical
Expert will be maintained and regularly updated.