Prospective, Multi-Center, Single-Arm Study of Reverse Medical Barrel™ Vascular Reconstruction Device for Adjunctive Treatment to Embolic Coils in Wide-Neck, Intracranial, Bifurcating Aneurysms of Middle Cerebral and Basilar Arteries
Phase: NA
Conditions: Intracranial Bifurcating Aneurysms
Sponsor: Medtronic Neurovascular Clinical Affairs

PROPRIETARY DATA: This document and the information contained herein are confidential and may not be reproduced, used, or 
disclosed without written permission from Medtronic – Neurovascular Division 
Prospective, Multi-Center, Single-Arm Study of the 
Reverse Medical Barrel® Vascular Reconstruction Device (VRD) for Adjunctive Treatment
to Embolic Coils for Wide-Neck, Intracranial, Bifurcating/ Branching Aneurysms of 
Middle Cerebral and Basilar Arteries 
“The BARREL Study” 
Clinical Protocol 
Protocol number: VRD-001 
IDE Number: G130185 
Revision C: May 18th, 2016
Sponsor: 
Medtronic Neurovascular 
9775 Toledo Way 
Irvine, California, USA 92618 
949/837-3700 (Main) 
949/837-2044 (Fax) 

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Table of Contents 
1. Investigator Signature Page ....................................................................................................................... 6
2. Study Contact Personnel ........................................................................................................................... 7
3. Study Synopsis .......................................................................................................................................... 8
4. Revision History ...................................................................................................................................... 11
4.1 
Summary of Changes ...................................................................................................................... 11 
5. Background for Proposed Trial ............................................................................................................... 14
6. Statistical Considerations and Analysis .................................................................................................. 16
6.1 
Determination of Historical Control ................................................................................................ 16 
6.2 
Primary Analysis ............................................................................................................................. 17 
6.3 
Sample Size Calculation .................................................................................................................. 18 
6.4 
Endpoint Analysis and Reporting of Results ................................................................................... 18 
6.5 
Statistical Analysis Sets ................................................................................................................... 18 
6.6 
Analysis of Primary Safety Endpoint .............................................................................................. 19 
6.7 
Analysis of Secondary Endpoints .................................................................................................... 19 
6.8 
Analysis of Baseline Demographics and Procedural Characteristics .............................................. 19 
6.9 
Pre-planned Subgroup Analyses ...................................................................................................... 19 
6.10 
Handling of Missing Data................................................................................................................ 20 
7. Objectives ................................................................................................................................................ 20
8. Overall Trial Design ................................................................................................................................ 20
8.1 
Primary Outcome Measures ............................................................................................................ 20 
8.1.1 
Primary Endpoints ........................................................................................................................... 20 
8.1.2 
Secondary Endpoints ....................................................................................................................... 20 
9. Trial Population ....................................................................................................................................... 21
9.1 
Number of Patients .......................................................................................................................... 21 
9.2 
Patient Inclusion Criteria ................................................................................................................. 21 
9.3 
Patient Exclusion Criteria ................................................................................................................ 21 
10. Device Descriptions ................................................................................................................................ 22
11. Study Materials ....................................................................................................................................... 27
11.1 
Instructions for Use ......................................................................................................................... 27 
11.2 
Device Accountability ..................................................................................................................... 27 

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12. Study Methods and Procedures ............................................................................................................... 27
12.1 
Enrollment Procedures .................................................................................................................... 27 
12.2 
Informed Consent ............................................................................................................................ 27 
12.3 
Physician Training ........................................................................................................................... 27 
12.4 
Schedule of Events .......................................................................................................................... 27 
12.5 
Procedure ......................................................................................................................................... 28 
12.6 
Study Evaluations ............................................................................................................................ 29 
12.6.1 Screening/Baseline Evaluations ...................................................................................................... 29 
12.6.2 Procedural Evaluations .................................................................................................................... 29 
12.6.3 Immediate Post-operative Evaluations ............................................................................................ 30 
12.6.4 Post-placement Antiplatelet Agents ................................................................................................ 30 
12.6.5 Follow-Up (30-day, 180-day, and 12-month) .................................................................................. 30 
12.6.6 Unscheduled Visits .......................................................................................................................... 31 
12.6.7 Study Exit ........................................................................................................................................ 31 
12.6.8 Termination of Subject Participation ............................................................................................... 31 
12.7 
Angiography Core Lab .................................................................................................................... 33 
12.7.1 Assessments ..................................................................................................................................... 33 
12.8 
Adverse Event Reporting................................................................................................................. 33 
12.8.1 Definitions ....................................................................................................................................... 34 
12.8.2 Device Specific Events .................................................................................................................... 37 
12.8.3 Event Reporting ............................................................................................................................... 37 
12.8.4 Protocol Deviations ......................................................................................................................... 37 
13. Risk Analysis .......................................................................................................................................... 37
14. Administrative Procedures ...................................................................................................................... 39
14.1 
Responsibilities................................................................................................................................ 39 
14.1.1 Investigator ...................................................................................................................................... 39 
14.1.2 Sponsor and Clinical Monitor .......................................................................................................... 39 
14.2 
Protection of Human Subjects ......................................................................................................... 39 
14.3 
Ethical Conduct of the Study ........................................................................................................... 39 
14.4 
Institutional Review Boards ............................................................................................................ 40 
14.5 
Protocol Changes ............................................................................................................................. 40 
14.6 
Subject Confidentiality .................................................................................................................... 40 

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14.7 
Study Data ....................................................................................................................................... 40 
14.8 
Documentation ................................................................................................................................ 41 
14.8.1 Source Documents ........................................................................................................................... 41 
14.8.2 eCRF Completion ............................................................................................................................ 41 
14.8.3 Study Summary ............................................................................................................................... 41 
14.8.4 Documentation Retention ................................................................................................................ 41 
14.8.5 Storage of Investigational Products ................................................................................................. 42 
14.8.6 Data Safety Monitoring Board (DSMB) .......................................................................................... 42 
14.8.7 Clinical Events Committee .............................................................................................................. 42 
14.8.8 Monitoring ....................................................................................................................................... 42 
14.9 
Quality Control and Quality Assurance ........................................................................................... 43 
14.9.1 Data Control .................................................................................................................................... 43 
14.9.2 Site Selection ................................................................................................................................... 43 
14.9.3 Site Training .................................................................................................................................... 43 
14.9.4 Site Initiation ................................................................................................................................... 44 
14.9.5 Data Quality Assurance ................................................................................................................... 44 
14.9.6 Data Handling .................................................................................................................................. 44 
14.10 Publications ..................................................................................................................................... 45 
15. References ............................................................................................................................................... 46

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Table of Tables 
Table 3-1 Schedule of Tests ........................................................................................................................................ 10 
Table 4-1 Protocol Revision History ........................................................................................................................... 11 
Table 6-1 Meta-Analysis for Historical Control .......................................................................................................... 16 
Table 6-2 Sample Size ................................................................................................................................................. 18 
Table 6-3 Safety Rates Reported in the Literature ....................................................................................................... 19 
Table 10-1 Materials Used in the Barrel® VRD .......................................................................................................... 24 
Table 12-1 Schedule of Tests ...................................................................................................................................... 28 
Table of Figures 
Figure 10-1 Detachment Zone and Delivery Wire of Barrel® VRD ............................................................................ 23 
Figure 10-2 Image of Actual Barrel® VRD ................................................................................................................. 23 
Figure 10-3 Cable Set .................................................................................................................................................. 25 
Figure 10-4 Reverse Medical Detachment Box ........................................................................................................... 26 

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1.
Investigator Signature Page
I agree to conduct the study as outlined in the Investigational Plan and in accordance with all applicable laws and 
regulations. In addition, I agree to provide all the information requested in the case report forms presented to me by 
the Sponsor in a manner to ensure completeness, legibility, and accuracy. I agree to actively enroll patients into this 
study. 
I also agree that all information provided to me by the Sponsor, including pre-clinical data, protocols, case report 
forms, and any verbal and written information, will be kept strictly confidential and confined to the clinical 
personnel involved in conducting the study. It is recognized that this information may be relayed in confidence to 
the Institutional Review Board. 
In addition, no reports or information about the study or its progress will be provided to anyone not involved in the 
study other than the Sponsor and the Institutional Review Board. Any such submission will indicate that the material 
is confidential. 
Investigator Signature 
Date 
Investigator Printed Name 

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2.
Study Contact Personnel

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3. Study Synopsis
Prospective Multi-Center Single-Arm Study of the Reverse Medical Barrel® VRD for Adjunctive Treatment to 
Embolic Coils for Wide-neck, Intracranial, Bifurcating/Branching Aneurysms of Middle Cerebral and Basilar 
Arteries: “The BARREL Study” 
Title: 
The BARREL Study 
Study Device: 
Reverse Medical Barrel® Vascular Reconstruction Device (“Barrel VRD”) 
Purpose: 
To evaluate the safety and effectiveness of the Reverse Medical Barrel® VRD for Adjunctive 
Treatment to Embolic Coils for Wide-neck, Intracranial, Bifurcating/Branching Aneurysms of 
Middle Cerebral and Basilar Arteries. 
Intended Use: 
For use with embolic coils for the treatment of wide-neck bifurcating or branching intracranial 
MCA and basilar aneurysms arising from a parent vessel with a diameter of  2mm and  4 
mm. “Wide-neck” is defined as having a neck width  4mm or a dome-to-neck ratio < 2. 
Study Design: 
The BARREL Study is a prospective multi-center, single-arm study of the Barrel® VRD.  A 
maximum of 159 patients will be enrolled (consented) at up to 28 centers to ensure 119 treated 
patients.  After obtaining informed consent, screening and baseline assessments, and eligibility 
confirmation, qualifying patients will receive the study treatment. 
Inclusion Criteria: 
•
Male or female between 18 and 85 years old.
•
A wide-neck aneurysm with a neck  4mm or a dome-to-neck ratio < 2, that is also a
bifurcating or branch MCA or basilar aneurysm and de novo or non-de novo MCA or
basilar aneurysm where no stent was utilized.
•
Subject's aneurysm arises from a parent vessel with a diameter  2mm and  4mm.
•
Appropriate informed consent obtainable as determined by local IRB.
•
Life expectancy > 24 months.
Exclusion 
Criteria: 
•
Aneurysm rupture within 30 days of enrollment.
•
MCA or basilar bifurcating aneurysms not treatable with coiling.
•
Subject with anatomy not accessible for Barrel VRD treatment.
•
Aneurysm neck > 8 mm.
•
Subject presents with an intracranial mass or is currently undergoing radiation therapy for
carcinoma of the head or neck region.
•
Subject has additional aneurysms for which treatment is planned within 18 months.
•
Subject has platelet count of <70,000.
•
Subject has had a previous intracranial stenting procedure associated with the target
aneurysm.
•
Subject has an International Normalized Ratio (INR)  1.7 or is on one of the following
anti-coagulant/anti-platelet medications : Aggrenox, Cilostazol, Apixaban, Dabigatran,
Fondaparinux, Lepirudin, Pradaxa, Rivaroxaban, Argatroban, Arixtra
•
Subject has serum creatinine level > 2mg/dl at baseline screening.
•
Subject has known allergies to nickel-titanium metal.
•
Subject has known allergies to aspirin or heparin.
•
Subject has a life-threatening allergy to contrast (unless treatment for allergy can be
tolerated).
•
Subject has a known cardiac disorder, likely to be associated with cardioembolic
symptoms such as atrial fibrillation (AFIB).

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•
Subject has any condition, which in the opinion of the treating physician, would place the
subject at a high risk of embolic stroke.
•
Subject is currently participating in another clinical research study.
•
Subject is pregnant or breastfeeding.
•
Subject has participated in a drug study within the last 30 days.
•
Subject cannot or is unwilling to take ASA and a P2Y12 Platelet Inhibitor as required by
the protocol following the procedure.
•
Subject is unable or unwilling to comply with protocol requirements and obtain required
clinical evaluations and follow-up.
Evaluation 
Criteria: 
Primary Endpoints 
•
Primary Efficacy Endpoint: The number of Barrel® VRD treated aneurysms achieving
Raymond Grade I (100% occlusion) at 12 months ± 8 weeks in the absence of
retreatment, parent artery stenosis (> 50%), or target aneurysm rupture.
•
Primary Safety Endpoint: Incidence of neurological death or major ipsilateral stroke
(National Institutes of Health Stroke Scale [NIHSS] increase of  4 for >24 hours) at any
time during the follow-up period (12 months ± 8 weeks).
Secondary Endpoints 
•
Any cause death within 30 days or neurological death within 12 months ± 8 weeks.
•
Number of Barrel® VRD treated aneurysms achieving Raymond Grade I or II at 12
months ± 8 weeks in the absence of retreatment, parent artery stenosis (> 50%), or target
aneurysm rupture.
•
Number and percentage of successful device implants.
•
Angiographic evidence of in-stent stenosis at 12 months ± 8 weeks reported according to
the following ordinal groups: <25%, 25-50%, 51-75%, >75%.
•
Device-related Serious Adverse Events (SAEs).
•
The composite percentage of patients with modified Rankin Score of 0-2 or no change
from baseline at 12 months ± 8 weeks.
Schedule of 
Tests: 
The tests and evaluations to be conducted at baseline, procedurally, and during follow-up are 
summarized in Table 3-1. 
Statistical 
Considerations: 
The rate of the primary efficacy endpoint will be formally compared against a historical 
control.  The study will be conducted at up to 28 centers, and it will enroll up to 159 subjects to 
ensure 119 subjects are treated/undergo attempted treatment.   The statistical analysis plan is 
detailed in Section 6. 

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Table 3-1 Schedule of Tests 
Tests and Evaluations 
Screening/ 
Baseline 
Procedural 
(Day 0) 
30 days 
±14 days 
180 days 
±30 days 
12 months 
±8 weeks 
Unscheduled 
Visit 
Inclusion/Exclusion 
X 
Demographics 
X 
Medical history 
X 
Medications 
X 
X 
X 
X 
X 
X 
Blood Labs 
X 
Modified Rankin Score 
X 
X 
X 
X 
NIHSS Score 
X 
X 
X 
X5 
Adverse Events 
X 
X 
X 
X 
X 
Angiography1 
X2 
X 
X4 
X 
Raymond Grade Scale 
X3 
X 
X 
X 
1MRA is acceptable if performed according to the standard of practice at the participating institution. 
2The baseline angiogram must be taken no more than 180 calendar days prior to the procedure. 
3For previously coiled aneurysms 
4If an angiogram is performed as standard patient care it should be sent to the core laboratory for analysis. 
5If visit is related to target aneurysm or potentially associated adverse event 

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4. Revision History
The below table lists the protocol revision history for the BARREL study: 
Table 4-1 Protocol Revision History 
Revision 
Effective Date 
A 
March 10, 2014 
B 
February 20th, 2015 
C 
May 18th, 2016 
4.1 
Summary of Changes 
Revision A to Revision B 
Section 
Change 
Rationale 
Sponsor 
Sponsor name and study contacts changed from 
Reverse Medical to Covidien Neurovascular 
Covidien acquired Reverse Medical and 
is executing the study   
Study Design 
Increased the number of participating centers from 
20 to 28 
Updated to facilitate enrollment 
Exclusion criteria 
Added exclusion criteria for subject with anatomy 
not appropriate for Barrel VRD treatment  
To ensure enrollment of appropriate 
candidates  
Exclusion criteria 
Minor revision the INR and known anti-
coagulant/antiplatelet agents requirement 
Administrative change for clarity 
Exclusion criteria 
Post-placement Antiplatelet 
Agents 
Specified antiplatelet regimen dose and duration 
To standardize dual antiplatelet therapy 
in the study  
Secondary Endpoints 
Change from number/percentage of “device 
deployments” to “device implants” 
For accuracy in reporting device success 
Secondary Endpoints 
Change from the percentage of patients with mRS 
of 0-2 to also include patients with no change from 
baseline 
Patients with no worsening from baseline 
should also be included in an analysis of 
good outcomes 
Schedule of Tests 
Study Evaluations 
Added 180 day visit, widened 30 day visit window 
from ±7 days to ±14 days and allowed 30 day visit 
to be conducted via phone, added unscheduled visit 
and screening blood labs; added guidance for the 
medications to be collected  
To increase patient oversight and provide 
more specific instructions for 
unscheduled visits and medication 
collection 
Enrollment 
Updated definition to specify that enrollment occurs 
at the point of consent  
For clarity 
Statistical Analysis Sets 
Intention-to-treat (ITT) population definition 
changed from those treated with Barrel VRD to 
those who underwent attempted deployment of the 
Barrel VRD 
To include all subjects with an attempt to 
be treated into the ITT population 
Analysis of Primary Safety 
Endpoint 
Safety threshold lowered from 20 to 15% 
Change made per recommendation noted 
in FDA letter dated 11 Jun 2014; rates 
based on incidence in published literature 
Procedure 
Added instructions from Instructions for Use to 
address coiling: refined data to be recorded during 
the procedure 
Administrative change for clarity and to 
ensure that all important procedural data 
are captured by the investigator and/or 
Core Lab 
Termination of Subject 
Added section describing potential reasons and 
Administrative change for clarity 

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Revision A to Revision B 
Participation 
process for  termination of subject participation 
Core Lab 
Clarified evaluations to be performed by the Core 
Lab. Added instructions for assessments of 6 month 
and unscheduled images as applicable. Removed 
requirement to use blinded third party 
Administrative change for clarification 
and for consistency with standard 
process at Covidien  
Adverse Events 
Added ISO14155 definitions for adverse events. 
Updated severity definitions, updated relatedness 
categories, as well as device specific event and 
event reporting requirements 
To clarify collection of adverse events 
and for standardization with Covidien 
processes  
Adverse Events 
Risk Analysis 
Moved anticipated AEs to the risk analysis section 
in the protocol and revised the list to align with the 
IFU 
To align risks with IFU 
Responsibilities 
Rewrote the following sections to align with 
Covidien practices: CRFs, Document Retention, 
DSMB, CEC, Monitoring and Publications.    
Added the following sections: Ethical Conduct of 
Study, Institutional Review Boards, Quality Control 
and Quality Assurance 
Administrative change for 
standardization with Covidien processes 
Appendices 
Informed Consent 
Protection of Human 
Subjects 
Removed appendices (instructions for use and 
sample consent form) from protocol 
Administrative change; these documents 
are controlled outside of the protocol 
Revision B to Revision C
Section 
Change 
Rationale 
Sponsor 
Sponsor name changed from Covidien 
Neurovascular to Medtronic Neurovascular 
Medtronic acquired Covidien and is 
executing the study 
Inclusion / Exclusion Criteria 
Removed Prasugrel, Ticagrelor, and Ticlid from the 
disallowed concomitant medications list 
To allow for physician standard of care 
prior to the procedure and align with 
protocol requirements of any P2Y12 
inhibitor post procedure 
Inclusion / Exclusion Criteria 
Removed the requirement of non-allergy to 
clopidrogrel and ticlopidine. 
Clopidogrel is no longer a protocol 
required medication.   
Inclusion / Exclusion Criteria 
Changed the requirement from “subject cannot or is 
unwilling to take ASA/Clopidrogrel” to “Subject 
cannot or is unwilling to take ASA and a P2Y12 
Platelet Inhibitor” 
To align with revised dual anti-platelet 
therapy requirements 
Primary Endpoints 
Changed primary endpoint language from “absence 
of neurological death/major ipsilateral stroke…” to 
“incidence of neurological death/major ipsilateral 
stroke”. 
 Corrected the primary endpoint 
language for alignment with the primary 
safety endpoint a priori threshold of 15% 
Secondary Endpoints 
Changed secondary endpoint language from 
“absence of any cause death within 30 days…” to 
“Any cause death within 30 days…” 
To remain consistent with primary 
endpoint format 
Secondary Endpoints 
Added language to secondary endpoint indicating 
stenosis will be evaluated at 12 months ± 8 weeks 
Added for completeness as the timing of 
this endpoint had not been explicitly 
specified. 
Secondary Endpoints 
Changed secondary endpoint language from 
“absence of device-related serious adverse 
events…” to “device related serious adverse 
events…” 
To remain consistent with primary 
endpoint format 

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Revision B to Revision C
Section 
Change 
Rationale 
Sample Size Calculation 
•
The primary performance goal was increased
from 23% to 28%.
•
The estimated success rate of the trial was
increased from 33% to 41%, therefore
decreasing the necessary sample size to achieve
80% power for the trial.
•
Maintaining the assumption of a 10% dropout
rate, the number of subjects required for the
study changed from 164 to 119.
•
The maximum number of enrolled/consented
subjects was specified as 159 to allow for screen
fails.
•
•
In conjunction with increasing the
performance goal, the estimated
success rate of the trial was also
increased and the corresponding
sample size recalculated. Based on
higher estimated success rate, sample
size is being reduced.
The maximum number of subjects
enrolled/consented was specified to
account for up to 25% of subjects who
consent for the trial and may withdraw
prior to treatment or are determined to
be ineligible.
Statistical Analysis Sets 
Removed: Note that in the case of missing primary 
efficacy endpoint data, the subject will be 
considered a failure in the primary efficacy 
endpoint analysis.  
Added: The primary analyses for both the safety 
and effectiveness endpoints will be based on the 
observed data. 
Considering missing data as failure, 
known as the imputing worst case 
scenario, is an extreme imputation form 
and is not appropriate for the primary 
statistical analysis. Instead, we plan to 
perform primary statistical analysis based 
on observed cases.   
Handling of Missing Data 
Replaced tipping analysis for missing data with 
Multiple imputation technique and explanation of 
handling subjects who withdraw prior to the final 
assessment will be handled using the Markov Chain 
Monte Carlo algorithm to specify missing at 
random. 
As recommended by FDA, we will apply 
multiple imputation technique to handle 
missing primary endpoints. 
Post-Placement Anti-platelet 
Agents 
Changed the dual anti-platelet therapy requirement 
from a minimum of 325mg of Aspirin for 12 
months and 75mg of Clopidogrel daily for 3 months 
to the minimum of 81 mg of Aspirin for 12 months 
and any P2Y12 platelet inhibitor for 3 months. 
The standard of care for dual antiplatelet 
therapy varies across US institutions. 
This protocol has been updated to 
provide additional flexibility to 
investigators such that they may utilize 
antiplatelet regimens that are closer to 
their standard of care while also 
maintaining standardization of minimum 
antiplatelet requirements (minimum of 
two antiplatelet agents, minimum dosage 
and minimum duration) to prevent a wide 
variation in antiplatelet regimens in the 
study.  
Follow-up Visits 
Added descriptions to the 30-day and 180-day 
follow up visits 
Administrative update to provide a 
clearer presentation of visit requirements. 
There have been no changes to the visits 
or assessments required. 

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Revision B to Revision C
Section 
Change 
Rationale 
Study Exit 
Subject Discontinuation by 
Investigator 
Included statement regarding the  requirement for 
follow-up through the 30-day visit for subjects who 
are enrolled and undergo an attempt delivery with 
the Barrel VRD but are not implanted 
This existing statement was clarified in the ‘subject 
discontinuation by investigator’ section 
This requirement was added to the study 
exit section and revised in the ‘subject 
discontinuation by investigator’ section 
for clarity.  The purpose for this 
requirement is to ensure adequate safety 
follow-up for subjects who do not 
receive the Barrel implant.  
Adverse Events 
Updated relatedness definitions and added 
definitions for select neurological adverse events of 
interest 
To clarify collection of adverse events 
and for standardization with Medtronic 
processes 
DSMB Committee 
Reference to DSMB stopping rules and interim 
analyses have been removed 
Administrative change to reflect current 
DSMB Charter and no plan for an 
interim analysis. 
Clinical Events Committee 
Updated types of events to be reviewed to include: 
1) all Adverse Events associated with a change in
NIHSS (vs. only those with a sudden neurological 
worsening or deterioration  3 points on the 
NIHSS) and 2) any Adverse Event related to the 
Antiplatelet Therapy  
Expanded scope of adverse events to be 
adjudicated by the independent Clinical 
Events Committee for increased 
oversight 
Multiple 
Corrected spelling, grammatical, and formatting 
errors  throughout the document 
Administrative change for clarity 
5.
Background for Proposed Trial
In recent years, the treatment of intracranial aneurysms has shifted from a primarily surgical paradigm to one of 
endovascular management. The International Subarachnoid Aneurysm Trial (ISAT), published in 2002, 
demonstrated improved mortality and dependency rates at one year in those undergoing endovascular coil 
embolization to those undergoing clipping.1 However, anatomic challenges and technological limitations continue to 
limit the application of endovascular techniques for many aneurysms. 
In particular, wide-neck aneurysms have long been a challenge for endovascular techniques. As a result vascular 
remodeling (e.g., balloon or stent-assisted) embolic coiling has become increasingly common.  Additionally, recent 
success has also been encountered with the use of flow diversion technologies.2-4  However, limitations continue to 
exist, especially in branching locations for wide-neck aneurysms, which typically occur in the middle cerebral artery 
and basilar artery. Flow diversion is not currently approved for these locations. Recent published reports indicate 
that when flow diversion is used off-label in such locations, the results are dismal.5 Therefore, the Barrel® VRD was 
developed specifically to address these challenging locations.  Designed with an expanding central portion of the 
device, the Barrel® VRD is intended to protect both parent vessels for bifurcating and branching aneurysms.  
The lack of technologies specifically designed to address these aneurysm subtypes is reflected in lower successful 
embolization rates reported in the literature. There is a paucity of literature available that specifically evaluates only 
branching/bifurcating aneurysms.  However, in those studies that do provide evaluation, it is evident that this 
aneurysm subtype presents a substantially more challenging lesion with lower than typical success rates.  
In an early publication, Bavinski, et al. evaluated their experience in treating 45 basilar tip aneurysms over a six year 
period.9 They reported that in wide-necked basilar aneurysms complete occlusion was achieved only 15% of the 
time. This result was comparable to a number of other contemporaneous series. For instance, McDougall, et al. 
reported a 21% compete occlusion rate on follow up angiography for 19 basilar tip aneurysms and Raymond, et al. 
demonstrated a 19% complete occlusion rate for wide-neck basilar tip aneurysms, versus 67% complete occlusion in 
small neck basilar tip aneurysms.10,11 While these early studies pre-date many modern adjunctive technologies, they 

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clearly illustrate the challenges associated with wide-neck branching pathologies. 
More recent data demonstrates progress, but there are continued limitations when dealing with branching wide-neck 
aneurysms. A recent study by Lodi, et al. evaluating stent-assisted coiling in 87 aneurysms, of which 50 were 
located at branching (as opposed to side wall) locations, demonstrated a 31% complete occlusion rate.12 This study 
used modern stent-assisted technology in all cases and included a large number of ICA sidewall locations, that are 
known to experience better rates of occlusion, and yet still achieved a very low rate of complete occlusion, likely 
secondary to the inclusion of branching wide-neck aneurysms. It should also be noted that these results, as well as 
all the currently published series regarding this aneurysm subtype, are self reported and not adjudicated by a core 
lab.  A fact that is well documented to result in higher occlusion rates than core lab adjudicated series.13,14  
There are three very recent studies that specifically address bifurcating wide-neck basilar or MCA aneurysms.15-17
10,11,12 Unfortunately, all of these studies are retrospective and present self-reported outcomes.  The literature has 
repeatedly demonstrated that retrospective non-adjudicated studies consistently over-estimate treatment benefit and 
underestimate complications, however, these are the best data available. These data strongly demonstrate the 
continued limitations of current technology.  Fargen, et al. reported their results treating 45 wide-neck bifurcating 
aneurysms with the Y-stenting technique.  Despite experiencing an initial procedural/peri-procedural complication 
rate of 22.2%, they achieved an initial self-reported complete occlusion rate of 43%. Unfortunately, they only 
obtained follow-up imaging in 30 of their patients, preventing a reasonable assessment of their follow-up occlusion 
rates. Despite there being a high likelihood of selection bias towards the successfully treated aneurysms in the 
patients with follow-up, they demonstrated a self-reported 56% complete occlusion rate on follow up (when 
counting the two deaths as failures).15  Overall, for their entire cohort they demonstrated successful complete 
occlusion on last known angiogram in 40% of patients. Spiotta, et al. likewise reported their retrospective non-
adjudicated results treating 19 patients with bifurcating aneurysms with stent-assisted coiling.16 They experienced a 
32% complication rate and achieved an initial self-reported complete occlusion rate of 26%.  On follow-up imaging 
they self-reported a 53% complete occlusion rate (without re-treatment), and for their entire cohort they 
demonstrated 47% of patients having complete occlusion on last known angiogram. The final series evaluating 
stent-assisted embolization of wide-neck bifurcating basilar aneurysms is a very recent publication by Zhang, et al.17 
They report their results with treating 23 wide-necked basilar aneurysms. In this study, the authors report a self-
adjudicated complete occlusion rate of 39.1%.  Mean angiographic follow-up at 13.5 months was reported for 16 
patients.  Within that selected cohort they experienced a self-reported complete occlusion rate of 62%, with a self-
reported all patients’ complete occlusion rate of 43%.17   
Despite substantial progress over the past decade, endovascular treatment of bifurcating aneurysms remains a 
significant challenge. Despite the lack of independent adjudication, a composite analysis (all complete occlusions 
divided by the total number of patients), of the above reviewed modern studies demonstrate only a 42% overall 
complete occlusion rate at follow-up.  The mean and standard deviation of all three studies (treating each study as a 
single entity) is 43% and 3.5%, respectively.  Again, it is worth noting that all of these studies were retrospective 
and un-adjudicated, significant contrasts to the proposed prospective adjudicated study, and a methodology well 
demonstrated to overestimate successful occlusion rates and underestimate complication rates.  However, these data 
are the best available for this disease state.    

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6. Statistical Considerations and Analysis
The primary efficacy endpoint to be evaluated in this study is the outcome of treated aneurysms from study subjects 
achieving Raymond18 Grade I (100% occlusion) at 12 months ± 8 weeks in the absence of retreatment, parent artery 
stenosis (> 50%), or target aneurysm rupture.  The rate of the primary efficacy endpoint will be formally compared 
to a historical control, which is derived using a meta-analysis of the three very recent studies that specifically 
address bifurcating wide-neck basilar or MCA aneurysms (Fargen et al, 201315; Spiotta et al, 201116; and Zhang et 
al, 201417) as summarized in the Table 6-1.  The study will be conducted at up to 28 centers and will enroll up to 
159 subjects to ensure treatment/attempted treatment of 119 subjects (107 evaluable assuming a 10% loss to follow-
up rate). 
6.1 
Determination of Historical Control 
The BARREL Study is designed as a single-arm trial, which will be compared against a historical control derived 
from a meta-analysis of the rate of primary efficacy endpoint. i.e. outcome of treated aneurysms from study subjects 
achieving Raymond Grade I (100% occlusion) at 12 months ± 8 weeks in the absence of retreatment, parent artery 
stenosis (> 50%), or target aneurysm rupture. A follow-up target of 12 months was chosen specifically because it 
matches the mean follow-up of the meta-analysis.18  The Table 6-1 summarizes types of aneurysms, demographic 
information, and clinical outcomes of three very recent studies that specifically address wide-necked basilar and 
MCA aneurysms. Information about these studies is summarized in Section 5, “Background for Proposed Trial”.  An 
overall estimate of the rate of the primary efficacy endpoint derived from the meta-analysis of these three trials is 
42.5% with the 95% confidence interval of (31.90%, 53.06%).  This overall estimate provides the basis for deriving 
the historical control. 
Table 6-1 Meta-Analysis for Historical Control

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;
)
1(
;
1
2
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i
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The estimation of the rate of the primary endpoint derived from the three referenced studies, using the weighted 
proportion and its standard error (SE), was calculated using the following formula:  
 is the combined rate of complete occlusion; 
is the rate of complete occlusion in each referenced study; 
where ni is the sample size of each reviewed study; 
 
and the 95% confidence interval (CI) is 
± 1.96 * SE(
). 
6.2 
Primary Analysis 
The goal of the primary analysis will be to demonstrate that the Barrel® VRD device performs better than the 
combined historical control treatments for complete occlusion rate at 12 months. The hypothesis to be tested is: 
H0: B = HC versus HA: B > HC 
Where B is the proportion of successful outcomes for the Barrel® VRD device and HC is the combined overall
historical control success rate. Success is defined as a subject with a Raymond Grade of 1 (100% occlusion) at 12 
months ± 8 weeks in the absence of retreatment, parent artery stenosis (> 50%), or target aneurysm rupture.  This 
hypothesis will be tested using an exact one sample binomial test at ( = 0.025).  Exact 95% confidence intervals 
will be constructed. 
The meta-analysis analysis mentioned above provides an overall estimate for historical control success rate of 
42.48% with a 95% confidence interval of (31.90%, 53.06%).   
Although the meta-analysis provides the basis for deriving a historical control success rate, it does not allow exact 
comparison due to the author-evaluated Raymond Grades used in the studies versus the proposed core laboratory 
grade reporting. Moreover, the reported rates in the published literature do not take into account patients lost to 
follow-up in their final calculation of occlusion rates. Conversely, the Barrel study employs a more stringent intent-
to-treat (ITT) methodology that treats those patients lost to follow up as treatment failures. A review of the literature 
shows that onsite angiographic evaluators report 20 to 60% higher Raymond Grade success rates than those reported 
by core laboratories.13,14  Rezek et al. (2013)14 states “Core laboratories tend to report higher rates of unfavorable 
outcomes compared with self–reporting centers. Indeed, the rate of unfavorable outcomes was 43.6% greater in core 
laboratories compared with noncore laboratory studies.”  McDougall CG et al. (2014)19 states, “in 36% of cases, the 
local investigators reported a better degree of occlusion than did the core laboratory.” 
Unfortunately only one paper, Rezek et al. (2014)13, provided sufficient detail of the operator and core laboratory 
P
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Pˆ
Pˆ
ip

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results, in a population that is representative of the patient population that is proposed in the protocol, to allow 
statistical analysis of the difference. 
An analysis of this data provided an adjustment of 36% between the operator results and the core laboratory results. 
This difference was consistent with the other published results.  After adjustment, the estimated historical success 
rate for core lab results is 28%.  The corresponding adjusted confidence interval is (23%, 33%).  
6.3 
Sample Size Calculation 
In actuality, the real objective of this study is to demonstrate that the Barrel® VRD is comparable to historical 
controls. Therefore the historical success rate of 28% was selected as the historical control value.  The Barrel® VRD 
will be considered successful if its lower 95% confidence limit is greater than 28%.   
Table 6-2 presents the sample size necessary to have an 80% power with a significance level of 2.5% for rejecting 
the null hypothesis in favor of the alternative when the true success rate for the Barrel® VRD is as specified.  The 
hypotheses to be tested are: 
H0: B = 28% versus HA: B > 28% 
Where B is the proportion of successful outcomes for the Barrel® VRD device.
Table 6-2 Sample Size 
True Success Rate for Barrel® VRD Device 
% Raymond 
Grade 1 
38% 
39% 
40% 
41% 
42% 
43% 
44% 
45% 
Sample Size 
177 
145 
123 
107 
92 
80 
71 
62 
Principal Investigator J Mocco, MD and the clinical team agree that there is potentially an advantage to the Barrel®
VRD device and thus a 41% success rate is the expected performance. Assuming a 10% dropout rate, the number of 
subjects required to be treated for the study is 119. The total number of subjects enrolled will be 159 to account for 
up to 25% of subjects who consent for the trial and withdraw prior to treatment or are determined to be ineligible.  
6.4 
Endpoint Analysis and Reporting of Results 
All statistical analyses will be performed using SAS Version 9.2 or higher or other valid statistical software. 
Descriptive summary statistics will be provided for endpoints along with 95% confidence intervals as appropriate. 
Subject data listings and tabular and graphical presentations (e.g., bar graphs, pie charts, line graphs) of results will 
also be provided. 
6.5 
Statistical Analysis Sets 
The primary analysis set will be based on the intention-to-treat (ITT) population set.  For this study, all subjects who 
meet the study entry criteria, sign the written informed consent (enrolled), and undergo attempted delivery with the 
Barrel VRD will be counted in the primary analysis set of ITT.   

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Analysis will also be performed on the per-protocol population set, defined as all subjects included in the ITT 
population set who have complied with the protocol without major protocol deviations, and have completed the 12-
month angiographic evaluation. 
The primary analyses for both the safety and effectiveness endpoints will be based on the observed data. 
6.6 
Analysis of Primary Safety Endpoint 
The primary safety endpoint is defined as the incidence of neurological death or major ipsilateral stroke (National 
Institute of Health Stroke Scale [NIHSS] increase of  4 for >24 hours) at any time during the follow-up period (12 
months ± 8 weeks).  Total number and frequency of subjects with neurological death or major ipsilateral stroke will 
be presented with two-sided 95% confidence intervals of the rate. 
The primary safety endpoint will be met if the upper bound of the confidence interval is  15%. Table 6-3 below 
summarizes the clinical outcomes of the three studies from the background that specifically address endovascular 
treatment of wide-necked basilar and MCA aneurysms. Information about these studies is summarized in Section 5, 
“Background for Proposed Trial”. A complication rate was identified for each article by including events which 
could indicate stroke (i.e., thromboembolic events, ischemic events, artery dissection, hemorrhage, aneurysm 
rupture, and cranial nerve palsy).  The overall weighted average of the incidence rate derived from the meta-analysis 
of these three trials was 13%. This provides the basis for selecting 15% for the primary safety endpoint of the Barrel 
study. 
Table 6-3 Safety Rates Reported in the Literature 
Study 
Number of Patients in the Trial 
Number of Aneurysms in the Trial 
Number of Events 
Complication* 
Rate 
Fargen 2013 
45 
45 
6 
13.3% 
Spiotta 2011 
19 
19 
4 
21.1% 
Zhang 2014 
23 
23 
1 
4.3% 
Total / Weighted Average 
87 
87 
11 
12.6% 
* Complications include events that could indicate stoke (i.e., thromboembolic events, ischemic events, artery dissection, hemorrhage, aneurysm rupture and cranial 
nerve palsy) 
Note: These articles were reviewed closely to ensure that if the information was available, that patients with multiple complications were counted only once, as well as
to ensure that asymptomatic events and events resolving within 24 hours were excluded. 
6.7 
Analysis of Secondary Endpoints 
Secondary endpoints will be analyzed with descriptive statistics along with a 95% confidence interval. Descriptive 
statistics for categorical variables will include the number and percentage of subjects in each category, with two-
sided 95% confidence intervals of the percentage of subjects in each category. Descriptive statistics of continuous 
variables will include sample size, mean, standard deviation, minimum, maximum, and 95% confidence interval of 
the mean. 
6.8 
Analysis of Baseline Demographics and Procedural Characteristics 
All clinically relevant baseline variables will be tabulated using descriptive statistics. 
6.9 
Pre-planned Subgroup Analyses  
Subgroup analysis of demographic factors of age group ( 65 and > 65) and gender (male and female) will be 

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performed. 
6.10 
 Handling of Missing Data 
Multiple imputation technique will be implemented to assess the impact of missing data on the analysis of efficacy 
endpoint. For the parameters summarized based on the incidence, an imputed dataset where the binary outcome for 
subjects who withdraw prior to the scheduled assessment will be derived using the Markov Chain Monte Carlo 
(MCMC) algorithm specifying missing at random (MAR). The subject characteristics and demographic factors to be 
included in the multiple imputation procedure to generate the imputed datasets for analysis will be defined in the 
Statistical Analysis Plan (SAP). 
7. Objectives
The purpose of this study is to evaluate the safety and efficacy of the Reverse Medical Barrel® VRD for Adjunctive 
Treatment to Embolic Coils for Wide-neck, Intracranial, Bifurcating/Branching Aneurysms of Middle Cerebral and 
Basilar Arteries.  
8. Overall Trial Design
The BARREL Study is a prospective multi-center single-arm study of the Barrel® VRD.  Up to 159 subjects will be 
enrolled at up to 28 centers to ensure 119 subjects are treated.  After obtaining informed consent, screening and 
baseline assessments, and eligibility confirmation, qualifying patients will receive the study treatment. 
8.1 
Primary Outcome Measures 
8.1.1 Primary Endpoints 
•
Primary Efficacy Endpoint:  The number of Barrel® VRD treated aneurysms achieving
Raymond Grade I (100% occlusion) at 12 months ± 8 weeks in the absence of retreatment,
parent artery stenosis (> 50%), or target aneurysm rupture.18 The primary efficacy endpoint
will be met if the lower bound of the 95% confidence interval is > 23%.
•
Primary Safety Endpoint: Incidence of neurological death or major ipsilateral stroke (National
Institutes of Health Stroke Scale [NIHSS] increase of  4 for >24 hours) at any time during the
follow-up period (12 months ± 8 weeks). The primary safety endpoint will be met if the upper
bound of the confidence interval is  15%.
8.1.2 Secondary Endpoints 
•
Any cause death within 30 days or neurological death within 12 months ± 8 weeks.
•
Number of Barrel® VRD treated aneurysms achieving Raymond Grade I or II at 12 months ± 8
weeks in the absence of retreatment, parent artery stenosis (> 50%), or target aneurysm rupture.
•
Number and percentage of successful device implants
•
Angiographic evidence of in-stent stenosis at 12 months ± 8 weeks reported according to the
following ordinal groups: <25%, 25-50%, 51-75%, >75%.
•
Device-related Serious Adverse Events (SAEs).
•
The composite percentage of patients with modified Rankin Score of 0-2 or no change from

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baseline at 12 months ± 8 weeks. 
9. Trial Population
9.1 
Number of Patients 
A maximum of 159 subjects will be enrolled (consented) into the study at up to 28 centers to ensure the study has an 
adequate number of treated subjects; up to 119. The duration of the study participation is 12 months ± 8 weeks and 
the total expected study duration, including completion of all follow-up requirements, is approximately 2.5 years. 
9.2 
Patient Inclusion Criteria 
A subject who meets all of the following criteria may be included in the trial: 
1.
Male or female between 18 and 85 years old.
2.
A wide-neck aneurysm with a neck  4mm or a dome-to-neck ratio < 2, that is also a bifurcating or
branch MCA or basilar aneurysm and de novo or non-de novo MCA or basilar aneurysm where no
stent was utilized.
3.
Subject's aneurysm arises from a parent vessel with a diameter  2mm and  4mm.
4.
Appropriate informed consent obtainable as determined by local IRB.
5.
Life expectancy > 24 months.
9.3 
Patient Exclusion Criteria 
A subject who meets any of the following criteria will not be included in the trial: 
1.
Aneurysm rupture within 30 days of enrollment.
2.
MCA or basilar bifurcating aneurysms not treatable with coiling.
3.
Subject with anatomy not accessible for Barrel VRD treatment.
4.
Aneurysm neck > 8 mm.
5.
Subject presents with an intracranial mass or is currently undergoing radiation therapy for
carcinoma of the head or neck region.
6.
Subject has additional aneurysms for which treatment is planned within 18 months.
7.
Subject has platelet count of <70,000.
8.
Subject has had a previous intracranial stenting procedure associated with the target aneurysm.
9.
Subject has an International Normalized Ratio (INR)  1.7 or is on one of the following anti-
coagulant/anti-platelet medications: Aggrenox, Cilostazol, Apixaban, Dabigatran, Fondaparinux,
Lepirudin, Pradaxa, Rivaroxaban, Argatroban, Arixtra.
10. Subject has serum creatinine level > 2mg/dl at baseline screening.
11. Subject has known allergies to nickel-titanium metal.
12. Subject has known allergies to aspirin or heparin.
13. Subject has a life-threatening allergy to contrast (unless treatment for allergy can be tolerated).
14. Subject has a known cardiac disorder, likely to be associated with cardioembolic symptoms such as
atrial fibrillation (AFIB).
15. Subject has any condition, which in the opinion of the treating physician, would place the subject at
a high risk of embolic stroke.
16. Subject is currently participating in another clinical research study.
17. Subject is pregnant or breastfeeding.

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18. Subject has participated in a drug study within the last 30 days.
19. Subject cannot or is unwilling to take ASA and a P2Y12 Platelet Inhibitor as required by the
protocol following the procedure.
20. Subject is unable or unwilling to comply with protocol requirements and obtain required clinical
evaluations and follow-up.
Before any subject is enrolled in the study, the baseline angiogram will be reviewed by a Barrel expert to ensure that 
the target intracranial aneurysm (IA) is amenable to treatment with the Barrel VRD device. 
10. Device Descriptions
The Barrel® VRD features a self-expanding design that allows it to be completely deployed and fully retrieved. 
The Barrel® VRD is comprised of nitinol and several platinum marker bands. The proximal marker band attaches to 
a wire that pushes the device through a commercially available 0.021” microcatheter to the intended treatment site. 
The delivery wire detaches from the Barrel® VRD by electrolytic means after deployment with the Reverse 
Medical® Detachment System (Model ED2-RM-VRD).  
The Barrel® VRD is packaged as a single unit with the detachable delivery wire and introducer sheath. The system is 
provided sterile, non-pyrogenic, and is intended for single use only. The Barrel® VRD is not commercially available 
and is considered investigational in this study. The Barrel® VRD and components are required to be used per the 
protocol and as specified in the IDE Instructions for Use (IFU) document.  
The Reverse Medical® Detachment System is a battery-operated device designed to initiate and control detachment 
of Reverse Medical® detachable implants within the vasculature.  The Reverse Medical® Detachment System is 
designed for multiple uses, but the battery must be removed and the unit cleaned after each procedure.  A new 
battery should always be inserted into the Detachment Box before each procedure. 
The Reverse Medical® Detachment System is designed to apply a constant current and detect System detachment.  It 
maintains a current by sensing the amount of resistance to current flow and adjusting the voltage required to 
maintain a constant current. 
The Reverse Medical® Detachment System is designed to identify the changes in voltage required by the System 
associated with detachment.  Once detachment is identified, the Detachment System indicates detachment with an 
audible and visual “Detach” signal and stops the flow of current to the System. 
A Reverse Medical Cable Set – 275 cm length (Model RMCS – 2.75VRD) is provided sterile and is for single use 
only. The cable set connects to the Detachment Box through a bayonet type dual pin connector that ensures correct 
polarity.  The Reverse Medical Cable Set and Detachment Box will be provided at no charge separately. One 9-volt 
battery and a sterile needle (20 G or 22 G) will also be needed for the embolization procedure. 
The Barrel® VRD is specifically designed for use with the Reverse Medical® Detachment System and Cable Set. 
This Reverse Medical® Detachment System will be provided separately. The Barrel® VRD and Detachment System 
are depicted in Figures 10-1 through 10-4 and Table 10-1. 

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Figure 10-1 Detachment Zone and Delivery Wire of Barrel® VRD
Figure 10-2 Image of Actual Barrel® VRD
Figure 10-2 Image of Actual Barrel® VRD
1. Barrel™ VRD
2. Detachment Zone
3. Delivery Wire (DW)
1
2
3

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Table 10-1 Materials Used in the Barrel® VRD  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Nitinol Wire (Heat treated, Laser Cut, Electropolished)
Platinum Wire 
Steel, Stainless 301 
Solder 
Sheath, Polypropylene 
Urethane Adhesive 
Cyanoacrylate Adhesive 
Platinum Marker band 
Urethane Adhesive 

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Figure 10-3 Cable Set 
 
Item 
Description / Material 
1 
Clip - ABS plastic, copper wire 
2 
Cable – copper wire, silicone jacket insulation  (2.75M in length) 
3 
Connector - ABS plastic, copper wire 
 
 
 
 
 
 
 
 
 

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Figure 10-4 Reverse Medical Detachment Box 
 
Detachment box housing: ABS plastic 
Width:  79mm 
Depth (without I.V. clamp):  33mm 
Depth (with I.V. clamp):  72mm 
Height:  126mm 
 
 
 

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11.  Study Materials 
11.1  Instructions for Use 
Instructions for the delivery and release of the Barrel® Vascular Reconstruction Device are outlined in the Barrel® 
VRD Instructions For Use (IFU) and the Reverse Medical® Detachment System IFU.  
11.2 Device Accountability 
Investigators will be provided with sterile investigational products including Barrel® VRDs, Cable Sets, and 
Detachment Boxes. Complete accountability for each device must be maintained. Any unused devices must be 
returned to the Sponsor at the conclusion of the study or upon product expiration.   
12. Study Methods and Procedures 
12.1  Enrollment Procedures 
Prospective patients, as defined by the inclusion and exclusion criteria, will be considered for enrollment in this trial. 
Enrollment will be considered the point of consent. Prior to enrolling a patient, it must be verified that all criteria are 
met. Patients must meet all of the inclusion criteria and none of the exclusion criteria prior to treatment in the study.  
12.2  Informed Consent 
This protocol requires written informed consent, in accordance with applicable federal, state, and study center 
regulations. This consent shall be obtained from each patient, or appropriate surrogate, prior to the investigational 
procedure. The Investigator will retain a copy of the signed informed consent document in each subject’s record, and 
provide a copy to the subject. The Investigator shall not request the written informed consent of any patient, and 
shall not allow any patient to participate in the study before obtaining Institutional Review Board (IRB) approval. 
Prior to starting the study, the Investigator will provide Medtronic with a copy of the Informed Consent Document 
approved by the IRB with documented evidence that the protocol has received IRB approval.   
12.3  Physician Training 
Physicians who participate in this study will be trained using a phantom or bench-top model of the Barrel® VRD 
under fluoroscopic visualization.  
12.4  Schedule of Events 
The tests and evaluations to be conducted at baseline, procedurally, and during follow-up are summarized in the 
Table 12-1. 

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Table 12-1 Schedule of Tests 
Tests and Evaluations 
Screening/ 
Baseline 
Procedural 
(Day 0) 
30 days 
±14 days 
180 days 
±30 days 
12 months 
±8 weeks 
Unscheduled 
Visit 
Inclusion/Exclusion 
X 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
Medications 
X 
X 
X 
X 
X 
X 
Blood Labs 
X 
 
 
 
 
 
Modified Rankin Score 
X 
 
X 
X 
X 
 
NIHSS Score 
X 
 
 
X 
X 
X5 
Adverse Events 
 
X 
X 
X 
X 
X 
Angiography1 
X2 
X 
 
X4 
X 
 
Raymond Grade Scale 
X3 
X 
 
X 
X 
 
1MRA is acceptable if performed according to the standard of practice at the participating institution. 
2The baseline angiogram must be taken no more than 180 calendar days prior to the procedure. 
3For previously coiled aneurysms 
4If an angiogram is performed as standard patient care it should be sent to the core laboratory for analysis. 
5If visit is related to target aneurysm or potentially associated adverse event 
12.5  Procedure 
Access the targeted vessel and perform an angiogram using standard technique. Advance the Barrel® VRD through a 
0.021 microcatheter to the desired position and deploy the device utilizing the delivery wire. Detach the delivery 
wire from the Barrel® VRD using the Reverse Medical® Detachment System and remove the microcatheter from the 
subject.  
Use the following steps to administer coils: 
a. 
Use a guidewire and microcatheter to access the aneurysm through the device’s struts.  
b. After the microcatheter has been positioned within the aneurysm, detachable embolization coils can be 
deposited into the aneurysm per manufacturer’s instructions.  
c. 
Warning – Observe the VRD’s marker position during the coiling procedure to ensure the VRD does 
not migrate from detached position.  
d. After placement of the last coil, verify the VRD has remained patent and properly positioned.  
e. Carefully remove the microcatheter from the VRD’s struts. 
 

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12.6  Study Evaluations 
12.6.1 Screening/Baseline Evaluations   
The following information will be collected: 
• Inclusion/Exclusion Criteria 
• Demographics  
• Medical History   
• Medications 
• Modified Rankin Score 
• NIHSS Score 
• Angiography data 
• Raymond Grade for previously coiled aneurysms 
All medications that a patient is taking starting 30 days prior to screening will be collected and followed for 
the duration of the study. In addition, the following medications will be collected throughout the study: 
antithrombotic, antiplatelet, anticoagulant, inhibitor of ADP-induced platelet aggregation, all medications 
administered during the study procedure, and medications associated with adverse events. 
12.6.2 Procedural Evaluations   
During the operative procedure the following information will be recorded: 
• 
Devices and components used (Barrel® VRD, guidewires, and delivery catheters) including 
manufacturer and model number 
• 
Puncture time 
• 
Detachment time 
• 
Location of aneurysm 
• 
Coiling packing density 
• 
Device implant success (yes/no), defined as the ability to implant the device in the target area  
• 
Stenosis in the parent artery 
• 
Intra-operative complications 
• 
Presence of vasospasms (time of onset, vessels involved, time resolved). Vasospasm will be 
recorded as an AE only if it led to a subsequent thrombotic or ischemic event. 
• 
Medications  
 
 
 

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12.6.3 Immediate Post-operative Evaluations   
The following information will be recorded during the immediate post-operative evaluation: 
• 
Angiographic assessment 
o 
Stenosis    
o 
Raymond Grade18 
Class 1: Complete occlusion - complete obliteration of the aneurysm. 
Class 2: Residual neck - persistence of any portion of the original defect of the arterial 
wall as seen on any single projection, but without opacification of the 
aneurysmal sac.  
Class 3:  Residual aneurysm - opacification of the aneurysmal sac. 
• 
Description of adverse events 
• 
Medications 
12.6.4 Post-placement Antiplatelet Agents 
Antiplatelet agents will be given after the Barrel device placement procedure as defined below: 
• 
Aspirin: At least 81 mg daily for a minimum of 12 months 
• 
P2Y12 Platelet Inhibitor:  Daily for a minimum of 3 months 
Medications could be continued beyond above regimen if medically indicated. 
12.6.5 Follow-Up (30-day, 180-day, and 12-month)  
The following assessment will be completed at the specified time points below. All visits should be 
completed by study subjects with successful implant of the Barrel VRD. Subjects that underwent attempted 
delivery with the Barrel VRD, but were not implanted should complete the 30-day visit and be exited from 
the study.  
• 
30 Day ± 14 Days 
o 
Neurologic Evaluation 
 
The Investigator is responsible for ensuring that the administration of the modified 
Rankin Score is conducted by a trained person with appropriate qualifications to 
perform these evaluations. 
o 
Details of any additional (subsequent) procedures or additional treatments 
o 
Description of adverse events, including the time of onset  
o 
Medication Usage 
o 
30 day evaluations may be performed remotely via telephone if subject is not available for a 
visit to the study center.  

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• 180 Day ± 30 days 
o 
Neurologic Evaluation 
o 
The Investigator is responsible for ensuring that the administration of the NIHSS and 
modified Rankin Score are conducted by a trained person with appropriate 
qualifications to perform these evaluations. 
o 
Details of any additional (subsequent) procedures or additional treatments 
o 
Angiographic assessment (if done as standard of care)  
o 
Stenosis  
o 
Raymond grade 
o 
Description of adverse events, including the time of onset  
o 
Medication Usage 
• 12 month ± 60 days 
o 
Neurologic Evaluation 
The Investigator is responsible for ensuring that the administration of the NIHSS and 
modified Rankin Score are conducted by a trained person with appropriate qualifications to 
perform these evaluations. 
o 
Details of any additional (subsequent) procedures or additional treatments 
o 
Angiographic assessment  
 
Stenosis  
 
Raymond grade 
o 
Description of adverse events, including the time of onset  
o 
Medication Usage 
 
12.6.6 Unscheduled Visits 
Any visit by the subject to the Investigator related to the target IA treated or a potentially associated adverse event 
should include a neurologic examination using NIHSS. The Investigator should document the review of the adverse 
event status and all relevant medications taken by the subject.  
12.6.7 Study Exit 
Upon completion of the specified study follow-up at 12 months the subject will be exempt from further data 
collection. The subject will be seen by the treating physician according to standard care following intracranial 
aneurysm treatment. If the subject underwent attempted delivery with the Barrel VRD but did not receive a Barrel 
VRD implant, the subject will be exited from the study following the 30 day visit. 
12.6.8 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. 

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12.6.8.1 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 and clear documentation of the subject’s withdrawal should be provided to the Sponsor. 
12.6.8.2 
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. If a subject is withdrawn from the 
study, the Investigator will promptly inform the subject and Sponsor. If a subject is enrolled and undergoes 
attempted delivery with the Barrel VRD without successful implant of the investigational device, the subject will be 
exited from the study following the 30 day visit.  
12.6.8.3 
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 the 1 year visit. The site must document a minimum of three (3) attempts, and the final documented 
attempt should be made via registered letter. 
 
12.6.8.4 
Discontinuation by IRB 
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. 
12.6.8.5 
Study Discontinuation by Sponsor 
The Sponsor may choose to discontinue the study should the Sponsor discover additional information during the 
study that may cause harm to 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. 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 
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12.7  Angiography Core Lab  
12.7.1 Assessments 
The following assessments will be made by the Angiography Core Lab from images submitted from the sites.  The 
images will be submitted by site with all subject identifiers removed and only the assigned subject study number on 
the images.  
Procedural- pre, peri and post images 
o 
Aneurysm location 
o 
Raymond grade (pre-procedure required only for previously coiled aneurysms) 
o 
Stenosis of parent and branch arteries (pre-procedure) 
180 days ± 30 days post-procedure 
o 
Stenosis of parent and branch arteries 
o 
Raymond grade 
o 
In-stent stenosis 
12 months ± 8 weeks post-procedure 
o 
Stenosis of parent and branch arteries 
o 
Raymond grade 
o 
In-stent stenosis 
 
Unscheduled  
o 
Stenosis of parent and branch arteries 
o 
Raymond grade  
o 
In-stent stenosis 
 
12.8 Adverse Event Reporting 
All adverse events will be collected during the course of the study on the eCRFs. 
Adverse event status will be evaluated throughout the study. These will include events occurring from the point of 
consent until a subject exits the study. 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 unexpected 
event requiring notification to the Sponsor, regulatory agency, and as applicable, IRB/EC, within the specified 
reporting timeframe. AEs will be categorized using the definitions in Section 12.8.1. 
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 AEs will be followed by the Investigator until resolution or until the end of the 
12 month follow-up. A list of potential anticipated adverse events is provided in Section 13. 
All relevant medical conditions reported at screening/baseline visit will be recorded in the medical history form, 
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12.8.1 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) 
Note 1: This includes events related to the investigational device or the comparator. 
Note 2: This includes events related to the procedures involved (any procedure in the clinical investigational plan). 
Note 3: For users or other persons this is restricted to events related to the investigational medical device. 
 
An Adverse Device Effect (ADE) is defined as an adverse event related to the use of an investigational medical 
device. (ISO 14155:2011) The investigational medical devices for this study are the Barrel® VRD, and the Reverse 
Medical® Detachment System. 
Note 1: This includes any adverse event resulting from insufficiencies or inadequacies in the instructions for use, the 
deployment, the implantation, the installation, the operation, or any malfunction of the investigational device.  
Note 2: This includes any event that is a result of a use error or intentional misuse of the investigational medical 
device. 
A Serious Adverse Event (SAE) is defined as an AE that: 
a) Led to death, 
b) Led to serious deterioration in the health of the subject, that either resulted in 
1. A life-threatening illness or injury, or 
2. A permanent impairment of a body structure or a body function, or 
3. In-patient or prolonged hospitalization, or  
4. Medical or surgical intervention to prevent permanent 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) 
Note 1: This includes device deficiencies that might have led to a serious adverse event if a) 
suitable action had not been taken or b) intervention had not been made or c) if circumstances had 
been less fortunate. These are handled under the SAE reporting system. 
Note 2: A planned hospitalization for pre-existing condition, or a procedure required by the 
Clinical Investigational Plan, without a serious deterioration in health, is not considered to be 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) 
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) 
Note: Anticipated: an effect which by its nature, incidence, severity or outcome has been previously identified in the 
risk analysis report. 
An Unanticipated Adverse Device Effect (UADE) is defined as any serious adverse effect on health or safety or 
any life-threatening problem or death caused by, or associated with, a device, if that effect, problem, or death was 
not previously identified in nature, severity, or degree of incidence in the investigational plan or application 
(including a supplementary plan or application), or any other unanticipated serious problem associated with a device 
that relates to the rights, safety, or welfare of subjects. (21 CFR 812.3) 

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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. 
Relatedness: 
• 
Study Disease-related: Event is clearly attributable to the underlying study disease state (aneurysm) or 
concomitant medications taken for these with no temporal relationship to the device, procedure , or concomitant 
medications. 
• 
Concomitant disease-related: Event is clearly attributable to an underlying concomitant disease state or 
concomitant medication taken for these with no temporal relationship to the device, procedure/treatment, or 
study disease state. 
• 
Procedure-related: Event has a strong temporal relationship to the study procedure. This includes AEs 
attributable to any device(s) other than the Barrel® VRD, Detachment Box, or Detachment Cables used at 
procedure (day 0), such as access devices, delivery microcatheters, embolic coils, non-ionic contrast, 
guidewires, or any other adjunctive, approved/cleared device for treatment of intracranial aneurysms.  
• 
Device-related: Event has a strong temporal relationship to the study device (the Barrel® VRD, Detachment 
Box, or Detachment Cables), and alternative etiology is less likely.  
All events considered “device-related” will be further characterized as either: 
o 
Anticipated: When the event was previously identified in nature, severity or degree of incidence in 
the investigational plan. Or 
o 
Unanticipated: When the event was not previously identified in nature, severity or degree of 
incidence in the investigational plan.  
• 
Non-index procedure related: This includes AEs attributable to any device(s) used at procedures other than day 
0, such as access devices, delivery microcatheters, non-ionic contrast, guidewires, or any other adjunctive, 
approved/cleared device for treatment of intracranial aneurysms.  
• 
Antiplatelet therapy-related: Event is clearly attributable to antiplatelet therapy with no temporal relationship to 
the device, treatment, or medical history  
• 
Unknown: Event relationship cannot be attributed to any of the above categories, and remains undetermined. 
A 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.  
The definition includes: 
• 
Subjects presenting with clinical signs and symptoms suggestive of subarachnoid hemorrhage, 
intracerebral hemorrhage, or cerebral infarction.  

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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. 
• 
Transient ischemic attacks, in which the symptoms resolve on their own within 24 hours 
Stroke severity will be graded by the CEC as major or minor: 
• 
Major Stroke:  A stroke which increases the NIH Stroke Scale of the subject by  4. 
• 
Minor Stroke:  A stroke which increases the NIH Stroke Scale of the subject by  3. 
The term “ipsilateral” in the primary safety endpoint definition will be defined as “on the same side of the brain as 
the target aneurysm” for MCA aneurysms and as “in the territory supplied by the treated artery” for basilar 
aneurysms. 
Each stroke event will be adjudicated for “Ipsilateral” site of occurrence: 
• 
Ipsilateral for MCA strokes 
• 
In the territory supplied by the treated artery for Basilar artery strokes as adjudicated by the Clinical Events 
Committee 
A Neurological Death is any subject death due to neurological reasons. 
An Intra-Cranial Hemorrhage (ICH) is a hemorrhage within the fixed vault of the cranium (skull). These will be 
further categorized as:  
• 
Intra Cerebral Hemorrhage: 
o 
Intra Ventricular Hemorrhage (IVH): Hemorrhage within the ventricles  
o 
Intra Parenchymal Hemorrhage (IPH): Bleeding within the cerebral matter (brain parenchyma), 
not involving the ventricles 
*Acute Ischemic Stroke with hemorrhagic transformations included in IPH will be explained in comments. 
• 
Sub Arachnoid Hemorrhage (SAH) 
o 
A subarachnoid hemorrhage is bleeding into the subarachnoid space—the area between the 
arachnoid membrane and the pia mater surrounding the brain 
• 
Sub-Dural Hematoma (SDH) 
o 
Subdural hematoma occurs when there is tearing of the bridging vein between the cerebral cortex 
and a draining venous sinus 
• 
Epidural Hematoma (EDH) 
o 
A rapidly accumulating hematoma between the dura mater and the cranium 
 

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12.8.2 Device Specific Events 
Any device-specific event (DSE) is any malfunction or deficiency of the device.    
A device deficiency is defined as inadequacy of a medical device with respect to its identity, quality, durability, 
reliability, safety or performance (ISO 14155:2011 3.15) 
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 of Clinical Investigational Plan (ISO 14155:2011 
3.27). 
All device-specific events must be reported to both the Sponsor 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 reportable to 
the Sponsor.  
12.8.3 Event Reporting 
The Investigator is required to report all SAEs within 72 hours and any UADEs/USADEs within 24 hours after first 
learning of the event to the Sponsor. The primary method of reporting SAEs will be through the eCRFs. If the 
database is unavailable the investigator may fax or email in the information. As soon as the database becomes 
available, the investigator must complete data entry. The investigator will also send all available supporting 
documentation (de-identified as to the subjects’ identity).  
As additional information becomes available, copies of that source documentation which contain significant 
information related to the event such as progress notes, consultations, nurse’s notes, operative reports, imaging 
studies and subject summaries etc. are requested for a complete evaluation of the event. 
In regard to subject deaths, it is requested that a copy of the death certificate and a copy of the autopsy report, if 
applicable, be sent to the Sponsor when available. Any other source documents related to the death should also be 
provided to the Sponsor. In the event that no source documents are available, the PI is requested to describe the 
circumstances of the subject’s death in a letter, e-mail or other written communication. 
UADEs/USADEs have expedited reporting requirements. Any event that meets the definition of UADE must be 
reported to FDA, all Investigators and reviewing IRBs within 10 working days after becoming aware of information 
that an UADE has occurred.  
The site will notify the reviewing IRB within 10 working days after becoming of aware of the effect. The Sponsor 
will notify the all Investigators, IRBs and the FDA within 10 working days after first receiving notification of the 
event. In addition, the Sponsor will comply with Medical Device Reporting / MDR regulations where applicable. 
 
12.8.4  Protocol Deviations 
Reports of any deviation from the protocol conducted in an emergency situation, to protect the life or physical 
wellbeing of a subject, will be reported to the Sponsor and IRB as soon as possible, but no later than 5 days from the 
time of the event. 
13. Risk Analysis 
The Barrel® VRD is intended for patients who have a bifurcating aneurysm or aneurysm occurring at a branch and 
require embolization of an MCA or basilar aneurysm and protection of the parent vessel. The potential benefit of 
this interventional procedure includes facilitation of endovascular coiling of wide-neck intracranial, MCA or basilar 

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aneurysms with embolic coils, while ensuring patency of the parent vessel, and to potentially improve clinical 
outcomes.  However, the benefit of the Barrel® VRD device has not been established.  
Evidence from investigations involving laboratory animals has suggested that the Barrel® VRD is safe for clinical 
investigation. With any interventional procedure there are risks of serious complications, including death. The 
inclusion and exclusion criteria for this population have been carefully established to limit the risk of mortality. 
Potential risks associated with utilization of embolic coils within brain aneurysms should be discussed with the 
subject within the coiling procedure Informed Consent document.  
It is expected that the fluoroscopy time of the procedure will be similar to the time required for other interventional 
neuroradiology procedures.  
• 
Potential adverse events that may occur during or after a procedure placing this device include, but are not 
limited to:  
o 
Adverse reaction to antiplatelet/anticoagulation agents or contrast media 
o 
Air embolus 
o 
Allergic reaction/toxic effects 
o 
Bleeding 
o 
Coma 
o 
Death 
o 
Device migration or misplacement 
o 
Device Fracture 
o 
Dissection of the parent artery 
o 
Embolism 
o 
Fever 
o 
Foreign material embolic event 
o 
Groin injury 
o 
Headache 
o 
Hemolysis 
o 
Hemorrhage 
o 
Hydrocephalus 
o 
Infection 
o 
Intracerebral bleeding 
o 
Ischemia 
o 
Mass Effect 
o 
Neurological deficits 
o 
Occlusion of unintended vessel 
o 
Parent Artery Stenosis 
o 
Perforator occlusion 
o 
Peripheral embolism 
o 
Post-procedure bleeding 
o 
Ruptured or perforated aneurysm 
o 
Recanalization 
o 
Residual flow 
o 
Seizure 
o 
Stroke/TIA 
o 
Surgical intervention 
o 
Thromboembolism 
o 
Vascular access site complication 
o 
Vasospasm  
o 
Vessel perforation 
o 
Vessel trauma/perforation 
o 
Vessel occlusion 
o 
Vision impairment 
 

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As a result of some of these complications, the subject may require treatment.  
Eligibility criteria for this trial exclude subjects who are at higher risk for anticipated adverse events.  Physician 
training and careful application of the Barrel® VRD, with close subject monitoring after the procedure, will also help 
to minimize risks. Risks of infection and risks associated with the access site are minimized by standard hospital 
procedures. The investigational site will be selected based on proficiency in neurointerventional procedures. 
Although there are no guaranteed benefits from participation in this trial, the Barrel® VRD may potentially facilitate 
endovascular coiling of a wide-neck, intracranial, bifurcating aneurysm and protect the parent artery by preventing 
coils from protruding into the parent artery.  This study is justified in order to establish whether this device can be 
used safely and effectively in this patient population.  
Alternatives to treatment with the Barrel® VRD include treatment with other currently marketed, vascular 
reconstruction devices or surgical clipping. 
 
14.  Administrative Procedures 
14.1  Responsibilities 
14.1.1 Investigator 
The Investigator and study site are required to conduct the clinical investigation in accordance with the protocol, all 
applicable laws and federal regulations, and any conditions or restrictions imposed by the governing IRB (21 CFR 
812, and 21 CFR 54).  
14.1.2 Sponsor and Clinical Monitor 
Medtronic is responsible as the Sponsor to ensure proper monitoring of the study. Ongoing monitoring visits of the 
investigational center will be conducted to compare the data recorded on the CRFs with the information contained in 
the subjects' hospital records. The Investigator will provide the monitor access to all necessary records to ensure the 
integrity of the data (21 CFR 812). 
14.2  Protection of Human Subjects 
Written informed consent, in accordance with applicable federal, state and study center regulations, shall be 
obtained from each patient, or from their legal guardian, prior to the investigational procedures. The Investigator 
will retain a copy of the signed informed consent document in each subject’s record, and provide a copy to the 
subject. The Investigator shall not request the written informed consent of any subject, and shall not allow any 
subject to participate in the investigation before obtaining IRB approval. 
Prior to starting the study, the Investigator will provide Medtronic with a copy of the Informed Consent Document 
approved by the IRB with documented evidence that the IRB has approved the protocol (21 CFR 50).   
14.3 Ethical Conduct of the Study 
This study is to be conducted in alignment with ethical principles that have their base in the Declaration of Helsinki 
concerning medical research in humans and applicable regulations. 
The Investigator agrees by participating in the conduct of this protocol to adhere to 21 CFR 812, the instructions and 
procedures described, and to adhere to the principals of Good Clinical Practice. 

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14.4 Institutional Review Boards 
The Sponsor and/or Investigator must submit this protocol to the appropriate IRB, 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, ICF, etc.) and the date of 
the review should be clearly stated on the written IRB 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 Sponsor. 
Any amendment or modification to the protocol should be sent to the IRB. The IRB should also be informed of any 
event likely to affect the safety of subjects or the conduct of the study. 
The ICF used by the Investigator for obtaining the subjects informed consent must be reviewed and approved by the 
Sponsor prior to submission to the appropriate IRB for approval/favorable opinion (21 CFR 56). 
Any report of withdrawal of IRB approval will be submitted to the Sponsor within 5 working days. 
14.5 Protocol Changes 
The Investigator should not implement changes to the protocol without approval by Medtronic and prior review and 
documented approval from the governing IRB. The only exception to this requirement is the necessity to eliminate 
immediate hazards to study subjects, or when changes involve only administrative aspects (e.g., change in monitors, 
telephone numbers, etc.). 
14.6 Subject Confidentiality 
Appropriate precautions will be taken to maintain confidentiality of subject medical records and personal 
information. However, the subject’s name may be disclosed to the Sponsor, Medtronic, or other health authorities if 
they inspect the study records. A report of this study may be published; however the subjects’ identities will not be 
disclosed. 
14.7  Study Data 
The primary efficacy endpoint in this study is Raymond Grade I (100% aneurysm angiographic occlusion) at 12 
months ± 8 weeks. The sample size is based on a review of the modern literature, where the composite percent total 
occlusion reported is 43%8 (see Background and Statistical Analysis sections for more detail).  
Secondary endpoints will be presented in descriptive terms with incidence and 95% confidence intervals.  
Subject demographic and clinical characteristics across sites, including age, gender, baseline, modified Rankin 
Score, NIHSS score, and Raymond grade will be reported and compared to determine whether significant 
differences exist from site to site. 
Study outcome data, Raymond grade at 12 months± 8 weeks, and the rate of clinically significant procedural 
complications will be presented for the study and stratified by each site. If there is a significant difference among 
sites, a separate analysis excluding outlier sites will be presented to support the primary analysis results. Each site 
will follow the same protocol, and no single site will be allowed to enroll more than 20% of the total subjects.  

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14.8  Documentation 
14.8.1 Source Documents 
Source documents may include a subject’s medical record, hospital charts, clinic charts, the Investigator’s study 
files, questionnaires, as well as the results of diagnostic tests such as laboratory tests, angiograms, x-rays, CT or 
MRI scans.  
The following information should be included in the subject’s study records: 
• 
Subject’s name and contact information; 
• 
The study title/reference number; 
• 
The date the subject was enrolled into the trial and the subject ID number; 
• 
A statement that written informed consent was obtained; 
• 
Date of procedure and device lot numbers; 
• 
Dates of all visits; 
• 
Lists of medications; 
• 
Documentation of AEs; 
• 
Date subject exited the study, and a notation as to whether the subject completed the study or 
discontinued, with the reason for early termination. 
14.8.2  eCRF Completion 
Study data will be collected using eCRFs 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 analysis 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 and approving 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 eCRFs. 
 
Further information regarding eCRF navigation and use may be found in the eCRF completion guidelines. 
14.8.3  Study Summary 
The Investigator is responsible for submitting a study summary to Medtronic within a short time after completion of 
the study, and for supplying this summary to the governing IRB. 
14.8.4  Documentation Retention 
All study-related correspondence, subject records, consent forms, records of the distribution and use of the 
investigational products, and copies of CRFs should be maintained on file.  
The Investigator shall retain study documentation during the study and for a period of two (2) years after the latter of 
the following two dates: The date on which the investigation is terminated or completed, or the date that the records 
are no longer required for purposes of supporting a premarket approval application. 
Medtronic requires notification in writing if the Investigator wishes to relinquish ownership of the data so that 
mutually agreed upon arrangements can be made for transfer of ownership to a qualified entity (21 CFR 812.140). 

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14.8.5  Storage of Investigational Products 
The investigational devices must be stored in a secure area and administered only to subjects enrolled in the study, at 
no cost to the subjects, in accordance with the conditions specified in this protocol. The Investigator must keep an 
accurate accounting of the number of units received, dispensed, and returned. 
14.8.6  Data Safety Monitoring Board (DSMB) 
The DSMB will be an independent group that will serve as a data monitoring committee to the Sponsor of this 
Study. The DSMB will be comprised of individuals who are independent of the investigational sites and of 
representatives from multiple disciplines including but not limited to neurology, biostatistics/epidemiology, 
neurosurgery and interventional neuroradiology. 
In the safety monitoring role, this board shall provide recommendations to the Sponsor regarding stopping 
/continuing enrollment in the study. The DSMB will establish proposed monitoring criteria for the study and will 
establish any required analyses for assessing safety. The group will also establish a mission statement and operating 
procedures. 
The DSMB will also advise the Sponsor concerning the content of interim reports and the analyses that are required 
for data interpretation. 
14.8.7 Clinical Events Committee 
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. All AEs will 
be collected and documented prior to adjudication by the CEC. This committee will be responsible for the review 
and adjudication to the study endpoints of the following events reported by the site: 
1. Neurological adverse events with a corresponding worsening of NIHSS  
2. All Device related adverse events 
3. All Procedure related adverse events 
4. All SAEs 
5. All Antiplatelet therapy related events 
The CEC will independently adjudicate to specified endpoint event definitions, 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. 
14.8.8  Monitoring 
The Sponsor will be responsible for ensuring that monitoring will be done in accordance to applicable regulations 
and will be outlined in the study’s Clinical Monitoring Plan. All monitoring personnel for this study will be 
qualified by training, education and/or experience to perform their respective tasks. 
The primary contact for the study is: 
Clinical Affairs 
9775 Toledo Way 
Irvine, CA 92618 
Tel:  (949) 837-3700 

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Study monitors will conduct site visits to ensure accuracy of data, timeliness of data submissions, compliance with 
applicable laws and regulations, compliance with the protocol, compliance with the signed Investigator agreement, 
and compliance with IRB conditions and guidelines.  Any non-compliance with these items that is not adequately 
addressed by the PI/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 treatment, follow-up visits and phone conversations/interviews are to be fully documented either on the 
source document worksheets or in the subject’s medical records.  All information entered onto 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 source documents may be photocopied, if required.  The study 
monitor will also check the Investigator Site File (ISF) to ensure that all study-related documents are current. 
14.9  Quality Control and Quality Assurance 
14.9.1  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 prior to the 
start of the study. The Sponsor will review eCRFs for accuracy and completeness and any discrepancies will be 
resolved with the Investigator or designee, as appropriate. 
14.9.2  Site Selection 
The Sponsor or representative of the Sponsor will assess each potential site to ensure the PI 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 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: 
• 
Previous experience with clinical research and coil embolization of intracranial aneurysms 
• 
An Investigator trained and on either phantom or bench-top model of the Barrel® VRD under 
fluoroscopic visualization. 
• 
Commitment from the participating physician to pursue details of any safety outcomes 
• 
Commitment from the participating physician to enroll only patients meeting inclusion and 
exclusion criteria 
• 
A dedicated study coordinator who can enter data and respond to queries. 
• 
Ability to perform required clinical testing and study procedures 
• 
Ability and willingness to provide the Sponsor’s representatives access to the hospital records, 
study files, and subject files as they pertain to the study 
14.9.3  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. Training to the investigational 
plan will include the following topics: 
 

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• 
Study objectives 
• 
Protocol review 
• 
Delegation of authority for study-related tasks 
• 
Informed Consent process, including any relevant IRB requirements; Confidentiality/HIPAA 
(Health Insurance Portability and Accountability Act of 1996) 
• 
eCRFs and completion instructions 
• 
Documentation of protocol deviations 
• 
AE reporting 
• 
Device-specific events reporting 
• 
IFU of the Barrel® VRD and Reverse Medical® Detachment System 
• 
Device tracking and accountability 
• 
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. 
14.9.4  Site Initiation 
The Sponsor or a designated representative will conduct a training session with study Investigators and respective 
staff to review the protocol, eCRFs, the informed consent process, IRB involvement 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 approval for the Investigational Plan 
• 
IRB and Sponsor-approved ICF for the study 
• 
Signed Clinical Study Agreement (CSA) 
• 
Documentation that verifies the appropriate study staff has been trained on the protocol, eCRFs 
and study conduct. 
• 
Financial Disclosure(s) for the PI and Sub-I(s) 
• 
PI and Sub-I(s) curriculum vitae (CV) 
14.9.5  Data Quality Assurance 
ORACLE Clinical Remote Data Capture (OC/RDC) is the electronic data capture (EDC) system that will be used 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). Training will be 
conducted by qualified individuals and on a continuing basis, as needed. 
14.9.6  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. 

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14.10  Publications 
The Sponsor intends to publish the results of this multicenter study. Individual investigators are therefore asked to 
refrain from reporting results from their study participants prior to publication of the main multicenter report. The 
Sponsor will establish authorship criteria for such publications for the study group, based on the study conduct and 
compliance, contribution to the study design, management or enrollment, and willingness to accept the rights and 
responsibilities of an author. The Sponsor will enter the study into a public clinical trials repository such as 
ClinicalTrials.gov. 

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15. 
References 
The complete articles referenced in this protocol are provided in the Report of Prior Investigations section of this 
IDE application, along with additional articles relevant to treatment of intracranial aneurysms. 
1 
Molyneux, A. et al. International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus 
endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial. Lancet 360, 
1267-1274 (2002). 
2 
Chestnut Medical Technologies. Summary of Safety and Effectiveness Pipeline Embolization Device 
P100018. 
3 
Chalouhi, N. et al. Treatment of recurrent intracranial aneurysms with the Pipeline Embolization Device. J. 
Neurointerv. Surg., doi:10.1136/neurintsurg-2012-010612 (2013). 
4 
Kallmes, D. F. et al. International Retrospective Study of the Pipeline Embolization Device: A Multicenter 
Aneurysm Treatment Study. AJNR Am. J. Neuroradiol., doi:10.3174/ajnr.A4111 (2014). 
5 
Siddiqui, A. H. et al. Panacea or problem: flow diverters in the treatment of symptomatic large or giant 
fusiform vertebrobasilar aneurysms. J. Neurosurg. 116, 1258-1266, doi:10.3171/2012.2.JNS111942 (2012). 
6 
Lozier, A. P., Connolly, E. S., Jr., Lavine, S. D. & Solomon, R. A. Guglielmi detachable coil embolization 
of posterior circulation aneurysms: a systematic review of the literature. Stroke 33, 2509-2518 (2002). 
7 
Henkes, H. et al. Endovascular coil occlusion of 1811 intracranial aneurysms: early angiographic and 
clinical results. Neurosurgery 54, 268-280; discussion 280-265 (2004). 
8 
Chalouhi, N. et al. Safety and efficacy of endovascular treatment of basilar tip aneurysms by coiling with 
and 
without 
stent 
assistance: 
a 
review 
of 
235 
cases. 
Neurosurgery 
71, 
785-794, 
doi:10.1227/NEU.0b013e318265a416 (2012). 
9 
Bavinzski, G. et al. Treatment of basilar artery bifurcation aneurysms by using Guglielmi detachable coils: 
a 6-year experience. J. Neurosurg. 90, 843-852, doi:10.3171/jns.1999.90.5.0843 (1999). 
10 
McDougall, C. G. et al. Endovascular treatment of basilar tip aneurysms using electrolytically detachable 
coils. J. Neurosurg. 84, 393-399, doi:10.3171/jns.1996.84.3.0393 (1996). 
11 
Raymond, J., Roy, D., Bojanowski, M., Moumdjian, R. & L'Esperance, G. Endovascular treatment of 
acutely ruptured and unruptured aneurysms of the basilar bifurcation. J. Neurosurg. 86, 211-219, 
doi:10.3171/jns.1997.86.2.0211 (1997). 
12 
Lodi, Y. et al. Single Stage versus Multi-staged Stent-assisted Endovascular Repair of Intracranial 
Aneurysms. J. Vasc. Interv. Neurol. 4, 24-28 (2011). 
13 
Rezek, I. et al. Differences in the angiographic evaluation of coiled cerebral aneurysms between a core 
laboratory reader and operators: results of the Cerecyte Coil Trial. AJNR Am. J. Neuroradiol. 35, 124-127, 
doi:10.3174/ajnr.A3623 (2014). 
14 
Rezek, I., Mousan, G., Wang, Z., Murad, M. H. & Kallmes, D. F. Effect of core laboratory and multiple-
reader interpretation of angiographic images on follow-up outcomes of coiled cerebral aneurysms: a 
systematic review and meta-analysis. AJNR Am. J. Neuroradiol. 34, 1380-1384, doi:10.3174/ajnr.A3398 
(2013). 
15 
Fargen, K. M. et al. A multicenter study of stent-assisted coiling of cerebral aneurysms with a Y 
configuration. Neurosurgery 73, 466-472, doi:10.1227/NEU.0000000000000015 (2013). 
16 
Spiotta, A. M. et al. Mid-term results of endovascular coiling of wide-necked aneurysms using double 
stents in a Y configuration. Neurosurgery 69, 421-429, doi:10.1227/NEU.0b013e318214abbd (2011). 
17 
Zhang, J. Z. et al. Stent-assisted coiling strategies for the treatment of wide-necked basilar artery 

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bifurcation aneurysms. J. Clin. Neurosci. 21, 962-967, doi:10.1016/j.jocn.2013.08.025 (2014). 
18 
Roy, D., Milot, G. & Raymond, J. Endovascular treatment of unruptured aneurysms. Stroke 32, 1998-2004 
(2001). 
19 
McDougall, C. G. et al. Bioactive versus bare platinum coils in the treatment of intracranial aneurysms: the 
MAPS 
(Matrix 
and 
Platinum 
Science) 
trial. 
AJNR 
Am. 
J. 
Neuroradiol. 
35, 
935-942, 
doi:10.3174/ajnr.A3857 (2014).