SMART - A Prospective, Multicenter Registry Assessing the Embolization of Neurovascular Lesions Using the Penumbra SMART COIL® System
Phase: NA
Conditions: Intracranial Aneurysm
Sponsor: Penumbra Inc.

 
 
 
 
 
 
 
SMART – A prospective, multicenter registry assessing 
the embolization of neurovascular lesions using the  
Penumbra SMART COIL® System 
 
 
 
Protocol  
CLP 10023.B 
 
Release Date 
August 23, 2016 
 
 
Device Name 
Penumbra SMART COIL® System 
 
 
Sponsor 
Penumbra, Inc. 
One Penumbra Place 
Alameda, CA 94502 
USA 
 
 
 
Contacts 
 
Brooke Lawson 
Amaëlle Vuillame 
Clinical Project Manager 
Director Clinical Affairs Europe 
Telephone: 
+ 1.510.995.2183 
Telephone: + 33.634.30.21.12 
E-mail: 
brooke.lawson@penumbrainc.com 
E-mail: 
avuillaume@penumbrainc.com 
 

 
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TABLE OF CONTENTS 
Contents 
1. 
PROTOCOL SYNOPSIS ....................................................................................................... 3 
2. 
INTRODUCTION .................................................................................................................. 4 
3. 
REGISTRY OVERVIEW ...................................................................................................... 7 
4. 
REGISTRY PROCEDURES ................................................................................................. 8 
5. 
INVESTIGATOR RESPONSIBILITIES ............................................................................. 9 
6. 
SPONSOR RESPONSIBILITIES ........................................................................................13 
7. 
CONTACT INFORMATION ..............................................................................................14 
8. 
ETHICAL REQUIREMENTS .............................................................................................15 
9. 
STATISTICAL PROCEDURES ..........................................................................................15 
10. 
PUBLICATION OF INFORMATION ..............................................................................16 
11. 
BIBLIOGRAPHY ...............................................................................................................17 
 
 

 
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1. 
PROTOCOL SYNOPSIS 
CLP 10023.B Protocol Synopsis 
Registry Title: 
SMART – A prospective, multicenter registry assessing the embolization 
of neurovascular lesions using the Penumbra SMART COIL® System 
Objective: 
The primary objective of this registry is to gather post market data on the Penumbra 
SMART COIL® System (Smart System) in the treatment of intracranial aneurysms 
and other malformations.  
Registry Design: 
This is a prospective, multi-center registry of patients treated in accordance with the 
cleared indications for Smart, Penumbra Coil 400TM (PC 400), and Penumbra 
Occlusion Device (POD®). Data for each patient are collected in accordance with the 
standard of care at each participating hospital through one-year follow-up.  
Patient 
Population: 
Approximately 1,000 patients with intracranial aneurysms or other malformations 
treated by Smart at up to 100 centers will be enrolled.  
Sample Size 
Justification: 
Approximately 1,000 patients will be enrolled in this post market registry. Assuming 
an observed rate of 8.3% for the primary endpoint of re-treatment at follow-up, the 
sample size precision is ± 2% for this endpoint. Assuming an observed rate of 1.7% 
for the primary endpoint of procedural device-related serious adverse events at 
immediate post-procedure, the sample size precision is ± 1% for this endpoint. These 
precision estimates are based on binomial 95% confidence intervals. The sample size 
provides an adequate level of precision for these primary endpoints. 
Inclusion 
Criteria: 
Patients enrolled in this registry must sign the Informed Consent Form and be treated 
according to the cleared indications for Smart, PC 400, and POD, which include the 
embolization of: 
1. Intracranial aneurysms 
2. Other neurovascular abnormalities such as arteriovenous malformations and 
arteriovenous fistulae 
Exclusion 
Criteria: 
1. Life expectancy less than one year 
2. Smart, PC 400, or POD account for less than 75% of total number of coils 
implanted 
3. Patient previously enrolled in the SMART Registry 
4. Participation in another clinical investigation that could confound the 
evaluation of the registry device 
Endpoints: 
1. Retreatment through follow-up  
2. Procedural device-related serious adverse events  
3. Ability to achieve adequate occlusion immediate post procedure 
4. Number of times re-access with guidewire was required due to catheter 
kickout 
Registry Period: 
It is anticipated patient enrollment will take 3 years. All patients are to be assessed in 
accordance with the standard of care at each participating hospital through one year 
follow-up.  

 
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2. 
INTRODUCTION 
 
Intracranial aneurysms are a significant health problem in the United States with 
an estimated 1% to 6% of the adult population harboring cerebral aneurysms.1,2  
The annual risk of rupture of an intact intracranial aneurysm is estimated to be 
approximately 1.9%.2 If an intracranial aneurysm ruptures, blood leaks into the 
highly sensitive subarachnoid space around the brain, resulting in a subarachnoid 
hemorrhage (SAH). SAH is known to be a major risk factor for a stroke due to the 
irritation of the outer layer of the nearby blood vessels surrounding the brain.  
This condition is associated with a high rate of mortality; close to half of ruptured 
aneurysms result in death within six months.2-4 Patients who survived the initial 
SAH are at significant risk of subsequent re-rupture.  Various reports indicate that 
if left untreated, there is a re-bleeding rate of more than 50% within the first six 
months from initial presentation of a SAH.4,5 
 
Even if an intracranial aneurysm does not rupture, it can lead to severe 
complications.  As the aneurysm grows, it can press on nerves, put pressure on 
brain tissue, or interfere with other arteries or veins. Blindness, paralysis, and 
other morbidities often result. Thrombus can also form within the aneurysmal sac, 
break off, travel downstream, and cause an ischemic stroke. It has been reported 
that 2.2% to 23% of patients with unruptured aneurysms may eventually 
experience a rupture.7,8 The International Study of Unruptured Intracranial 
Aneurysms evaluated the natural history of 1,937 unruptured aneurysms in 1,449 
patients with a mean follow-up of 8.3 years.8 It reported that 2.2% of these 
patients had a confirmed rupture during follow-up, but 66% of them were fatal.  
Juvela et al. reported on the long term natural history of unruptured intracranial 
aneurysms in a series of 142 patients.7 With a median follow-up of 19.7 years, 
23% of the patients experienced a SAH, which corresponds to an annualized rate 
of 1.3%. The cumulative rate of SAH tended to increase with time, with a rupture 
rate of 10.5% at 10 years, 23% at 20 years, and 30.3% at 30 years after diagnosis. 
Approximately half of the SAH patients did not survive. Thus, regardless of the 
rate of occurrence, fatality associated with this event is high in this cohort.7, 8 
 
Prior to 1995, the traditional treatment for intracranial aneurysms was surgical 
clipping, in which the skull is surgically opened so metal clips can be applied to 
the aneurysm’s neck to occlude it from the parent artery to prevent a rupture.1 
This treatment, while effective, is high risk, highly invasive, requires an extended 
hospital convalescence, and is technically difficult to perform in certain regions of 
the brain (such as the posterior circulation).  Thus, this treatment modality is not a 
viable option for a significant number of patients, particularly during the acute 
phase of SAH, when the presence of cerebral edema and evolving thrombi 
formation render aneurysm access difficult, if not impossible. 
  
In the early 1990’s, an endovascular treatment technique for intracranial 
aneurysms was first introduced by Guido Guglielmi, who used electrolytically 
detachable platinum coils to pack and embolize the aneurysmal sac.9, 10 The 

 
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rationale was to exclude the aneurysm from the circulation and thus reduce the 
risk of a rupture and SAH.  The Guglielmi detachable coil (GDC) was not 
universally accepted at first but gained significant credibility after obtaining 
approval from the FDA for the intracranial aneurysm indication.  Moreover, a few 
well-conducted, prospective, randomized studies of both ruptured and unruptured 
aneurysms have demonstrated that angiographic and clinical outcomes from this 
treatment modality were equivalent, if not better, than those obtained from 
surgical clipping.6,8,11,12 Results were found to be similar for both treatments 
regardless of the inter-study differences in definitions for these outcome 
measures.6,8,11,12 The most important landmark study was the International 
Subarachnoid Aneurysm Trial (ISAT) in which a total of 2,143 patients with 
ruptured intracranial aneurysms were randomized to either neurosurgical clipping 
or endovascular GDC coiling. The results showed that at one year follow-up, 
30.6% of the patients treated by neurological clipping were either functionally 
dependent or dead as vs. 23.7% of those treated by GDC coiling, which resulted 
in a risk reduction rate of 22.6%. And thus, embolic coiling has now become the 
standard of care worldwide for endovascular occlusion for both incidental and 
ruptured intracranial aneurysms.   
 
In light of the natural history of the disease, the primary focus for management of 
an intracranial aneurysm must be to prevent its rupture and sequelae.   
 
The Penumbra SMART COIL® System (Smart System), a new generation of 
detachable coils, is the latest in Penumbra’s line of embolization tools.  It has 
recently received 510k clearance in the U.S. and CE Mark in Europe.  This coil 
system is specifically designed to promote aneurysm embolization. 
 
Coil technology has evolved considerably since the initial introduction of the 
GDC coil over 25 years ago.  In recent history, coil development has mostly 
focused on the delivery system, or pusher technology, and detachment. The new 
Smart System not only addresses improvements in the delivery system, but 
importantly incorporates new technology into the actual coil implant itself.  Smart 
technology enables an individual coil to become progressively softer as it is 
deployed, utilizes advanced materials to improve stretch resistance, and 
incorporates new processes to create accurate complex and helical shapes. 
 
Current coils available to physicians have three principal levels of softness, 
standard, soft and extra soft. A conventional coil currently has only one level of 
softness, derived from using smaller platinum filaments than a standard coil to 
make soft and extra soft coils.  The level of softness of the Smart coils is 
determined not only by the diameter of the platinum filament, but also by 
a proprietary structural element inside the coil.  This unique development enables 
the Penumbra Smart System to become progressively softer along the length of a 
single individual coil as it is being deployed.  For example, deployment of a 
standard Smart coil begins with an atraumatic soft 2D loop, becomes standard for 
the body of the coil, and finishes with a soft proximal end. This progressive 

 
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softness enables the coil to be densely packed into a delicate lesion while 
maintaining catheter position and mitigating catheter kick-back at the end of 
delivery, which can preclude the successful complete embolization of the lesion. 
In addition, Smart uses the latest ultra high molecular weight polymers for stretch 
resistance, which are 3 times stronger than current stretch resistant materials such 
as polypropylene (found in most 10-system coils). 
 
The Penumbra Coil 400TM (PC400) system received 510k in the U.S. and has CE 
Mark. 
 
PC400 fundamentally differs from other embolic products for treatment of brain 
aneurysms by offering the largest outer diameter coil available. PC400 has up to 
four times more volume per unit length than most other embolic coils available 
while still maintaining a soft and compliant feel.  Together, these characteristics 
represent the potential to improve the ability to densely fill larger aneurysms and 
other neurovascular abnormalities such as arteriovenous malformations and 
arteriovenous fistulae, thus triggering the healing process.  
 
Penumbra Occlusion Device (POD®), was developed to address a specific clinical 
need to rapidly and precisely occlude a target vessel. Current options for vessel 
occlusion are limited. Coils designed for aneurysms are not ideally suited for 
vessel embolization due to their tendency to migrate with antegrade flow.  Other 
options, such as vascular plug technology for larger vessels, require access with 
large diagnostic catheters or even larger bore sheaths.  
 
POD utilizes technology that delivers both variable sizing and softness to provide 
a solution for rapid and precise embolization of the target vessel. 
The technology achieves this range of features through the design of a distal 
anchoring segment, thereby immediately anchoring the device in a range of vessel 
diameters. The proximal segment of the POD achieves dense occlusion by 
packing a softer, smaller diameter segment tightly behind the anchored portion.  
 
All three systems (Smart, PC 400, and POD) above consist of: an implantable 
Coil constructed of 92% Platinum and 8% Tungsten round wire, an attached 
detachment pusher, and a detachment handle (packaged separately). The 
detachment pusher is comprised of a shaft with a radiopaque positioning marker, 
a distal detachment tip, and a pull wire. The detachment handle is used to detach 
the coil implant from the detachment pusher. All three systems are designed for 
endovascular embolization of aneurysms and other neurovascular abnormalities 
such as arteriovenous malformations and arteriovenous fistulae.  The intended 
users for this device are physicians who have received appropriate training in 
interventional neuroradiology.   
 
These devices provide a comprehensive product family for the management of 
intracranial aneurysms and other neurovascular abnormalities such as 
arteriovenous malformations and arteriovenous fistulae.  

 
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3. 
REGISTRY OVERVIEW 
 
This is the first multicenter post market registry examining Smart and its primary 
objective is to gather real world experience and data on the Smart System in the 
treatment of intracranial aneurysms and other neurovascular abnormalities such as 
arteriovenous malformations and arteriovenous fistulae.  
 
3.1 
Registry Design 
 
This is a prospective, multi-center registry of patients treated in accordance with 
the cleared indications for the Penumbra Smart System, Penumbra Coil 400™ (PC 
400), and Penumbra Occlusion Device (POD®) for intracranial aneurysms and 
other neurovascular abnormalities. Data for each patient are collected in 
accordance with the standard of care at each participating hospital through one-
year follow-up. 
 
3.2 
Registry Objectives/Endpoints 
 
This is the first multicenter post market registry examining the Penumbra Smart 
System.  Its purpose is to gather real world experience on the Smart System in the 
treatment of intracranial aneurysms and other neurovascular abnormalities such as 
arteriovenous malformations and arteriovenous fistulae.  
 
Approximately 1,000 patients with intracranial aneurysms or other malformations 
treated by the Penumbra Smart System, PC 400, and/or POD at up to 100 centers 
will be enrolled. 
 
3.2.1 The Endpoints are: 
• Retreatment through follow-up 
• Procedural device-related serious adverse events at immediate post-
procedure 
• Ability to achieve adequate occlusion - based on investigator’s 
adjudication of adequate occlusion given anatomical and other 
considerations immediate post-procedure 
• Number of times re-access with guidewire was required due to catheter 
kickout  
 
3.3 
Registry Population 
 
Patients enrolled in this registry must sign the informed consent form and be 
treated in accordance with the cleared indications outlined in the Instructions for 
Use for Smart, PC 400, and/or POD. Patients will be considered enrolled at the 
time of consent and procedure has begun with the intent of implanting coils. 

 
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Patients who fail to meet entry criteria pertaining to coil selection will be 
considered a screen fail and monitored through discharge for safety reasons.  
 
3.3.1 Inclusion Criteria 
Embolization of: 
• Intracranial aneurysms 
• Other neurovascular abnormalities such as arteriovenous 
malformations and arteriovenous fistulae 
3.3.2 Exclusion Criteria 
• Life expectancy less than one year  
• Smart, PC 400, or POD account for less than 75% of total number of 
coils implanted 
• Patient previously enrolled in the SMART Registry 
• Participation in another clinical investigation that could confound the 
evaluation of the registry device 
 
4. 
REGISTRY PROCEDURES 
 
All registry procedures are to be conducted in accordance with the cleared 
indications outlined in the Instructions for Use for Smart, PC 400, and POD. 
 
 SCHEDULE OF ASSESSMENTS 
 
* Single follow-up visit to be conducted in accordance to the standard of care at the 
participating hospital. Period for which to capture follow-up visit is within one year 
±6 months 
** Only for patients in which mRS would be captured as standard of care 
+ Required for patients with SAH only  
++Proportion of SMART coils implanted, target location access attempts, radiation 
exposure, coiling start/end time 
  
Assessment 
Admission 
Evaluation 
Immediate 
Post-
Procedure 
Discharge 
One Year 
Follow-
Up* 
History 
√ 
 
 
 
Modified Rankin 
Scale** 
√ 
 
 
√ 
Hunt and Hess+ 
√ 
 
 
 
Aneurysm Occlusion 
 
√ 
 
√ 
Procedural Data 
Points++  
 
√ 
 
 
Adverse Events 
 
√ 
√ 
√ 

 
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5. 
INVESTIGATOR RESPONSIBILITIES 
 
5.1 
Institutional Review Board Approval / Ethics Committee Approval 
 
Prior to enrolling patients into the registry, the investigator will ensure that proper 
Institutional Review Board (IRB) / Ethics Committee (EC) approval is obtained, 
in accordance with applicable local state and federal laws and regulations.  The 
IRB/EC shall approve all registry documents, including the final protocol, 
amendments to the protocol, and the informed consent.   
 
5.2 
Informed Consent 
 
The investigator is responsible for ensuring that a signed informed consent is 
obtained according to national and state requirements prior to inclusion of patients 
in the registry. For patients being treated in emergent cases (i.e. ruptured 
aneurysm) patients will be allowed to be enrolled if they sign consent no longer 
than 1 calendar day after the procedure, or if a legally authorized representative 
signs the informed consent on the patient’s behalf.  
 
5.3 
Adherence to Protocol/Amendments and Applicable Law 
 
The investigator is responsible for ensuring that the registry is conducted 
according to this protocol and in accordance with the relevant aspects of EN ISO 
14155:2011, Declaration of Helsinki, along with any conditions imposed by the 
reviewing Institutional Review Board (IRB) or Ethics Committee (EC), and all 
other applicable regulations.The investigator shall approve and adhere to this 
protocol and any amendments that arise during the course of the registry. 
It is the investigator's responsibility to ensure that the staff assisting with the 
registry have the appropriate qualifications, are fully instructed on the registry 
procedures, and will respect the confidentiality statement. 
 
5.4 
Case Report Form Completion 
 
The investigator and registry staff shall complete the electronic case report forms 
(eCRFs) associated with this registry.  Patient numbers shall be used to identify 
individual patients in this registry.  The eCRFs should be a complete and accurate 
record of patient data collected during the registry.  It is the investigator's 
responsibility to ensure the quality of the data collected and recorded. 
 
5.5 
Reports 
 
The investigator will be responsible for the following reports: 
 

 
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5.5.1 Protocol Deviation 
Any deviations from the protocol identified during monitoring or through other 
means should be clearly documented. These include but are not limited to: 
• Subject does not meet inclusion/exclusion criteria 
• Incomplete or missing data 
• Failure to sign informed consent 
• Improperly signed or incomplete informed consent 
• Delayed reporting of serious, device related, or unexpected adverse 
events 
• Out of window visits or assessments 
 
5.5.2 Adverse Event Reporting 
Since this a post market registry, we will only be collecting Adverse Events 
(AEs) related to the procedure or device, unanticipated adverse device effects 
(UADE), and all Serious Adverse Events (SAEs) from the time of consent 
through registry exit. If an AE occurs that is not related to the procedure or 
device, it is not reportable under this Protocol.  
 
5.5.2.1 
Definitions 
• Adverse Event (AE) : An AE is any undesirable clinical event 
occurring to a patient, during a clinical trial, whether or not it is 
considered related to the device. This includes a change in a 
patient's condition or laboratory results which has or could have a 
deleterious effect on the patient's health or well-being. 
 
• Adverse Device Effect (ADE): An adverse device effect related to 
registry device(s). 
 
• Serious Adverse Event (SAE): A SAE is an event that:  
a. 
Led to death 
b. 
Led to a serious deterioration in the health of the patient that: 
− Resulted in life-threatening illness or injury 
− Resulted in permanent impairment of a body structure or a 
body function 
− Required in-patient hospitalization or prolongation of 
existing hospitalization 
− Resulted in medical or surgical intervention to arrest 
permanent impairment to body structure or a body function 
− Led to fetal distress, fetal death or a congenital abnormality 
or birth defect 
 
• Unanticipated Adverse Device Event (UADE): An event that has 
an Adverse  Device Effect, the specificity or severity of which is 

 
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not consistent with the with the risk information described in the 
Instruction for Use or the clinical protocol. 
 
5.5.2.2 
Relationship to the Registry Device 
An AE is considered to be device-related when it is reasonable to believe 
that the event may have been caused by or is related to the device. 
Following definitions will be used to assess the relationship of the 
adverse event to the use of registry device. Any grading for relatedness 
other than ‘unrelated’ will be considered device related. 
• Definite:  The temporal sequence is relevant and the event abates 
upon device application completion/removal, or reappearance of the 
event on repeat device application 
• Probable:  The temporal sequence is relevant or the AE abates 
upon device application completion/removal or the AE cannot be 
reasonably explained by the subject’s condition or 
comorbidities.  The AE is related or most likely associated with the 
device 
• Possible: The temporal sequence between the device and the AE is 
such that the relationship is not unlikely or there is no contradicting 
evidence that can reasonably explain the registry subject’s 
condition.  There is a possibility of a relationship between the AE 
and the device 
• Unrelated:  The AE is not associated with the device.  There is no 
relation between the AE and the device 
Similar grading will be used for assessing the relationship to procedure.  
5.5.2.3 
Adverse Event Severity 
For the purposes of this trial, the investigator will use the following 
definitions to rate the severity of each adverse event. 
• Mild: Awareness of a sign or symptom that does not interfere with 
the patient’s usual activity or is transient, resolves without treatment 
and with no sequelae 
• Moderate: interferes with routine activity and/or requires 
symptomatic therapy 
• Severe: Severe discomfort and significant impact on the subject’s 
ability to perform routine activities despite symptomatic therapy 
 
Minimum requirements of data to be recorded are: type of event, duration of event 
(start through end), severity, seriousness, action taken, outcome and, if 
appropriate, causality. 
 

 
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The Investigator is required to report any device or procedure related AE, UADE 
and/or SAEs to the Sponsor or its designee as soon as possible, but no later than 
24 hours after the event is known.  All serious adverse events or serious device 
effects must document an explanation of any medical treatment administered.  
The form must be completed and submitted to the Sponsor or its designee within 
five working days.   
 
An event need not be reported as a SAE if it represents only a relapse or an 
expected change or progression of the condition that was the cause of treatment 
without any other symptoms and signs than those present before treatment. This 
type of event is considred an AE, and may not be reportable. 
 
When appropriate, the IRB/EC shall be informed by the investigator about serious 
adverse events and adverse device effects associated with the use of the product, 
and Penumbra is responsible for informing the Health Authorities and other 
investigators of such events as appropriate. 
 
5.6 
Withdrawal of Approval 
 
The investigator shall report to Penumbra immediately if, for any reason, the 
approval to conduct the investigation is withdrawn by the IRB/EC. The report will 
include a complete description of the reason(s) for which approval was 
withdrawn. The investigator shall submit all reports in a timely manner. 
 
5.7 
Records Retention 
 
The investigator shall maintain the records associated with this registry for a 
period of at least two years after the date on which the investigation is completed.  
These records include the following: 
 
• Correspondence with the Sponsor or designee, the medical monitor, and other 
investigators. 
• Patient records, including informed consent forms, copies of all completed 
eCRFs, and supporting documents. 
• Current registry protocol with dates and details of reasons for any deviations 
from the protocol that could affect the scientific quality of the registry or the 
rights, safety, or welfare of the patients. 
• Reports of any serious adverse event or adverse device effects. 
• A copy of all approvals related to the clinical investigation. 
• The approved, blank, informed consent form. 
• Certification that the investigational plan has been approved by the IRB/EC. 
• Signed investigator agreements and current signed and dated curriculum vitae 
of the registry investigator and all participating investigators. 
 
 
 

 
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6. 
SPONSOR RESPONSIBILITIES 
 
6.1 
Training 
 
During registry initiation, the Sponsor will train the investigator and registry staff 
on the protocol as well as the eCRFs. 
 
6.2 
Investigator List 
 
The Sponsor shall keep a list of the names, addresses, and professional positions 
of the investigators for the registry. 
 
6.3 
 Adverse Event Reporting 
 
The Sponsor shall evaluate adverse event reports received from the registry sites 
and those found during data monitoring and shall report them to the regulatory 
bodies and other investigational sites as appropriate.  
 
6.4 
Data Monitoring 
 
Sponsor will be utilizing both centralized and on-site monitoring during the trial. 
Standardized eCRFs will be used for queries and query resolution.  A Penumbra 
employee or designate will conduct the following site visits: 
 
6.4.1 Site Initiation Visit 
 
This is conducted on site or remotely to train the registry staff on registry 
requirements, and other relevant training. 
 
6.4.2 Interim Monitoring Visit 
 
Conducted as needed to ensure the registry site is operating in compliance 
with this protocol, and completing the eCRFs. Clinical monitoring will 
include review and resolution of missing or inconsistent data and source 
document checks to ensure the accuracy of the reported data. eCRFs for 
all enrolled patients will be made available to the Sponsor for review as 
agreed with the investigator.  The Sponsor will evaluate and summarize 
the results of each site visit in written reports, identifying repeated data 
problems with any investigator and specifying recommendations for 
resolution of noted deficiencies. To facilitate this monitoring, certain 
source documents may be requested. These may include, but are not 
limited to, patient informed consent, history and physical, operative report, 
imaging reports, and discharge summary.  
 
 
 

 
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6.4.3 Registry Close-Out Visit 
 
This visit is conducted at the termination of the registry to resolve any 
outstanding data queries and reconcile trial documents. 
 
6.5 
Data Management 
All registry data will be entered into an electronic data capture (EDC) system 
provided by a vendor. Registry personnel will have individual login and password 
to access the clinical registry information based upon each individual’s roles and 
responsibilities. For data security, the system operates within the Secure Socket 
Layer (SSL) 256-bit encryption protocol. This application is designed to support 
compliance with the appropriate regulations and guidance for industry.  
 
Data entry will be performed at the investigational sites. Standardized eCRFs will 
be provided for use at all investigational sites. Investigators are responsible for 
completion and timely submission of the data to Penumbra, Inc. This EDC system 
requires no on-site software installation or specific hardware to operate. 
Investigators, clinical coordinators, data managers, and Penumbra clinical 
personnel access project information and registry data centrally via a Web 
browser. Incoming data are to be reviewed for quality and consistency before 
being locked for data export. Questions or problems with submitted data will be 
addressed with the principal investigator or designee via an electronic querying 
system, or through direct contact.  
 
All hard copy forms and data files will be secured to ensure confidentiality. 
Investigators are required to maintain source documents required by the protocol, 
including laboratory results, patient report forms, supporting medical records, and 
Informed Consent Forms. The source documents will be used during the regular 
monitoring visits to verify information submitted on the eCRFs.  
 
7. 
CONTACT INFORMATION 
 
The address of Penumbra Incorporated is: 
 
Penumbra, Inc. 
One Penumbra Place 
Alameda, CA 94502 
Tel. (510) 748-3200 
Fax (510) 814-8305 
 
Key contacts for the SMART registry include: 
Brooke Lawson, MS CCRA 
Clinical Project Manager 
+1.510.995.2183 
Melissa Dillman, RN 
Director, Clinical Operations 
+1.317.490.4422 
Michaella Corso 
Director, Clinical Affairs 
+1.510.995.2079 
Amaëlle Vuillaume 
Director, Clinical Affairs Europe 
+ 33.634.30.21.12  

 
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8. 
ETHICAL REQUIREMENTS 
 
8.1 
IRB/EC Approval 
 
The investigator is responsible for ensuring that the registry is conducted 
according to any conditions imposed by the reviewing Institutional Review Board 
(IRB) or Ethics Committee (EC), and all other applicable regulations. It is the 
responsibility of the investigator to obtain approval of the registry protocol from 
the IRB/EC and to keep the IRB/EC informed of any unexpected serious adverse 
events, serious adverse device effects, and amendments to the protocol, as 
applicable. All correspondence with the IRB/EC should be filed by the 
investigator and copies sent to the Sponsor or its designee. 
 
8.2 
Patient Information and Consent 
 
It is the responsibility of the investigator to give each patient full and adequate 
verbal and written information regarding the objective and procedure of the 
registry and the possible risks involved and to obtain signed informed consent 
from all patients prior to inclusion in the registry unless the patient's health 
condition does not allow informed consent, in which case the state and national 
procedures will be applied. For patients being treated in emergent cases (i.e. 
ruptured aneurysm), patients will be allowed to be enrolled if they sign consent no 
longer than 1 calendar day after the procedure or if a legally authorized 
representative signs the informed consent form on the patient’s behalf. The 
original, signed consent is filed with the patient registry records, and a copy is 
provided to the patient or legally authorized representative. 
 
8.3 
Patient Data Protection 
 
The patients will be identified in the eCRFs with a unique patient identifier.  Only 
the investigator will have access to individual patient data, as will the Sponsor or 
its designee for monitoring purposes only. Furthermore, the patients should be 
informed about the possibility of inspection of relevant parts of the hospital 
records, including angiograms and other imaging scans, by the Sponsor or other 
health authorities, including the FDA. 
 
9. 
STATISTICAL PROCEDURES 
 
9.1 
Sample Size Justification 
  
Approximately 1,000 patients will be enrolled in this post market registry. 
Assuming an observed rate of 8.3% for the endpoint of re-treatment at follow-up, 
the sample size precision is greater than ± 2% for this endpoint (95% CI: 6.6% to 
10.0%).14-21 Assuming an observed rate of 1.7% for the primary endpoint of 
procedural device-related serious adverse events at immediate post-procedure 

 
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(data on file at sponsor), the sample size precision is greater than ± 1% for this 
endpoint (95% CI: 0.93% to 2.5%). These precision estimates are based on 
binomial 95% confidence intervals. Hence, the sample size provides an adequate 
level of precision for these primary endpoints. 
 
9.2 
General Statistical Methods 
 
This registry is a single-treatment design. Hence, descriptive statistics will 
provide a basis for the majority of the analyses with a 95% two-sided confidence 
interval presented. For binary outcomes, the 95% two-sided confidence intervals 
will be calculated using binomial intervals. For numeric measures, a confidence 
bound for the mean or mean change from admission will be constructed. 
  
Summary tables (descriptive statistics and/or frequency tables) will be provided 
for all baseline variables, effectiveness variables, and safety variables, as 
appropriate. Continuous variables will be summarized with descriptive statistics 
(n, mean, standard deviation, range, and median). Frequency counts and 
percentage of patients within each category will be provided for categorical data.  
 
Results collected at multiple visits will be summarized at each visit for which they 
are collected. Summaries for all measures will include all observed data for each 
visit. 
 
9.3 
Safety 
 
Tabulations of adverse events will be presented with descriptive statistics at 
immediate post procedure and follow-up visits. Adverse event incidence rates will 
be summarized by category and seriousness of the adverse event. Events will also 
be reported by relationship to the device.  
 
10. 
PUBLICATION OF INFORMATION 
 
The results of this registry may be offered for publication and/or presentation. The 
investigators and the Sponsor shall collaborate in the writing of the registry to 
ensure accuracy. The investigator agrees to use this data only in connection with 
this registry and will not use it for other purposes without written permission from 
the Sponsor. 
 
 
 

 
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11. 
BIBLIOGRAPHY 
 
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2. 
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3. 
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4. 
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11. Molyneux AJ, Kerr RS, Yu LM et al.  International Subarachnoid Aneurysm 
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20. Smith MJ, Mascitelli J, Santillan A, et al. Bare platinum vs matrix 
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