SUMMARY OF SAFETY AND PROBABLE BENEFIT

**I. GENERAL INFORMATION**

Device Generic Name: Intravascular Stent

Device Trade Name: Neuroform Microdelivery Stent System

Applicant's Name and Address: SMART Therapeutics, Inc.

2551 Merced St.

> San Leandro, CA 94577 USA

Humanitarian Device Exemption Number: H020002

Date of Humanitarian Use Device Designation: August 14, 2000

Date of Panel Recommendation: Not applicable

Date of Good Manufacturing Practices Inspection: August 12, 2002

Date of Notice to the Applicant: September 11, 2002

**II. INDICATIONS FOR USE**

The Neuroform Microdelivery Stent System is intended for use with
embolic coils for the treatment of wide neck, intracranial, saccular
aneurysms arising from a parent vessel with a diameter of ≥2mm and
≤4.5mm that are not amenable to treatment with surgical clipping. Wide
neck aneurysms are defined as having a neck of ≥4mm or a dome-to-neck
ratio of \<2.

III. **CONTRAINDICATION**

The Neuroform Microdelivery Stent System is contraindicated for use in
patients in whom antiplatelet and/or anticoagulation therapy is
contraindicated.

IV. **WARNINGS AND PRECAUTIONS**

See the *Warnings* and *Precautions* sections in the final labeling
(*Instructions for Use*) for the Neuroform Microdelivery Stent System.

V.  **DEVICE DESCRIPTION**

The Neuroform Microdelivery Stent System consists of a self-expanding,
neurovascular, nitinol Stent and Delivery System intended for use with
embolic coils. The Stent is deployed onto healthy vascular tissue. Once
the Stent is deployed, embolic coils are delivered through the struts of
the Stent. The Stent is used to retain embolic coils within the
aneurysm. The Neuroform Microdelivery Stent System is provided sterile
to the user (EO sterilized).

The Neuroform Microdelivery Stent System consists of the following
components:

-   1 Neuroform Microdelivery Stent

-   1 - 3F Microdelivery Catheter

-   1 - 2F Stabilizer Catheter

-   1 Peelable Sheath

-   2 Rotating Hemostasis Valves

A more detailed description of each of the five components of the
Neuroform Microdelivery Stent System follows:

**[Neuroform Microdelivery Stent]{.underline}** - The Stent has a
tubular mesh (zig-zag struts) design. There are 4, 6, or 8 distinct
sections along the length of the Stent, depending on the Stent length.
Sections are joined by 2 interconnecting struts. It is made from
nitinol. There are 8 radiopaque markerbands, 4 per end, which are
secured to tabs on the Stent. The Stent is available in five diameters
(2.5mm to 4.5mm) and three lengths (10mm, 15mm, and 20mm).

**[3F Microdelivery Catheter]{.underline}** - The 3F Microdelivery
Catheter is used to deliver the Stent to the treatment site within the
patient\'s parent artery. The 3F Microdelivery Catheter is a single
lumen, over-the-wire microcatheter. The material composition of the
catheter shaft changes over the length of it to create three distinct
stiffness regions: proximal, middle, and distal. The proximal end has a
strain relief and standard, female luer fitting. The 3F Microdelivery
Catheter is hydrophilically coated. The 3F Microdelivery Catheter is
provided sterile with the Stent and Peelable Sheath preloaded. The shaft
has an overall nominal working length of 135cm.

**[2F Stabilizer Catheter]{.underline}** - The 2F Stabilizer Catheter is
used within the 3F Microdelivery Catheter to hold the Stent stationary
and enable deployment. The 2F Stabilizer Catheter contains a proximal
hub, polymer tubing, and a radiopaque markerband at the distal tip. The
2F Stabilizer Catheter is provided sterile and has an overall nominal
working length of 162cm.

**[Peelable Sheath]{.underline}** - The Peelable Sheath is used to
facilitate guidewire backloading into the 3F Microdelivery Catheter and
through the preloaded Stent. The Peelable Sheath is comprised of a
single piece of notched tubing (i.e., slit through its length). The
Peelable Sheath is provided to the user pre-inserted through the
preloaded Stent with a portion extending from the distal tip of the 3F
Microdelivery Catheter. After backloading the guidewire and prior to
insertion of the Neuroform Microdelivery Stent System into the patient,
the Peelable Sheath is removed from the 3F Microdelivery Catheter and
peeled from the guidewire by the physician.

**[Rotating Hemostatic Valves]{.underline}** - The Rotating Hemostatic
Valves (RHVs) are used to provide reliable hemostasis while allowing
continuous heparinized saline flush through both the 2F Stabilizer
Catheter and 3F Microdelivery Catheter. Each RHV has a standard Y-shaped
configuration with (1) one standard male connector and (2) one standard
Tuoghy-Borst connector with an adjustable hemostasis port. One RHV is
included in each sterile catheter pouch. Prior to clinical use, the RHV
is secured to the proximal end of the 3F Microdelivery Catheter and 2F
Stabilizer Catheter.

Table 1 summarizes the sizing guidelines for the Neuroform
Microdelivery Stent System.

**Table 1: Recommended Sizing Guidelines**

  ---------------------------------------------------------------------------------------------------------
  **Labeled   **Labeled   **Self     **Recommended   **Useable 3F    **Useable 2F **Maximum    **Minimum
  Stent       Stent       Expanded   Vessel          Microdelivery   Stabilizer   Guidewire    Guide
  Diameter    Length^1^   Stent      Diameter^2^     Catheter        Catheter     Diameter**   Catheter
  (mm)**      (mm)**      Diameter   (mm)**          Length**        Length**                  Inner
                          (mm)**                                                               Diameter**
  ----------- ----------- ---------- --------------- --------------- ------------ ------------ ------------
  2.5         10          3.0        \>2.0 and ≤ 2.5 131 cm          161 cm       0.014 in     0.050 in

  2.5         15          3.0        \>2.0 and ≤ 2.5                                           

  2.5         20          3.0        \>2.0 and ≤ 2.5                                           

  3.0         10          3.5        \>2.5 and ≤ 3.0                                           

  3.0         15          3.5        \>2.5 and ≤ 3.0                                           

  3.0         20          3.5        \>2.5 and ≤ 3.0                                           

  3.5         10          4.0        \>3.0 and ≤ 3.5                                           

  3.5         15          4.0        \>3.0 and ≤ 3.5                                           

  3.5         20          4.0        \>3.0 and ≤ 3.5                                           

  4.0         10          4.5        \>3.5 and ≤ 4.0                                           

  4.0         15          4.5        \>3.5 and ≤ 4.0                                           

  4.0         20          4.5        \>3.5 and ≤ 4.0                                           

  4.5         10          5.0        \>4.0 and ≤ 4.5                                           

  4.5         15          5.0        \>4.0 and ≤ 4.5                                           

  4.5         20          5.0        \>4.0 and ≤ 4.5                                           
  ---------------------------------------------------------------------------------------------------------

^1^Select a Stent length that is at least 8mm longer than the aneurysm
neck to maintain a minimum of 4mm on each side of the aneurysm neck
along the parent vessel.

^2^Select a Stent diameter based on the sizing recommendations in Table
1 and based on the larger vessel diameter (proximal or distal reference
vessel diameter).

VI. **ALTERNATIVE PRACTICES AND PROCEDURES**

Wide neck aneurysms are often untreatable surgically or endovascularly
with the devices that are currently approved for neurovascular use,
which are clipping and coiling.

Clipping involves surgically placing an implantable clip over the neck
of the aneurysm, thereby isolating the aneurysm from the circulation.
This technique involves precise placement of the clip and requires
access to the vessel from the outside to completely capture the neck of
the aneurysm. However, some wide neck aneurysms in vessels deep within
the brain are not amendable to being treated by open brain surgery.

Coiling involves endovascular placement of embolization coils into the
aneurysm sac in order to exclude the aneurysm from the circulation. The
advantage is that the coils can be placed from within the vessel.
Limitations to coiling wide neck aneurysms include (1) aneurysm neck
instability that could lead to coil protrusion and/or embolization and
(2) achieving and maintaining sufficiently dense coil packing of the
aneurysm to permanently exclude blood flow.

If left untreated or inadequately treated, the wide neck aneurysms are
at risk of rupture, resulting in a high risk of patient morbidity and
mortality.

**VII. MARKETING HISTORY**

The Neuroform Microdelivery Stent System has not yet been marketed in
any country.

**VIII. ADVERSE EFFECTS OF THE DEVICE ON HEALTH**

***Potential Adverse Effects***

The potential adverse events listed below, as well as others, may be
associated with the use of the Neuroform Microdelivery Stent System or
with the procedure:

> Aneurysm perforation or rupture
>
> Cerebral ischemia
>
> Coagulopathy
>
> Coil herniation through Stent into parent vessel
>
> Confusion
>
> Death
>
> Embolic stroke
>
> Hematoma, pain, and/or infection at access site
>
> Incomplete aneurysm occlusion
>
> Intimal dissection
>
> Intracerebral/intracranial hemorrhage
>
> Peripheral thromboembolic events
>
> Post-procedure bleeding
>
> Pseudoaneurysm formation
>
> Renal failure
>
> Stent migration
>
> Stent misplacement
>
> Stent occlusion
>
> Vasospasm
>
> Vessel perforation
>
> Vessel thrombosis

***Observed Adverse Effects***

Tables 2 and 3 identify the adverse events observed in the clinical
study conducted with the Neuroform Microdelivery Stent System.
Twenty-nine patients were implanted with the Stent. The tables include
all adverse events through 6 months. Of the 29 patients implanted with
the Stent, 17 patients had 1 or more adverse events and 5 had 1 or more
serious adverse events. There were 12 serious adverse events and 21
other adverse events, all of which occurred prior to or by the time of
discharge. None occurred between discharge and the 6-month timepoint.
Nine patients had 1 adverse event, 4 patients had 2 adverse events, 1
patient had 3 adverse events, 2 patients had 4 adverse events, and 1
patient had 5 adverse events.

Table 2 summarizes the patient rates for observed serious adverse
events. Table 3 summarizes the patient rates for all other observed
adverse events.

> **Table 2: Serious Device or Procedure-Related Adverse Events**

  -------------------------------------------------------- --------------
  **Serious Adverse Event^1^**                             **n (%)**

  Death^2^                                                 1 (3.4%)

  Aneurysm Perforation^2,3^                                2 (6.9%)

  Arterial Perforation^4^                                  1 (3.4%)

  Subarachnoid/Interventricular Hemorrhage^2,3^            2 (6.9%)

  Thromboembolic Stroke^4^                                 1 (3.4%)

  Intracerebral Hematoma^4^                                1 (3.4%)

  Left Hemiparesis^4^                                      1 (3.4%)

  Intraparenchymal Bleeding^3^                             1 (3.4%)

  Retroperitoneal Hematoma^5^                              1 (3.4%)

  Confusion^6^                                             1 (3.4%)
  -------------------------------------------------------- --------------

> ^1^Five patients had these 12 serious adverse events. The "n" reflects
> the number of occurrences of that adverse event. The % is based on 29
> patients who were assessed before or at discharge when all adverse
> events occurred.
>
> ^2^One patient had 3 serious adverse events. There was perforation of
> the aneurysm dome with the micro guidewire during the initial
> catheterization of the aneurysm resulting in
> subarachnoid/interventricular hemorrhage and death. Death was due to
> complications from aneurysm perforation leading to bleeding and
> pre-existing hepatitis and management of anticoagulation therapy.
>
> ^3^One patient had 3 serious adverse events. There was perforation of
> the aneurysm with the microcatheter during coil placement resulting in
> subarachnoid hemorrhage and subsequent intraparenchymal bleeding (from
> the ventricular drainage line).
>
> ^4^One patient had 4 serious adverse events. Arterial perforation
> occurred with the tip of the exchange length guidewire prior to Stent
> insertion, resulting in an intracerebral hematoma. This patient also
> had a thromboembolic stroke that led to left hemiparesis.
>
> ^5^One patient had a retroperitoneal hematoma.
>
> ^6^One patient had confusion. Confusion was categorized by the
> protocol as a non-serious adverse event; however, it was determined by
> the clinical study investigator to be a serious adverse event because
> the patient required a prolonged hospital stay.
>
> **Table 3: Other Device or Procedure-Related Adverse Events**

  ------------------------------------------------ ----------------------
  **Other Adverse Event^1^**                       **n (%)**

  Right Hemiparesis                                1 (3.4%)

  Embolic Event^2^                                 4 (13.8%)

  Vasospasm^3^                                     5 (17.2%)

  Intimal Dissection^4^                            1 (3.4%)

  Seizure^5^                                       1 (3.4%)

  Access Site Hematoma^6^                          2 (6.9%)

  Liver Failure                                    1 (3.4%)

  Vomiting                                         1 (3.4%)

  Headache                                         3 (10.3%)

  Fever of Unknown Origin                          1 (3.4%)

  Urinary Tract Infection                          1 (3.4%)
  ------------------------------------------------ ----------------------

> ^1^Fifteen patients had these 21 adverse events. The "n" reflects the
> number of occurrences of that adverse event. The % is based on 29
> patients who are accounted for and were assessed before or at
> discharge when all adverse events occurred.
>
> ^2^Includes embolic ischemic lesion, small embolic lesion,
> asymptomatic microemboli to brain detected by MRI, and left prolonged
> reversible ischemic neurological deficit (PRIND). All embolic events
> resulted in mild neurological deficits. Three completely resolved, and
> 1 patient was discharged to a rehabilitation facility.
>
> ^3^Includes 4 mild and 1 moderate case. All completely resolved.
>
> ^4^Occurred during placement of the guide catheter in the cervical
> internal carotid prior to Stent placement, not in the portion of the
> vessel treated with the device.
>
> ^5^One patient with a history of epilepsy experienced a seizure with
> no permanent sequelae while in the hospital.
>
> ^6^Includes 1 mild and 1 moderate case. Both resolved.

**IX. SUMMARY OF PRECLINICAL STUDIES**

***Biocompatibility Testing***

Biocompatibility testing of the Stent alone and combined the Neuroform
Microdelivery Stent System was shown to be acceptable by the following
tests that were performed in accordance with the provisions of ISO
10993-1 and Good Laboratory Practice (GLP) Regulations, 21 CFR 58:

-   Acute Intracutaneous Reactivity (Irritation)

-   Acute Systemic Toxicity

-   Sensitization (Guinea Pig Maximization)

-   Cytotoxicity - MEM Elution

-   Hemolysis - Direct Contact

-   Pyrogenicity - Material Mediated

-   Genotoxicity

-   Mouse Lymphoma.

Additional *in vivo* testing was performed to establish
hemocompatibility and thrombogenicity of the Stent implant alone and of
the combined Neuroform Microdelivery Stent System.

All test results met the acceptance criteria and demonstrated that the
Stent alone and the combined Neuroform Microdelivery Stent System were
biocompatible, hemocompatible, nontoxic, and nonmutagenic.

[]{.mark}

***Sterility***

The Neuroform Microdelivery Stent System is sterilized using ethylene
oxide (EO). The EO cycle was validated to a sterility assurance level of
10^-6^ per ISO 11135. The System was tested and met specifications after
two sterilization exposures.

***Shelf Life***

A 1-year shelf life was validated using a combined real time and
accelerated aging study of finished devices. Package integrity testing
included pouch seal integrity, label integrity, dye penetration, pouch
burst, and ship testing. Device functionality testing included System
functionality testing, Stent characteristic testing (length, diameter,
and Austenite finish (A~f~)), 3F Microdelivery Catheter characteristic
testing, 2F Stabilizer Catheter characteristic testing, and Peelable
Sheath characteristic testing (see ***Mechanical Testing*** Section
below). Both package integrity and device testing met specifications to
support a 1-year expiration date.

***Magnetic Resonance Imaging (MRI) Compatibility***

The Stent was shown to be MRI compatible in MRI systems operating at a
field strength of 1.5 Tesla or less. MRI laboratory evaluation
demonstrated that no significant image distortion or heating was created
by the presence of the Stents at scanning sequences commonly used during
MRI procedures for the given test.

***Mechanical Testing***

All mechanical testing was performed on the finished, sterile Neuroform
Microdelivery Stent System, as well as on individual components of the
System. All system functionality testing and individual component
testing passed the acceptance criteria.

System functionality testing included:

-   Verification of Stent Integrity

-   Verification of Trackability of System over Guidewire

-   Verification of Trackability of System Passage through a Guide
    Catheter

-   Verification of Stent Accessibility of Target Deployment Zone

-   Verification of Stent Deployability in Target Deployment

-   Verification of Self-Expansion of Stents.

Stent component testing included:

-   Stent Potentiodynamic Polarization Test

-   Direct Galvanic Coupling Test

-   Stent Fatigue Life Testing

-   Finite Element Re-Analysis

-   Verification of Stent Free Area

-   Stent Length Calculation Verification

-   Strut Spacing Calculations for Stent "Pore Size" Verification

-   Actual Deployed Stent Length Verification

-   Actual Deployed Stent Outer Diameter Verification

-   Stent Hydrogen Content Test

-   Verification of Stent Radial Pressure

-   Verification of Stent Contact Pressure

-   Verification of Stent Recoil

-   Verification of Stent Platinum Markerband Joint

-   Stent Surface Characterization.

3F Microdelivery Catheter component testing included:

-   Verification of Hub Taper

-   Verification of Lumen Diameter

-   Verification of Outer Diameter (Markerband)

-   Verification of Outer Diameter (Mid-Joint)

-   Verification of Catheter Length

-   Verification of Catheter Distal Flexible Length

-   Verification of Middle Flexible Transition Zone

-   Hub Air Aspiration Test

-   Markerband Removal Force

-   Distal Joint Break Force

-   Center Joint Break Force

-   Hub Bond Break Force

-   Verification of Catheter Integrity

-   Verification that Catheter is Free of Particulate.

Peelable Sheath component testing included:

-   Outer Diameter Verification Test

-   Inner Diameter Verification Test

-   Length Test

-   Peelability Test.

2F Stabilizer Catheter component testing included:

-   Verification of Hub Taper

-   Verification of Lumen Diameter

-   Verification of Outer Diameter (Markerband)

-   Verification of Outer Diameter (Mid-Joint)

-   Verification of Stabilizer Length

-   Verification of Stabilizer Distal Flexible Length

-   Hub Air Aspiration Test

-   Markerband Removal Force

-   Mid-Joint Break Force

-   Hub Bond Break Force

-   Verification of Catheter Integrity.

Rotating Hemostasis Valve component testing included:

-   Female Luer Hub Test

-   Male Luer Hub Test

-   Leak Test

-   Valve Maximum Outer Diameter Test.

***Animal Testing***

Earlier versions of the subject Stent were tested in 35 New Zealand
rabbits in which wide neck aneurysms were created at the origin of the
right common carotid artery. The study had several purposes including
assessing the technical feasibility of the delivery system, the ability
to tightly pack the aneurysm with coils, and the stability of the coil
bundles. The Stent deployed successfully in 33 of 35 cases. Transient
adverse events occurred in 3 of 35 cases.

Animals were sacrificed for analysis at 30 days (10 animals), 90 days
(15 animals), and 180 days (10 animals). Excised vessel and organ
samples were submitted for histopathology, scanning electron microscopy,
and morphometric analyses. The findings showed 30-day and 90-day mild to
moderate circumferential neointimal hyperplasia and a reduction in the
thickness of the neointima at 180 days. The internal elastic lamina
remained generally intact with smooth muscle cell maturation and
contraction at 180 days. There were minimal to mild inflammatory changes
consisting of macrophages and rare giant cells associated with the Stent
struts at 30 days with no giant cells seen at 90 days and 180 days. The
Stent was completely endothelialized within 30 days. No inflammatory
reaction was observed through 180 days.

With respect to angiographic assessment, the study found that 9 of 10
animals exhibited 100% aneurysm occlusion at 30 days, 12 of 15 animals
exhibited 100% aneurysm occlusion after 90 days, and 8 of 10 animals
exhibited 100% occlusion at 180 days. There was no angiographic evidence
of parent vessel stenosis in the immediate post-implant or follow-up
films.

Based on this animal study, the Neuroform Microdelivery Stent System
can be safely deployed and implanted in rabbit carotid arteries. No
adverse hematologic, histologic, thrombogenic, or morphologic responses
were observed. There was no angiographic evidence of parent vessel
stenosis or flow abnormalities during implantation or follow-up. Acute
and subacute thrombosis of the Stents and delivery system (acute only)
were unremarkable.

X.  **SUMMARY OF CLINICAL INFORMATION**

This was a European clinical study. The patient inclusion criteria were:
(1) wide neck, ruptured or unruptured, saccular, intracranial aneurysm
or aneurysm on the level of the skull base, where a wide neck is defined
as a dome-to-neck ratio \<2 and/or neck length of ≥4mm; (2) aneurysm is
in artery with diameter ≥1.5mm and ≤5.5mm; (3) patient is ≥18 years old;
and (4) patient provided written informed consent.

There were 31 patients entered into the study. Five (16%) were male and
26 (84%) were female. Fifty-two percent of the patients were
asymptomatic prior to treatment. Two of the 31 patients did not receive
the Stent because of failure to access based on anatomy. The remaining
29 patients enrolled in the study had 30 aneurysms (1 patient had 2
aneurysms that were treated with one Stent). Previous attempts had been
made to treat 17 of the 30 aneurysms (57%) using other devices.

Table 4 summarizes the locations of the 30 aneurysms. Table 5 summarizes
the sizes of the 30 aneurysms.

> **Table 4: Aneurysm Location**

  ----------------------------------------------- ---------- -------------
  **Location**                                    **n**      **%**

  Carotid ophthalmic                              7          24%

  Posterior communicating artery                  7          24%

  Carotid cavernous                               5          17%

  Anterior choroidal                              2          7%

  Basilar tip                                     2          6%

  Carotid bifurcation                             1          3%

  Middle cerebral artery                          1          3%

  Anterior cerebral artery                        1          3%

  Vertebral artery                                1          3%

  Posterior inferior cerebellar artery            1          3%

  Basilar trunk                                   1          3%

  Other                                           1          3%
  ----------------------------------------------- ---------- -------------

**Table 5: Aneurysm Size**

  ---------------------------------- ------- ---------- -------- --------- ---------
  **Measurement**                    **n**   **Mean**   **SD**   **Min**   **Max**

  Dome width (mm)                    30      7.4        4.3      2.1       20.0

  Neck length (mm)                   30      4.9        1.8      2.1       11.0

  Dome to neck ratio                 30      1.5        0.5      0.8       2.7

  Parent vessel pre-aneurysm (mm)    30      3.6        0.6      2.4       4.8

  Parent vessel post-aneurysm (mm)   30      3.2        0.7      1.7       4.4

  Parent vessel caliber differential 30      1.0        1.0      0.3       1.7
  (mm)                                                                     
  ---------------------------------- ------- ---------- -------- --------- ---------

The 29 patients were implanted with 39 Stents to treat their 30
aneurysms. Twenty (69%) patients had 1 Stent, 8 (28%) patients had 2
Stents, and 1 (3%) patient had 3 Stents. The Stents implanted ranged
from 3.5mm to 4.5mm. One patient required a secondary endovascular
procedure to place a second Stent in the correct location because the
original Stent was inadvertently not deployed at the aneurysm site; this
counts for 2 of the Stents. One patient had the original Stent
successfully deployed but the Stent was removed during the embolic
coiling procedure when the clinical study investigator attempted to
snare the errant coil loop and dislodged the Stent. A replacement Stent
was implanted in its place, and this counts for 2 of the Stents. For 7
patients, multiple Stents were used to treat one aneurysm in cases where
(1) the embolic coiling procedure left the tail of an embolic coil in
the vessel or (2) the neck of aneurysm was estimated at an incorrect
width and a second or third Stent was necessary to cover the neck of the
aneurysm.

With regard to patient accounting, 31 patients were originally entered
into the study; however, 2 did not receive the Stent. One patient died
immediately after the procedure. There are adverse event data on 29
patients, including the one death. Therefore, there were 28 patients of
31 who were expected for evaluation through 6 months. At discharge, 28
of the expected 28 were evaluated for a follow-up rate of 100%. At 6
months, 26 of 28 patients were evaluated for a follow-up rate of 93%.

The study endpoints were (1) adverse events, (2) technical feasibility,
and (3) clinical outcome. The incidence of all adverse events, device or
procedure-related, were assessed. Technical feasibility was assessed by
the ability to access the aneurysm and place the Stent accurately across
the aneurysm neck. Clinical outcome was assessed by percent angiographic
aneurysm occlusion

Adverse events were presented in Tables 2 and 3 in Section VIII above.

Table 6 below summarizes the patient rates with regard to technical
feasibility.

> **Table 6: Technical Feasibility**

  ----------------------------------------- -----------------------------
  **Technical Feasibility**                 **n (%)**

  Ability to access aneurysm                29/31 (93.5%) patients^1^

  Ability to place Stent across neck        29/29 (100%) patients^2,3^
  ----------------------------------------- -----------------------------

> ^1^Two patients could not be accessed based on anatomy.
>
> ^2^One patient required a secondary endovascular procedure to place a
> second Stent in the correct location because the original Stent was
> inadvertently not deployed at aneurysm site.
>
> ^3^There were 2 intraoperative device malfunctions involving the
> markerband of the 2F Stabilizer Catheter inadvertently detaching from
> the shaft of the 2F Stabilizer Catheter after Stent deployment. In one
> patient, the 2F Stabilizer Catheter was inside the patient at the time
> of the device malfunction, and the separated markerband embolized in a
> small, distal intracranial artery. This patient had no adverse events
> from this event. In the second patient, the 2F Stabilizer Catheter was
> outside the patient at the time of the device malfunction. SMART
> Therapeutics has since increased its markerband bond strength.

Table 7 below summarizes the patient rates with regard to clinical
outcome.

> **Table 7: Clinical Outcome**

  -------------------------------------------- --------------------------
  **Clinical Outcome^1^**                      **n (%)**

  \% occlusion at discharge^2^                 

  100%                                         17 (58.6%)

  95-99%                                       13 (44.8%)

  \% occlusion at 6 months                     

  100%                                         18 (69.2%)

  95-99%                                       8 (30.8%)
  -------------------------------------------- --------------------------

> ^1^The "n" reflects the number of occurrences. The % is based on 29
> patients at discharge and 26 patients at 6 months.
>
> ^2^One patient had 2 aneurysms, each with different resulting %
> occlusion. Therefore, this patient is reported twice.

Other clinical outcomes included:

-   No Stent stenosis or migration.

-   No embolic coil migration.

-   No parent vessel thrombosis, occlusion, or dissection.

-   Neurological status: Of 26 patients evaluated at 6 months, 17 (65%)
    had an unchanged (normal) neurological assessment as compared to
    baseline, 3 (16%) had an improved (from abnormal to normal)
    neurological assessment as compared to baseline, 5 (19%) had an
    unchanged (abnormal) neurological assessment as compared to
    baseline, and 1 (4%) had a worsened (abnormal moderate confusion to
    abnormal severe confusion) neurological assessment as compared to
    baseline.

**XI. RISK/PROBABLE BENEFIT ANALYSIS**

As stated in Section VI above, there are limitations to the alternative
treatments for wide neck aneurysms. The Neuroform Stent is designed to
address the limitations associated with coiling of wide neck aneurysms
that are not amendable to treatment by clipping by combining two
endovascular techniques (stents and coils). First, the Neuroform Stent
is placed across the neck of the aneurysm. Second, the embolic coil
delivery catheter is passed between the struts of the Stent to obtain
and maintain dense coil packing within the aneurysm. The Neuroform
Stent stabilizes the neck of the aneurysm and acts as a physical barrier
to stabilize embolic coils and minimize coil protrusion and/or
embolization.

Clinical study data on the Neuroform Microdelivery Stent System were
provided. Adverse events, technical feasibility, angiographic and
clinical outcome were reported for 29 patients at discharge and 26
patients at 6 months. Patients with ruptured and unruptured aneurysms
were treated.

There were 12 serious adverse events in 5 patients. There were 21 other
adverse events. All adverse events occurred prior to or by the time of
discharge; none occurred between discharge and the 6-month timepoint.
The one patient death was not related to the device. Table 2 of Section
VIII summarizes the patient rates for observed serious adverse events.
Table 3 of Section VIII summarizes the patient rates for all other
observed adverse events.

Variable adverse event rates for endovascular treatment of wide neck
aneurysms are reported in the medical literature. This variability is
related to differences in patient selection criteria, patient outcome
measures, follow-up duration, and small sample sizes for coiling
studies. However, within the context of the adverse event rates reported
in the medical literature, there is no evidence that patients will be
exposed to an unreasonable or significant risk of injury from use of the
Neuroform Microdelivery Stent System as compared to coiling as a means
of treatment for wide neck aneurysms.

In terms of the clinical benefit of the Neuroform Microdelivery Stent
System, 100% (26 of 26 patients) had ≥95% occlusion of their aneurysm(s)
and 96% (25 of 26 patients) had no deterioration in neurological status
at 6-month follow-up. Aneurysm occlusion of ≥90% is generally considered
successful by the clinical community.

Extensive mechanical testing was performed on the Neuroform
Microdelivery Stent System, as a whole, as well as on the individual
components. All tests met the stated acceptance criteria. Animal testing
provided evidence that the Neuroform Microdelivery Stent System could
be safely deployed and implanted in rabbit carotid arteries. Refer to
Section IX for details.

Therefore, it is reasonable to conclude that the probable benefit to
health from using the Neuroform Microdelivery Stent System with embolic
coils for wide neck aneurysms outweighs the risk of illness or injury
when used in accordance with the instructions for use and when taking
into account the probable risks and benefits of currently available
devices or alternative forms of treatment.

**XII. PANEL RECOMMENDATION**

Review of this HDE application was performed by a member of the
Neurological Devices Advisory Panel. The Panel member stated that the
Neuroform Stent offers a probable benefit in the endovascular
management of wide neck aneurysms and that there is no evidence that
patients will be exposed to an unreasonable or excessive risk of injury
from use of the device. It was determined that the preclinical and
clinical issues raised by the HDE did not require full Panel review.

**XIII. CDRH DECISION**

CDRH determined that, based on the data submitted in the HDE, the
Neuroform Microdelivery System will not expose patients to an
unreasonable or significant risk of illness or injury, and the probable
benefit to health from using the System with embolic coils for the
treatment of wide neck, intracranial, saccular aneurysms that are not
amenable to treatment with surgical clipping outweighs the risks of
illness or injury, and issued an approval order on September 11, 2002.

**XIV. APPROVAL SPECIFICATIONS**

**Indications for Use:** See *Instructions for Use* (Attachment 1)

**Information for the Patient:** See *Patient Brochure* (Attachment 2)

**Hazards to Health from Use of the Device:** See Indications,
Contraindications, Warnings, Precautions, and Adverse Events in the
*Instructions for Use* (Attachment 1).

**XV. REFERENCES**

None