###### Summary of Safety and Effectiveness Data

**1. General Information**

> Device Generic Name: Endovascular Graft and Delivery System

Device Trade Name: Zenith^^ AAA Endovascular Graft with the

H&L-B One-Shot Introduction System

> Applicant's Name and Address: Cook Incorporated
>
> 750 North Daniels Way
>
> Bloomington, Indiana 47404
>
> Date of Panel Recommendation: April 10, 2003
>
> Premarket Approval (PMA)
>
> Application Number: P020018
>
> Date of Notice of Approval
>
> to Applicant: May 23, 2003

**2. Indications and Usage**

The Zenith^®^ AAA Endovascular Graft with the H&L-B One-Shot
Introduction System and ancillary components is indicated for the
endovascular treatment of patients with abdominal aortic or aorto-iliac
aneurysms having morphology suitable for endovascular repair, including:

Adequate iliac/femoral access compatible with the required introduction
systems

Non-aneurysmal infrarenal aortic segment (neck) proximal to the
aneurysm:

-   with a length of at least 15 mm,

-   with a diameter measured outer wall to outer wall of no greater than
    28 mm and no less than 18 mm,

-   with an angle less than 60 degrees relative to the long axis of the
    aneurysm, and

-   with an angle less than 45 degrees relative to the axis of the
    suprarenal aorta.

Iliac artery distal fixation site greater than 10 mm in length and
7.5-20 mm in diameter (measured outer wall to outer wall).

**3. Contraindications**

There are no known contraindications.

**4. Warnings and Precautions**

See *Warnings and Precautions* in the labeling (Instructions for Use).

**5. Device Description**

The Cook Zenith^^ AAA Endovascular Graft (Zenith) is a modular system
of components consisting of multiple endovascular graft configurations
and additional ancillary pieces. All components in this system use
common self-expanding Z-stents sewn to traditional, currently marketed
Dacron graft material using currently marketed braided polyester and
monofilament polypropylene suture materials.

The main endovascular graft is selected based upon patient anatomy and
implanted to exclude the aneurysmal chamber. The various ancillary
components can be used to correct for inaccuracies in device size
selection or to compensate for difficult anatomy encountered during the
implant procedure. These ancillary components include aortic main body
extensions, iliac leg extensions, converters, and occluders.

**5.1. Zenith Main Endovascular Graft**

The main endovascular graft (depicted in Figure 5.1-1) is a modular
three component device (an aortic main body and two iliac legs), the
sizes of which can be selected to match a variety of patient anatomies
and specific treatment goals. These components are manufactured in a
number of standard stock sizes and are supplied sterile, preloaded onto
delivery systems, and ready for use with minimal pre-deployment
preparation. Currently available main bodies are listed in Table 5.1-1.
Currently available iliac legs are listed in Table 5.1-2.

![](media/image1.jpeg){width="4.444444444444445in"
height="1.7708333333333333in"}

### Figure 5.1-1. Zenith^®^ AAA Endovascular Graft

## The bifurcated main body component, comprised of an aortic section having an uncovered, barbed suprarenal stent at the proximal end and one long iliac limb and one short contralateral iliac limb at the distal end, is introduced via one iliac artery. An iliac leg is delivered via the contralateral iliac artery, and is docked with the short limb of the main body to form a continuous channel into the contralateral iliac artery. A second iliac leg is delivered via the ipsilateral iliac artery, and is docked with the long limb of the main body to form a continuous channel into the ipsilateral iliac artery. (The aortic main body extensions and iliac leg extensions described in Section 5.2 can be used to provide additional length to their respective portions of the endovascular graft.) 

## Table 5.1-1. Catalog/reorder numbers for Zenith bifurcated main bodies

+----------+-----------+-----------+-----------+----------+----------+
| **22     | **24 mm** | **26 mm** | **28 mm** | **30     | **32     |
| mm**     |           |           |           | mm**     | mm**     |
+----------+-----------+-----------+-----------+----------+----------+
| T        | TFB-24-74 | TFB-26-74 | TFB-28-74 | T        | T        |
| FB-22-74 |           |           |           | FB-30-74 | FB-32-74 |
|          | TFB-24-88 | TFB-26-88 | TFB-28-88 |          |          |
| TFB      |           |           |           | T        | T        |
| \--22-88 | T         | TFB26-103 | T         | FB-30-88 | FB-32-88 |
|          | FB-24-103 |           | FB-28-103 |          |          |
| TF       |           | T         |           | TF       | TF       |
| B-22-103 | T         | FB-26-117 | T         | B-30-103 | B-32-103 |
|          | FB-24-117 |           | FB-28-117 |          |          |
| T        |           | T         |           | TF       | TF       |
| FB22-117 | T         | FB-26-132 | TFB28-132 | B-30-117 | B-32-117 |
|          | FB-24-132 |           |           |          |          |
| TF       |           |           |           | TF       | TF       |
| B-22-132 |           |           |           | B-30-132 | B-32-132 |
+----------+-----------+-----------+-----------+----------+----------+

**Note:** Catalog number indicates diameter (mm) x contralateral limb
length (mm).

**Table 5.1-2.** Catalog/reorder numbers for Zenith iliac legs

+------------+--------------+--------------+-------------+------------+
| **8 mm**   | **10 mm**    | **12 mm**    | **14 mm**   | **16 mm**  |
+------------+--------------+--------------+-------------+------------+
| TFLE-8-37  | TFLE-10-37   | TFLE-12-37   | TFLE-14-37  | TFLE-16-37 |
|            |              |              |             |            |
| TFLE-8-54  | TFLE-10-54   | TFLE-12-54   | TFLE-14-54  | TFLE-16-54 |
|            |              |              |             |            |
| TFLE-8-71  | TFLE-10-71   | TFLE-12-71   | TFLE-14-71  | TFLE-16-71 |
|            |              |              |             |            |
| TFLE-8-88  | TFLE-10-88   | TFLE-12-88   | TFLE-14-88  | TFLE-16-88 |
|            |              |              |             |            |
| TFLE-8-105 | TFLE-10-105  | TFLE-12-105  |             |            |
|            |              |              |             |            |
| TFLE-8-122 | TFLE-10-122  | TFLE-12-122  |             |            |
+------------+--------------+--------------+-------------+------------+
| **18 mm**  | **20 mm**    | **22 mm**    | **24 mm**   | none       |
+------------+--------------+--------------+-------------+------------+
| TFLE-18-37 | TFLE-20-37   | TFLE-22-37   | TFLE-24-37  |            |
|            |              |              |             |            |
| TFLE-18-54 | TFLE-20-54   | TFLE-22-54   | TFLE-24-54  |            |
|            |              |              |             |            |
| TFLE-18-71 | TFLE-20-71   | TFLE-22-71   | TFLE-24-71  |            |
|            |              |              |             |            |
| TFLE-18-88 | TFLE-20-88   | TFLE-22-88   | TFLE-24-88  |            |
+------------+--------------+--------------+-------------+------------+

**Note:** Catalog number indicates distal diameter (mm) x length (mm).

Zenith^^ AAA Endovascular Graft components are constructed using
full-thickness woven Dacron graft material sewn to self-expanding
stainless steel Cook-Z^^ stents with standard surgical braided
polyester and monofilament polypropylene sutures. Components are
fully-stented, and are intended to provide stability and the expansile
force necessary to open the lumen of the graft during deployment.
Additionally, they provide the necessary attachment and seal of the
Zenith^^ AAA Endovascular Graft to the vessel wall. Cook-Z^^ stents
are located on the inside of the graft material at the locations of
vessel seal sites and portions of the overlap joints, but are located on
the outside of the remainder of the graft to allow the lumen to be as
smooth as possible. There is an uncovered stent at the proximal end of
the graft, shown in Figure 5.1-1, which features 10-12 barbs (depending
upon graft diameter) for positive attachment to the vessel wall. This
uncovered stent is attached with multiple sutures at each graft
material/stent attachment site.

The Cook-Z^^ stents are highly visible during deployment. In addition,
radiopaque markers are located on the most lateral aspect of the short
limb of the main body to facilitate proper graft orientation with
respect to the contralateral iliac artery. There are also radiopaque
markers on the most proximal aspect of the graft material to allow
proper longitudinal adjustment of the graft relative to the renal
arteries.

**5.2. Zenith^^ AAA Endovascular Graft Ancillary Components**

The Zenith^^ AAA Endovascular Graft ancillary components consist of
aortic main body extensions, iliac leg extensions, converters and
occluders. The aortic main body extensions and iliac leg extensions can
be used to provide additional length to their respective portions of the
endovascular graft. The converters and occluders can be used to convert
a bifurcated graft into an aorto-uniiliac graft, if necessary (e.g.
cases of Type 3 endoleak, limb occlusion, or unattainable contralateral
limb cannulation). Examples of each ancillary component are shown in
Figure 5.2-1.

![](media/image2.jpeg){width="4.444444444444445in"
height="1.6597222222222223in"}

Ancillary components are manufactured in a number of standard stock
sizes and are supplied sterile, preloaded onto their delivery systems,
and ready for use with minimal pre-deployment preparation. Currently
available ancillary components are listed in Table 5.2-1.

## Table 5.2-1. Catalog/reorder numbers for Zenith ancillary components

+--------------+------------+-------------------+---------------------+
| **           | **O        | **Iliac Leg       | **Main Body         |
| Converters** | ccluders** | Extensions**      | Extensions**        |
+--------------+------------+-------------------+---------------------+
| ESC-24-12-80 | ESP-14-20  | ESLE-8-55         | ESBE-22-36          |
|              |            |                   |                     |
| ESC-28-12-80 | ESP-16-20  | ESLE-10-55        | ESBE-24-36          |
|              |            |                   |                     |
| ESC-32-12-80 | ESP-20-20  | ESLE-12-55        | ESBE-26-36          |
|              |            |                   |                     |
|              | ESP-24-20  | ESLE-14-55        | ESBE-28-36          |
|              |            |                   |                     |
|              |            | ESLE-16-55        | ESBE-30-36          |
|              |            |                   |                     |
|              |            | ESLE-18-55        | ESBE-32-36          |
|              |            |                   |                     |
|              |            | ESLE-20-55        |                     |
|              |            |                   |                     |
|              |            | ESLE-22-55        |                     |
|              |            |                   |                     |
|              |            | ESLE-24-55        |                     |
+--------------+------------+-------------------+---------------------+

**Note:** Catalog number for converters indicates proximal diameter
(mm), distal diameter (mm), and length (mm). Catalog number for
occluders and extensions indicates diameter (mm) x length (mm).

**5.3. H&L-B One-Shot Introduction System Description**

The Zenith^^ AAA Endovascular Graft is shipped preloaded onto the H&L-B
One-Shot Introduction System. It has a simple sequential deployment
method with built-in features to provide continuous control of the
endovascular graft throughout the deployment procedure. The H&L-B
One-Shot Introduction System enables precise positioning and has the
ability to readjust the final graft position before deploying the barbed
suprarenal Z-stent.

Modular components of the Zenith^^ AAA Endovascular Graft are preloaded
onto the H&L-B One-Shot Introduction System. There are four sizes of
delivery systems used for deployment (14, 16, 18, and 20 Fr). All sizes
of each modular Zenith^^ AAA Endovascular Graft component (main bodies,
main body extensions, iliac legs, iliac leg extensions, converters, and
occluders) are deployed using one of these four delivery system sizes.
All delivery systems are operated by retracting the sheath over the grey
positioner to expose the preloaded, self-expanding component. Additional
delivery system features are operated, as appropriate. All systems are
compatible with an 0.035 inch wire guide.

**5.3.1. 18 Fr and 20 Fr Delivery Systems Description**

The 18 Fr and 20 Fr H&L-B One-Shot Introduction Systems are used to
deploy various sizes of main bodies, main body extensions, and
converters in the Zenith^^ AAA Endovascular Graft family of modular
components. Table 5.3.1-1 lists the catalog/reorder numbers of the main
bodies deployed using these two sizes of H&L-B One-Shot Introduction
Systems. Zenith^^ AAA Endovascular Graft main bodies ranging in
diameter from 22 - 26 mm are deployed using the 18 Fr system. Zenith^^
AAA Endovascular Graft main bodies ranging in diameter from 28 - 32 mm
are deployed using the 20 Fr system.

**Table 5.3.1-1.** Zenith bifurcated main bodies deployed with 18 Fr and
20 Fr systems

+---------------+---------+---------+----------+----------+----------+
| **H&L-B       | **Main  |         |          |          |          |
| One-Shot     | Bo      |         |          |          |          |
| Introduction  | dy^1^** |         |          |          |          |
| System**      |         |         |          |          |          |
+---------------+---------+---------+----------+----------+----------+
|               | **74    | **88    | **103    | **117    | **132    |
|               | mm**    | mm**    | mm**     | mm**     | mm**     |
+---------------+---------+---------+----------+----------+----------+
| 18 Fr System  | TF      | TF      | TF       | TF       | TF       |
|               | B-22-74 | B-22-88 | B-22-103 | B-22-117 | B-22-132 |
|               |         |         |          |          |          |
|               | TF      | TF      | TF       | TF       | TF       |
|               | B-24-74 | B-24-88 | B-24-103 | B-24-117 | B-24-132 |
|               |         |         |          |          |          |
|               | TF      | TF      | TF       | TF       | TF       |
|               | B-26-74 | B-26-88 | B-26-103 | B-26-117 | B-26-132 |
+---------------+---------+---------+----------+----------+----------+
| 20 Fr System  | TF      | TF      | TF       | TF       | TF       |
|               | B-28-74 | B-28-88 | B-28-103 | B-28-117 | B-28-132 |
|               |         |         |          |          |          |
|               | TF      | TF      | TF       | TF       | TF       |
|               | B-30-74 | B-30-88 | B-30-103 | B-30-117 | B-30-132 |
|               |         |         |          |          |          |
|               | TF      | TF      | TF       | TF       | TF       |
|               | B-32-74 | B-32-88 | B-32-103 | B-32-117 | B-32-132 |
+---------------+---------+---------+----------+----------+----------+

1 Catalog number indicates diameter (mm) x contralateral limb length
(mm).

Table 5.3.1-2 lists the catalog/reorder numbers of the main body
extensions and converters deployed using these two sizes of H&L-B
One-Shot Introduction Systems. Zenith^^ AAA Endovascular Graft main
body extensions and converters ranging in diameter from 22 - 26 mm are
deployed using the 18 Fr system. Zenith^^ AAA Endovascular Graft main
body extensions and converters ranging in diameter from 28 - 32 mm are
deployed using the 20 Fr system. In addition, Table 5.3.1-2 lists the
iliac leg extensions deployed with the 18 Fr delivery system.

**Table 5.3.1-2.** Zenith ancillary components deployed with 18 Fr and
20 Fr systems

+----------------------+---------------+--------------+----------------+
| **H&L-B One-Shot    | **Main Body   | **Converter  | **Iliac Leg**  |
| Introduction         | Extension     | ^2^**        |                |
| System**             | ^1^**         |              | **Extension    |
|                      |               |              | ^1^**          |
+----------------------+---------------+--------------+----------------+
| 18 Fr System         | ESBE-22-36    | ESC-24-12-80 | ESLE-22-55     |
|                      |               |              |                |
|                      | ESBE-24-36    |              | ESLE-24-55     |
|                      |               |              |                |
|                      | ESBE-26-36    |              |                |
+----------------------+---------------+--------------+----------------+
| 20 Fr System         | ESBE-28-36    | ESC-28-12-80 | none           |
|                      |               |              |                |
|                      | ESBE-30-36    | ESC-32-12-80 |                |
|                      |               |              |                |
|                      | ESBE-32-36    |              |                |
+----------------------+---------------+--------------+----------------+

1 Catalog number for main body extension and iliac leg extension
indicates diameter (mm) x length (mm).

2 Catalog number for converter indicates proximal diameter (mm), distal
diameter (mm), and length (mm).

When configured for main body deployment, these systems contain
sideports for angiography using contrast injection through the hub, dual
trigger-wire release mechanisms with safety locks, a top cap assembly
coupled with the dilator tip (covered by sheath in Figure 5.3.1-1), and
a bottom cap assembly (covered by sheath in Figure 5.3.1-1). These
features lock the Zenith main body onto the delivery system at both ends
of the component, giving the physician both longitudinal and rotational
control of the endovascular graft after sheath retraction. Therefore,
accurate positioning relative to the renal arteries and appropriate
orientation of the contralateral limb are possible.

Figure 5.3.1-1 depicts this configuration. The top cap assembly
constrains the barbed, uncovered, suprarenal Z-stent until: 1) removal
of its corresponding trigger-wire (black trigger-wire release); and 2)
release of the Z-stent from within the cap which is achieved by
loosening the pin vise and advancing the top cap inner cannula. The
bottom cap assembly and its corresponding trigger-wire constrain the
ipsilateral limb of the main body until removal of its trigger-wire
(white trigger-wire release).

![](media/image3.jpeg){width="5.0in" height="1.7680555555555555in"}

When configured for main body extension deployment, these systems
contain a single trigger-wire release mechanism with safety lock and
bottom cap assembly. No top cap is included with the dilator tip because
the main body extension component does not contain a barbed suprarenal
Z-stent. After sheath retraction and exposure of the self-expanding
component, the distal trigger-wire is removed freeing the body extension
from the H&L-B One-Shot Introduction System. Figure 5.3.1-2 depicts
this configuration.

![](media/image4.jpeg){width="5.0in" height="1.7708333333333333in"}

When configured for iliac leg (as well as converter and iliac leg
extension) deployment, these systems have no trigger-wire release
mechanisms, top cap, or bottom cap assemblies. Deployment is achieved by
simple sheath retraction. Figure 5.3.1-3 depicts this configuration.

![](media/image5.jpeg){width="5.0in" height="2.46875in"}

**5.3.2. 14 Fr and 16 Fr delivery systems description**

The 14 Fr and 16 Fr H&L-B One-Shot Introduction Systems are used to
deploy various sizes of the iliac legs and iliac leg extensions in the
Zenith^^ AAA Endovascular Graft family of modular components. These
delivery systems have no trigger-wire release mechanisms, top cap, or
bottom cap assemblies. Deployment is achieved by simple sheath
retraction.

Table 5.3.2-1 lists the catalog/reorder numbers of the iliac legs
deployed using these two sizes of H&L-B One-Shot Introduction Systems.
Zenith^^ AAA Endovascular Graft iliac legs ranging in diameter from 8 -
16 mm are deployed using the 14 Fr system. Zenith^^ AAA Endovascular
Graft iliac legs ranging in diameter from 18 - 24 mm are deployed using
the 16 Fr system.

**Table 5.3.2-1.** Zenith iliac legs deployed with 14 Fr and 16 Fr
systems

+-------------+----------+-----------+-----------+----------+----------+
| **H&L-B**   | ##       |           |           |          |          |
|             | # Iliac  |           |           |          |          |
| **One-Shot | Legs ^1^ |           |           |          |          |
| I           |          |           |           |          |          |
| ntroduction |          |           |           |          |          |
| System**    |          |           |           |          |          |
+-------------+----------+-----------+-----------+----------+----------+
| 14 Fr       | T        | T         | T         | TF       | TF       |
| System      | FLE-8-37 | FLE-10-37 | FLE-12-37 | LE-14-37 | LE-16-37 |
|             |          |           |           |          |          |
|             | T        | T         | T         | TF       | TF       |
|             | FLE-8-54 | FLE-10-54 | FLE-12-54 | LE-14-54 | LE-16-54 |
|             |          |           |           |          |          |
|             | T        | T         | T         | TF       | TF       |
|             | FLE-8-71 | FLE-10-71 | FLE-12-71 | LE-14-71 | LE-16-71 |
|             |          |           |           |          |          |
|             | T        | T         | T         | TF       | TF       |
|             | FLE-8-88 | FLE-10-88 | FLE-12-88 | LE-14-88 | LE-16-88 |
|             |          |           |           |          |          |
|             | TF       | TF        | TF        |          |          |
|             | LE-8-105 | LE-10-105 | LE-12-105 |          |          |
|             |          |           |           |          |          |
|             | TF       | TF        | TF        |          |          |
|             | LE-8-122 | LE-10-122 | LE-12-122 |          |          |
+-------------+----------+-----------+-----------+----------+----------+
| 16 Fr       | TF       | T         | T         | TF       | none     |
| System      | LE-18-37 | FLE-20-37 | FLE-22-37 | LE-24-37 |          |
|             |          |           |           |          |          |
|             | TF       | T         | T         | TF       |          |
|             | LE-18-54 | FLE-20-54 | FLE-22-54 | LE-24-54 |          |
|             |          |           |           |          |          |
|             | TF       | T         | T         | TF       |          |
|             | LE-18-71 | FLE-20-71 | FLE-22-71 | LE-24-71 |          |
|             |          |           |           |          |          |
|             | TF       | T         | T         | TF       |          |
|             | LE-18-88 | FLE-20-88 | FLE-22-88 | LE-24-88 |          |
+-------------+----------+-----------+-----------+----------+----------+

1 Catalog number indicates distal diameter (mm) x length (mm).

Table 5.3.2-2 lists the catalog/reorder numbers of the iliac leg
extensions deployed using these two sizes of H&L-B One-Shot
Introduction Systems. Zenith^^ AAA Endovascular Graft iliac leg
extensions ranging in diameter from 8 - 16 mm are deployed using the 14
Fr system. Zenith^^ AAA Endovascular Graft iliac leg extensions ranging
in diameter from 18 - 20 mm are deployed using the 16 Fr system.

**Table 5.3.2-2.** Zenith ancillary components deployed with 14 Fr and
16 Fr systems

+----------------------------------------+-----------------------------+
| **H&L-B One-Shot**                     | **Iliac Leg Extensions      |
|                                        | ^1^**                       |
| **Introduction System**                |                             |
+----------------------------------------+-----------------------------+
| 14 Fr System                           | ESLE-8-55                   |
|                                        |                             |
|                                        | ESLE-10-55                  |
|                                        |                             |
|                                        | ESLE-12-55                  |
|                                        |                             |
|                                        | ESLE-14-55                  |
|                                        |                             |
|                                        | ESLE-16-55                  |
+----------------------------------------+-----------------------------+
| 16 Fr System                           | ESLE-18-55                  |
|                                        |                             |
|                                        | ESLE-20-55                  |
+----------------------------------------+-----------------------------+

1.  Catalog number indicates diameter (mm) x length (mm).

**5.3.3. Occluder Cartridge Description**

A delivery sheath is used together with a preloaded cartridge (transfer
capsule) for occluder deployment. Table 5.3.3-1 lists the
catalog/reorder numbers of the occluders deployed using the delivery
sheath. All Zenith^^ AAA Endovascular Graft occluders are deployed
using an 18 Fr sheath.

**Table 5.3.3-1.** Zenith occluders deployed with 18 Fr systems

+-----------------------------------+----------------------------------+
| ### Delivery Sheath               | **Occluders ^1^**                |
+-----------------------------------+----------------------------------+
| 18 Fr System                      | ESP-14-20                        |
|                                   |                                  |
|                                   | ESP-16-20                        |
+-----------------------------------+----------------------------------+
|                                   | ESP-20-20                        |
|                                   |                                  |
|                                   | ESP-24-20                        |
+-----------------------------------+----------------------------------+

1 Catalog number for occluders indicates diameter (mm) x length (mm).

To deploy the occluder, the preloaded cartridge containing the occluder
is docked with the back of the hemostatic valve on the end of the
sheath, after the sheath has been placed within the iliac artery. A
blunt pusher included with the occluder cartridge kit is then used to
push the occluder out of the cartridge and into the sheath, transferring
it to the delivery sheath. Once transferred, the occluder is then
advanced with the blunt pusher through the sheath to the location of
deployment within the artery. The occluder cartridge, blunt positioner,
and delivery sheath are depicted in Figure 5.3.3-1.

![](media/image6.jpeg){width="5.0in" height="2.5625in"}

**6. Alternate Practices and Procedures**

The traditional standard of care for treatment of abdominal aortic
aneurysms is surgical implantation of a synthetic graft within the
diseased vessel. Surgical repair of AAA is indicated when the risk of
rupture is judged to be greater than the risks of the procedure.

Patients who are unacceptable surgical or anesthesia candidates may be
medically managed and closely monitored or recommended for endovascular
repair.

**7. Marketing History**

The Zenith^^ AAA Endovascular Graft with the H&L-B One-Shot
Introduction System is currently available throughout the world
including European countries (Austria, Belgium, Czech Republic, Denmark,
Finland, France, Germany, Greece, Hungary, Ireland, Italy, Netherlands,
Poland, Portugal, Spain, Sweden, Switzerland, and the United Kingdom),
Argentina, Australia, Brazil, Canada, Chile, China, Hong Kong, India,
Israel, Lebanon, Malaysia, New Zealand, Saudi Arabia, Singapore, and
South Africa. The Zenith^^ AAA Endovascular Graft with the H&L-B
One-Shot Introduction System has not been withdrawn from marketing for
any reason relating to safety and effectiveness.

**8. Adverse Events**

**8.1. Observed Adverse Events**

A U.S. multicenter, prospective study conducted at 15 centers which
included 352 endovascular patients (200 standard risk, 100 high risk and
52 roll-in) and 80 control patients provide the basis of the observed
adverse event rates in Table 8.1-1.

**Table 8.1-1**. Death and rupture from clinical study

+---------------+-----------+-----------+----+-----------+------------+
| **Death and   | *         | **S       | *  | *         | **Zenith** |
| rupture**     | *Zenith** | urgical** | ** | *Zenith** |            |
|               |           |           | P* |           | *          |
|               | *         | *         | v  | **High    | *Roll-in** |
|               | *Standard | *Standard | al | Risk**    |            |
|               | Risk**^1^ | Risk**    | ue |           |            |
|               |           |           | ** |           |            |
+---------------+-----------+-----------+----+-----------+------------+
| All death     | 0.5%      | 2.5%      | .  | 2.0%      | 1.9%       |
|               | (1/199)   | (2/80)    | 20 | (2/100)   | (1/52)     |
| (0-30         |           |           |    |           |            |
| days)^2^      |           |           |    |           |            |
+---------------+-----------+-----------+----+-----------+------------+
| (31-365 days) | 3.0%      | 1.3%      | .  | 7.1%      | 9.8%       |
| ^2,\ 3^       | (6/198)   | (1/78)    | 68 | (7/98)    | (5/51)     |
|               |           |           |    |           |            |
| AAA-related   | 0.0%      | 1.3%      | .  | 3.1%      | 0.0%       |
|               | (0/198)   | (1/78)    | 29 | (3/98)    | (0/51)     |
| No            |           |           |    |           |            |
| n-AAA-related | 3.0%      | 0.0%      | .  | 4.1%      | 9.8%       |
|               | (6/198)   | (0/78)    | 19 | (4/98)    | (5/51)     |
+---------------+-----------+-----------+----+-----------+------------+
| (0-365 days)  | 3.5%      | 3.8%      | \  | 9.0%      | 11.5%      |
| ^2,\ 3,\ 4^   | (7/199)   | (3/80)    | >. | (9/100)   | (6/52)     |
|               |           |           | 99 |           |            |
| AAA-related   | 0.5%      | 3.8%      |    | 5.0%      | 1.9%       |
|               | (1/199)   | (3/80)    | .  | (5/100)   | (1/52)     |
| No            |           |           | 07 |           |            |
| n-AAA-related | 3.0%      | 0.0%      |    | 4.0%      | 9.6%       |
|               | (6/199)   | (0/80)    | .  | (4/100)   | (5/52)     |
|               |           |           | 19 |           |            |
+---------------+-----------+-----------+----+-----------+------------+
| Rupture       | 0.0%      | n/a       | n  | 0.0%      | 0.0%       |
|               | (0/199)   |           | /a | (0/100)   | (0/52)     |
| (0-30 days)   |           |           |    |           |            |
+---------------+-----------+-----------+----+-----------+------------+
| (31-365 days) | 0.0%      | n/a       | n  | 1.0%      | 0.0%       |
|               | (0/198)   |           | /a | (1/98)    | (0/51)     |
+---------------+-----------+-----------+----+-----------+------------+
| (0-365 days)  | 0.0%      | n/a       | n  | 1.0%      | 0.0%       |
|               | (0/199)   |           | /a | (1/100)   | (0/52)     |
+---------------+-----------+-----------+----+-----------+------------+
| 1 Denominator |           |           |    |           |            |
| of 199        |           |           |    |           |            |
| because one   |           |           |    |           |            |
| standard risk |           |           |    |           |            |
| patient did   |           |           |    |           |            |
| not receive a |           |           |    |           |            |
| device.       |           |           |    |           |            |
+---------------+-----------+-----------+----+-----------+------------+
| 2 All deaths  |           |           |    |           |            |
| (0-30 days)   |           |           |    |           |            |
| were          |           |           |    |           |            |
| considered    |           |           |    |           |            |
| AAA and       |           |           |    |           |            |
| procedure     |           |           |    |           |            |
| related.      |           |           |    |           |            |
+---------------+-----------+-----------+----+-----------+------------+
| 3 Of the      |           |           |    |           |            |
| deaths        |           |           |    |           |            |
| (31-365       |           |           |    |           |            |
| days), four   |           |           |    |           |            |
| were          |           |           |    |           |            |
| considered    |           |           |    |           |            |
| AAA related:  |           |           |    |           |            |
| 1 surgical    |           |           |    |           |            |
| (septic shock |           |           |    |           |            |
| from ischemic |           |           |    |           |            |
| colitis) and  |           |           |    |           |            |
| 3 high risk   |           |           |    |           |            |
| (pancreatitis |           |           |    |           |            |
| with renal    |           |           |    |           |            |
| failure and   |           |           |    |           |            |
| sepsis,       |           |           |    |           |            |
| hemorrhage    |           |           |    |           |            |
| from upper    |           |           |    |           |            |
| abdominal     |           |           |    |           |            |
| aneurysm      |           |           |    |           |            |
| \[not treated |           |           |    |           |            |
| AAA\], and    |           |           |    |           |            |
| multiple      |           |           |    |           |            |
| system        |           |           |    |           |            |
| failure).     |           |           |    |           |            |
+---------------+-----------+-----------+----+-----------+------------+
| 4 Of the      |           |           |    |           |            |
| deaths (0-365 |           |           |    |           |            |
| days), ten    |           |           |    |           |            |
| were          |           |           |    |           |            |
| considered    |           |           |    |           |            |
| AAA related:  |           |           |    |           |            |
| 1 standard    |           |           |    |           |            |
| risk (cardiac |           |           |    |           |            |
| failure), 3   |           |           |    |           |            |
| surgical      |           |           |    |           |            |
| (massive      |           |           |    |           |            |
| hemorrhage,   |           |           |    |           |            |
| mesenteric    |           |           |    |           |            |
| ischemia, and |           |           |    |           |            |
| septic shock  |           |           |    |           |            |
| from ischemic |           |           |    |           |            |
| colitis), 5   |           |           |    |           |            |
| high risk     |           |           |    |           |            |
| (respiratory  |           |           |    |           |            |
| failure,      |           |           |    |           |            |
| cardiac       |           |           |    |           |            |
| failure with  |           |           |    |           |            |
| pulmonary     |           |           |    |           |            |
| embolism,     |           |           |    |           |            |
| pancreatitis  |           |           |    |           |            |
| with renal    |           |           |    |           |            |
| failure and   |           |           |    |           |            |
| sepsis,       |           |           |    |           |            |
| hemorrhage    |           |           |    |           |            |
| from upper    |           |           |    |           |            |
| abdominal     |           |           |    |           |            |
| aneurysm      |           |           |    |           |            |
| \[not treated |           |           |    |           |            |
| AAA\], and    |           |           |    |           |            |
| multiple      |           |           |    |           |            |
| system        |           |           |    |           |            |
| failure) and  |           |           |    |           |            |
| 1 roll-in     |           |           |    |           |            |
| (suspected    |           |           |    |           |            |
| cardiac       |           |           |    |           |            |
| failure).     |           |           |    |           |            |
+---------------+-----------+-----------+----+-----------+------------+

**Table 8.1-2.** Adverse events^1^ in clinical study

+-----------------+-----------+---------+----+-----------+-----------+
|                 | *         | **S     | *  | *         | #         |
|                 | *Zenith** | urgical | ** | *Zenith** | ## Zenith |
|                 |           | S       | P* |           |           |
|                 | *         | tandard | v  | **High    | ##        |
|                 | *Standard | Risk**  | al | Risk**    | # Roll-in |
|                 | Risk**    |         | ue |           |           |
|                 |           |         | ** |           |           |
+-----------------+-----------+---------+----+-----------+-----------+
| Freedom from    | 80%       | 58%     | \< | 68%       | 73%       |
| Morbidity       | (160/200) | (46/80) | .0 | (68/100)  | (38/52)   |
|                 |           |         | 01 |           |           |
| (0-30 days)     |           |         |    |           |           |
+-----------------+-----------+---------+----+-----------+-----------+
| Cardiovascular  | 3.0%      | 11%     | .  | 14%       | 1.9%      |
| ^2^             | (6/200)   | (9/80)  | 02 | (14/100)  | (1/52)    |
+-----------------+-----------+---------+----+-----------+-----------+
| Pulmonary ^3^   | 1.0%      | 15%     | \< | 2.0%      | 0.0%      |
|                 | (2/200)   | (12/80) | .0 | (2/100)   | (0/52)    |
|                 |           |         | 01 |           |           |
+-----------------+-----------+---------+----+-----------+-----------+
| Renal ^4,9^     | 2.5%      | 10%     | .  | 6.0%      | 5.8%      |
|                 | (5/200)   | (8/80)  | 01 | (6/100)   | (3/52)    |
+-----------------+-----------+---------+----+-----------+-----------+
| Bowel ^5^       | 1.0%      | 3.8%    | .  | 1.0%      | 1.9%      |
|                 | (2/200)   | (3/80)  | 14 | (1/100)   | (1/52)    |
+-----------------+-----------+---------+----+-----------+-----------+
| Wound ^6^       | 4.5%      | 7.5%    | .  | 2.0%      | 3.8%      |
|                 | (9/200)   | (6/80)  | 38 | (2/100)   | (2/52)    |
+-----------------+-----------+---------+----+-----------+-----------+
| Neurologic ^7^  | 0.0%      | 2.5%    | .  | 0.0%      | 0.0%      |
|                 | (0/200)   | (2/80)  | 08 | (0/100)   | (0/52)    |
+-----------------+-----------+---------+----+-----------+-----------+
| Vascular ^8,11^ | 11%       | 31%     | \< | 20%       | 19%       |
|                 | (21/200)  | (25/80) | .0 | (20/100)  | (10/52)   |
|                 |           |         | 01 |           |           |
+-----------------+-----------+---------+----+-----------+-----------+
| Freedom from    | 91%       | 86%     | .  | 79%       | 86%       |
| Morbidity       | (181/198) | (67/78) | 25 | (77/98)   | (44/51)   |
|                 |           |         |    |           |           |
| (31-365 days)   |           |         |    |           |           |
+-----------------+-----------+---------+----+-----------+-----------+
| Ca              | 2.5%      | 3.8%    | .  | 5.1%      | 2.0%      |
| rdiovascular^2^ | (5/198)   | (3/78)  | 69 | (5/98)    | (1/51)    |
+-----------------+-----------+---------+----+-----------+-----------+
| Pulmonary ^3^   | 0.5%      | 1.3%    | .  | 4.1%      | 0.0%      |
|                 | (1/198)   | (1/78)  | 49 | (4/98)    | (0/51)    |
+-----------------+-----------+---------+----+-----------+-----------+
| Renal ^4,10^    | 0.5%      | 0.0%    | \  | 3.1%      | 0.0%      |
|                 | (1/198)   | (0/78)  | >. | (3/98)    | (0/51)    |
|                 |           |         | 99 |           |           |
+-----------------+-----------+---------+----+-----------+-----------+
| Bowel ^5^       | 0.5%      | 1.3%    | .  | 0.0%      | 0.0%      |
|                 | (1/198)   | (1/78)  | 49 | (0/98)    | (0/51)    |
+-----------------+-----------+---------+----+-----------+-----------+
| Wound ^6^       | 2.0%      | 5.1%    | .  | 3.1%      | 2.0%      |
|                 | (4/198)   | (4/78)  | 23 | (3/98)    | (1/51)    |
+-----------------+-----------+---------+----+-----------+-----------+
| Neurologic ^7^  | 1.0%      | 0.0%    | \  | 1.0%      | 3.9%      |
|                 | (2/198)   | (0/78)  | >. | (1/98)    | (2/51)    |
|                 |           |         | 99 |           |           |
+-----------------+-----------+---------+----+-----------+-----------+
| Vascular ^8^    | 3.0 %     | 3.8%    | .  | 8.2%      | 5.9 %     |
|                 | (6/198)   | (3/78)  | 72 | (8/98)    | (3/51)    |
+-----------------+-----------+---------+----+-----------+-----------+
| Freedom from    | 76%       | 49%     | \< | 55%       | 62%       |
| Morbidity       | (151/200) | (39/80) | .0 | (55/100)  | (32/52)   |
|                 |           |         | 01 |           |           |
| (0-365 days)    |           |         |    |           |           |
+-----------------+-----------+---------+----+-----------+-----------+
| Ca              | 5.0%      | 14%     | .  | 19%       | 3.8%      |
| rdiovascular^2^ | (10/200)  | (11/80) | 02 | (19/100)  | (2/52)    |
+-----------------+-----------+---------+----+-----------+-----------+
| Pulmonary ^3^   | 1.5%      | 16 %    | \< | 6.0 %     | 0.0%      |
|                 | (3/200)   | (13/80) | .0 | (6/100)   | (0/52)    |
|                 |           |         | 01 |           |           |
+-----------------+-----------+---------+----+-----------+-----------+
| Renal ^4,9,10^  | 2.5%      | 10%     | .  | 9.0%      | 5.8%      |
|                 | (5/200)   | (8/80)  | 01 | (9/100)   | (3/52)    |
+-----------------+-----------+---------+----+-----------+-----------+
| Bowel ^5^       | 1.5%      | 3.8%    | .  | 1.0%      | 1.9%      |
|                 | (3/200)   | (3/80)  | 36 | (1/100)   | (1/52)    |
+-----------------+-----------+---------+----+-----------+-----------+
| Wound ^6^       | 5.5%      | 13%     | .  | 5.0%      | 5.8%      |
|                 | (11/200)  | (10/80) | 08 | (5/100)   | (3/52)    |
+-----------------+-----------+---------+----+-----------+-----------+
| Neurologic ^7^  | 1.0%      | 2.5%    | .  | 1.0%      | 3.8%      |
|                 | (2/200)   | (2/80)  | 32 | (1/100)   | (2/52)    |
+-----------------+-----------+---------+----+-----------+-----------+
| Vascular ^8,11^ | 12%       | 33%     | \< | 25%       | 23%       |
|                 | (24/200)  | (26/80) | .0 | (25/100)  | (12/52)   |
|                 |           |         | 01 |           |           |
+-----------------+-----------+---------+----+-----------+-----------+
| 1 From the      |           |         |    |           |           |
| morbidity       |           |         |    |           |           |
| index.          |           |         |    |           |           |
+-----------------+-----------+---------+----+-----------+-----------+
| 2               |           |         |    |           |           |
| Cardiovascular  |           |         |    |           |           |
| included:       |           |         |    |           |           |
| Q-wave and      |           |         |    |           |           |
| non-Q-wave      |           |         |    |           |           |
| myocardial      |           |         |    |           |           |
| infarctions,    |           |         |    |           |           |
| congestive      |           |         |    |           |           |
| heart failure,  |           |         |    |           |           |
| arrhythmias     |           |         |    |           |           |
| requiring new   |           |         |    |           |           |
| medication or   |           |         |    |           |           |
| treatment,      |           |         |    |           |           |
| cardiac         |           |         |    |           |           |
| ischemia        |           |         |    |           |           |
| requiring       |           |         |    |           |           |
| intervention,   |           |         |    |           |           |
| inotropic       |           |         |    |           |           |
| support,        |           |         |    |           |           |
| medically       |           |         |    |           |           |
| intractable     |           |         |    |           |           |
| hypertension.   |           |         |    |           |           |
+-----------------+-----------+---------+----+-----------+-----------+
| 3 Pulmonary     |           |         |    |           |           |
| included:       |           |         |    |           |           |
| reintubation or |           |         |    |           |           |
| ventilation     |           |         |    |           |           |
| \>24 hours,     |           |         |    |           |           |
| pneumonia       |           |         |    |           |           |
| requiring       |           |         |    |           |           |
| antibiotics,    |           |         |    |           |           |
| supplemental    |           |         |    |           |           |
| oxygen at       |           |         |    |           |           |
| discharge.      |           |         |    |           |           |
+-----------------+-----------+---------+----+-----------+-----------+
| 4 Renal         |           |         |    |           |           |
| included:       |           |         |    |           |           |
| dialysis in     |           |         |    |           |           |
| patients with   |           |         |    |           |           |
| normal          |           |         |    |           |           |
| preoperative    |           |         |    |           |           |
| renal function, |           |         |    |           |           |
| creatinine rise |           |         |    |           |           |
| \>30% from      |           |         |    |           |           |
| baseline on two |           |         |    |           |           |
| or more         |           |         |    |           |           |
| follow-up       |           |         |    |           |           |
| tests.          |           |         |    |           |           |
+-----------------+-----------+---------+----+-----------+-----------+
| 5 Bowel         |           |         |    |           |           |
| included: bowel |           |         |    |           |           |
| obstruction,    |           |         |    |           |           |
| bowel ischemia, |           |         |    |           |           |
| aorto-enteric   |           |         |    |           |           |
| fistula,        |           |         |    |           |           |
| paralytic ileus |           |         |    |           |           |
| \>4 days.       |           |         |    |           |           |
+-----------------+-----------+---------+----+-----------+-----------+
| 6 Wound         |           |         |    |           |           |
| included:       |           |         |    |           |           |
| infection       |           |         |    |           |           |
| requiring       |           |         |    |           |           |
| antibiotic      |           |         |    |           |           |
| treatment,      |           |         |    |           |           |
| hernia, lymph   |           |         |    |           |           |
| fistula,        |           |         |    |           |           |
| dehiscence,     |           |         |    |           |           |
| necrosis        |           |         |    |           |           |
| requiring       |           |         |    |           |           |
| debridement.    |           |         |    |           |           |
+-----------------+-----------+---------+----+-----------+-----------+
| 7 Neurological  |           |         |    |           |           |
| includes:       |           |         |    |           |           |
| stroke, TIA,    |           |         |    |           |           |
| spinal cord     |           |         |    |           |           |
| isch            |           |         |    |           |           |
| emia/paralysis. |           |         |    |           |           |
+-----------------+-----------+---------+----+-----------+-----------+
| 8 Vascular      |           |         |    |           |           |
| included: limb  |           |         |    |           |           |
| thrombosis,     |           |         |    |           |           |
| distal          |           |         |    |           |           |
| embolization    |           |         |    |           |           |
| resulting in    |           |         |    |           |           |
| tissue loss or  |           |         |    |           |           |
| requiring       |           |         |    |           |           |
| intervention,   |           |         |    |           |           |
| transfusion     |           |         |    |           |           |
| post-procedure  |           |         |    |           |           |
| (resulting from |           |         |    |           |           |
| pseudoaneurysm, |           |         |    |           |           |
| vascular        |           |         |    |           |           |
| injury,         |           |         |    |           |           |
| aneurysm leak   |           |         |    |           |           |
| or other        |           |         |    |           |           |
| pr              |           |         |    |           |           |
| ocedure-related |           |         |    |           |           |
| causes),        |           |         |    |           |           |
| pseudoaneurysm, |           |         |    |           |           |
| vascular injury |           |         |    |           |           |
| (such as        |           |         |    |           |           |
| inadvertent     |           |         |    |           |           |
| occlusion,      |           |         |    |           |           |
| dissection or   |           |         |    |           |           |
| other procedure |           |         |    |           |           |
| related         |           |         |    |           |           |
| causes),        |           |         |    |           |           |
| aneurysm leak   |           |         |    |           |           |
| or rupture,     |           |         |    |           |           |
| increase in     |           |         |    |           |           |
| aneurysm size   |           |         |    |           |           |
| by more than    |           |         |    |           |           |
| 0.5 cm relative |           |         |    |           |           |
| to the smallest |           |         |    |           |           |
| of any prior    |           |         |    |           |           |
| measurement.    |           |         |    |           |           |
+-----------------+-----------+---------+----+-----------+-----------+
| 9 Investigators |           |         |    |           |           |
| reported one    |           |         |    |           |           |
| additional high |           |         |    |           |           |
| risk patient to |           |         |    |           |           |
| have occlusion  |           |         |    |           |           |
| of an accessory |           |         |    |           |           |
| renal artery    |           |         |    |           |           |
| and one         |           |         |    |           |           |
| additional high |           |         |    |           |           |
| risk patient to |           |         |    |           |           |
| have chronic    |           |         |    |           |           |
| renal           |           |         |    |           |           |
| insufficiency   |           |         |    |           |           |
| as "other"      |           |         |    |           |           |
| adverse events. |           |         |    |           |           |
+-----------------+-----------+---------+----+-----------+-----------+
| 10              |           |         |    |           |           |
| Investigators   |           |         |    |           |           |
| reported one    |           |         |    |           |           |
| additional      |           |         |    |           |           |
| roll-in patient |           |         |    |           |           |
| to have renal   |           |         |    |           |           |
| insufficiency   |           |         |    |           |           |
| and one         |           |         |    |           |           |
| additional      |           |         |    |           |           |
| surgical        |           |         |    |           |           |
| patient to have |           |         |    |           |           |
| renal           |           |         |    |           |           |
| insufficiency   |           |         |    |           |           |
| as "other"      |           |         |    |           |           |
| adverse events. |           |         |    |           |           |
+-----------------+-----------+---------+----+-----------+-----------+
| 11              |           |         |    |           |           |
| Investigators   |           |         |    |           |           |
| reported one    |           |         |    |           |           |
| additional      |           |         |    |           |           |
| roll-in patient |           |         |    |           |           |
| to have         |           |         |    |           |           |
| experienced     |           |         |    |           |           |
| intraoperative  |           |         |    |           |           |
| aortic plaque   |           |         |    |           |           |
| rupture         |           |         |    |           |           |
| resulting in    |           |         |    |           |           |
| renal artery    |           |         |    |           |           |
| occlusion as an |           |         |    |           |           |
| "other" adverse |           |         |    |           |           |
| event.          |           |         |    |           |           |
+-----------------+-----------+---------+----+-----------+-----------+

Table 8.1-3. Other complications to 12 months

+---------------+-----------+-----------+----+-----------+-----------+
|               | *         | *         | *  | *         | #         |
|               | *Zenith** | *Surgical | ** | *Zenith** | ## Zenith |
|               |           | Standard  | P* |           |           |
|               | *         | Risk**    | v  | **High    | ##        |
|               | *Standard |           | al | Risk**    | # Roll-in |
|               | Risk**    |           | ue |           |           |
|               |           |           | ** |           |           |
+---------------+-----------+-----------+----+-----------+-----------+
| Other (0 to   | 15%       | 38%       | \< | 16%       | 31%       |
| 30 days)      | (30/200)  | (30/80)   | .0 | (16/100)  | (16/52)   |
|               |           |           | 01 |           |           |
+---------------+-----------+-----------+----+-----------+-----------+
| Other (31-365 | 8.1%      | 7.7%      | \  | 11%       | 12%       |
| days)         | (16/198)  | (6/78)    | >. | (11/98)   | (6/51)    |
|               |           |           | 99 |           |           |
+---------------+-----------+-----------+----+-----------+-----------+
| Other (0 to   | 22%       | 40%       | \  | 25%       | 35%       |
| 365 days)     | (43/200)  | (32/80)   | <. | (25/100)  | (18/52)   |
|               |           |           | 01 |           |           |
+---------------+-----------+-----------+----+-----------+-----------+

Investigators reported the following as \"other\" adverse events
(surgical and endovascular arms, surgical listed in italics), that is,
events not identified and defined prospectively as reportable events for
the study: abdominal pain (3), *abnormal wound healing (e.g., wound
drainage)*, acute respiratory distress, anemia (4), angina (2),
anorexia, *anxiety*, appendiceal adenocarcinoma, atelectasis,
atheroembolic event, back pain (3), bilateral ecchymosis, bladder tumor
(3), *blindness in right eye*, *bradycardia (treated by holding
medication)*, bronchitis, *candida in urine (prolonged ICU stay)*,
carcinoma of the iliocecal junction, cardiomyopathy, carotid stenosis
(2), chest pain (2, *1*), chronic lower extremity pain, claudication (3,
*1*), confusion (1, *1*), *congestive heart failure exacerbation*,
constipation (2, *1*), COPD exacerbation, deep vein thrombosis (3, *1*),
dehydration (3, *1*), difficile colitis, difficulty urinating,
difficulty with blood pressure management, duodenal ulcer, edema,
*elevation of liver enzymes*, embolization without tissue loss, enlarged
heart, fatigue, fever (3, *1*), foot pain, gastroenteritis, gout,
hematuria (1, *1*), hemoglobin volume depletion, hepatocellular
carcinoma, *hyperkeratotic wound*, hypertension, hypoglycemic episode,
hypotension, *impotence (2)*, *incisional pain*, left ventricular
thrombus, lost pedal pulse, lymphocele, mitral regurgitation,
neurological changes, neuropathy, numbness in groin, *oral thrush*,
pancreatitis (1, *1*), paresthesia of lower extremity, *PEG tube
placement*, *pleural effusion*, *positive blood culture*, pressure sore,
prolonged intubation (\<24 hours), pulmonary edema (1, *1*), pulmonary
embolism, purpura, reaction to transfusion, *respiratory distress*,
respiratory insufficiency (1, *1*), *retrograde ejaculation*,
scrotal/penile swelling, *sepsis*, seroma, shingles (2), shortness of
breath, *sinus surgery*, *splenectomy*, stroke induced dysphagia,
syncopal episode, testicular infarction, testicular pain (2), testicular
swelling, thrombocytopenia, *thrombus in distal lower extremity (treated
with embolectomy)*, *tracheobronchitis*, *tracheostomy*, upper GI bleed
(2), urinary frequency (2), urinary retention (2), urinary tract
infection (2, *1*), urosepsis, ventricular tachycardia (asymptomatic,
not requiring treatment), vomiting/nausea (3), *winged scapula*, wound
slough with debridement, *yeast in urinary tract*.

**8.2. Potential Adverse Events**

> Adverse events that may occur and/or require intervention include, but
> are not limited to:

-   Amputation

-   Anesthetic complications and subsequent attendant problems (e.g.,
    aspiration)

-   Aneurysm enlargement

-   Aneurysm rupture and death

-   Aortic damage, including perforation, dissection, bleeding, rupture,
    and death

-   Arterial or venous thrombosis and/or pseudoaneurysm

-   Arteriovenous fistula

-   Bleeding, hematoma, or coagulopathy

-   Bowel (e.g., ileus, transient ischemia, infarction, necrosis)

-   Cardiac complications and subsequent attendant problems (e.g.,
    arrhythmia, myocardial infarction, congestive heart failure,
    hypotension, hypertension)

-   Claudication (e.g. buttock, lower limb)

-   Death

-   Edema

-   Embolization (micro and macro) with transient or permanent ischemia

-   Endoleak

-   Endoprosthesis: improper component placement; incomplete component
    deployment; component migration, suture break; occlusion; infection;
    stent fracture; graft material wear, dilatation, erosion, puncture,
    perigraft flow, barb separation and corrosion

-   Fever and localized inflammation

-   Genitourinary complications and subsequent attendant problems (e.g.,
    ischemia, erosion, fistula, incontinence, hematuria, infection)

-   Graft or native vessel occlusion

-   Hepatic failure

-   Impotence

-   Infection of the aneurysm, device or access site, including abscess
    formation, transient fever and pain

-   Lymphatic complications and subsequent attendant problems (e.g.,
    lymph fistula)

-   Neurologic local or systemic complications and subsequent attendant
    problems (e.g., stroke, transient ischemic attack, paraplegia,
    paraparesis, paralysis)

-   Occlusion of device or native vessel

-   Pulmonary/respiratory complications and subsequent attendant
    problems (e.g., pneumonia, respiratory failure, prolonged
    intubation)

-   Renal complications and subsequent attendant problems (e.g., artery
    occlusion, contrast toxicity, insufficiency, failure)

-   Surgical conversion to open repair

-   Vascular access site complications, including infection, pain,
    hematoma, pseudoaneurysm, arterio-venous fistula

-   Vessel damage

-   Wound complications and subsequent attendant problems (e.g.,
    dehiscence, infection)

-   Vascular spasm or vascular trauma (e.g., ilio-femoral vessel
    dissection, bleeding, rupture, death)

**9. Summary of Pre-Clinical Results**

**9.1. Biocompatibility**

Toxicology and biocompatibility testing was conducted for materials in
the Zenith AAA Endovascular Graft and the H&L-B One-Shot Introduction
System by an independent laboratory (NAMSA, Northwood, OH). Testing was
conducted in accordance with Federal Good Laboratory Practices per 21
CFR §58. The Zenith AAA Endovascular Graft was classified per ISO
10993-1 Biological Evaluation of Medical Device as an implant device
with permanent contact. The H&L-B One-Shot Introduction System was
classified as an externally communicating device with limited exposure
(≤ 24 hr). Table 9.1-1 summarizes biocompatibility testing for the
implant. Table 9.1-2 summarizes biocompatibility testing for the
delivery system.

**Table 9.1-1.** Summary of Biocompatibility Tests for the Zenith AAA
Endovascular Graft, All With Acceptable Results

  -----------------------------------------------------------------------
  Biocompatibility Test
  -----------------------------------------------------------------------
  Physicochemical Study (Nonaqueous Extract)

  Cytotoxicity Study Using the ISO Elution Method (1X MEM Extract)

  ISO Sensitization Study in the Guinea Pig (Maximization Method)

  ISO Acute Intracutaneous Reactivity Study in the Rabbit (Extracts)

  ISO Acute Systemic Toxicity Study in the Mouse (Extracts)

  ISO Rabbit Pyrogen Study (Material Mediated)

  Genotoxicity: Bacterial Reverse Mutation Study (Saline Extract)

  Genotoxicity: Bacterial Reverse Mutation Study (DMSO Extract)

  Genotoxicity: *In Vitro* Chromosomal Aberration Study in Mammalian
  Cells (Extract)

  Mouse Bone Marrow Micronucleus Study

  *In Vitro* Hemolysis Study (Modified ASTM -- Extraction Method)

  Plasma Recalcification Time Coagulation Study

  C3a Complement Activation Assay

  Subchronic Intravenous Toxicity Study in the Rat (14 Day, Saline
  Extract)

  ISO Muscle Implantation Study in the Rabbit with Histopathology (4
  Weeks)

  ISO Muscle Implantation Study in the Rabbit with Histopathology (12
  Weeks)

  ISO Muscle Implantation Study in the Rabbit with Histopathology (26
  Weeks)
  -----------------------------------------------------------------------

**Table 9.1-2.** Summary of Biocompatibility Tests for the H&L-B
One-Shot Delivery System, All With Acceptable Results.

+-----------------------------------------------------------------------+
| ######## **Biocompatibility Test**                                    |
+-----------------------------------------------------------------------+
| USP Physicochemical Study                                             |
+-----------------------------------------------------------------------+
| Physicochemical Study (Nonaqueous Extract)                            |
+-----------------------------------------------------------------------+
| Cytotoxicity Study using the ISO Elution Method (1X MEM Extract)      |
+-----------------------------------------------------------------------+
| ISO Sensitization Study in the Guinea Pig (Maximization Method)       |
+-----------------------------------------------------------------------+
| ISO Acute Intracutaneous Reactivity Study in the Rabbit (Extracts)    |
+-----------------------------------------------------------------------+
| ISO Acute Systemic Toxicity Study in the Mouse (Extracts)             |
+-----------------------------------------------------------------------+
| *In Vitro* Hemolysis Study (Modified ASTM -- Extraction Method)       |
+-----------------------------------------------------------------------+
| Rabbit Pyrogen Study (Material Mediated)                              |
+-----------------------------------------------------------------------+

**9.2. Product Testing**

Cook conducted non-clinical bench and analytical testing on the
Zenith^^ AAA Endovascular Graft and the H&L-B One-Shot Introduction
System considering methodology from multiple national and international
standards and guidances. Compilation and cross-referencing of guidance
methodology from these documents in light of the Zenith^^ AAA
Endovascular Graft and the H&L-B One-Shot Introduction System design is
the basis for tests presented in this summary. Documents considered
include the following:

**Table 9.2-1.** International Standards and Guidances Considered in the
Zenith Testing Plan

  ------------------------ ----------------------------------------------
  **Document**             **Title**

  ANSI/AAMI 10993-1-1994   Biological Evaluation of Medical Devices

  ANSI/AAMI VP20-1994      Cardiovascular Implants - Vascular Prostheses

  AAMI/CDV-1 14971-1998    Medical devices - Risk management -
                           Application of risk management to medical
                           devices (committee draft for vote)

  ISO/DIS 7198-1-1990      Cardiovascular Implants - Tubular Vascular
                           Prostheses (draft standard)

  ISO/CD 15539-1998        Cardiovascular implants - Endovascular devices
                           (committee draft for comment)

  FDA Guidance-1993        Guidance for the Preparation of Research and
                           Marketing Applications for Vascular Graft
                           Prostheses (draft guidance)

  FDA Guidance-1994        Guidance for the Submission of Research and
                           Marketing Applications for Interventional
                           Cardiology Devices: PTCA Catheters,
                           Atherectomy Catheters, Lasers, Intravascular
                           Stents

  prEN 12006-2-1995        Vascular Prostheses and Cardiovascular Patches
                           (European draft standard)

  prEN 12006-3-1998        Non-active surgical implants; particular
                           requirements for cardiac and vascular implants
                           Part 3: Endovascular devices (European draft
                           standard)
  ------------------------ ----------------------------------------------

The express intent of this *in vitro* testing was to verify that the
performance attributes of the Zenith^^ AAA Endovascular Graft and the
H&L-B One-Shot Introduction System are sufficient to minimize adverse
events under anticipated clinical conditions.

**9.2.1. Delivery System Test Results Summary**

The following table summarizes testing performed to assess the delivery
system's ability to access the implant location, accurately deploy the
implant, safely withdraw, and maintain hemostasis.

**Table 9.2.1-1.** Summary of Results Related to H&L-B One-Shot
Introduction System Functionality

+-----------+-----------------+----------------------------------------+
| ***In     | **Relevant      | **Summary of Test Result**             |
| Vitro*    | Functional      |                                        |
| Test**    | Requirement**   |                                        |
+===========+=================+========================================+
| Tensile/  | -   Ability to  | The tensile strengths of the bonds and |
| Bond      |     access the  | joints of the H&L-B One-Shot          |
| Strength  |     intended    | Introduction System were determined. A |
|           |     location    | total of 220 catheter bonds were       |
|           |                 | tested and shown to have tensile       |
|           | -   Ability to  | strengths between 10.6 and 73.2 lbf.   |
|           |     deploy the  | Results indicate that there is at      |
|           |     implant     | least a 95% confidence level that the  |
|           |                 | minimum tensile strength of each       |
|           | -   Ability to  | catheter bond will exceed the          |
|           |     withdraw    | established acceptance criterion.      |
|           |     the         |                                        |
|           |     delivery    |                                        |
|           |     system      |                                        |
+-----------+-----------------+----------------------------------------+
| Torsional | -   Ability to  | The torsional strengths of the bonds   |
| Bond      |     access the  | and joints of the H&L-B One-Shot      |
| Strength  |     intended    | Introduction System were determined. A |
|           |     location    | total of 130 catheter bonds were       |
|           |                 | tested and shown to have torque        |
|           | -   Ability to  | strengths between 11.7 and 58.1        |
|           |     deploy the  | in.-oz. Mean bond strength met the     |
|           |     implant     | acceptance criterion for each joint    |
|           |                 | tested.                                |
+-----------+-----------------+----------------------------------------+
| Di        | -   Ability to  | Dimensional checks are part of         |
| mensional |     access the  | internal QC records verifying          |
| Ver       |     intended    | conformance to design specifications   |
| ification |     location    | for each device.                       |
|           |                 |                                        |
|           | -   Ability to  |                                        |
|           |     deploy the  |                                        |
|           |     implant     |                                        |
+-----------+-----------------+----------------------------------------+
| Crossing  | -   Ability to  | Crossing profile was analyzed for all  |
| Profile   |     access the  | four delivery system sizes (14, 16,    |
|           |     intended    | 18, and 20 Fr) and shown to range      |
|           |     location    | between 5.4 and 7.8 mm. All delivery   |
|           |                 | systems passed the established         |
|           | -   Ability to  | acceptance criterion, demonstrating    |
|           |     deploy the  | the delivery systems are capable of    |
|           |     implant     | being inserted into the vasculature    |
|           |                 | during clinical use.                   |
|           | -   Ability to  |                                        |
|           |     withdraw    |                                        |
|           |     the         |                                        |
|           |     delivery    |                                        |
|           |     system      |                                        |
|           |                 |                                        |
|           | -   Hemostasis  |                                        |
|           |     of the      |                                        |
|           |     delivery    |                                        |
|           |     system      |                                        |
+-----------+-----------------+----------------------------------------+
| Top Cap   | -   Ability to  | A total of 10 top caps were split in   |
| Mi        |     deploy the  | half and microscopically examined.     |
| croscopic |     implant     | Inspection of the lumens revealed only |
| I         |                 | slight surface scratches which could   |
| nspection | -   Ability to  | be attributed to manufacturing,        |
|           |     withdraw    | loading, or deployment. There was no   |
|           |     the         | evidence of pitting or gouging of the  |
|           |     delivery    | top cap material by the suprarenal     |
|           |     system      | stent barbs. Results of microscopic    |
|           |                 | examination demonstrate that the top   |
|           |                 | cap of the H&L-B One-Shot             |
|           |                 | Introduction System is unlikely to pit |
|           |                 | or gouge during deployment of the      |
|           |                 | barbed suprarenal Z-stent.             |
+-----------+-----------------+----------------------------------------+
| D         | -   Ability to  | Comprehensive evaluation of *in vitro* |
| eployment |     access the  | deployment was conducted in a          |
| Test      |     intended    | clinically relevant model. A total of  |
|           |     location    | 113 finished sterilized devices were   |
|           |                 | tested with 100% deployment success.   |
|           | -   Ability to  | Results of deployment testing          |
|           |     deploy the  | demonstrate the ability of all four    |
|           |     implant     | sizes (14, 16, 18, and 20 Fr) of the   |
|           |                 | H&L-B One-Shot Introduction System to |
|           | -   Ability to  | deliver the Zenith in a safe,          |
|           |     withdraw    | consistent and accurate manner.        |
|           |     the         | Delivery systems are capable of        |
|           |     delivery    | deploying all modular components (main |
|           |     system      | bodies, main body extensions, iliac    |
|           |                 | legs, iliac leg extensions,            |
|           |                 | converters, and occluders) in the      |
|           |                 | entire product line. The deployment    |
|           |                 | mechanisms of the delivery systems     |
|           |                 | functioned to release the pre-loaded   |
|           |                 | endovascular graft components. After   |
|           |                 | release, each component expanded in    |
|           |                 | the intended deployment location, and  |
|           |                 | the delivery system was withdrawn      |
|           |                 | successfully.                          |
+-----------+-----------------+----------------------------------------+
| Minimum   | -   Ability to  | A total of 108 delivery systems (all   |
| Bend      |     access the  | four sizes: 14, 16, 18, and 20 Fr)     |
| Radius    |     intended    | containing the largest and smallest    |
| Test      |     location    | diameters of main bodies, main body    |
|           |                 | extensions, iliac legs, iliac leg      |
|           | -   Ability to  | extensions, converters and occluders   |
|           |     deploy the  | were passed through a                  |
|           |     implant     | clinically-relevant model mimicking    |
|           |                 | percutaneous introduction and then     |
|           | -   Ability to  | deployed. 100% successful deployment   |
|           |     withdraw    | was achieved for all components. All   |
|           |     the         | delivery systems passed the            |
|           |     delivery    | established acceptance criterion,      |
|           |     system      | demonstrating the Zenith components    |
|           |                 | may be deployed after worst case       |
|           |                 | (percutaneous introduction) insertion  |
|           |                 | into patient vasculature.              |
+-----------+-----------------+----------------------------------------+
| Catheter  | -   Ability to  | The lower bound of catheter body       |
| Body      |     deploy      | maximum pressure was calculated to be  |
| Maximum   |     accurately  | 58.6 ksi, considerably higher than     |
| Pressure  |                 | that expected from a typical power     |
| Test      |                 | contrast injector. Therefore, the      |
|           |                 | H&L-B One-Shot Introduction System is |
|           |                 | considered suitable for contrast       |
|           |                 | injection.                             |
+-----------+-----------------+----------------------------------------+

The results of *in vitro* testing demonstrate that the Zenith^^ AAA
Endovascular Graft has met the physical and mechanical design goals.

**9.2.2. Implant Test Results Summary**

The following table summarizes testing performed to assess the implant's
deployment accuracy, fixation effectiveness, durability, ability to
exclude the aneurysm, modularity, sizing, patency, and MRI
compatibility.

**Table 9.2.2-1.** Summary of Test Results Related to Zenith^^ AAA
Endovascular Graft Functionality

+-----------+----------------+----------------------------------------+
| ***In     | **Relevant     | **Summary of Test Result**             |
| Vitro*    | Functional     |                                        |
| Test**    | Requirement**  |                                        |
+===========+================+========================================+
| Graft     | -   Testing of | The full thickness Dacron graft        |
| Material  |     the        | material used in Zenith construction   |
| M         |     modularity | is a currently-marketed device         |
| echanical |     of the     | (cleared for marketing by FDA in       |
| P         |                | 1993). As such, base graft porosity,   |
| roperties |   endovascular | longitudinal tensile strength,         |
| Test      |     system     | circumferential tensile strength,      |
|           |                | probe burst strength, suture retention |
|           | -              | strength, kink radius, and wall        |
|           |    Appropriate | thickness data obtained are consistent |
|           |     sizing of  | with vascular grafts.                  |
|           |     the        |                                        |
|           |     implant    |                                        |
|           |                |                                        |
|           | -   Durability |                                        |
|           |     and        |                                        |
|           |     integrity  |                                        |
|           |     of the     |                                        |
|           |     implanted  |                                        |
|           |     device     |                                        |
+-----------+----------------+----------------------------------------+
| Stainless | -   Durability | All sizes of stainless steel wire used |
| Steel     |     and        | in Zenith construction were chemically |
| Material  |     integrity  | analyzed and quantified. The material  |
| Analysis  |     of the     | analysis meets the manufacturing       |
| Test      |     implanted  | material specification.                |
|           |     device     |                                        |
+-----------+----------------+----------------------------------------+
| Stainless | -   Durability | Tensile testing was performed on all   |
| Steel     |     and        | three stent wire sizes to characterize |
| M         |     integrity  | the mechanical properties of the       |
| echanical |     of the     | material. These properties include     |
| P         |     implanted  | modulus of elasticity, yield strength, |
| roperties |     device     | and ultimate strength. In addition,    |
| Test      |                | rotary beam fatigue testing was        |
|           |                | conducted on all three stent wire      |
|           |                | sizes (at three different stress       |
|           |                | levels) to characterize wire fatigue   |
|           |                | parameters. Results indicate the wire  |
|           |                | used in Zenith construction meets the  |
|           |                | manufacturing specification.           |
+-----------+----------------+----------------------------------------+
| Solder    | -   Durability | The solder used in Zenith construction |
| Material  |     and        | was chemically analyzed and            |
| Analysis  |     integrity  | quantified. The material analysis      |
|           |     of the     | meets the manufacturing material       |
|           |     implanted  | specification.                         |
|           |     device     |                                        |
+-----------+----------------+----------------------------------------+
| Time-Ac   | -   Durability | A total of 12 stent samples were       |
| celerated |     and        | immersed in an accelerated corrosion   |
| Corrosion |     integrity  | bath for various periods of time and   |
| Test      |     of the     | then removed for examination. The      |
|           |     implanted  | resistance of the stainless steel      |
|           |     device     | wire, solder, and gold markers to      |
|           |                | general, pitting, crevice, and         |
|           |                | galvanic corrosion was evaluated.      |
|           |                | There is a potential for solder loss   |
|           |                | due to corrosion, however, the loss in |
|           |                | solder is not anticipated to be        |
|           |                | greater than 50% over 10 years and     |
|           |                | there is a redundancy in design        |
|           |                | intended to provide additional         |
|           |                | protection from migration as a result  |
|           |                | of barb slippage due to solder loss    |
|           |                |                                        |
|           |                | . Results demonstrate no apparent      |
|           |                | corrosion of the stainless steel wire  |
|           |                | and gold markers after 12 years of     |
|           |                | simulated implant time.                |
+-----------+----------------+----------------------------------------+
| Barb      | -   Durability | A total of 36 barbs were tensile       |
| A         |     and        | tested after immersion in an           |
| ttachment |     integrity  | accelerated corrosion bath. Mean barb  |
| Strength  |     of the     | attachment (shear) strength was        |
| Test      |     implanted  | approximately 6 times the acceptance   |
| (after    |     device     | criterion after 12 years of simulated  |
| corrosion |                | implant (corrosion) time.              |
| test)     |                |                                        |
+-----------+----------------+----------------------------------------+
| Cannula   | -   Durability | A total of 11 stent cannula were       |
| (portion  |     and        | tensile tested after immersion in an   |
| of        |     integrity  | accelerated corrosion bath. Minimum    |
| Z-stent)  |     of the     | cannula tensile strength was           |
| Tensile   |     implanted  | approximately 6 times the acceptance   |
| Test      |     device     | criterion after 12 years of simulated  |
| (after    |                | implant (corrosion) time.              |
| corrosion |                |                                        |
| test)     |                |                                        |
+-----------+----------------+----------------------------------------+
| Stent     | -   Patency of | Stent free-area percentages were       |
| Free-Area |     the        | calculated for the stent               |
| P         |     implant    | configurations used in the suprarenal  |
| ercentage |                | stent position. Free-area percentages  |
|           |                | for these Z-stents are 82% and 84%     |
|           |                | respectively, for the worst case       |
|           |                | (smallest aorta) conditions.           |
+-----------+----------------+----------------------------------------+
| Radial    | -   Expansion  | Radial force testing was performed on  |
| Force     |     and        | 45 samples of Z-stents, which included |
| Test      |     sealing    | configurations used in the entire      |
|           |                | Zenith product line. Results           |
|           |  effectiveness | demonstrate the ability of the Z-stent |
|           |     of the     | to exert an outward non-zero radial    |
|           |     implant    | force on the graft material even under |
|           |                | worst case (largest resting diameter)  |
|           | -              | conditions allowing the Z-stents to    |
|           |    Appropriate | expand and maintain an open lumen and  |
|           |     sizing of  | provide sealing in a variety of        |
|           |     the        | patient anatomies.                     |
|           |     implant    |                                        |
|           |                |                                        |
|           | -   Patency of |                                        |
|           |     the        |                                        |
|           |     implant    |                                        |
+-----------+----------------+----------------------------------------+
| Time-Ac   | -   Durability | Time-accelerated pulsatile fatigue     |
| celerated |     and        | testing was conducted on 31 bifurcated |
| Pulsatile |     integrity  | grafts to an equivalent of 10 years.   |
| Fatigue   |     of the     | At 10 years, there was no loss of      |
| Test      |     implanted  | device function, fragmentation, barb   |
|           |     device     | separation, suprarenal stent breaks,   |
| (Th       |                | or cannula separations. No component   |
| ree-piece |                | separations, migrations, graft kinks,  |
| b         |                | or graft twists were observed and all  |
| ifurcated |                | grafts were patent. A single Z-stent   |
| graft)    |                | vertex break was observed. This test   |
|           |                | was not designed to assess suture and  |
|           |                | graft material abrasion, although it   |
|           |                | was noted. Binomial statistics         |
|           |                | demonstrate with at least 95%          |
|           |                | confidence that 99% of the Zenith      |
|           |                | stents will not fracture after 10      |
|           |                | years of implant time meeting the      |
|           |                | acceptance criteria for this test.     |
+-----------+----------------+----------------------------------------+
| Time-Ac   | -   Durability | Time-accelerated longitudinal fatigue  |
| celerated |     and        | testing of the double-sutured          |
| Lon       |     integrity  | suprarenal stent attachment site was   |
| gitudinal |     of the     | conducted on 30 attachment sites to an |
| Fatigue   |     implanted  | equivalent of 10 years. At 10 years,   |
| Test      |     device     | there were no failures of the          |
|           |                | suprarenal attachment sutures or graft |
| (S        | -   Fixation   | material at the suprarenal attachment  |
| uprarenal |                | sites. Therefore, fatigue failure is   |
| At        |  effectiveness | unlikely to occur under normal         |
| tachment) |     of the     | conditions, when the device is used in |
|           |     implant    | accordance with the IFU.               |
+-----------+----------------+----------------------------------------+
| Finite    | -   Durability | Force versus diameter curves and       |
| Element   |     and        | maximum stress (in the loop or eye of  |
| Analysis  |     integrity  | the stent points) versus diameter      |
|           |     of the     | curves were generated demonstrating    |
|           |     implanted  | the ability of the Z-stent to          |
|           |     device     | self-expand the graft during           |
|           |                | deployment. Fatigue analysis of the    |
|           |                | Z-stents and their barbs demonstrated  |
|           |                | that fatigue failure is unlikely to    |
|           |                | occur during the expected implant life |
|           |                | of the Zenith under normal conditions, |
|           |                | when the device is used in accordance  |
|           |                | with the IFU.                          |
+-----------+----------------+----------------------------------------+
| Magnetic  | -   MRI        | The MR safety and compatibility of the |
| Resonance |                | Zenith^®^ AAA Endovascular Graft has   |
| Imaging   |  compatibility | been evaluated through bench testing   |
| Test      |                | in MRI systems with static fields of ≤ |
|           |                | 1.5 Tesla, gradient magnetic fields of |
|           |                | ≤ 20 Tesla/second, and whole body      |
|           |                | averaged specific absorption rate      |
|           |                | (SAR) of 1.2 W/kg for 30 minutes of    |
|           |                | imaging. The Zenith^®^ AAA             |
|           |                | Endovascular Graft was found to        |
|           |                | exhibit torque and deflection of the   |
|           |                | stainless steel metallic component of  |
|           |                | the endovascular graft and therefore   |
|           |                | did not meet standard 'MR Safe' bench  |
|           |                | test criteria. The Zenith^®^ AAA       |
|           |                | Endovascular Graft may affect image    |
|           |                | quality (image artifact) depending on  |
|           |                | the pulse sequence that is used for MR |
|           |                | imaging.                               |
+-----------+----------------+----------------------------------------+
| Di        | -   Ability to | Records from work orders indicate that |
| mensional |     accurately | production processes are outlined      |
| Ver       |     deploy     | sufficiently to enable repeatable      |
| ification |                | dimensional characteristics from       |
|           | -              | lot-to-lot of manufacturing.           |
|           |    Appropriate |                                        |
|           |     sizing of  |                                        |
|           |     the        |                                        |
|           |     implant    |                                        |
+-----------+----------------+----------------------------------------+
| Water     | -   Ability to | Water permeability of the Zenith was   |
| Per       |     exclude    | determined to be 165.0±109.7           |
| meability |     the        | (ml/cm^2^/min) using the methods       |
| Test      |     aneurysm   | defined in ANSI/AAMI VP:20 -- 1994     |
|           |                | using 9 samples containing sutures.    |
|           | -   Testing of | Results of this test demonstrate that  |
|           |     the        | the addition of sutures, during Zenith |
|           |     modularity | manufacturing, does not significantly  |
|           |     of the     | increase the mean permeability of­ the  |
|           |                | Zenith above that of the virgin graft  |
|           |   endovascular | material. Zenith samples met the       |
|           |     system     | acceptance criterion for this test.    |
+-----------+----------------+----------------------------------------+
| Graft to  | -   Durability | Mean attachment strength of 27 test    |
| Stent     |     and        | sample sutures was determined to range |
| A         |     integrity  | between 4.98 and 6.15 lbf which is     |
| ttachment |     of the     | more than twice the acceptance         |
| Strength  |     implanted  | criterion for attachment strength.     |
| Test      |     device     | Results indicate that detachment of    |
| (         |                | the graft material from the Z-stents   |
| attaching |                | due to inadequate graft to stent       |
| s         |                | attachment strength is unlikely.       |
| uprarenal |                |                                        |
| stent and |                |                                        |
| body      |                |                                        |
| stents to |                |                                        |
| graft )   |                |                                        |
+-----------+----------------+----------------------------------------+
| Kink      | -   Ability to | The radius at which component kinking  |
| Radius    |     accurately | occurs was measured for a total of 90  |
| Test      |     deploy     | test samples. Acceptance criteria for  |
|           |                | the main body components are based     |
|           | -   Fixation   | upon the anatomical restrictions       |
|           |                | established for angulation between the |
|           |  effectiveness | aortic neck and the longitudinal axis  |
|           |     of the     | of the aneurysm. Kink radius test      |
|           |     implant    | results demonstrate the Zenith is      |
|           |                | expected to resist kinking when        |
|           | -   Patency of | implanted within aortas having a       |
|           |     the        | degree of angulation ≤ 60º.            |
|           |     implant    |                                        |
+-----------+----------------+----------------------------------------+
| Migration | -   Fixation   | Forces acting to cause migration *in   |
| R         |                | vivo* were estimated using analytical  |
| esistance |  effectiveness | and CFD methods. Migration resistance  |
| Test      |     of the     | of the main body, ipsilateral leg,     |
|           |     implant    | contralateral leg, main body           |
|           |                | extension, iliac leg extension, and    |
|           | -   Testing of | occluder were compared to these        |
|           |     the        | estimates and found to meet the        |
|           |     modularity | acceptance criteria established for    |
|           |     of the     | this test. Based upon these results,   |
|           |                | component migration appears unlikely.  |
|           |   endovascular |                                        |
|           |     system     |                                        |
+-----------+----------------+----------------------------------------+

**9.3. Shelf Life Testing**

Results demonstrate that the H&L-B One-Shot Introduction System is
capable of deploying the Zenith^^ AAA Endovascular Graft after three
years of simulated aging. The endovascular graft has been shown to
self-expand and the delivery system components have been shown to
function satisfactorily. Tensile and torque test results demonstrate the
delivery system retains adequate component and bond strength.
Dimensional measurements indicate the endovascular graft retains
dimensional stability. Therefore, based upon these test results, a three
year expiration date has been established for all sizes of every
component in the Zenith^^ AAA Endovascular Graft family (main bodies,
main body extensions, iliac legs, iliac leg extensions, converters, and
occluders).

**9.4. Animal Studies**

Throughout development, the Zenith^^ AAA Endovascular Graft was
evaluated in multiple animal studies. Eight studies involving 85 animals
evaluated device placement accuracy, device deployment, aneurysm
exclusion, potential for adverse events, histology and survival. These
studies demonstrated that the delivery system is capable of accessing
the aneurysm site, accurately deploying the Zenith^^ AAA Endovascular
Graft in an infrarenal position with good visibility and ease of
operation, and can be withdrawn effectively, all with minimal blood loss
during the procedure. The implant was shown to be capable of
self-expanding into its deployed position. It successfully excluded the
aneurysm while remaining patent and in position after implant,
demonstrating the effectiveness of the design and appropriateness of the
device sizing method. In these studies, there was a low incidence of
adverse events. Histological and pathological analyses demonstrated
implantation of the Zenith^^ AAA Endovascular Graft to be minimally
traumatic and non-reactive in these early studies.

In addition, a definitive animal study performed under U.S. FDA Good
Laboratory Practice regulations was conducted on the final design for
the U.S. clinical trial to provide histopathology and gross anatomical
observations to demonstrate device safety before clinical approval and
to provide controlled histology not available from clinical studies.
Study results demonstrate the safety of the Zenith^^ AAA Endovascular
Graft. Table 9.4-1 summarizes the results of the definitive animal
study.

**Table 9.4-1.** Summary of definitive non-clinical *in vivo* study

+-----------+--------+----------+------------+------------------------+
| **Animal  | **\# / | **Test   | *          | *                      |
| Study**   | Type   | A        | *Methods** | *Results/Conclusions** |
|           | of     | rticle** |            |                        |
|           | An     |          |            |                        |
|           | imal** |          |            |                        |
+-----------+--------+----------+------------+------------------------+
| Su        | 15     | Hum      | Catheter   | All acceptance         |
| b-Chronic | C      | an-Sized | delivery   | criteria were met.     |
| and       | anines | Zenith   | and device | 100% successful        |
| Chronic   |        | Co       | fun        | deployment of the      |
| Study of  |        | mponents | ctionality | Zenith in an           |
|           |        | and      | were       | infrarenal position    |
| Tapered   |        | H&L-B    | assessed   | was achieved and 100%  |
| Endop     |        | O        | sub-c      | device patency at 1,   |
| rosthesis |        | ne-Shot | hronically | 3, and 6 months was    |
|           |        | Intr     | and        | evidenced by           |
|           |        | oduction | c          | angiography. There was |
|           |        | System   | hronically | no thrombosis, aortic  |
|           |        |          | in 15      | rupture, or death      |
|           |        |          | animals.   | observed in the animal |
|           |        |          | Four       | study. Qualitative     |
|           |        |          | canines    | histopathologic        |
|           |        |          | were       | evaluation performed   |
|           |        |          | maintained | by an independent      |
|           |        |          | for one    | board-certified        |
|           |        |          | month,     | pathologist            |
|           |        |          | five       | demonstrates minimal   |
|           |        |          | canines    | injury and             |
|           |        |          | were       | inflammation.          |
|           |        |          | maintained |                        |
|           |        |          | for three  |                        |
|           |        |          | months and |                        |
|           |        |          | six        |                        |
|           |        |          | canines    |                        |
|           |        |          | were       |                        |
|           |        |          | maintained |                        |
|           |        |          | for six    |                        |
|           |        |          | months.    |                        |
+-----------+--------+----------+------------+------------------------+

**10. Summary of Clinical Studies**

**10.1. Objectives**

The objective of the clinical study was to investigate the safety and
effectiveness of the Zenith^®^ AAA Endovascular Graft as an alternative
to open surgical repair in the primary treatment of infrarenal abdominal
aortic, or aorto-iliac aneurysms through assessment of device safety as
measured by the incidence of adverse events and factors related to
morbidity and device effectiveness as measured by technical, procedural,
and treatment success, and rupture-free survival at 12 months.
Additionally, measures related to the procedure, patient recovery,
clinical utility, and quality of life were assessed.

**10.2. Zenith^^ AAA Endovascular Graft with the H&L-B One-Shot
Introduction System Study Design**

The clinical study was a multicenter, concurrently controlled study
comparing standard risk endovascular patients having anatomy suitable
for the Zenith^^ AAA Endovascular Graft with the H&L-B One-Shot
Introduction System to a control group comprised of standard risk
surgical patients. Two additional endovascular treatment groups, one
which allowed high medical risk patients to be treated with the
Zenith^^ AAA Endovascular Graft with the H&L-B One-Shot Introduction
System , and the other a roll-in treatment group of initial cases.
Fifteen centers enrolled 200 standard risk, 80 surgical control, 100
high risk, and 52 roll-in patients. Clinical and imaging follow-up were
scheduled for post-procedure and 1 month, 6 months, 12 months, and
annually thereafter. Patient follow-up and accountability at 1 month, 12
months, and 24 months are presented in Table 10.2-2 as these were the
primary data analysis time points. Data provided in this summary are
based on findings from an independent core lab that reviewed CT scans,
abdominal x-rays, and ultrasound scans to assess aneurysm changes,
device position and integrity, and endoleaks.

**Table 10.2-2.** Patient follow-up and accountability: standard risk
and surgical patients

+---------------------------------+-----+-----+-----+-----+-----+-----+
| Treatment                       | Zen |     |     | Su  |     |     |
|                                 | ith |     |     | rgi |     |     |
|                                 |     |     |     | cal |     |     |
|                                 | St  |     |     |     |     |     |
|                                 | and |     |     | St  |     |     |
|                                 | ard |     |     | and |     |     |
|                                 | R   |     |     | ard |     |     |
|                                 | isk |     |     | R   |     |     |
|                                 |     |     |     | isk |     |     |
+---------------------------------+-----+-----+-----+-----+-----+-----+
| Interval                        | 1   | 12  | 24  | 1   | 12  | 24  |
|                                 | mo. | mo. | mo. | mo. | mo. | mo. |
+---------------------------------+-----+-----+-----+-----+-----+-----+
| No Device                       | 1   | 1   | 1   | 0   | 0   | n/a |
|                                 |     | ^2^ | ^2^ |     |     |     |
+---------------------------------+-----+-----+-----+-----+-----+-----+
| Conversion to Open Repair       | 0   | 2   | 2   | n/a | n/a | n/a |
|                                 |     | ^2^ | ^2^ |     |     |     |
+---------------------------------+-----+-----+-----+-----+-----+-----+
| Expired                         | 1   | 7   | 17  | 2   | 3   | n/a |
+---------------------------------+-----+-----+-----+-----+-----+-----+
| Withdrawn/Lost to Follow-up     | 0   | 0   | 2   | 0   | 4   | n/a |
+---------------------------------+-----+-----+-----+-----+-----+-----+
| Available                       | 198 | 190 | 178 | 78  | 73  | n/a |
+---------------------------------+-----+-----+-----+-----+-----+-----+
| Site CT Imaging                 | 191 | 168 | 110 | 69  | 58  | n/a |
+---------------------------------+-----+-----+-----+-----+-----+-----+
| Core Lab CT Imaging             | 190 | 165 | 99  | 69  | 59  | n/a |
+---------------------------------+-----+-----+-----+-----+-----+-----+
| Site KUB Imaging                | 179 | 153 | 108 | n/a | n/a | n/a |
+---------------------------------+-----+-----+-----+-----+-----+-----+
| Core Lab KUB Imaging            | 178 | 149 | 93  | n/a | n/a | n/a |
+---------------------------------+-----+-----+-----+-----+-----+-----+
| Site Evaluated for Endoleak     | 187 | 163 | 107 | n/a | n/a | n/a |
+---------------------------------+-----+-----+-----+-----+-----+-----+
| Core Lab Evaluated for Endoleak | 161 | 148 | 92  | n/a | n/a | n/a |
+---------------------------------+-----+-----+-----+-----+-----+-----+
| Site Evaluated for Aneurysm     | n/a | 149 | 104 | n/a | n/a | n/a |
| Enlargement                     |     |     |     |     |     |     |
+---------------------------------+-----+-----+-----+-----+-----+-----+
| Core Lab Evaluated for Aneurysm | n/a | 151 | 94  | n/a | n/a | n/a |
| Enlargement                     |     |     |     |     |     |     |
+---------------------------------+-----+-----+-----+-----+-----+-----+

1 Data analysis sample size varies for each of the timepoints above and
in the following tables. This variability is due to patient availability
for follow-up, as well as, quantity and quality of images available from
specific timepoints for evaluation. For example, the number and quality
of images available for evaluation of endoleak at 12 months is different
than the number and quality of images available at 24 months due to
variation in the number of image exams performed, the number of images
provided from the clinical site to the Core Lab, and/or the number of
images with acceptable evaluation quality. Totals at time points are not
cumulative, unless otherwise noted.

2 Totals at time points are cumulative.

**10.3. Patient Demographics**

Tables 10.3-1 and 10.3-2 tabulate patient demographics and comorbid
conditions and present the distribution of initial aneurysm diameters
for the four study groups.

**Table 10.3-1. Patient Demographics and Comorbid Conditions**

+-------------------+-----------+----------+----+----------+----------+
| ##### Item        | *         | **Su     | *  | **       | **       |
|                   | *Zenith** | rgical** | ** | Zenith** | Zenith** |
|                   |           |          | P* |          |          |
|                   | *         | **       | v  | **High   | **R      |
|                   | *Standard | Standard | al | Risk**   | oll-in** |
|                   | Risk**    | Risk**   | ue |          |          |
|                   |           |          | ** |          |          |
+-------------------+-----------+----------+----+----------+----------+
| Age (years)       | 71 ± 7    | 69 ± 7   | .  | 77 ± 7   | 74 ± 8   |
|                   |           |          | 03 |          |          |
+-------------------+-----------+----------+----+----------+----------+
| Gender male       | 94%       | 89%      | .  | 92%      | 90%      |
|                   | (187/200) | (71/80)  | 22 | (92/100) | (47/52)  |
+-------------------+-----------+----------+----+----------+----------+
| Current medical   |           |          |    |          |          |
| conditions        |           |          |    |          |          |
+-------------------+-----------+----------+----+----------+----------+
| Peripheral vasc.  | 16%       | 25%      | .  | 24%      | 9.6%     |
| disease           | (31/195)  | (19/76)  | 12 | (23/96)  | (5/52)   |
+-------------------+-----------+----------+----+----------+----------+
| Hypertension      | 64%       | 83%      | .0 | 68%      | 67%      |
|                   | (127/200) | (65/78)  | 01 | (67/99)  | (35/52)  |
+-------------------+-----------+----------+----+----------+----------+
| Renal failure     | 0.0%      | 0.0%     | \  | 5.2%     | 1.9%     |
|                   | (0/197)   | (0/79)   | >. | (5/97)   | (1/52)   |
|                   |           |          | 99 |          |          |
+-------------------+-----------+----------+----+----------+----------+
| COPD              | 20%       | 18%      | .  | 34%      | 22%      |
|                   | (39/199)  | (14/78)  | 87 | (33/98)  | (11/51)  |
+-------------------+-----------+----------+----+----------+----------+
| Thromboembolic    | 4.5%      | 7.7%     | .  | 7.1%     | 1.9%     |
| event             | (9/199)   | (6/78)   | 38 | (7/99)   | (1/52)   |
+-------------------+-----------+----------+----+----------+----------+
| Liver disease     | 2.1%      | 5.1%     | .  | 1.0%     | 1.9%     |
|                   | (4/192)   | (4/79)   | 24 | (1/99)   | (1/52)   |
+-------------------+-----------+----------+----+----------+----------+
| Diabetes Mellitus | 12%       | 15%      | .  | 17%      | 14%      |
|                   | (24/199)  | (12/79)  | 55 | (17/99)  | (7/51)   |
+-------------------+-----------+----------+----+----------+----------+
| Insulin-dependent | 17%       | 8.3%     | .  | 24%      | 43%      |
|                   | (4/24)    | (1/12)   | 65 | (4/17)   | (3/7)    |
+-------------------+-----------+----------+----+----------+----------+
| Previous medical  |           |          |    |          |          |
| conditions        |           |          |    |          |          |
+-------------------+-----------+----------+----+----------+----------+
| MI                | 39%       | 29%      | .  | 35%      | 35%      |
|                   | (74/192)  | (23/80)  | 13 | (34/98)  | (18/52)  |
+-------------------+-----------+----------+----+----------+----------+
| Congestive heart  | 5.0%      | 12%      | .  | 16%      | 10%      |
| failure           | (10/199)  | (9/78)   | 07 | (16/100) | (5/50)   |
+-------------------+-----------+----------+----+----------+----------+
| Angina            | 49%       | 39%      | .  | 45%      | 44%      |
|                   | (98/198)  | (31/79)  | 14 | (44/98)  | (23/52)  |
+-------------------+-----------+----------+----+----------+----------+
| Arrhythmia        | 20%       | 22%      | .  | 28%      | 24%      |
|                   | (40/197)  | (17/78)  | 87 | (27/98)  | (12/51)  |
+-------------------+-----------+----------+----+----------+----------+
| Cerebrovascular   | 9.5%      | 16%      | .  | 20%      | 9.8%     |
| disease           | (19/199)  | (13/79)  | 14 | (20/99)  | (5/51)   |
+-------------------+-----------+----------+----+----------+----------+
| Systemic          | 1.0%      | 0.0%     | \  | 3.1%     | 0.0%     |
| infection         | (2/196)   | (0/78)   | >. | (3/97)   | (0/49)   |
|                   |           |          | 99 |          |          |
+-------------------+-----------+----------+----+----------+----------+
| Cancer            | 22%       | 19%      | .  | 31%      | 29%      |
|                   | (43/200)  | (15/80)  | 74 | (31/99)  | (15/51)  |
+-------------------+-----------+----------+----+----------+----------+
| Family history of | 16%       | 27%      | .  | 14%      | 26%      |
|                   | (24/150)  | (17/63)  | 09 | (11/77)  | (10/38)  |
| aneurysmal        |           |          |    |          |          |
| disease           |           |          |    |          |          |
+-------------------+-----------+----------+----+----------+----------+
| Previous surgery  | 10%       | 15%      | .  | 10%      | 14%      |
| at site           | (20/200)  | (12/79)  | 22 | (10/99)  | (7/51)   |
+-------------------+-----------+----------+----+----------+----------+
| Previous          | 0.5%      | 0.0%     | \  | 2.0%     | 2.0%     |
| radiation at site | (1/197)   | (0/79)   | >. | (2/100)  | (1/51)   |
|                   |           |          | 99 |          |          |
+-------------------+-----------+----------+----+----------+----------+
| Excessive alcohol | 3.6%      | 10%      | .  | 3.1%     | 4.0%     |
| use               | (7/193)   | (8/77)   | 04 | (3/96)   | (2/50)   |
+-------------------+-----------+----------+----+----------+----------+
| Tobacco use       | 10%       | 5.0%     | .  | 14%      | 24%      |
|                   | (20/193)  | (4/80)   | 03 | (13/96)  | (12/49)  |
| Never smoked      |           |          |    |          |          |
|                   | 69%       | 60%      |    | 69%      | 57%      |
| Past smoker       | (133/193) | (48/80)  |    | (66/96)  | (28/49)  |
|                   |           |          |    |          |          |
| Still smokes      | 21%       | 35%      |    | 18%      | 18%      |
|                   | (40/193)  | (28/80)  |    | (17/96)  | (9/49)   |
+-------------------+-----------+----------+----+----------+----------+

####  

#### Table 10.3-2. Aneurysm Diameter Distribution

+-------------+--------------+--------------+------------+------------+
| **Diameter  | **Zenith**   | **Surgical** | **Zenith** | **Zenith** |
| Range**     |              |              |            |            |
|             | **Standard   | **Standard   | **High     | *          |
|             | Risk**       | Risk**       | Risk**     | *Roll-in** |
+-------------+--------------+--------------+------------+------------+
| \< 30 mm    | 0.0% (0/199) | 0.0% (0/78)  | 0.0%       | 0.0%       |
|             |              |              | (0/100)    | (0/52)     |
+-------------+--------------+--------------+------------+------------+
| 30-39 mm    | 0.5% (1/199) | 0.0% (0/78)  | 1.0%       | 0.0%       |
|             |              |              | (1/100)    | (0/52)     |
+-------------+--------------+--------------+------------+------------+
| 40-49 mm    | 23% (45/199) | 7.7% (6/78)  | 15%        | 13% (7/52) |
|             |              |              | (15/100)   |            |
+-------------+--------------+--------------+------------+------------+
| 50-59 mm    | 48% (95/199) | 33% (26/78)  | 47%        | 40%        |
|             |              |              | (47/100)   | (21/52)    |
+-------------+--------------+--------------+------------+------------+
| 60-69 mm    | 24% (47/199) | 29% (23/78)  | 27%        | 42%        |
|             |              |              | (27/100)   | (22/52)    |
+-------------+--------------+--------------+------------+------------+
| 70-79 mm    | 3.0% (6/199) | 21% (16/78)  | 5.0%       | 1.9%       |
|             |              |              | (5/100)    | (1/52)     |
+-------------+--------------+--------------+------------+------------+
| 80-89 mm    | 2.5% (5/199) | 6.4% (5/78)  | 1.0%       | 0.0%       |
|             |              |              | (1/100)    | (0/52)     |
+-------------+--------------+--------------+------------+------------+
| ≥ 90 mm     | 0.0% (0/199) | 2.6% (2/78)  | 1.0%       | 0.0%       |
|             |              |              | (1/100)    | (0/52)     |
+-------------+--------------+--------------+------------+------------+

Aneurysm diameter distribution was not assessed in three high and one
roll-in patient.

**10.4. Results**

**10.4.1. Devices Implanted**

Table 10.4.1-1 lists the devices implanted in the U.S. pivotal trial.
Devices were implanted intraoperatively unless otherwise noted.

##### Table 10.4.1-1. Devices implanted 

+----------------------------+---------------+------------+------------+
| ## Item                    | #### Zenith   | **Zenith** | **Zenith** |
|                            |               |            |            |
|                            | ####          | **High     | *          |
|                            | Standard Risk | Risk**     | *Roll-in** |
+----------------------------+---------------+------------+------------+
| Main body and legs         | 99.5%         | 100%       | 100%       |
|                            | (199/200)\*   | (1         | (52/52)    |
|                            |               | 00/100)^1^ |            |
+----------------------------+---------------+------------+------------+
| Main body extension^2^     | 1.5% (3/199)  | 1% (1/100) | 5.8%       |
|                            |               |            | (3/52)     |
+----------------------------+---------------+------------+------------+
| Ipsilateral iliac leg      | 9.5% (19/199) | 11%        | 0% (0/52)  |
| extension^3,5^             |               | (11/100)   |            |
+----------------------------+---------------+------------+------------+
| Contralateral iliac leg    | 11% (21/199)  | 11%        | 13.5%      |
| extension^4,5^             |               | (11/100)   | (7/52)     |
+----------------------------+---------------+------------+------------+
| Converter                  | 0.5%          | 0% (0/100) | 0% (0/52)  |
|                            | (1/199)\*\*   |            |            |
+----------------------------+---------------+------------+------------+
| Occluder                   | 0% (0/199)    | 0% (0/100) | 0% (0/52)  |
+----------------------------+---------------+------------+------------+
| \* One standard risk       |               |            |            |
| patient did not receive a  |               |            |            |
| device due to tortuosity   |               |            |            |
| and calcification of the   |               |            |            |
| access vessel.             |               |            |            |
+----------------------------+---------------+------------+------------+
| \*\* Converter was used    |               |            |            |
| without occluder           |               |            |            |
+----------------------------+---------------+------------+------------+
| ^1^ One device was custom. |               |            |            |
+----------------------------+---------------+------------+------------+
| ^2^ Two standard risk and  |               |            |            |
| one high risk patient      |               |            |            |
| received main body         |               |            |            |
| extensions post-procedure; |               |            |            |
| one standard risk patient  |               |            |            |
| received two main body     |               |            |            |
| extensions.                |               |            |            |
+----------------------------+---------------+------------+------------+
| ^3^ Two standard risk and  |               |            |            |
| one high risk patient      |               |            |            |
| received ipsilateral leg   |               |            |            |
| extensions post-procedure. |               |            |            |
+----------------------------+---------------+------------+------------+
| ^4^ Four standard risk,    |               |            |            |
| two high risk and one      |               |            |            |
| roll-in patient received   |               |            |            |
| contralateral leg          |               |            |            |
| extensions post-procedure. |               |            |            |
+----------------------------+---------------+------------+------------+
| ^5^Three standard risk and |               |            |            |
| three high risk patients   |               |            |            |
| received both ipsilateral  |               |            |            |
| and contralateral          |               |            |            |
| extensions during the      |               |            |            |
| procedure; one standard    |               |            |            |
| risk received both         |               |            |            |
| ipsilateral and            |               |            |            |
| contralateral extensions   |               |            |            |
| post-procedure.            |               |            |            |
+----------------------------+---------------+------------+------------+

##### 10.4.2. Primary Results

Measures of mortality, rupture, conversion and adverse events are
presented in Table 10.4.2-1. and Figures 10.4.2-1 and 10.4.2-2. Where
available, 24-month data are provided. Control patients were not
followed beyond 12 months and some data have not yet been adjudicated
beyond 12 months. Therefore, some results are presented to 12 months
while other results are presented to 24 months in this section. Figures
10.4.2-1 and 10.4.2-2 depict all-cause and AAA-related survival,
respectively. An independent clinical events committee adjudicated all
deaths for possible relationship to aneurysm repair. All early deaths
(0-30 days) were considered AAA-related. Deaths after 30 days were
considered AAA-related if AAA disease or device involvement was
confirmed. Zenith^®^ AAA Endovascular Graft patients exhibited no
significant differences between males and females for survival and
freedom from major adverse events. (Error bars in Figures 10.4.2-1,
10.4.2-2 and 10.4.2-3 represent 95% confidence limits.) Table 10.4.2-3.
presents success measures.

##### Table 10.4.2-1. Principal safety results

+---------------------+---------+---------+-----+---------+----------+
| ### Item            | **Z     | **Sur   | **  | **Z     | **       |
|                     | enith** | gical** | *P* | enith** | Zenith** |
|                     |         |         | v   |         |          |
|                     | **S     | **S     | alu | **High  | **R      |
|                     | tandard | tandard | e** | Risk**  | oll-in** |
|                     | Ri      | Risk**  |     |         |          |
|                     | sk^1^** |         |     |         |          |
+---------------------+---------+---------+-----+---------+----------+
| All death (0-30     | 0.5%    | 2.5%    | .20 | 2.0%    | 1.9%     |
| days) ^2^           | (1/199) | (2/80)  |     | (2/100) | (1/52)   |
+---------------------+---------+---------+-----+---------+----------+
| All death (31-365   | 3.0%    | 1.3%    | .68 | 7.1%    | 9.8%     |
| days) ^2,\ 3^       | (6/198) | (1/78)  |     | (7/98)  | (5/51)   |
|                     |         |         | .29 |         |          |
| AAA-related         | 0.0%    | 1.3%    |     | 3.1%    | 0.0%     |
|                     | (0/198) | (1/78)  | .19 | (3/98)  | (0/51)   |
| Non-AAA-related     |         |         |     |         |          |
|                     | 3.0%    | 0.0%    |     | 4.1%    | 9.8%     |
|                     | (6/198) | (0/78)  |     | (4/98)  | (5/51)   |
+---------------------+---------+---------+-----+---------+----------+
| All death (0-365    | 3.5%    | 3.8%    | \>  | 9.0%    | 11.5%    |
| days) ^2,\ 3,\ 4^   | (7/199) | (3/80)  | .99 | (9/100) | (6/52)   |
|                     |         |         |     |         |          |
| AAA-related         | 0.5%    | 3.8%    | .07 | 5.0%    | 1.9%     |
|                     | (1/199) | (3/80)  |     | (5/100) | (1/52)   |
| Non-AAA-related     |         |         | .19 |         |          |
|                     | 3.0%    | 0.0%    |     | 4.0%    | 9.6%     |
|                     | (6/199) | (0/80)  |     | (4/100) | (5/52)   |
+---------------------+---------+---------+-----+---------+----------+
| Rupture (0-30 days) | 0.0%    | n/a     | n/a | 0.0%    | 0.0%     |
|                     | (0/199) |         |     | (0/100) | (0/52)   |
+---------------------+---------+---------+-----+---------+----------+
| Rupture (31-365     | 0.0%    | n/a     | n/a | 1.0%    | 0.0%     |
| days)               | (0/198) |         |     | (1/98)  | (0/51)   |
+---------------------+---------+---------+-----+---------+----------+
| Rupture (0-365      | 0.0%    | n/a     | n/a | 1.0%    | 0.0%     |
| days)               | (0/199) |         |     | (1/100) | (0/52)   |
+---------------------+---------+---------+-----+---------+----------+
| Conversion (0-30    | 0.0%    | n/a     | n/a | 0.0%    | 0.0%     |
| days)               | (0/199) |         |     | (0/100) | (0/52)   |
+---------------------+---------+---------+-----+---------+----------+
| Conversion (31-365  | 1.0%    | n/a     | n/a | 1.0%    | 0.0%     |
| days) ^5^           | (2/199) |         |     | (1/100) | (0/52)   |
+---------------------+---------+---------+-----+---------+----------+
| Conversion (0-365   | 1.0%    | n/a     | n/a | 1.0%    | 0.0%     |
| days) ^5^           | (2/199) |         |     | (1/100) | (0/52)   |
+---------------------+---------+---------+-----+---------+----------+
| Adverse Events      | 20%     | 43%     | \<. | 32%     | 27%      |
| (0-30 days)^6^      | (       | (34/80) | 001 | (       | (14/52)  |
|                     | 40/200) |         |     | 32/100) |          |
+---------------------+---------+---------+-----+---------+----------+
| Adverse Events      | 8.6%(   | 14%     | .25 | 21%     | 14%      |
| (31-365 days) ^6^   | 17/199) | (11/78) |     | (21/98) | (7/51)   |
+---------------------+---------+---------+-----+---------+----------+
| Adverse Events      | 25%     | 51%     | \<. | 45%     | 38%      |
| (0-365 days) ^6^    | (       | (41/80) | 001 | (       | (20/52)  |
|                     | 49/200) |         |     | 45/100) |          |
+---------------------+---------+---------+-----+---------+----------+
| ^1^ Denominator of  |         |         |     |         |          |
| 199 because one     |         |         |     |         |          |
| standard risk       |         |         |     |         |          |
| patient did not     |         |         |     |         |          |
| receive a device.   |         |         |     |         |          |
+---------------------+---------+---------+-----+---------+----------+
| ^2^ All deaths      |         |         |     |         |          |
| (0-30 days) were    |         |         |     |         |          |
| considered AAA and  |         |         |     |         |          |
| procedure related.  |         |         |     |         |          |
+---------------------+---------+---------+-----+---------+----------+
| ^3^ Of the deaths   |         |         |     |         |          |
| (31-365 days), four |         |         |     |         |          |
| were considered AAA |         |         |     |         |          |
| related: 1 surgical |         |         |     |         |          |
| (septic shock from  |         |         |     |         |          |
| ischemic colitis)   |         |         |     |         |          |
| and 3 high risk     |         |         |     |         |          |
| (pancreatitis with  |         |         |     |         |          |
| renal failure and   |         |         |     |         |          |
| sepsis, hemorrhage  |         |         |     |         |          |
| from upper          |         |         |     |         |          |
| abdominal aneurysm  |         |         |     |         |          |
| \[not treated       |         |         |     |         |          |
| AAA\], and multiple |         |         |     |         |          |
| system failure).    |         |         |     |         |          |
+---------------------+---------+---------+-----+---------+----------+
| ^4^ Of the deaths   |         |         |     |         |          |
| (0-365 days), ten   |         |         |     |         |          |
| were considered AAA |         |         |     |         |          |
| related: 1 standard |         |         |     |         |          |
| risk (cardiac       |         |         |     |         |          |
| failure), 3         |         |         |     |         |          |
| surgical (massive   |         |         |     |         |          |
| hemorrhage,         |         |         |     |         |          |
| mesenteric          |         |         |     |         |          |
| ischemia, and       |         |         |     |         |          |
| septic shock from   |         |         |     |         |          |
| ischemic colitis),  |         |         |     |         |          |
| 5 high risk         |         |         |     |         |          |
| (respiratory        |         |         |     |         |          |
| failure, cardiac    |         |         |     |         |          |
| failure with        |         |         |     |         |          |
| pulmonary embolism, |         |         |     |         |          |
| pancreatitis with   |         |         |     |         |          |
| renal failure and   |         |         |     |         |          |
| sepsis, hemorrhage  |         |         |     |         |          |
| from upper          |         |         |     |         |          |
| abdominal aneurysm  |         |         |     |         |          |
| \[not treated       |         |         |     |         |          |
| AAA\], and multiple |         |         |     |         |          |
| system failure) and |         |         |     |         |          |
| 1 roll-in           |         |         |     |         |          |
| (suspected cardiac  |         |         |     |         |          |
| failure).           |         |         |     |         |          |
+---------------------+---------+---------+-----+---------+----------+
| ^5^ Standard risk   |         |         |     |         |          |
| patients underwent  |         |         |     |         |          |
| conversions due to  |         |         |     |         |          |
| a persistent,       |         |         |     |         |          |
| proximal Type I     |         |         |     |         |          |
| endoleak and a new  |         |         |     |         |          |
| suprarenal aortic   |         |         |     |         |          |
| aneurysm. Three     |         |         |     |         |          |
| surgical patients   |         |         |     |         |          |
| had massive         |         |         |     |         |          |
| hemorrhages, of     |         |         |     |         |          |
| which 2 required    |         |         |     |         |          |
| re-operation and    |         |         |     |         |          |
| one died.           |         |         |     |         |          |
+---------------------+---------+---------+-----+---------+----------+
| ^6^ Adverse events  |         |         |     |         |          |
| included in the     |         |         |     |         |          |
| morbidity index     |         |         |     |         |          |
+---------------------+---------+---------+-----+---------+----------+

> Figure 10.4.2-1 presents all-cause survival to 24 months. The
> accompanying table presents the Kaplan-Meier analysis at 1, 6, 12, and
> 24 months.

**Figure 10.4.2-1.** Survival at 24 Months

![](media/image7.wmf)

  ------------------ ------- ---------- -------- ---------- -------- ---------- -------- ----------
                     1 month            6 months            12                  24       
                                                            months              months   

                     n       \%         n        \%         n        \%         n        \%
                             survival            survival            survival            survival

  Zenith Standard    198     99.5       194      98.0       190      96.5       97       90.9
  Risk                                                                                   

  Surgical Standard  78      97.5       73       96.2       67       96.2       n/a      n/a
  Risk                                                                                   

  n= patients alive                                                                      
  and available for                                                                      
  follow-up at the                                                                       
  end of the                                                                             
  interval                                                                               

  P=.81                                                                                  
  ------------------ ------- ---------- -------- ---------- -------- ---------- -------- ----------

Figure 10.4.2-2 presents AAA-related survival (determined by Clinical
Events Committee) to 24 months. The accompanying table presents the
Kaplan-Meier analysis at 1, 6, 12, and 24 months.

**Figure 10.4.2-2.** AAA-related Survival at 24 Months

[]{.mark}

![](media/image8.wmf)

  ----------------- ------- ---------- -------- ---------- -------- ---------- -------- ----------
                    1 month            6 months            12                  24       
                                                           months              months   

                    n       \%         n        \%         n        \%         n        \%
                            survival            survival            survival            survival

  Zenith Standard   198     99.5       194      99.5       190      99.5       97       99.0
  Risk                                                                                  

  Surgical Standard 78      97.5       73       96.2       67       96.2       n/a      n/a
  Risk                                                                                  

  n= patients alive                                                                     
  and available for                                                                     
  follow-up at the                                                                      
  end of the                                                                            
  interval                                                                              

  P=.04                                                                                 
  ----------------- ------- ---------- -------- ---------- -------- ---------- -------- ----------

#### Table 10.4.2-3. Success Measures

+-----------------+--------------+-----------+-----------+-----------+
| ##### Item      | **Zenith**   | **S       | *         | *         |
|                 |              | urgical** | *Zenith** | *Zenith** |
|                 | **Standard   |           |           |           |
|                 | Risk**       | *         | **High    | **        |
|                 |              | *Standard | Risk**    | Roll-In** |
|                 |              | Risk**    |           |           |
+=================+==============+===========+===========+===========+
| Technical       | 99.5%        | 98.8%     | 100%      | 100%      |
| success^1^      | (199/200)    | (79/80)   | (100/100) | (52/52)   |
+-----------------+--------------+-----------+-----------+-----------+
| Procedural      | 95.1%        | 88%       | 86%       | 91%       |
| success at 30   | (155/163)    | (60/68)   | (70/81)   | (30/33)   |
| days^2^         |              |           |           |           |
+-----------------+--------------+-----------+-----------+-----------+
| Treatment       | 89%          | 85%       | 70%       | 87%       |
| success at 12   | (122/137)    | (52/61)   | (44/63)   | (26/30)   |
| months^3^       |              |           |           |           |
+-----------------+--------------+-----------+-----------+-----------+

^1^Patent graft following deployment.

^2^Technical success with no major complications, patent graft and no
Type I or Type III endoleaks at 30 days.

^3^Procedural success extended to 12 months with no aneurysm enlargement
(\>5 mm).

Figure 10.4.2-3 presents freedom from morbidity (events in the morbidity
index). The accompanying table presents the Kaplan-Meier analysis at 1,
6, and 12 months.

**Figure 10.4.2-3.** Freedom from Morbidity (0-365 days)

![](media/image9.wmf)

  ---------------------- ------- ----------- -------- ----------- -------- ----------
                         1 month             6 months             12       
                                                                  months   

                         n       \%          n        \%          n        \%
                                                                           survival

  Zenith Standard Risk   162     81.0        154      78.5        133      77.4

  Surgical Standard Risk 45      57.1        39       52.0        33       47.8

  n= patients alive and                                                    
  free of morbidity at                                                     
  the end of the                                                           
  interval                                                                 

  P\<.001                                                                  
  ---------------------- ------- ----------- -------- ----------- -------- ----------

Tables 10.4.2-4 through 10.4.2-7 describe results of the Zenith^®^ AAA
Endovascular Graft subjects as reported by the Core Lab. Device
performance factors analyzed by the Core Lab include device integrity
(Table 10.4.2-4), device patency (Table 10.4.2-5), migration (Table
10.4.2-6), and limb separation (Table 10.4.2-7).

**Table 10.4.2-4.** Abdominal Radiographic Findings - Device Integrity

+---------------------------+-------------+-------------+-------------+
| ##### Item                | **Zenith**  | **Zenith**  | **Zenith**  |
|                           |             |             |             |
|                           | **Standard  | **High      | **Roll-In** |
|                           | Risk**      | Risk**      |             |
+---------------------------+-------------+-------------+-------------+
| Stent Pre-discharge       | 0.0%        | 0.0% (0/81) | 0.0% (0/39) |
|                           | (0/172)     |             |             |
+---------------------------+-------------+-------------+-------------+
| Fractures^1^ 30 day       | 0.0%        | 0.0% (0/83) | 0.0% (0/43) |
|                           | (0/172)     |             |             |
+---------------------------+-------------+-------------+-------------+
| 6 month                   | 0.0%        | 0.0% (0/78) | 0.0% (0/35) |
|                           | (0/166)     |             |             |
+---------------------------+-------------+-------------+-------------+
| 12 month                  | 0.0%        | 0.0% (0/60) | 0.0% (0/28) |
|                           | (0/148)     |             |             |
+---------------------------+-------------+-------------+-------------+
| 24 month                  | 0.0% (0/93) | 0.0% (0/42) | 0.0% (0/19) |
+---------------------------+-------------+-------------+-------------+
| Barb Pre-discharge        | 0.0%        | 0.0% (0/86) | 0.0% (0/39) |
|                           | (0/176)     |             |             |
+---------------------------+-------------+-------------+-------------+
| Separation^2^ 30 day      | 0.0%        | 0.0% (0/86) | 0.0% (0/43) |
|                           | (0/178)     |             |             |
+---------------------------+-------------+-------------+-------------+
| 6 month                   | 1.2%        | 2.5% (2/80) | 0.0% (0/35) |
|                           | (2/167)     |             |             |
+---------------------------+-------------+-------------+-------------+
| 12 month                  | 2.0%        | 1.7% (1/60) | 0.0% (0/28) |
|                           | (3/149)     |             |             |
+---------------------------+-------------+-------------+-------------+
| 24 month                  | 1.1% (1/93) | 0.0% (0/42) | 0.0% (0/19) |
+---------------------------+-------------+-------------+-------------+
| Graft material            | 0.0%        | 0.0% (0/86) | 0.0% (0/39) |
| Pre-discharge             | (0/176)     |             |             |
+---------------------------+-------------+-------------+-------------+
| rupture 30 day            | 0.0%        | 0.0% (0/86) | 0.0% (0/43) |
|                           | (0/178)     |             |             |
+---------------------------+-------------+-------------+-------------+
| 6 month                   | 0.0%        | 0.0% (0/80) | 0.0% (0/35) |
|                           | (0/167)     |             |             |
+---------------------------+-------------+-------------+-------------+
| 12 month                  | 0.0%        | 0.0% (0/60) | 0.0% (0/28) |
|                           | (0/149)     |             |             |
+---------------------------+-------------+-------------+-------------+
| 24 month                  | 0.0% (0/93) | 0.0% (0/42) | 0.0% (0/19) |
+---------------------------+-------------+-------------+-------------+

^1^Stent fracture percentages are for main body. There were also no
right iliac leg, left iliac leg, occluder, converter, left iliac
extension, right iliac extension, or main body extension fractures
observed by the core lab.

^2^Patients with separation of 1 or 2 barbs (of 10 or 12 total); no
adverse clinical sequelae.

**Table 10.4.2-5.** CT Findings -- Graft Patency

+---------------------------+-------------+-------------+-------------+
| ##### Item                | **Zenith**  | **Zenith**  | **Zenith**  |
|                           |             |             |             |
|                           | **Standard  | **High      | **Roll-In** |
|                           | Risk**      | Risk**      |             |
+---------------------------+-------------+-------------+-------------+
| Graft 30 day              | 100%        | 99% (85/86) | 100%        |
|                           | (185/185)   |             | (47/47)     |
+---------------------------+-------------+-------------+-------------+
| patency 6 month           | 99%         | 100%        | 100%        |
|                           | (183/184)   | (74/74)     | (39/39)     |
+---------------------------+-------------+-------------+-------------+
| 12 month                  | 99%         | 100%        | 100%        |
|                           | (153/155)   | (62/62)     | (30/30)     |
+---------------------------+-------------+-------------+-------------+
| 24 month                  | 100%        | 100%        | 100%        |
|                           | (96/96)     | (33/33)     | (25/25)     |
+---------------------------+-------------+-------------+-------------+

**Table 10.4.2-6.** CT Findings -- Graft (Main Body) Migration

+---------------------------+-------------+-------------+-------------+
| ##### Item                | **Zenith**  | **Zenith**  | **Zenith**  |
|                           |             |             |             |
|                           | **Standard  | **High      | **Roll-In** |
|                           | Risk**      | Risk**      |             |
+---------------------------+-------------+-------------+-------------+
| Graft migration (\>5 mm)  | 0.0%        | 0.0% (0/71) | 0.0% (0/34) |
| at 12 months              | (0/162)     |             |             |
|                           |             |             |             |
| with clinical sequelae^1^ |             |             |             |
| or intervention           |             |             |             |
+---------------------------+-------------+-------------+-------------+
| without clinical          | 2.5%        | 2.8% (2/71) | 0.0% (0/34) |
| sequelae^1^ or            | (4/162)     |             |             |
| intervention              |             |             |             |
+---------------------------+-------------+-------------+-------------+
| Graft migration (\>10 mm) | 0.0%        | 0.0% (0/71) | 0.0% (0/34) |
|                           | (0/162)     |             |             |
+---------------------------+-------------+-------------+-------------+

^1^Migration with clinical sequelae would include endoleak, conversion,
rupture or AAA-related death.

**Table 10.4.2-7.** Abdominal Radiograph Findings -- Limb Separation

+---------------------------+-------------+-------------+-------------+
| ##### Item                | **Zenith**  | **Zenith**  | **Zenith**  |
|                           |             |             |             |
|                           | **Standard  | **High      | **Roll-In** |
|                           | Risk**      | Risk**      |             |
+---------------------------+-------------+-------------+-------------+
| Limb Pre-discharge        | 0.0%        | 0.0% (0/86) | 0.0% (0/39) |
|                           | (0/176)     |             |             |
+---------------------------+-------------+-------------+-------------+
| separation 30 day         | 0.0%        | 0.0% (0/86) | 0.0% (0/43) |
|                           | (0/178)     |             |             |
+---------------------------+-------------+-------------+-------------+
| 6 month                   | 0.0%        | 0.0% (0/80) | 0.0% (0/35) |
|                           | (0/167)     |             |             |
+---------------------------+-------------+-------------+-------------+
| 12 month                  | 0.0%        | 0.0% (0/60) | 0.0% (0/28) |
|                           | (0/149)     |             |             |
+---------------------------+-------------+-------------+-------------+
| 24 month                  | 0.0% (0/93) | 0.0% (0/42) | 0.0% (0/19) |
+---------------------------+-------------+-------------+-------------+

Table 10.4.2-8 presents the incidence of endoleaks by evaluation
interval, as identified by the Core Lab for the standard risk, high
risk, and roll-in patients, respectively.

**Table 10.4.2-8.** Endoleaks (all types, new and persistent)

+-----------------+-------------------+-----------------+---------------+
| ## Item         | **Zenith**        | **Zenith**      | **Zenith**    |
|                 |                   |                 |               |
|                 | **Standard Risk** | **High Risk**   | **Roll-in**   |
+-----------------+-------------------+-----------------+---------------+
| Endoleaks       |                   |                 |               |
+-----------------+-------------------+-----------------+---------------+
| Pre-discharge   | 15% (23/153)      | 14% (11/78)     | 12% (3/26)    |
+-----------------+-------------------+-----------------+---------------+
| 30 day^1^       | 9.9% (16/161)     | 12% (9/75)      | 6.3% (2/32)   |
+-----------------+-------------------+-----------------+---------------+
| 6 month^1^      | 8.7% (15/172)     | 11% (8/70)      | 8.6% (3/35)   |
+-----------------+-------------------+-----------------+---------------+
| 12 month^1^     | 7.4% (11/148)     | 8.8% (5/57)     | 3.4% (1/29)   |
+-----------------+-------------------+-----------------+---------------+

^1^Includes both persistent endoleaks and new observations

#### 

Tables 10.4.2-9 -- 10.4.2-11 present the incidence of first occurrence
of an endoleak according to evaluation interval, as identified by the
Core Lab at or before the 30 day, 6 month, and 12 month exams for the
standard risk, high risk, and roll-in patients, respectively. The number
of patients who are leak-free thereafter is also given.

#### Table 10.4.2-9. First occurrence of endoleak^1^ for standard risk patients 

<table>
<colgroup>
<col style="width: 31%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 7%" />
</colgroup>
<thead>
<tr class="header">
<th rowspan="2"><h5 id="item-9">Item</h5></th>
<th colspan="3"><p><strong>To One Month</strong></p>
<p><strong>Exam</strong></p>
<p><strong>N=179</strong></p></th>
<th colspan="3"><p><strong>Six Month</strong></p>
<p><strong>Exam</strong></p>
<p><strong>N=172</strong></p></th>
<th colspan="3"><p><strong>Twelve Month Exam</strong><sup>3</sup></p>
<p><strong>N=148</strong></p></th>
</tr>
<tr class="odd">
<th>%</th>
<th>Endo-leak<sup>1</sup></th>
<th>Leak-free there-after<sup>2</sup></th>
<th>%</th>
<th>Endo-leak<sup>1</sup></th>
<th>Leak-free there-after<sup>2</sup></th>
<th>%</th>
<th>Endo-leak<sup>1</sup></th>
<th>Leak-free there-after<sup>2</sup></th>
</tr>
</thead>
<tbody>
<tr class="odd">
<td>Endoleaks</td>
<td>17</td>
<td>31</td>
<td>17</td>
<td>2.3</td>
<td>4</td>
<td>3</td>
<td>3.4</td>
<td>5</td>
<td>2</td>
</tr>
<tr class="even">
<td>Proximal Type I</td>
<td>2.8</td>
<td>5</td>
<td>4</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
</tr>
<tr class="odd">
<td>Distal Type I</td>
<td>1.7</td>
<td>3</td>
<td>1</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
<td>0.7</td>
<td>1</td>
<td>1</td>
</tr>
<tr class="even">
<td>Type II</td>
<td>9.5</td>
<td>17</td>
<td>9</td>
<td>2.3</td>
<td>4</td>
<td>3</td>
<td>1.4</td>
<td>2</td>
<td>1</td>
</tr>
<tr class="odd">
<td>Type III</td>
<td>1.1</td>
<td>2</td>
<td>2</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
<td>0.7</td>
<td>1</td>
<td>0</td>
</tr>
<tr class="even">
<td>Type IV</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
</tr>
<tr class="odd">
<td>Multiple</td>
<td>1.1</td>
<td>2</td>
<td>1</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
</tr>
<tr class="even">
<td>Unknown</td>
<td>1.1</td>
<td>2</td>
<td>0</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
<td>0.7</td>
<td>1</td>
<td>0</td>
</tr>
</tbody>
</table>

^1^Identified by Core Lab

^2^Subsequent endoleaks may have been of difference type than original

^3^Only 2 patients had new endoleaks after 12 months; follow-up after 24
months not available

**Table 10.4.2-10.** First occurrence of endoleak^1^ for high risk
patients

<table>
<colgroup>
<col style="width: 32%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 8%" />
<col style="width: 8%" />
</colgroup>
<thead>
<tr class="header">
<th rowspan="2"><h5 id="item-10">Item</h5></th>
<th colspan="3"><p><strong>To One Month Exam</strong></p>
<p><strong>N=88</strong></p></th>
<th colspan="3"><p><strong>Six Month Exam</strong></p>
<p><strong>N=70</strong></p></th>
<th colspan="3"><strong>Twelve Month Exam</strong><sup>3</sup>
<strong>N=57</strong></th>
</tr>
<tr class="odd">
<th>%</th>
<th>Endo-leak<sup>1</sup></th>
<th>Leak-free there-after<sup>2</sup></th>
<th>%</th>
<th>Endo-leak<sup>1</sup></th>
<th>Leak-free there-after<sup>2</sup></th>
<th>%</th>
<th>Endo-leak<sup>1</sup></th>
<th>Leak-free there-after<sup>2</sup></th>
</tr>
</thead>
<tbody>
<tr class="odd">
<td>Endoleaks</td>
<td>18</td>
<td>16</td>
<td>6</td>
<td>2.9</td>
<td>2</td>
<td>0</td>
<td>3.5</td>
<td>2</td>
<td>1</td>
</tr>
<tr class="even">
<td>Proximal Type I</td>
<td>2.3</td>
<td>2</td>
<td>1</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
</tr>
<tr class="odd">
<td>Distal Type I</td>
<td>1.1</td>
<td>1</td>
<td>1</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
</tr>
<tr class="even">
<td>Type II</td>
<td>9.1</td>
<td>8</td>
<td>3</td>
<td>1.4</td>
<td>1</td>
<td>0</td>
<td>1.8</td>
<td>1</td>
<td>0</td>
</tr>
<tr class="odd">
<td>Type III</td>
<td>0.0</td>
<td>0.0</td>
<td>0</td>
<td>1.4</td>
<td>1</td>
<td>0</td>
<td>1.8</td>
<td>1</td>
<td>1</td>
</tr>
<tr class="even">
<td>Type IV</td>
<td>0.0</td>
<td>0.0</td>
<td>0</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
</tr>
<tr class="odd">
<td>Multiple</td>
<td>4.5</td>
<td>4</td>
<td>0</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
</tr>
<tr class="even">
<td>Unknown</td>
<td>1.1</td>
<td>1</td>
<td>1</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
</tr>
</tbody>
</table>

^1^Identified by Core Lab

^2^Subsequent endoleaks may have been of difference type than original

^3^No endoleaks after 12 months; follow-up after 24 months not available

####  

#### Table 10.4.2-11. First occurrence of endoleak^1^ for roll-in patients 

<table>
<colgroup>
<col style="width: 33%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 6%" />
<col style="width: 7%" />
<col style="width: 7%" />
</colgroup>
<thead>
<tr class="header">
<th rowspan="2"><h5 id="item-11">Item</h5></th>
<th colspan="3"><p><strong>To One Month Exam</strong></p>
<p><strong>N=36</strong></p></th>
<th colspan="3"><p><strong>Six Month Exam</strong></p>
<p><strong>N=35</strong></p></th>
<th colspan="3"><p><strong>Twelve Month Exam</strong><sup>3</sup></p>
<p><strong>N=29</strong></p></th>
</tr>
<tr class="odd">
<th>%</th>
<th>Endo-leak<sup>1</sup></th>
<th>Leak-free there-after<sup>2</sup></th>
<th>%</th>
<th>Endo-leak<sup>1</sup></th>
<th>Leak-free there-after<sup>2</sup></th>
<th>%</th>
<th>Endo-leak<sup>1</sup></th>
<th>Leak-free there-after<sup>2</sup></th>
</tr>
</thead>
<tbody>
<tr class="odd">
<td>Endoleaks</td>
<td>11</td>
<td>4</td>
<td>2</td>
<td>2.9</td>
<td>1</td>
<td>0</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
</tr>
<tr class="even">
<td>Proximal Type I</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
</tr>
<tr class="odd">
<td>Distal Type I</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
</tr>
<tr class="even">
<td>Type II</td>
<td>5.6</td>
<td>2</td>
<td>1</td>
<td>2.9</td>
<td>1</td>
<td>0</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
</tr>
<tr class="odd">
<td>Type III</td>
<td>2.8</td>
<td>1</td>
<td>0</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
</tr>
<tr class="even">
<td>Type IV</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
</tr>
<tr class="odd">
<td>Multiple</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
</tr>
<tr class="even">
<td>Unknown</td>
<td>2.8</td>
<td>1</td>
<td>1</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
<td>0.0</td>
<td>0</td>
<td>0</td>
</tr>
</tbody>
</table>

^1^Identified by Core Lab

^2^Subsequent endoleaks may have been of difference type than original

^3^No endoleaks after 12 months; follow-up after 24 months not available

Tables 10.4.2-12 -- 10.4.2-14 present the change in aneurysm diameter
for the endovascular patients, as identified by the Core Lab. Table
10.4.2-12 presents maximum aneurysm diameter change by interval. Tables
10.4.2-13 and 10.4.2-14 present aneurysm change and endoleak at 12 and
24 months respectively.

> **Table 10.4.2-12.** Change in Maximum Aneurysm Diameter by Interval

+--------------------------+-------------+-------------+-------------+
| **Item**                 | **Zenith**  | **Zenith**  | **Zenith**  |
|                          |             |             |             |
|                          | **Standard  | **High      | **Roll-In** |
|                          | Risk**      | Risk**      |             |
+--------------------------+-------------+-------------+-------------+
| From pre-discharge       |             |             |             |
+--------------------------+-------------+-------------+-------------+
| 30-day Decrease \>5 mm   | 1.7%        | 4.8% (4/84) | 0.0% (0/40) |
|                          | (3/180)     |             |             |
+--------------------------+-------------+-------------+-------------+
| Unchanged                | 97%         | 94% (79/84) | 97.5%       |
|                          | (174/180)   |             | (39/40)     |
+--------------------------+-------------+-------------+-------------+
| Increase \>5 mm          | 1.7%        | 1.2% (1/84) | 2.5% (1/40) |
|                          | (3/180)     |             |             |
+--------------------------+-------------+-------------+-------------+
| Change from              |             |             |             |
| pre-discharge            |             |             |             |
+--------------------------+-------------+-------------+-------------+
| 6-month Decrease \>5 mm  | 36%         | 41% (30/73) | 49% (18/37) |
|                          | (63/173)    |             |             |
+--------------------------+-------------+-------------+-------------+
| Unchanged                | 62%         | 59% (43/73) | 51% (19/37) |
|                          | (108/173)   |             |             |
+--------------------------+-------------+-------------+-------------+
| Increase \>5 mm          | 1.2%        | 0.0% (0/73) | 0.0% (0/37) |
|                          | (2/173)     |             |             |
+--------------------------+-------------+-------------+-------------+
| Change from              |             |             |             |
| pre-discharge            |             |             |             |
+--------------------------+-------------+-------------+-------------+
| 12-month Decrease \>5 mm | 68%         | 63% (39/62) | 67% (20/30) |
|                          | (102/151)   |             |             |
+--------------------------+-------------+-------------+-------------+
| Unchanged                | 31%         | 35% (22/62) | 33% (10/30) |
|                          | (47/151)    |             |             |
+--------------------------+-------------+-------------+-------------+
| Increase \>5 mm          | 1.3%        | 1.6% (1/62) | 0.0% (0/30) |
|                          | (2/151)     |             |             |
+--------------------------+-------------+-------------+-------------+
| Change from              |             |             |             |
| pre-discharge            |             |             |             |
+--------------------------+-------------+-------------+-------------+
| 24-month Decrease \>5 mm | 78% (74/94) | 75% (27/36) | 71% (17/24) |
+--------------------------+-------------+-------------+-------------+
| Unchanged                | 19% (18/94) | 25% (9/36)  | 25% (6/24)  |
+--------------------------+-------------+-------------+-------------+
| Increase \>5 mm          | 2.1% (2/94) | 0.0% (0/36) | 4.2% (1/24) |
+--------------------------+-------------+-------------+-------------+

Only includes subjects with interpretable films and measurements of
aneurysm change

**Table 10.4.2-13. Change in Aneurysm Size and Endoleak at 12 Months**

<table>
<colgroup>
<col style="width: 38%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 6%" />
</colgroup>
<tbody>
<tr class="odd">
<td><strong>Item</strong></td>
<td colspan="3"><p><strong>Zenith</strong></p>
<p><strong>Standard Risk</strong></p>
<p>N=140</p></td>
<td colspan="3"><p><strong>Zenith</strong></p>
<p><strong>High Risk</strong></p>
<p>N=53</p></td>
<td colspan="3"><p><strong>Zenith</strong></p>
<p><strong>Roll-In</strong></p>
<p>N=27</p></td>
</tr>
<tr class="even">
<td rowspan="2"><p>Aneurysm size change</p>
<p>from pre-discharge to 12 months</p></td>
<td></td>
<td colspan="2">Endoleak</td>
<td></td>
<td colspan="2">Endoleak</td>
<td></td>
<td colspan="2">Endoleak</td>
</tr>
<tr class="odd">
<td>N</td>
<td>N</td>
<td>%</td>
<td>N</td>
<td>N</td>
<td>%</td>
<td>N</td>
<td>N</td>
<td>%</td>
</tr>
<tr class="even">
<td><p id="decrease-5-mm" class="heading">Decrease &gt;5 mm</p></td>
<td>96</td>
<td>3</td>
<td>3</td>
<td>35</td>
<td>3</td>
<td>9</td>
<td>20</td>
<td>0</td>
<td>0</td>
</tr>
<tr class="odd">
<td>Unchanged</td>
<td>42</td>
<td>8</td>
<td>19</td>
<td>17</td>
<td>2</td>
<td>12</td>
<td>7</td>
<td>1</td>
<td>14</td>
</tr>
<tr class="even">
<td>Increase &gt;5 mm</td>
<td>2</td>
<td>0</td>
<td>0</td>
<td>1</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
</tr>
</tbody>
</table>

**Table 10.4.2-14. Change in Aneurysm Size and Endoleak at 24 Months**

<table>
<colgroup>
<col style="width: 38%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 6%" />
</colgroup>
<tbody>
<tr class="odd">
<td><strong>Item</strong></td>
<td colspan="3"><p><strong>Zenith</strong></p>
<p><strong>Standard Risk</strong></p>
<p>N=90</p></td>
<td colspan="3"><p><strong>Zenith</strong></p>
<p><strong>High Risk</strong></p>
<p>N=31</p></td>
<td colspan="3"><p><strong>Zenith</strong></p>
<p><strong>Roll-In</strong></p>
<p>N=21</p></td>
</tr>
<tr class="even">
<td rowspan="2"><p>Aneurysm size change</p>
<p>from pre-discharge to 24 months</p></td>
<td></td>
<td colspan="2">Endoleak</td>
<td></td>
<td colspan="2">Endoleak</td>
<td></td>
<td colspan="2">Endoleak</td>
</tr>
<tr class="odd">
<td>N</td>
<td>N</td>
<td>%</td>
<td>N</td>
<td>N</td>
<td>%</td>
<td>N</td>
<td>N</td>
<td>%</td>
</tr>
<tr class="even">
<td><p id="decrease-5-mm-1" class="heading">Decrease &gt;5 mm</p></td>
<td>71</td>
<td>3</td>
<td>4</td>
<td>24</td>
<td>1</td>
<td>4</td>
<td>16</td>
<td>0</td>
<td>0</td>
</tr>
<tr class="odd">
<td>Unchanged</td>
<td>18</td>
<td>1</td>
<td>6</td>
<td>7</td>
<td>3</td>
<td>43</td>
<td>5</td>
<td>0</td>
<td>0</td>
</tr>
<tr class="even">
<td>Increase &gt;5 mm</td>
<td>1</td>
<td>1</td>
<td>100</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
</tr>
</tbody>
</table>

######## AAA-related secondary interventions within the first year were performed in 11% of the Zenith Standard Risk, 13% Zenith High Risk and 5.8% Zenith Roll-in subjects as shown in Table 10.4.2-15. Greater than 50% of the secondary interventions involved catheterization to treat an endoleak. AAA-related secondary interventions within the second year were performed in 4.2% of the Zenith Standard Risk, 2.2% Zenith High Risk and 2.3% Zenith Roll-in subjects as shown in Table 10.4.2-16.

**Table 10.4.2-15. Secondary Interventions (to 12 Months)**

+------------------------------+------+-----+-------+-----+-----+-----+
| > **Intervention**           | ##   |     | ### Z |     | #   |     |
|                              | # Ze |     | enith |     | ##  |     |
|                              | nith |     |       |     | Zen |     |
|                              |      |     | *     |     | ith |     |
|                              | **   |     | *High |     |     |     |
|                              | Stan |     | R     |     | **  |     |
|                              | dard |     | isk** |     | Rol |     |
|                              | Ri   |     |       |     | l-I |     |
|                              | sk** |     | N=100 |     | n** |     |
|                              |      |     |       |     |     |     |
|                              | N    |     |       |     | N   |     |
|                              | =199 |     |       |     | =52 |     |
+------------------------------+------+-----+-------+-----+-----+-----+
|                              | N    | \%  | N     | \%  | N   | \%  |
+------------------------------+------+-----+-------+-----+-----+-----+
| > Conversion to Open Repair  | 2    | 1   | 1     | 1   | 0   | 0   |
+------------------------------+------+-----+-------+-----+-----+-----+
| > Subjects with              | 21   | 11  | 13    | 13  | 3   | 5.8 |
| > [\>]{.underline}1          |      |     |       |     |     |     |
| > Intervention               |      |     |       |     |     |     |
+------------------------------+------+-----+-------+-----+-----+-----+
| > Treat an Endoleak          | 5    | 2.5 | 3     | 3   | 1   | 2   |
|                              |      |     |       |     |     |     |
| Embolization                 |      |     |       |     |     |     |
+------------------------------+------+-----+-------+-----+-----+-----+
| > Ancillary Component        | 6    | 3   | 4     | 4   | 1   | 2   |
+------------------------------+------+-----+-------+-----+-----+-----+
| > Stent                      | 1    | 0.5 | 0     | 0   | 0   | 0   |
+------------------------------+------+-----+-------+-----+-----+-----+
| > Angioplasty                | 0    | 0   | 1     | 1   | 0   | 0   |
+------------------------------+------+-----+-------+-----+-----+-----+
| > Treat an Aneurysm Increase | 0    | 0   | 0     | 0   | 0   | 0   |
| >                            |      |     |       |     |     |     |
| > Embolization               |      |     |       |     |     |     |
+------------------------------+------+-----+-------+-----+-----+-----+
| > Treat a Limb Occlusion     | 1    | 0.5 | 3     | 3   | 1   | 2   |
+------------------------------+------+-----+-------+-----+-----+-----+
| > Treat a Limb Stenosis      | 1    | 0.5 | 0     | 0   | 0   | 0   |
+------------------------------+------+-----+-------+-----+-----+-----+
| > Treat a Renal Artery       | 5    | 2.5 | 0     | 0   | 0   | 0   |
+------------------------------+------+-----+-------+-----+-----+-----+
| > Treat Infra-inguinal       | 1    | 0.5 | 1     | 1   | 0   | 0   |
| > Ischemia                   |      |     |       |     |     |     |
+------------------------------+------+-----+-------+-----+-----+-----+
| > Treat Multiple Events      | 1    | 0.5 | 1     | 1   | 0   | 0   |
+------------------------------+------+-----+-------+-----+-----+-----+

Table 10.4.2-16. Secondary Interventions (\>12 to 24 Months)

+------------------------------+-------+------+-----+-----+-----+-----+
| > **Intervention**           | ### Z |      | #   |     | #   |     |
|                              | enith |      | ##  |     | ##  |     |
|                              |       |      | Zen |     | Zen |     |
|                              | **Sta |      | ith |     | ith |     |
|                              | ndard |      |     |     |     |     |
|                              | R     |      | **H |     | **  |     |
|                              | isk** |      | igh |     | Rol |     |
|                              |       |      | Ris |     | l-I |     |
|                              | N=190 |      | k** |     | n** |     |
|                              |       |      |     |     |     |     |
|                              |       |      | N   |     | N   |     |
|                              |       |      | =90 |     | =44 |     |
+------------------------------+-------+------+-----+-----+-----+-----+
|                              | N     | \%   | N   | \%  | N   | \%  |
+------------------------------+-------+------+-----+-----+-----+-----+
| > Conversion to Open Repair  | 1     | >    | 1   | 1.1 | 0   | 0.0 |
|                              |       |  0.5 |     |     |     |     |
+------------------------------+-------+------+-----+-----+-----+-----+
| > Subjects with              | 8     | >    | 2   | 2.2 | 1   | 2.3 |
| > [\>]{.underline}1          |       |  4.2 |     |     |     |     |
| > Intervention               |       |      |     |     |     |     |
+------------------------------+-------+------+-----+-----+-----+-----+
| > Treat an Endoleak          | 3^1^  | 1.6  | 0   | 0   | 1   | 2.3 |
|                              |       |      |     |     | ^2^ |     |
| Embolization                 |       |      |     |     |     |     |
+------------------------------+-------+------+-----+-----+-----+-----+
| > Ancillary Component        | 1     | 0.5  | 0   | 0   | 0   | 0   |
+------------------------------+-------+------+-----+-----+-----+-----+
| Stent                        | 0     | 0    | 1   | 1.1 | 0   | 0   |
+------------------------------+-------+------+-----+-----+-----+-----+
| > Angioplasty                | 0     | 0    | 0   | 0   | 0   | 0   |
+------------------------------+-------+------+-----+-----+-----+-----+
| > Treat an Aneurysm Increase | 1     | 0.5  | 0   | 0   | 1   | 2.3 |
| >                            |       |      |     |     | ^2^ |     |
| > Embolization               |       |      |     |     |     |     |
+------------------------------+-------+------+-----+-----+-----+-----+
| > Treat a Limb Occlusion     | 1     | 0.5  | 0   | 0   | 0   | 0   |
+------------------------------+-------+------+-----+-----+-----+-----+
| > Treat a Limb Stenosis      | 0     | 0    | 0   | 0   | 0   | 0   |
+------------------------------+-------+------+-----+-----+-----+-----+
| > Treat a Renal Artery       | 0     | 0    | 1   | 1.1 | 0   | 0   |
+------------------------------+-------+------+-----+-----+-----+-----+
| > Treat Infra-inguinal       | 1     | 0.5  | 0   | 0   | 0   | 0   |
| > ischemia                   |       |      |     |     |     |     |
+------------------------------+-------+------+-----+-----+-----+-----+
| > Treat Multiple Events      | 1     | 0.5  | 0   | 0   | 0   | 0   |
+------------------------------+-------+------+-----+-----+-----+-----+

^1^ Patient also received ancillary component

^2^ Patient underwent intervention to treat aneurysm increase and
endoleak

**10.4.3. Secondary Outcome Measures**

As described in Table 10.4.3-1, treatment of AAA with the Zenith^®^ AAA
Endovascular Graft with the H&L-B One-Shot Introduction System compared
to the surgical control group demonstrated significant benefits in
recovery and quality of life measures. Secondary measures included
anesthesia time, procedure time, blood bank products received and blood
loss. In addition, clinical utility was assessed through a number of
clinical measures obtained before hospital discharge, including days in
the ICU, days to discharge, days to oral fluids, days to normal diet,
days to normal bowel function, days to ambulation, hours of intubation,
and maximum core body temperature.

**Table 10.4.3-1. Secondary Outcomes by Treatment Group**

+---------------+------------+------------+----+----------+----------+
| **Item**      | **Zenith** | **         | *  | **       | **       |
|               |            | Surgical** | ** | Zenith** | Zenith** |
|               | **Standard |            | P* |          |          |
|               | Risk**     | **Standard | v  | **High   | **R      |
|               |            | Risk**     | al | Risk**   | oll-in** |
|               |            |            | ue |          |          |
|               |            |            | ** |          |          |
+---------------+------------+------------+----+----------+----------+
| Anesthesia    | 221.6 ±    | 304.5 ±    | \< | 218.9 ±  | 213.9 ±  |
| time (min)    | 67.3       | 102.7      | .0 | 69.6     | 57.7     |
|               |            |            | 01 |          |          |
+---------------+------------+------------+----+----------+----------+
| Procedure     | 153.2 ±    | 238.7 ±    | \< | 153.5 ±  | 155.9 ±  |
| time (min)    | 56.3       | 92.2       | .0 | 58.6     | 43.2     |
|               |            |            | 01 |          |          |
+---------------+------------+------------+----+----------+----------+
| Blood bank    | 5.0%       | 84%        | \< | 12%      | 3.8%     |
|               | (10/200)   | (67/80)    | .0 | (12/100) | (2/52)   |
| products      |            |            | 01 |          |          |
| received      |            |            |    |          |          |
+---------------+------------+------------+----+----------+----------+
| Blood loss    | 299 ± 324  | 1676 ±     | \< | 356 ±    | 265 ±    |
| (cc)          |            | 1676       | .0 | 514      | 226      |
|               |            |            | 01 |          |          |
+---------------+------------+------------+----+----------+----------+
| Days in ICU   | 0.4 ± 0.9  | 3.4 ± 4.6  | \< | 0.5 ±    | 0.5 ±    |
|               |            |            | .0 | 1.2      | 0.9      |
|               |            |            | 01 |          |          |
+---------------+------------+------------+----+----------+----------+
| Days to       | 2.6 ± 1.7  | 8.8 ± 5.6  | \< | 3.0 ±    | 2.7 ±    |
| discharge     |            |            | .0 | 2.8      | 1.5      |
|               |            |            | 01 |          |          |
+---------------+------------+------------+----+----------+----------+
| Days to oral  | 0.5 ± 0.8  | 3.9 ± 2.5  | \< | 0.5 ±    | 0.7 ±    |
| fluids        |            |            | .0 | 0.6      | 0.5      |
|               |            |            | 01 |          |          |
+---------------+------------+------------+----+----------+----------+
| Days to       | 1.3 ± 1.2  | 6.6 ± 4.9  | \< | 1.3 ±    | 1.1 ±    |
| normal diet   |            |            | .0 | 0.8      | 0.7      |
|               |            |            | 01 |          |          |
+---------------+------------+------------+----+----------+----------+
| Days to       | 2.6 ± 1.4  | 4.2 ± 2.1  | \< | 2.6 ±    | 2.0 ±    |
| normal bowel  |            |            | .0 | 1.5      | 1.2      |
| function      |            |            | 01 |          |          |
+---------------+------------+------------+----+----------+----------+
| Days to       | 1.2 ± 0.7  | 3.5 ± 3.4  | \< | 1.2 ±    | 1.2 ±    |
| ambulation    |            |            | .0 | 0.7      | 0.6      |
|               |            |            | 01 |          |          |
+---------------+------------+------------+----+----------+----------+
| Hours of      | 1.9 ± 2.2  | 11.7 ±     | \< | 1.2 ±    | 2.6 ±    |
| intubation    |            | 13.6       | .0 | 1.7      | 4.6      |
|               |            |            | 01 |          |          |
+---------------+------------+------------+----+----------+----------+
| Maximum       | 101.1 ±    | 100.7 ±    | .  | 100.8 ±  | 101.0 ±  |
| temperature   | 1.3        | 1.2        | 06 | 1.1      | 1.2      |
+---------------+------------+------------+----+----------+----------+

**10.4.4. Evaluation of Gender Bias**

The occurrence of AAA disease is known to be higher in men than women
and the ratio of men to women enrolled in this study reflects the
general population. In order to more carefully evaluate possible gender
based differences in outcomes of treatment with the Zenith^®^ AAA
Endovascular Graft with the H&L-B One-Shot Introduction System, Cook
requested and was granted approval to establish a registry for the
treatment of AAA disease in women with standard medical risk. Measures
of survival, 30-day morbidity, conversion and death using these combined
data sets are presented in Table 10.4.4-1 through Table 10.4.4-3.

Zenith^^ AAA Endovascular Graft subjects exhibited no significant
differences between males and females for survival and 30-day morbidity
(31 measures). No gender based differences were identified in
AAA-related mortality after treatment with the Zenith^®^ AAA
Endovascular Graft with the H&L-B One-Shot Introduction System.

## Table 10.4.4-1. Kaplan-Meier AAA-related survival rates by gender: All Zenith pivotal + female, and surgical

+------------------+---------+--------+--------+------+------+------+
| **Item**         | **All   |        |        | **   |      |      |
|                  | Zenith  |        |        | Surg |      |      |
|                  | Pi      |        |        | ical |      |      |
|                  | votal + |        |        | Stan |      |      |
|                  | Female  |        |        | dard |      |      |
|                  | Reg     |        |        | Ri   |      |      |
|                  | istry** |        |        | sk** |      |      |
+------------------+---------+--------+--------+------+------+------+
|                  | *       | **Fe   | *      | **Ma | **   | ***  |
|                  | *Male** | male** | **P*** | le** | Fema | P*** |
|                  |         |        |        |      | le** |      |
|                  |         |        | **v    |      |      | *    |
|                  |         |        | alue** |      |      | *Val |
|                  |         |        |        |      |      | ue** |
+------------------+---------+--------+--------+------+------+------+
| Survival rate at | 98.8%   | 100%   | .49    | 9    | 100% | .61  |
| 30 days          |         |        |        | 7.2% |      |      |
+------------------+---------+--------+--------+------+------+------+
| Survival rate at | 97.5%   | 100%   | .35    | 9    | 100% | .26  |
| 365 days         |         |        |        | 7.0% |      |      |
+------------------+---------+--------+--------+------+------+------+

## Table 10.4.4-2. 30-day morbidity (31 measures) by gender: All Zenith pivotal + female, and surgical 

+-------------+---------+---------+------+---------+---------+------+
| ## Item     | **All   |         |      | **S     |         |      |
|  {#item-12} | Zenith  |         |      | urgical |         |      |
|             | Pi      |         |      | S       |         |      |
|             | votal + |         |      | tandard |         |      |
|             | Female  |         |      | Risk**  |         |      |
|             | Reg     |         |      |         |         |      |
|             | istry** |         |      |         |         |      |
+-------------+---------+---------+------+---------+---------+------+
|             | *       | **F     | *    | *       | **F     | *    |
|             | *Male** | emale** | **P* | *Male** | emale** | **P* |
|             |         |         | val  |         |         | val  |
|             | (N=326) | (N=41)  | ue** | (N=71)  | (N=9)   | ue** |
+-------------+---------+---------+------+---------+---------+------+
| 30-day      | 0.34    | 0.39    | .66  | 0.86    | 1.44    | .28  |
| morbidity   | [       | [       |      | [       | [       |      |
|             | +]{.und | +]{.und |      | +]{.und | +]{.und |      |
|             | erline} | erline} |      | erline} | erline} |      |
|             | 0.73    | 0.63    |      | 1.46    | 2.00    |      |
+-------------+---------+---------+------+---------+---------+------+

## 

## Table 10.4.4-3. Conversion and death by gender: All Zenith pivotal + female, and surgical 

+---------------+----------+---------+------+---------+-------+------+
| ## It         | **All    |         |      | **Sur   |       |      |
| em {#item-13} | Zenith   |         |      | gical** |       |      |
|               | Pivotal  |         |      |         |       |      |
|               | (i       |         |      | **S     |       |      |
|               | ncluding |         |      | tandard |       |      |
|               | high     |         |      | Risk**  |       |      |
|               | risk     |         |      |         |       |      |
|               | pat      |         |      |         |       |      |
|               | ients) + |         |      |         |       |      |
|               | Female   |         |      |         |       |      |
|               | Re       |         |      |         |       |      |
|               | gistry** |         |      |         |       |      |
+---------------+----------+---------+------+---------+-------+------+
|               | **Male** | **F     | *    | *       | **Fem | *    |
|               |          | emale** | **P* | *Male** | ale** | **P* |
|               |          |         | val  |         |       | val  |
|               |          |         | ue** |         |       | ue** |
+---------------+----------+---------+------+---------+-------+------+
| Conversion    | 0.31%    | 5.0%    | .03  | n/a     | n/a   | n/a  |
| (0-365 days)  | (1/324)  | (2/40)  |      |         |       |      |
+---------------+----------+---------+------+---------+-------+------+
| All death     | 1.2%     | 0.0%    | \    | 2.8%    | 0.0%  | \    |
| (0-30 days)   | (4/326)  | (0      | >.99 | (2/71)  | (0/9) | >.99 |
|               |          | /40)^1^ |      |         |       |      |
+---------------+----------+---------+------+---------+-------+------+
| All death     | 6.8%     | 2.6%    | .49  | 3.0%    | 11%   | .32  |
| (0-365 days)  | (22/323) | (1/38)  |      | (2/67)  | (1/9) |      |
+---------------+----------+---------+------+---------+-------+------+
| AAA-related   | 2.5%     | 0.0%    | \    | 3.0%    | 11%   | .32  |
|               | (8/323)  | (0/38)  | >.99 | (2/67)  | (1/9) |      |
+---------------+----------+---------+------+---------+-------+------+
| Proc          | 2.2%     | 0.0%    | \-   | 3.0%    | 11%   | .32  |
| edure-related | (7/323)  | (0/38)  |      | (2/67)  | (1/9) |      |
+---------------+----------+---------+------+---------+-------+------+
| Tech          | 0.62%    | 0.0%    | \-   | 3.0%    | 11%   | .32  |
| nique-related | (2/323)  | (0/38)  |      | (2/67)  | (1/9) |      |
+---------------+----------+---------+------+---------+-------+------+
| D             | 0.0%     | 0.0%    | \-   | 0.0%    | 0.0%  | \-   |
| evice-related | (0       | (0/38)  |      | (0/67)  | (0/9) |      |
|               | /323)^2^ |         |      |         |       |      |
+---------------+----------+---------+------+---------+-------+------+

^1^One patient did not receive a device

^2^One high risk patient death was not device related but information
was insufficient to rule out device involvement.

**11. Conclusions Drawn from Studies**

The Zenith^^ AAA Endovascular Graft with the H&L-B One-Shot
Introduction System has undergone pre-clinical testing and clinical
evaluation in a prospective, multicenter U.S. trial. Study results met
the five study hypotheses of a reduced 30-day morbidity, equivalent
30-day and 12-month survival rates, equivalent 12-month treatment
success, and improved clinical utility for Zenith patients as compared
to surgical controls. The additional clinical benefits associated with
the Zenith^^ AAA Endovascular Graft with the H&L-B One-Shot
Introduction System compared to open surgical repair include reducing
the duration of intubation, reducing the number of days spent in the
hospital, reducing the number of days spent in the ICU, reducing the
number of days to the resumption of oral fluids, diet, and normal bowel
functions, reducing the number of days to ambulation, reducing
anesthesia time, reducing procedural time, reducing procedural blood
loss and the need for blood products. Most aneurysms (68%) had decreased
in size or remained stable (31%) at 12 months. Very low incidence of
aneurysm rupture and conversion to open repair were observed. Adequate
device integrity was also demonstrated, although isolated observations
illustrate the importance of periodic imaging follow-up.

**12. Panel Recommendation**

The Zenith^®^ AAA Endovascular Graft with the H&L-B One-Shot
Introduction System was presented to the Circulatory System Device Panel
on April 10, 2003. The Panel recommended approving the device with
conditions. The Panel's conditions included revisions to the intended
use of the device, removing references to isolated iliac aneurysm from
the indications for use, stressing the importance in the labeling of
lifelong clinical follow-up of patients following endograft placement,
and a post approval study as outlined in the PMA for follow-up of
patients in the pivotal study for 5 years. The Panel also recommended
modifications to the device labeling.

**13. FDA Decision**

FDA reviewed portions of the premarket application approval (PMA)
application under the modular PMA process (M010038). All of the modules
were incorporated into the review of the PMA (P020018).

FDA concurred with the Circulatory System Device Panel recommendations
of April 10, 2003. To address these conditions, Cook Incorporated agreed
to conduct a post approval study in order to gather 5-year follow-up
data on patients enrolled in the pivotal study and to revise the
labeling to address the concerns raised by the Panel, which was reviewed
by FDA and found acceptable.

The sponsor also agreed to provide a clinical update to physicians
annually on the performance of the device due to the number of problems
which historically have occurred with these types of device. This
condition is consistent with conditions of approval issued by FDA for
other marketed endovascular graft devices. During December 3-10, 2002,
the sponsor's manufacturing facilities were inspected and found to be in
compliance with the Quality System Regulation (21 CFR 820).

FDA issued an approval order for P020018 on: May 23, 2003

**14. Approval Specifications**

Directions for Use: See labeling

Hazards to Health from Use of the Device: See Indications,
Contraindications, Warnings, Precautions, and Adverse Events in the
Labeling

Post-approval Requirements, Restrictions: See approval order