GORE EXCLUDER ILIAC BRANCH ENDOPROSTHESIS

P020004S123 · W. L. Gore & Associates, Inc. · MIH · Feb 29, 2016 · Cardiovascular

Device Facts

• Record ID: P020004S123
• Device Name: GORE EXCLUDER ILIAC BRANCH ENDOPROSTHESIS
• Applicant: W. L. Gore & Associates, Inc.
• Product Code: MIH · Cardiovascular
• Decision Date: Feb 29, 2016
• Decision: APPR
• Device Class: Class 3
• Attributes: Therapeutic, Real-World Evidence

Real-World Evidence

Submission	Device	Sponsor	RWD Sources	RWE Use Summary	Key Tags
P020004S123 · Feb 29, 2016	GORE EXCLUDER ILIAC BRANCH ENDOPROSTHESIS	W. L. Gore & Associates, Inc.	Historical AAA endovascular clinical studies; Scientific publications; GORE registry data (GREAT and ICEBERG)	Retrospective data from historical clinical studies and literature were used to establish performance goals for safety and effectiveness endpoints in the pivotal clinical study. Ongoing registries are used for post-approval surveillance of bilateral device placement.	Performance goals; Meta-analysis; Historical controls; Registry data

Clinical Evidence

Study Design	Population	Comparator	Key Endpoints
Performance Goal Meta-Analysis; Random effects meta-analysis of historical data; Study Period: Historical	Subjects with common iliac artery aneurysms (CIAA) or aorto-iliac aneurysms (AIA) from historical studies	Not applicable for this study	Freedom from safety endpoint events; freedom from effectiveness endpoint events; freedom from buttock claudication

Indications for Use

The GORE® EXCLUDER® Iliac Branch Endoprosthesis (IBE Device) is indicated for use with the GORE® EXCLUDER® AAA Endoprosthesis to isolate the common iliac artery from systemic blood flow and preserve blood flow in the external iliac and internal iliac arteries in patients with a common iliac or aortoiliac aneurysm, who have appropriate anatomy, including: Adequate iliac / femoral access; Minimum common iliac diameter of 17 mm at the proximal implantation zone of the IBE; External iliac artery treatment diameter range of 6.5-25 mm and seal zone length of at least 10 mm; Internal iliac artery treatment diameter range of 6.5-13.5 mm and seal zone length of at least 10 mm; Adequate length from the lowest major renal artery to the internal iliac artery to accommodate the total endoprosthesis length, calculated by adding the minimum lengths of required components, taking into account appropriate overlaps between components.

Device Story

Endovascular graft system for common iliac/aortoiliac aneurysm repair; preserves internal iliac artery flow. System comprises Iliac Branch Component (IBC) and Internal Iliac Component (IIC), used with previously approved GORE® EXCLUDER® AAA components (Trunk-Ipsilateral Leg, Contralateral Leg, Extenders). Physician deploys IBC into common iliac artery; cannulates internal iliac gate; deploys IIC into internal iliac artery; bridges to aortic trunk via Contralateral Leg component. Performed in OR/cath lab by vascular specialists. Provides aneurysm exclusion without sacrificing internal iliac flow, reducing risk of buttock claudication, sexual dysfunction, and ischemic complications associated with traditional internal iliac artery occlusion. Modular design allows unilateral or bilateral treatment.

Clinical Evidence

Prospective, non-randomized, multi-center, single-arm study (IBE 12-04) of 63 subjects. Primary safety endpoint: 0% event rate (death, stroke, MI, etc.) at 30 days. Primary effectiveness endpoint: 95.1% freedom from reintervention/loss of patency at 6 months. Secondary endpoint: 100% freedom from new-onset buttock claudication on IBE side at 6 months. Technical success: 95.2%. Core Lab imaging confirmed no ruptures, migrations, or wire fractures.

Technological Characteristics

Modular endoprosthesis system. Materials: ePTFE, FEP, nitinol (nickel-titanium alloy), gold. Sensing/actuation: Delivery catheter with removable guidewire tube (RGT) for pre-cannulation; two-stage deployment via nested knobs. Connectivity: None. Sterilization: Ethylene oxide (EO). Software: None.

Indications for Use

Indicated for patients with common iliac or aortoiliac aneurysms requiring isolation of the common iliac artery while preserving flow to the external and internal iliac arteries. Contraindicated in patients with known sensitivities to device materials (ePTFE, FEP, nitinol, gold) or systemic infection.

Predicate Devices

• GORE® EXCLUDER® AAA Endoprosthesis (P020004)

Submission Summary (Full Text)

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# SUMMARY OF SAFETY AND EFFECTIVENESS DATA

# I. GENERAL INFORMATION

| Device Generic Name: | Endovascular Graft |
| --- | --- |
| Device Trade Name: | GORE® EXCLUDER® Iliac Branch Endoprosthesis |
| Device Procode: | MIH |
| Applicant's Name and Address: | W. L. Gore & Associates, Inc. (Gore) 1505 N. Fourth St. Flagstaff, Arizona 86004 |
| Date(s) of Panel Recommendation: | None |
| Premarket Approval Application (PMA) Number: | P020004/S123 |
| Date of FDA Notice of Approval: | February 29, 2016 |

The original GORE® EXCLUDER® AAA Endoprosthesis PMA (P020004) was approved on November 6, 2002, and is intended to exclude the aneurysm from the blood circulation in patients diagnosed with infrarenal abdominal aortic aneurysm (AAA) disease and who have appropriate anatomy as described below:

- Adequate iliac/femoral access
- Infrarenal aortic neck treatment diameter range of 19-29 mm and a minimum aortic neck length of 15 mm
- Proximal aortic neck angulation ≤ 60°
- Iliac artery treatment diameter range of 8-18.5 mm and iliac distal vessel seal zone length of at least 10 mm.

The iliac artery treatment diameter range extends up to 25 mm with the use of the Contralateral Leg Endoprosthesis (described below) as a distal extension.

The SSED to support this indication is available on the CDRH website and is incorporated by reference here. The current supplement was submitted to obtain premarket approval for the GORE® EXCLUDER® Iliac Branch Endoprosthesis for use in conjunction with the GORE® EXCLUDER® AAA Endoprosthesis in the treatment of aortoiliac and common iliac artery aneurysms.

# II. INDICATIONS FOR USE

# Iliac Branch and Internal Iliac Components

The GORE® EXCLUDER® Iliac Branch Endoprosthesis (IBE Device) is indicated for use with the GORE® EXCLUDER® AAA Endoprosthesis to isolate the common iliac

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artery from systemic blood flow and preserve blood flow in the external iliac and internal iliac arteries in patients with a common iliac or aortoiliac aneurysm, who have appropriate anatomy, including:

- Adequate iliac / femoral access
- Minimum common iliac diameter of 17 mm at the proximal implantation zone of the IBE
- External iliac artery treatment diameter range of 6.5-25 mm and seal zone length of at least 10 mm
- Internal iliac artery treatment diameter range of 6.5-13.5 mm and seal zone length of at least 10 mm
- Adequate length from the lowest major renal artery to the internal iliac artery to accommodate the total endoprosthesis length, calculated by adding the minimum lengths of required components, taking into account appropriate overlaps between components

The IBE Device is intended for use with the following GORE® EXCLUDER® AAA Endoprosthesis Components:

### Trunk-Ipsilateral Leg Endoprosthesis Components

The Trunk-Ipsilateral Leg Endoprosthesis is intended to provide proximal seal and fixation for the endovascular repair of the aneurysm. For more information on the Trunk-Ipsilateral Leg Component indications for use and deployment, see the GORE® EXCLUDER® AAA Endoprosthesis Instructions For Use.

### Contralateral Leg Endoprosthesis Components

The Contralateral Leg Endoprosthesis is intended to bridge the GORE® EXCLUDER® Trunk-Ipsilateral Leg Component to the GORE® EXCLUDER® Iliac Branch Endoprosthesis. Additionally, the Contralateral Leg Endoprosthesis is intended to be used for distal extension of the Iliac Branch Component in the external iliac artery. The Iliac Branch Component can treat external iliac artery diameters up to 13.5 mm. This ability to extend the Iliac Branch Component distally with any Contralateral Leg Endoprosthesis expands the external iliac artery treatment range up to 25 mm. For more information on the Trunk-Ipsilateral Leg and Contralateral Leg Endoprosthesis Component indications for use and deployment, see the GORE® EXCLUDER® AAA Endoprosthesis Instructions For Use.

### Aortic Extender Endoprosthesis and Iliac Extender Endoprosthesis Components

The Aortic and Iliac Extender Endoprostheses can be used after deployment of the GORE® EXCLUDER® Iliac Branch and AAA Endoprostheses. These extensions are used when additional length and / or sealing for aneurysmal exclusion is desired. For more information on Aortic Extender and Iliac Extender indications for use and deployment, see the GORE® EXCLUDER® AAA Endoprosthesis Instructions For Use.

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### III. CONTRAINDICATIONS

The GORE® EXCLUDER® Iliac Branch Endoprosthesis is contraindicated in:

- Patients with known sensitivities or allergies to the device materials. All components of the GORE® EXCLUDER® Iliac Branch Endoprosthesis and the GORE® EXCLUDER® AAA Endoprosthesis contain ePTFE, FEP, nitinol (nickel-titanium alloy), and gold.
- Patients with a systemic infection who may be at increased risk of endovascular graft infection.

### IV. WARNINGS AND PRECAUTIONS

The warnings and precautions can be found in the GORE® EXCLUDER® Iliac Branch Endoprosthesis labeling.

### V. DEVICE DESCRIPTION

The GORE® EXCLUDER® Iliac Branch Endoprosthesis (IBE Device) is an extension of the GORE® EXCLUDER® product family. The previously approved GORE® EXCLUDER® AAA Endoprosthesis (EXCLUDER AAA Device) components that are used with the IBE Device include the following: Trunk-Ipsilateral Leg Endoprosthesis, Contralateral Leg Endoprosthesis, Aortic Extender Endoprosthesis, and Iliac Extender Endoprosthesis, and their respective delivery systems. The Trunk-Ipsilateral Leg is intended to provide proximal seal and fixation for the endovascular repair of the aneurysm. The Contralateral Leg Endoprosthesis is intended to bridge the Trunk-Ipsilateral Leg Endoprosthesis to the IBE Device. The Aortic and Iliac Extender Endoprostheses and the Contralateral Leg Endoprosthesis can be used after deployment of the IBE Device and Trunk-Ipsilateral Leg Endoprosthesis. These extensions are used when additional diameter, length and / or sealing for aneurysmal exclusion is desired.

The Iliac Branch Component can treat external iliac artery diameters from 6.5 to 13.5 mm. The ability to extend the Iliac Branch Component distally with any Contralateral Leg Endoprosthesis expands the external iliac artery treatment range up to 25 mm. Throughout the remainder of this document, the Trunk-Ipsilateral Leg, Contralateral Leg, and Aortic and Iliac Extender Endoprostheses are referred to as “previously approved EXCLUDER components”.

The IBE Device is intended to isolate the common iliac artery from systemic pressure and to preserve blood flow to the internal iliac artery (also known as the hypogastric artery) in patients with common iliac artery aneurysms (CIAA) and aorto-iliac aneurysms (AIA). In addition to the information that follows, reference the IBE Device Instructions for Use for additional details.

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The IBE Device consists of two modular components. The two components are the GORE® EXCLUDER® Iliac Branch Component (IBC) and the GORE® EXCLUDER® Internal Iliac Component (IIC). The IBE Device is designed to be used in conjunction with the previously approved EXCLUDER components (Figure 1) to treat patients with CIAA or AIA. The IBC is positioned within the CIA such that the internal iliac gate is at or above the internal iliac artery (also known as the hypogastric artery) ostium. The IBC is deployed to the internal iliac gate within the CIA, and the internal iliac artery is then cannulated through the internal iliac gate. The IIC is deployed into the internal iliac gate of the IBC and extends into and seals within the internal iliac artery. The remaining portion of the IBC is then deployed to extend into and provide seal within the external iliac artery. A Trunk-Ipsilateral Leg Endoprosthesis is then deployed in the aorta, and a Contralateral Leg Endoprosthesis is deployed within both the Trunk-Ipsilateral Leg Endoprosthesis contralateral gate and the proximal portion of the IBC, to seal and bridge the Trunk-Ipsilateral Leg Endoprosthesis and the IBE Device. This results in aneurysm exclusion with preservation of blood flow into the internal iliac artery.

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Figure 1: GORE® EXCLUDER® IBE System with a GORE® EXCLUDER®AAA Trunk-Ipsilateral Leg and Contralateral Leg Device

The IBE Device can be used either unilaterally or bilaterally. Bilateral deployment is utilized in the treatment of bilateral iliac aneurysms. Figure 2 below demonstrates bilateral use of the IBE Device.

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Figure 2: Bilateral Placement of the IBE Device. 1) GORE® EXCLUDER® Trunk-Ipsilateral Leg Endoprosthesis. 2) GORE® EXCLUDER® Contralateral Leg Endoprosthesis. 3) GORE® EXCLUDER® Iliac Branch Component. 4) GORE® EXCLUDER® Internal Iliac Component

### GORE® EXCLUDER® Iliac Branch Component

The IBC (Figure 3) is similar in design, materials, and method of construction to the currently marketed 23 mm diameter GORE® EXCLUDER® Trunk-Ipsilateral Leg Endoprosthesis. As with the EXCLUDER AAA Device, the endoprosthesis is crushed into an expanded polytetrafluoroethylene (ePTFE) / fluorinated ethylene propylene (FEP) sewn sleeve and loaded onto the delivery catheter. The IBC distal diameter will be available in nominal diameters of 10, 12, and 14.5 mm and will treat external iliac artery diameters of 6.5 mm-13.5 mm (3). Please note, when a Contralateral Leg component is used to extend treatment in the external iliac artery, the maximum treatable diameter increases to 25 mm. The main differences between the 23 mm EXCLUDER Trunk-Ipsilateral Leg Endoprosthesis and the IBC are 1) a shorter device and the addition of a smaller (10 mm) ipsilateral leg to better accommodate intended iliac anatomy, and 2) the removal of the anchor row and sealing cuff as proximal seal and fixation to native artery is not intended for this device.


Figure 3: GORE® EXCLUDER® Iliac Branch Component

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# GORE® EXCLUDER® Iliac Branch Component Delivery System

The IBC delivery system is similar in design, materials, and method of construction to the currently marketed EXCLUDER AAA Device Delivery Systems. Figure 4 shows the IBC delivery catheter, which features a removable guidewire tube (RGT) that provides pre-cannulation of the internal iliac gate of the device when cannulated with a second guidewire prior to insertion into the patient.


Figure 4: Iliac Branch Component Delivery System

1) Leading end of RGT, 2) Leading end of delivery catheter, 3) Removable guidewire tube (RGT), 4) Clear window for RGT, 5) White outer deployment knob, 6) Trailing end of delivery catheter, 7) Tuohy-Borst valve, 8) Guidewire lumen, 9) Flushing port, 10) Constrained endoprosthesis, 11) Gray inner deployment knob

The IBC is deployed in two stages by actuating two dedicated deployment lines (Figure 5A). The outer knob initiates the first deployment with an ePTFE deployment line. The inner knob will not be accessible until the outer knob is removed and will be subsequently used for the second deployment. Deployment of the first knob releases the constrained endoprosthesis to the level of the hypogastric gate (Figure 5B), and the external iliac leg remains constrained on the catheter. This delivery system provides physicians with the option to rotate and distally reposition the IBC after partial deployment in order to facilitate cannulation of the internal iliac artery. The endoprosthesis opens rapidly, with deployment initiating from the leading (aortic) end toward the trailing (iliac) end of the endoprosthesis. The sleeve remains in place between the exterior surface of the endoprosthesis and the vessel wall.

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Figure 5: Two-Stage Deployment Overview

(A) Two-stage deployment using nested knobs on the GORE® EXCLUDER® Iliac Branch Endoprosthesis delivery catheter (B) The first knob releases the Endoprosthesis to the level of the pre-cannulated gate while the distal portion remains constrained on the catheter

### GORE® EXCLUDER® Internal Iliac Component

The IIC is designed to preserve blood flow to the internal iliac artery while allowing exclusion of the CIAA or AIA (Figure 6). The IIC is identical in materials and method of construction to the currently marketed Iliac Extender Endoprosthesis, except the middle gold marker band has been removed. On the Iliac Extender Endoprosthesis, this middle marker band is present to note a 3 cm overlap with other EXCLUDER AAA Devices. As the overlap for the IIC with the IBC is 2.5 cm, the middle gold marker is not necessary. The IIC distal diameter will be available in nominal sizes of 10, 12, and 14.5 mm and will treat internal iliac diameters of 6.5 mm to 13.5 mm.


Figure 6: GORE® EXCLUDER® Internal Iliac Component

GORE® EXCLUDER® Internal Iliac Component Delivery System

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The IIC is loaded on the catheter to accommodate insertion into the internal iliac artery through the internal iliac gate of the IBC, and will be deployed from the trailing end (common iliac) to leading end (internal iliac) (Figure 7).


Figure 7: Internal Iliac Component Delivery System

1) Leading end, 2) Trailing end, 3) Deployment knob, 4) Tuohy-Borst valve, 5) Constrained endoprosthesis, 6) Flushing port, 7) Guidewire lumen

# Device Configurations

Currently, the IBE Device includes the configurations outlined in Tables 1 and 2 below.

Table 1: Iliac Branch Component Configurations

| Part Number | Proximal IBC Diameter^{1} (mm) | Distal IBC Diameter^{1} (mm) | Overall Device Length (cm) | Length to Internal Iliac Gate (cm) | Intended External Iliac Vessel Diameter^{1} (mm) | Recommended Introducer Sheath^{2} (Fr) | Recommended Angioplasty Balloon Size (Distal) (mm x mm) |
| --- | --- | --- | --- | --- | --- | --- | --- |
| CEB231010A | 23 | 10 | 10 | 5.5 | 6.5 – 9 | 16 | 10 x 40 |
| CEB231210A | 23 | 12 | 10 | 5.5 | 10 – 11 | 16 | 12 x 40 |
| CEB231410A | 23 | 14.5 | 10 | 5.5 | 12 – 13.5 | 16 | 14 x 40 |

$^{1}$Recommended endoprosthesis oversizing relative to the vessel diameter is approximately 7-35% in the external iliac vessel.

$^{2}$GORE® DrySeal Introducer Sheaths are recommended to accommodate multiple guidewires.

Note: All dimensions are nominal.

Table 2: Internal Iliac Component Configurations

| Part Number | IIC Distal Diameter^{1} (mm) | Overall Device Length^{1} (cm) | Intended Internal Iliac Vessel Diameter^{2} (mm) | Recommended Introducer Sheath^{3} (Fr x cm) | Recommended Balloon Size for IBC-IIC Overlap (mm) | Recommended Angioplasty Balloon Size (Distal) (mm x mm) |
| --- | --- | --- | --- | --- | --- | --- |
| HGB161007A | 10 | 7 | 6.5 – 9 | 12 x 45 | 14 x 40 | 10 x 40 |
| HGB161207A | 12 | 7 | 10 – 11 | 12 x 45 | 14 x 40 | 12 x 40 |
| HGB161407A | 14.5 | 7 | 12 – 13.5 | 12 x 45 | 14 x 40 | 14 x 40 |

$^{1}$7 cm long Internal Iliac Component provides a maximum extension of 4.5 cm when placed into the Iliac Branch Component.

$^{2}$Recommended endoprosthesis oversizing relative to the vessel diameter is approximately 7-35% in the internal iliac vessel.

$^{3}$Flexible Reinforced sheath.

Note: All dimensions are nominal.

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**Table 3** lists sizing information for EXCLUDER Device Contralateral Leg components when used in conjunction with the IBE Device.

**Table 3: Contralateral Leg Bridging Component Sizing Information**

| Common Iliac Artery Diameter at Proximal Landing Zone^{1} (mm) | Contralateral Leg Endoprosthesis Distal Diameter^{2} (mm) | Overall Device Lengths^{3} (cm) | Recommended Angioplasty Balloon Size for IBC Overlap (mm x mm) |
| --- | --- | --- | --- |
| 17 – 18 | 23 | 10, 12, 14 | 18 x 40 |
| 19 – 20 | 23 | 10, 12, 14 | 20 x 40 |
| 20 – 21.5 | 23 | 10, 12, 14 | 22 x 40 |
| >21.5 | 27 | 10, 12, 14 | 24 x 40 |

$^{1}$Treatment diameters reflect use of Contralateral Leg Endoprosthesis as bridging component to IBC only. For traditional use of Contralateral Leg Endoprosthesis to provide arterial apposition, see the GORE® EXCLUDER® AAA Endoprosthesis Instructions for Use.

$^{2}$Recommended endoprosthesis oversizing relative to the IBC vessel diameter is 7-26%.

$^{3}$Labeled Contralateral Leg length includes 3 cm overlap in contralateral gate of Trunk-Ipsilateral Leg Endoprosthesis, and 3 cm overlap in proximal end of Iliac Branch Endoprosthesis.

Note: All dimensions are nominal. Please see GORE® EXCLUDER® AAA Endoprosthesis Instructions for Use.

**Tables 4 and 5** display the total endovascular system lengths when treating contralateral and ipsilateral sides.

**Table 4: Total Length – Bridge Component via Contralateral gate of Trunk-Ipsilateral Leg Component**

| Trunk-Ipsilateral Leg Endoprosthesis Diameter (mm) | Total Iliac Branch Endoprosthesis side length (mm)^{1} |
| --- | --- |
| 23, 26, 28.5 | 165 |
| 31 | 175 |
| 35 | 185 |

$^{1}$The recommended minimum lengths are calculated by adding the minimum lengths of the fully deployed required devices, taking into account taper lengths and appropriate overlaps between the devices in a straight anatomy configuration.

**Table 5: Total Length – Bridge Component via Ipsilateral Leg of Trunk-Ipsilateral Leg Component**

| Trunk-Ipsilateral Leg Endoprosthesis Diameter (mm) | Total Iliac Branch Endoprosthesis side length (mm)^{1} | |
| --- | --- | --- |
| | 23mm Bridge Component | 27mm Bridge Component |
| 23, 26, 28.5 | 195 | 205 |
| 31 | 205 | 215 |
| 35 | 215 | 225 |

$^{1}$The recommended minimum lengths are calculated by adding the minimum lengths of the fully deployed required devices, taking into account taper lengths and appropriate overlaps between the devices in a straight anatomy configuration.

## **VI. ALTERNATIVE PRACTICES AND PROCEDURES**

There are several other alternatives for the correction of common iliac or aortoiliac aneurysms, including medical management, open surgical repair, or internal iliac artery coverage or occlusion. Each alternative has its own advantages and disadvantages. A

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patient should fully discuss these alternatives with his/her physician to select the method that best meets expectations and lifestyle.

### VII. MARKETING HISTORY

The IBE Device is currently available in member states of the European Union and Australia. There have been no market withdrawals related to safety or effectiveness involving the IBE Device.

### VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH

Below is a list of the potential adverse effects (e.g., complications) associated with the use of the device.

- allergic reaction and/or anaphylactoid response to x-ray contrast dye, anti-platelet therapy, device materials
- amputation
- anesthetic complications
- aneurysm enlargement
- aneurysm 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 (e.g., arrhythmia, myocardial infarction, congestive heart failure, hypotension or hypertension)
- claudication (e.g., buttock, lower limb)
- death
- dissection, perforation, or rupture of the aortic vessel & surrounding vasculature
- edema
- embolization (micro and macro) with transient or permanent ischemia
- endoleak
- endoprosthesis: improper component placement; incomplete component deployment; component migration; separation of graft material from stent; occlusion; infection; stent fracture; graft material failure, dilatation, erosion, puncture, perigraft flow
- fever and localized inflammation
- genitourinary (e.g., ischemia, erosion, fistula, incontinence, hematuria, infection)
- hepatic failure
- impotence
- infection (e.g., aneurysm, device or access sites)
- lymph fistula / complications

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- multi-system organ failure
- neurologic damage, local or systemic (e.g., stroke, paraplegia, paraparesis)
- occlusion of device or native vessel
- post-implant syndrome
- pulmonary complications (e.g., pneumonia, respiratory failure)
- radiation injury, late malignancy
- renal (e.g., artery occlusion, contrast toxicity, insufficiency, failure)
- surgical conversion
- tissue necrosis
- wound complications (e.g., infection, dehiscence)
- vascular spasm or vascular trauma (e.g., ilio-femoral vessel dissection, seroma, bleeding, rupture, death)

For the specific adverse events that occurred in the clinical study, please see Section F. Safety and Effectiveness Results below.

## IX. SUMMARY OF PRECLINICAL STUDIES

The design of the IBE Device is derived from the from the previously approved EXCLUDER components. Therefore, the potential effects of the design modifications and the new intended use (as compared to the EXCLUDER AAA Device) formed the basis for the preclinical test strategy. Additionally, ISO 25539-1 and commercial experience with the previously approved EXCLUDER components were considered in developing the preclinical testing. Where the design changes incorporated in the IBE Device as compared to the previously approved EXCLUDER components are not expected to significantly affect the results of previous testing, these results continue to be applicable to the IBE Device, and testing was not repeated. Such testing includes aspects of biocompatibility, durability, and performance testing. This approach is acceptable because of the extensive similarities of the IBE Device to the EXCLUDER Device in terms of design, materials, and construction.

The manufacturer completed or appropriately leveraged comprehensive preclinical studies, including in vitro benchtop and analytical testing (Section A), biocompatibility testing (Section A), animal studies (Section B), and sterility, packaging, and shelf-life testing (Section C) to support the safety and effectiveness of the IBE Device.

### A. Laboratory Studies

#### In Vitro Benchtop and Analytical Testing

Appropriate in vitro and analytic testing was determined through reference to the testing of the previously approved EXCLUDER components and relevant standards. Where the design attributes incorporated in the IBE Device are not expected to significantly affect the results of previous testing, the previously approved EXCLUDER components results are applicable to the IBE Device, and testing was

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not repeated. Such testing includes aspects of biocompatibility, durability, and performance testing. This approach is acceptable because of the extensive similarities of the IBE Device to the previously approved EXCLUDER components in terms of design, materials, and construction.

Table 6 provides a summary of the benchtop testing conducted to evaluate the performance of the IBE Device. All testing was conducted on devices representative of the final IBE Device intended for commercial use and subjected to 2x EO sterilization. The results of the laboratory studies provide preliminary evidence that the IBE Device is safe and effective and performs comparably to the previously approved EXCLUDER components.

Table 6: Summary of In Vitro Testing Performed on the IBE Device

| Test | Test Summary | | Results |
| --- | --- | --- | --- |
| **Endovascular System** | | | |
| **Simulated Use - Deployment accuracy*** | This test measures the ability of the IBC and IIC components to be deployed at the intended vessel location in an anatomical model. **Acceptance Criteria:** The combination IBC/IIC shall be within ±5mm of the intended location before and after the deployment of an EXCLUDER® Device Trunk-Ipsilateral Leg and Contralateral Leg. | | **PASS** |
| **Stent Graft and Delivery Catheter Profile*** | This test measures profile of the stent graft constrained on the delivery catheter. **Acceptance Criteria:** Individual samples must pass through the ring gauge for each device type | | **PASS** |
| | Device Type | Ring Gauge | |
| | IBC | 16+ Fr | |
| | IIC | 12+ Fr | |

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| Endoprosthesis | | |
| --- | --- | --- |
| Simulated Use - Acute Migration* | In an anatomical model with physiological pressure and flow at 37°C, this test evaluates the migration resistance of the IBE device. **Acceptance Criteria:** Acutely measured migration in-vitro should be within +/- 1mm to ensure adequate clinical migration resistance. | PASS |
| FEA | This test predicts the maximum principal mean and alternating strains of the Nitinol wire frame of the proximal IBC in combination with a 23mm BAC and the distal end of the 10mm IBC and IIC, when subjected to in vivo pulsatile loading conditions due to radial compression. **Acceptance Criteria:** This test characterizes the mean and alternating strains of the IBC and IIC components. | The results demonstrate that the IBE component devices are consistent with currently marketed EXCLUDER components. |
| Integral Water Permeability* | The Integral Water Permeability is characterized and compared to existing EXCLUDER® Device data. The IBE Device is pressurized to 120mmHg with 37°C water to evaluate the leak rate of the device normalized by surface area. **Acceptance Criteria:** Characterize the integral water permeability of the device with modular components (IBC and IIC) in place and compare test results to existing data. | The integral water permeability of the IBE Device has been characterized and is comparable to existing data. |
| Radial Compression* | This test measures the force to compress the proximal end of the IBC in an Instron tester at 37°C. **Acceptance Criteria:** The radial compression strength of the endoprosthesis as it is being crushed using a 1 cm wide loop must be ≥ 0.07 lbf/cm at 10% compression and be ≥ 0.31 lbf/cm at 20% compression or comparable to existing data. | PASS |
| Simulated Use - Sealing/Leak* | This test compares the leakage of an IBE and EXCLUDER® Device compared to the current EXCLUDER® Device. In an anatomical model with physiological pressure and flow at 37°C, the leak rate into the aneurysm sac of the model is measured. **Acceptance Criteria:** Compare IBE Device test results to EXCLUDER® Device data. | The sealing and leakage of the IBE and EXCLUDER® Device has been characterized and is comparable to existing data. |
| Deployed Stent Graft Length* | This test measures length of a deployed IBC and IIC stent graft in a 37°C water bath. **Acceptance Criteria:** -The deployed lengths of the IBC and IIC must be within the required ranges. | PASS |

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| Compressed Stent Graft Length* | This test measures the compressed IBC and IIC stent graft on the IBC and IIC catheters. Acceptance Criteria: The IBC and IIC compressed stent graft lengths must be within the required ranges. | PASS |
| --- | --- | --- |
| Deployed Stent Graft Diameter* | This test measures proximal and distal diameter (OD) of a deployed IBC and IIC stent graft in a 37°C water bath. Acceptance Criteria: The proximal and distal diameters of the IBC and IIC must be within the required ranges. | PASS |
| Modular Component Separation Force* | The force to separate IBC and IIC modular components is evaluated. Devices are deployed in a 37°C water bath and tested in an environmental chamber. Acceptance Criteria: The force required to separate components (IBC-27mm contra, IBC-23mm contra, IBC-IIC) will be compared to existing data. | Modular component separation force was characterized and is comparable to existing data. |
| Magnetic Resonance Imaging Safety Test | Magnetic resonance imaging (MRI) compatibility is evaluated. Acceptance Criteria: The IBE Device will be labeled as MR Conditional at 1.5 and 3.0 Tesla. | PASS - The IBE Device does not present an additional hazard or risk when implanted in a patient undergoing an MRI procedure, or who may be present in an MRI environment of 1.5 or 3 Tesla. The IFU labels the IBE Device as MR Conditional. |
| Visibility / Radiopacity | This test evaluates the visibility of the IBC and IIC components under fluoroscopy Acceptance Criteria: The loaded Endoprosthesis and delivery catheter must demonstrate sufficient radiopacity for safe and efficacious clinical use. | The device demonstrated sufficient radiopacity. |

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| Delivery System | | |
| --- | --- | --- |
| Catheter Bond Tensile* | This test evaluates the tensile and torque strengths of selected catheter components. **Acceptance Criteria:** Force to separate body shaft to guidewire lumen must be ≥ 3.9 lbf. Force to separate the junction on the RGT must be ≥ 3.9 lbf. **Acceptance Criteria:** Force to pull the RGT through compressed stent graft will be characterized. **Acceptance Criteria:** Torque to remove male luer lock from distal 2-arm will be characterized. **Acceptance Criteria:** Torque to remove knob 1 and knob 2 from luer lock will be characterized. | **PASS** Required catheter tensile and torque strengths were characterized. |
| Loaded Delivery Catheter Length* | The device catheter working length is measured. **Acceptance Criteria:** The IBC and IIC catheter working lengths must be within the required ranges. | **PASS** |
| Simulated Use - Guidewire Component Compatibility* | The purpose of this test is to verify that the IBC and IIC delivery catheters are compatible with a 0.035" guidewire. **Acceptance Criteria:** The catheter must be compatible with a 0.035" guidewire. Insertion shall be without obstruction or excessive force. | **PASS** |
| Simulated Use - Introducer Sheath Component Compatibility* | The purpose of this test is to verify that IBC device is compatible with a 16Fr Gore DrySeal sheath and that the IIC device is compatible with a 12Fr Cook Flexor Sheath and a 12Fr Gore DrySeal Flex Sheath. **Acceptance Criteria:** The device must be able to successfully pass through the recommended sheath; the entire catheter must successfully exit the sheath. | **PASS** |
| Delivery System Deployment Force* | This test measures the force required to deploy the IBC and IIC in an aneurysm model in a water bath at 37°C. **Acceptance Criteria:** The deployment force for the IBC and IIC deployment lines must be ≤5 lbf. | **PASS** |

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| Simulated Use - Deployment Reliability Test* | This test evaluates various aspects of deployment including guidewire compatibility, pushability, trackability, torquability, and deployment, and retraction. **Acceptance Criteria:** The delivery catheter must be compatible with specified guidewires and sheaths in simulated anatomy and provide sufficient ability to torque. The endoprosthesis must fully deploy. All deployment lines, delivery catheters and sheaths must be fully removable without impacting the deployed device. The IBC must be able to reposition 5mm distally when partially deployed. Specified components must meet all relevant post-deployment dimensional and physical inspection requirements. | PASS |
| --- | --- | --- |
| Simulated Use - Catheter Angular Rotation to Failure | This test measures the number of IBC catheter rotations to failure with the leading end fixed in an aneurysm model at 37°C water bath. **Acceptance Criteria:** The proximal hub must rotate 360° without mechanical damage or failure when the distal end is fixed. | PASS |
| Simulated Use - IBC Septum Sealing* | This test measures leak rate through the IBC catheter handle in an aneurysm model pressurized in a 37°C water bath. **Acceptance Criteria:** At 120 mmHg, the sealing septum must exhibit a leakage rate less than the specified limit before initial deployment and after the proximal end of the device has been deployed. | PASS |
| Deployment Mechanism Knob to Line Tensile* | This test measures the tensile strength of the knob-to-line joints of the deployed IBC catheter. **Acceptance Criteria:** The deployment line attachment strength must be > 5.5 lbf. | PASS |
| Sheath Retraction Force | This test measures the force required to pull the IBC catheter through the introducer sheath. **Acceptance Criteria:** Sheath retraction force (distal olive over lip of introducer) must be < 8.1 lbf. | PASS |

*Indicates testing repeated at aging time points for shelf life evaluation.

### Biocompatibility Evaluation

The IBE Device was evaluated for biological safety as per FDA Memo #G95-1 “Use of International Standard ISO-10993, Biological Evaluation of Medical Devices Part-1: Evaluation and Testing” to demonstrate the suitability of the materials for their intended use in an abdominal stent graft system. Biocompatibility testing from other marketed Gore medical products with the same or similar materials and processing was leveraged for the IBC endoprosthesis, the IIC endoprosthesis, and the IIC delivery system. Due to differences in the materials and processing of the IBC delivery system (as compared to other marketed Gore medical products), biocompatibility testing was performed on the IBC delivery system. Table 7 summarizes the IBC delivery system testing.

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Table 7: Summary of IBC Catheter Biocompatibility Evaluation

| Test Performed | Extract(s) Conditions | Test Article and Control(s) Used | Acceptance Criteria | Results |
| --- | --- | --- | --- | --- |
| **Cytotoxicity** *MEM Elution Test* | The test article was extracted in MEM media with 10% FBS at 37°C for 24 hours at a ratio of 6 cm² / ml extract. | Test: IBC catheter. Neg. Control = media; high density polyethylene. Pos. Control = natural rubber. | No signs of cellular morphologic change or death that exceed a Grade of 2 should be seen for the test article extracts at 48 hours. | **PASS** Test article had no biological reactivity at 48 hours (Grade 0). Non-cytotoxic. |
| **Sensitization** *Kligman Maximization Test* | Extraction: 0.9% USP NaCl; cottonseed oil Conditions: 50 ± 2°C, 72 ± 2 hours. Extraction ratio 6 cm² / ml extract. | Test: IBC catheter. Neg. Control = 0.9% USP NaCl, cottonseed oil. Pos. Control = Dinitrochlorobenzene (DNCB). | A sensitizing response is not observed in more than 8% of the animals. This is a Grade 1 sensitization classification. | **PASS** No reaction (0%, sensitization) occurred in any of the test animals. Grade I weak allergenic potential. Non-sensitizing |
| **Irritation** *Intracutaneous Injection Test* | The test article was extracted in 0.9% USP NaCl and cottonseed oil at 50° C for 72 hours at a ratio of 6 cm² / ml extract. | Test: IBC catheter. Neg. Control = 0.9% USP NaCl, cottonseed oil. Pos. Control: N/A. | None of the test extract injection sites show a greater biological reaction than the control injection sites. The difference in the mean score for test and control is ≤ 1. | **PASS** None of the test sites showed a greater biological reaction than the controls sites. The difference in the mean score for test and control was 0. Non-irritant. |
| **Acute Systemic Toxicity** *Systemic Injection* | The test article was extracted in 0.9% USP NaCl and cottonseed oil at 50 C for 72 hours at a ratio of 6 cm² / ml extract. | Test: IBC catheter. Neg. Control = 0.9% USP NaCl, cottonseed oil. Pos. Control: N/A | Animal Weight: A body weight loss of no more than 10% in three of animals. Clinical Observations: none of the test animals show significantly greater biological reactions than controls. If two or more animals show either marked symptoms of toxicity or die, then the sample does not meet the requirements of the test. | **PASS** Four test and three control animals lost insignificant weight (< 8%), no systemic toxicity signs in any animals, no significantly greater biological reaction than controls. Non-toxic. |

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Table 7: Summary of IBC Catheter Biocompatibility Evaluation

| Test Performed | Extract(s) Conditions | Test Article and Control(s) Used | Acceptance Criteria | Results |
| --- | --- | --- | --- | --- |
| **Pyrogenicity** *Rabbit Pyrogen Test (Material Mediated)* | The test article was extracted in 0.9% USP NaCl at 50°C for 72 hours at a ratio of 6 cm^{2} / ml extract. | Test: IBC catheter. Neg. Control = 0.9% USP NaCl. Pos. Control: N/A. | None of the animals have a temperature increase ≥ 0.5°C. | **PASS** None of the test animals showed a temperature increase above baseline (0°) Non – pyrogenic. |
| **Hemocompatibility** *Hemolysis Direct Contact ASTM* | The test article was in direct contact with plasma at a ratio of 6 cm^{2} / ml. | Test: IBC catheter. Neg. Control = PBS; HDPE. Pos. control = Buta-N Rubber. | Percentage hemolysis must be < 5 % to be non-hemolytic. | **ACCEPTABLE**^{1} 7.39% hemolysis Hemolytic. |
| **Hemocompatibility** *Hemolysis Direct Contact ASTM* | The test articles were in direct contact with plasma at a ratio of 6 cm^{2} / ml. | Test: IBC catheter. Neg. Control = PBS; HDPE. Pos. control = Buta-N Rubber. | Percentage hemolysis must be < 5 % to be non-hemolytic. | **PASS** 0.0% hemolysis for both catheter and RGT. Non-Hemolytic. |
| **Hemocompatibility** *Hemolysis Direct Contact ASTM* | The test articles were in direct contact with plasma at a ratio of 6 cm^{2} / ml. | Test: IBC catheter. Neg. Control = PBS; HDPE. Pos. control = Buta-N Rubber. | Percentage hemolysis must be < 5 % to be non-hemolytic. | **PASS** 0.08% hemolysis Non-Hemolytic. |
| **Hemocompatibility** *Complement Activation Direct Contact* | The test article was in direct contact with plasma at a ratio of 6 cm^{2} / ml. | Test: IBC catheter. Neg. Control = HDPE plastic. Pos. Control = C3-A = latex rubber. SC5b-9 = cellulose acetate. | The test article concentration of C3a and SC5b-9 is not significantly greater that the concentration in either the untreated or negative control plasma. | **PASS** The plasma exposed to the test article for 90 min. did not exhibit a significant increase in C3a or SC5b-9 when compared to untreated or negative control plasma. The test sample does not activate complement. |
| **Hemocompatibility** *Prothrombin Time Assay Direct Contact* | The test article was in direct contact with plasma at a ratio of 6 cm^{2} / ml. | Test: IBC catheter. Neg. Control = Plasma a: without test article and b: in presence of HDPE. Pos. Control = Oxalic acid. | No statistically significant difference is found between the PT of the plasma exposed to the test article and that of the plasma exposed to either the negative control or the untreated control | **PASS** The average PT value for the test article (13.5 sec.) did not significantly differ from the mean of the negative (14.4 sec.) and untreated controls (13.5 sec.) No effect on coagulation. |

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**Table 7: Summary of IBC Catheter Biocompatibility Evaluation**

| Test Performed | Extract(s) Conditions | Test Article and Control(s) Used | Acceptance Criteria | Results |
| --- | --- | --- | --- | --- |
| **Hemocompatibility** *In Vivo* *Thrombogenicity* | The test article was in direct contact with blood in an *in vivo* canine model. | Test: IBC catheter. Control = HDPE. | A thrombosis score with a grade of < 3. | **PASS** Minimal Thrombosis with a grade 0 on one test article and Grade 1 on the other test article. Non-thrombogenic. |

$^{1}$The initial test of the IBC catheter for hemolysis resulted in a hemolysis index of 7.39% which is just above the hemolytic index acceptance criteria of < 5%. That test included the catheter and removable guidewire tube (RGT) in the same test sample. The hemolysis test was repeated using the same lot of catheters and RGT. The catheter and RGT were tested separately since the RGT is removed prior to use in the patient. This second test resulted in a hemolytic index of 0% for both the catheter and RGT. A third test of a new lot of catheters, without the RGT since it does not contact the patient, resulted in a hemolytic index of 0.08% well below the acceptance level of <5%. The initial hemolytic index of 7.39% was not confirmed in the two additional hemolysis tests. These results indicate that the IBC catheter is non-hemolytic and thus safe for use as a medical device.

The materials evaluated and used in the components of the IBE Device are considered biologically safe for use in a device classified as an Implant Device with permanent contact (>30 days) to circulating blood and tissues. The materials used in the components of the IBE Device delivery system are considered biologically safe for use in a device classified as an External Communicating Device with limited exposure (≤24 hours) to circulating blood (ISO 10993-1:2009).

## **B. Animal Studies**

No animal testing was conducted on the IBE Device. Information from clinical use and animal study data from the previously approved EXCLUDER components was appropriately leveraged based on the similarities in the IBE Device design and materials. Additionally, a validated bifurcated iliac animal model is not available to address delivery and deployment. These attributes were assessed in simulated use testing, as described above.

## **C. Additional Studies**

### **Sterilization, Packaging and Shelf Life**

The IBE Device has a labeled shelf-life of three years. Device packaging materials and the EO sterilization cycle are the same as those used with the previously approved EXCLUDER components. The sterilization and packaging testing was leveraged from the previously approved EXCLUDER components; no new testing was performed for the IBE Device.

Shelf life testing was performed on the IBE Device, with the relevant tests identified with asterisks in Table 6 above. Product testing was performed on samples that were 2X EO sterilized prior to aging. Accelerated aging studies on the IBE Device demonstrated that the device meets three-year shelf life specifications. Additionally,

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real-time aging studies out to three years have been completed with all acceptance criteria being met.

# X. SUMMARY OF PRIMARY CLINICAL STUDY

The applicant performed a clinical study to establish a reasonable assurance of safety and effectiveness of endovascular treatment with the IBE Device for CIAA and AIA in the US under IDE #G130038. Data from this clinical study were the basis for the PMA Supplement approval decision. A summary of the clinical study is presented below.

# A. Study Design

Patients were treated between October 2013 and January 2015. The database for this Panel Track Supplement reflected data collected through November 5, 2015, and included 64 unique patients. There were 28 investigational sites.

The study (IBE 12-04) was a prospective, non-randomized, multi-center, single-arm clinical study designed to assess the safety and effectiveness of the IBE Device in subjects with isolated common iliac artery aneurysms (CIAA) or aorto-iliac aneurysms (AIA) involving both the abdominal aorta and common iliac artery.

Subjects were classified as presenting with unilateral or bilateral common iliac aneurysm. Subjects with aneurysmal disease involving both iliac arteries could be treated with the IBE Device. In this circumstance, only one of the iliac arteries could be treated with the IBE Device. The internal iliac artery on the opposite side could be managed with coil embolization or surgical revascularization of the artery. Placement of the IBE Device could occur no less than 24 hours after the incision was made for the procedure performed to occlude the internal iliac artery on the opposite side or no less than 30 days after the incision was made for surgical revascularization of the internal iliac artery on the opposite side. One subject withdrew from the study prior to the IBE Device procedure, and one subject withdrew as a bilateral subject and re-enrolled as a unilateral subject before the IBE Device procedure. A total of 63 subjects underwent the IBE Device procedure. Two subjects undergoing the IBE Device procedure were not eligible for longer-term effectiveness analysis. One of these subjects underwent femoral aneurysm repair concomitant with the IBE Device procedure, which was a violation of exclusion criteria. The other subject received an Iliac Extender in place of the Internal Iliac Component (IIC) due to initial difficulty in sheath advancement. Subject enrollment and eligibility for analysis are outlined in Figure 8.

This study evaluated safety and effectiveness through comparison to performance goals. Performance goals were established through a review of data from historical AAA endovascular clinical studies and scientific publications examining internal iliac artery treatment. This resulted in a safety performance goal of 80% freedom from safety endpoint events at 30 days. With this performance goal and a planned sample size of 60 subjects to maintain statistical power >80%, and a one-sided proportion test

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with alpha=0.05, the study required at least 90% freedom from safety events in order to meet the performance goal.

With regards to effectiveness, the primary effectiveness endpoint was a composite of the following key events through the 6 month follow-up visit: reintervention on the Iliac Branch Component (IBC) or the Internal Iliac Component (IIC) due to Type IB or Type III endoleak as determined by the CEC, complete loss of blood flow in the leg of the IBC or the IIC due to thrombus or device failure as assessed by the Core Lab, and reintervention on the IBC or IIC to re-establish patency due to 60% occlusion or greater as determined by the CEC. The rate of reintervention or loss of patency across a number of publications was identified and summarized. A random effects meta-analysis resulted in a lower confidence limit of 85% freedom from such events. In order to show that outcomes with the IBE Device were consistent with historical performance of endovascular techniques, freedom from specified effectiveness endpoint events was required in >85% of subjects in order to statistically exceed the performance goal of 75% through the 6 month follow-up visit and a planned sample size of 60 subjects.

Patient related quality of life was assessed through a secondary endpoint of new onset buttock claudication arising from the side of the body treated with the IBC and IIC, as determined by the CEC through the six month follow-up visit. Buttock claudication can cause significant discomfort for a patient and is one of the more commonly reported complications associated with internal iliac artery coverage. The relative frequency of buttock claudication across a number of publications was identified and summarized. Using these results, a random effects meta-analysis was performed to estimate the overall frequency of buttock claudication when the internal iliac artery was sacrificed, and resulted in an upper confidence limit of 73% freedom from buttock claudication. In order to demonstrate clinical improvement, freedom from specified new claudication events was required in >83% of subjects in order to statistically exceed the performance goal of 73% through the 6 month follow-up visit and a planned sample size of 60 subjects.

This study utilized an independent Data Safety Monitoring Board (DSMB) that reviewed safety data during the accrual phase of the study and on an ongoing basis as needed. A Clinical Events Committee (CEC) reviewed adverse events for inclusion as endpoint events, all reinterventions through 12-month follow-up performed due to Type IB or Type III endoleak or 60% occlusion involving the investigational components, and inclusion/exclusion criteria deviations. Because IBE Device patients can present with bilateral iliac aneurysms but the study was limited to unilateral treatment, a Bilateral Recommendation Committee reviewed screening images and provided treatment recommendations. Finally, a Core Lab reviewed subject images for study critical events (e.g. endoleak, occlusion, stent fracture).

### 1. Clinical Inclusion and Exclusion Criteria

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Enrollment in the IBE 12-04 study was limited to patients who met the following inclusion criteria:

1. Common iliac to be treated must have a maximum diameter ≥25 mm with or without concomitant AAA along with:

- minimum diameter ≥17 mm within the proximal implantation zone of IBE as assessed by flow lumen; calcium excluded
- diameter ≥14 mm at the iliac bifurcation as assessed by flow lumen; calcium excluded

2. Adequate native anatomy to receive the GORE® EXCLUDER® and IBE Devices, including:

- Adequate iliac / femoral access
- Infrarenal aortic neck diameter 19-32 mm
- Infrarenal aortic neck length ≥15 mm
- Aortic neck angle ≤60°
- Iliac artery seal zone of at least 10 mm with treatment diameter ranges of the following as assessed by flow lumen and thrombus, if present; calcium excluded:
- 6.5–13.5 mm for the IBE side internal iliac artery
- 6.5–25 mm for the IBE side external iliac artery
- 8–25 mm for the non-IBE side iliac artery

3. An ICF signed by subject or legally authorized representative

4. Male or infertile female*
5. Able to comply with protocol requirements including following-up
6. Life expectancy >2 years
7. Age >21 years
8. Surgical candidate

* Infertile female – condition which prevents pregnancy, e.g., hysterectomy, tubal ligation or post-menopausal for greater than 1 year.

Patients were not permitted to enroll in the IBE 12-04 study if they met any of the following exclusion criteria:

1. Mycotic or ruptured aneurysm
2. Known concomitant thoracic aortic aneurysm which requires intervention
3. American Society of Anesthesiologists (ASA) class V (moribund patient not expected to live 24 hours with or without operation)
4. Renal insufficiency defined as creatinine >2.5 mg/dL or patient undergoing dialysis
5. NYHA class IV
6. Dissected, heavily calcified, or heavily thrombosed landing zone(s)
7. Tortuous or stenotic iliac and / or femoral arteries
8. Participating in another investigational device or drug study within 1 year of treatment
9. Systemic infection which may increase the risk of endovascular graft infection

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10. Known degenerative connective tissue disease, e.g., Marfan or Ehler-Danlos Syndrome

11. Planned concomitant surgical procedure or major surgery within 30 days of treatment date (with the exception of surgical procedures required for bilateral iliac artery treatment)

12. Known history of drug abuse

13. Known sensitivities or allergies to the device materials

## 2. Follow-up Schedule

All patients were scheduled to return for follow-up examinations at 1, 6, 12, 24, 36, 48, and 60 months postoperatively.

Preoperatively, patient demographics, medical history, and relevant baseline anatomical measurements were collected for each study subject. Postoperatively, the objective parameters measured during the study included site-reported measurements (maximum common iliac artery diameter on the IBE Device side) and Core Lab evaluations (maximum abdominal aortic diameter, maximum right common iliac artery diameter, maximum left common iliac artery diameter, device migration, intercomponent migration, endoleak, wire fracture, extrusion/erosion, lumen obstruction, device compression, patency, and rupture), using the assessments and testing listed in Table 8. Adverse events and complications were recorded at all visits.

Follow-up visits are scheduled at appointed times after the date of treatment. In order to provide flexibility for scheduling follow-up visits, a period during which each visit is recommended (i.e., ideal window) is provided below in Table 9. Also included in the table are the analysis windows used for this study. Analysis windows include all study days in order to include all data reported. All data in this report are presented by analysis window unless stated otherwise.

Table 8: Subject Schedule of Events

| Diagnostic Test | Pre-treatment | Treatment | 1 month | 6 months | 12, 24, 36, 48, and 60 months |
| --- | --- | --- | --- | --- | --- |
| Physical examination | X | | X | X | X |
| Creatinine concentration | X | | | | |
| Spiral computed tomography (contrast) | X | | X | X | X |
| Spiral computed | | | X | | |

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| **tomography (non contrast)** | | | | | |
| --- | --- | --- | --- | --- | --- |
| **Angiography** | **X^{1}** | **X** | | | |
| ^{1} Pre-enrollment angiogram not required if contrast enhanced spiral CT with 3-D reconstruction has been performed ≤ 180 Days prior to treatment | | | | | |

**Table 9: Protocol Windows**

| **Follow-up Visit** | **Ideal Window (days)** | **Analysis Window (days)** |
| --- | --- | --- |
| Procedure | 0 | 0 |
| Post-Procedure* | 1-14 | 1-14 |
| 1 Month | 23-44 | 15-59 |
| 6 Months | 150-210 | 60-242 |
| 12 Months | 275-455 | 243-546 |
| 24 Months | 640-820 | 547-911 |
| 36 Months | 1005-1185 | 912-1275 |
| 48 Months | 1370-1550 | 1276-1640 |
| 60 Months | 1735-1915 | 1641-2006 |
| *Post-Procedure visit is not required | | |

### 3. Clinical Endpoints

With regards to safety, the primary endpoint of this study was a composite of the following events through 30 days after the initial procedure: death, stroke, myocardial infarction, bowel ischemia, paraplegia, respiratory failure, renal failure, and conversion to open surgical repair as determined by the Clinical Events Committee (CEC) according to the protocol definitions, compared to the performance goal.

With regards to effectiveness, the primary effectiveness endpoint was a composite of the following key events through the 6 month follow-up visit: reintervention on the Iliac Branch Component (IBC) or the Internal Iliac Component (IIC) due to Type IB or Type III endoleak as determined by the CEC, complete loss of blood flow in the leg of the IBC or the IIC due to thrombus or device failure as assessed by the Core Lab, and reintervention on the IBC or IIC to re-establish patency due to 60% occlusion or greater as determined by the CEC, compared to the performance goal.

Patient related quality of life was assessed through a secondary endpoint of new onset buttock claudication arising from the side of the body treated with the IBC and IIC, as determined by the CEC through the six month follow-up visit.

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With regard to success/failure, study success was defined as meeting the primary safety and effectiveness endpoints. The IBE 12-04 study was considered successful if the null hypotheses for the test of primary safety (≤ 0.80) and effectiveness (≤ 0.75) were rejected.

## B. Accountability of PMA Cohort

At the time of database lock, of 64 unique patients enrolled in the PMA study, 98.4% (63) patients are available for primary safety endpoint analysis at 30 days and 96.9% (62) patients are available for primary effectiveness endpoint analysis at the 6 month post-operative visit.

Subjects were screened and enrolled per the criteria outlined above. One hundred seventy-three (173) subjects were screened for eligibility for the IBE 12-04 Study; 108 subjects were excluded from study participation and identified as screen failures (Figure 8). The most common primary reason for exclusion from the study was common iliac artery diameters (Inclusion 1) and adequate anatomy to receive the GORE® EXCLUDER® AAA Endoprosthesis and the IBE Device (Inclusion 2).

A total of 65 subjects were considered to be enrolled into the study; however, one subject withdrew then re-enrolled, resulting in a total of 64 unique study subjects. An additional subject withdrew from the study prior to the IBE Device procedure. One subject was not considered eligible for the primary endpoint and all effectiveness and device-specific safety analyses because they did not meet the selection criteria for the study. An additional subject did not receive both IBE device components so was included in the primary safety endpoint, but excluded from device-specific safety (i.e., serious and non-serious device events) and all effectiveness endpoints.

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Figure 8: Subject Enrollment and Analysis Inclusion

Table 10 provides the follow-up compliance and disposition for effectiveness eligible subjects. Note: three subjects were not effectiveness eligible due to not undergoing the IBE Device procedure, receiving an Iliac Extender in place of the IIC, and undergoing concomitant femoral aneurysm repair which was a violation of exclusion criteria, respectively. For a given study period, data presented include the number of

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subjects eligible for follow-up (i.e., number eligible from previous period minus subject deaths, subjects discontinued or not yet due for their next follow-up visit). All 61 subjects were eligible for the primary endpoint analysis at 6 months, 36 subjects were within the 12 month window and 23 subjects were within the 24 month window at time of datalock. A total of two subjects undergoing the IBE device procedure were no longer eligible for study follow-up due to death. No deaths were determined to be aneurysm-related, device-related, or procedure-related.

**Table 10** includes subjects eligible for all effectiveness endpoint analyses (Figure 8).

**Table 10. Subject Compliance and Disposition by Study Interval**

| Study Period | Eligible for follow-up | Follow-up Compliance^{1} | | | | | Events Prior to Next Interval^{1} | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | Subjects with Visit in Window^{2} | Physical Exam Performed | Any CT Scan Performed | Contrast CT Performed^{3} | Within Window No CT Yet^{4} | Death | Discontinued | Not Due for Next Window |
| Procedure | 61 | - | - | - | - | - | 0 | 0 | 0 |
| Post-Procedure | 61 | - | - | - | - | - | 0 | 0 | 0 |
| 1 Month | 61 | 60(98.4%) | 59(96.7%) | 60(98.4%) | 59(96.7%) | 0 | 0 | 0 | 0 |
| 6 Months | 61 | 58(95.1%) | 56(91.8%) | 57(93.4%) | 55(90.2%) | 0 | 1(1.6%) | 0 | 0 |
| 12 Months | 60 | 48(80.0%) | 46(76.7%) | 47(78.3%) | 43(71.7%) | 11(18.3%) | 1(1.7%) | 0 | 36(60.0%) |
| 24 Months | 23 | 1(4.3%) | 1(4.3%) | 1(4.3%) | 1(4.3%) | 22(95.7%) | 0 | 0 | 23(100.0%) |

Study period definitions: Procedure(0-0 days) Post-Procedure(1-14 days) 1 Month(15-59 days) 6 Months(60-242 days) 12 Months(243-546 days) 24 Months(547-911 days)

$^{1}$Percentages are based on number of subjects eligible for follow-up in study period.

$^{2}$Any visit consisting of physical exam, CT scan, or MR scan.

$^{3}$Contrast CT is necessary for Core Lab determination of endoleak, lumen obstruction, patency, or rupture.

$^{4}$Subjects still within the study window out of those who have not yet had a CT scan.

Analysis of pre-treatment and follow-up radiologic images was conducted by an independent Core Lab. **Table 11** presents the Core Lab assessments performed for follow-up imaging, and the percentage of subjects with assessments in each study period. Core Lab evaluation of endoleak, lumen obstruction, patency, and rupture was dependent on the availability of contrast-enhanced CT scan. Other assessments could be made using non-contrast CT. Critical parameters could be evaluated in over 85% of study subjects at 6 months.

Wire fracture observations are described in terms of the Stent Integrity Grading Scale where class 0 represents no fracture, class I is single tine fracture, class II is multiple tine fractures, class III is stent fracture with preserved alignment of components, class IV is stent fracture with mal-alignment of components, and class V is stent fracture in a trans-axial spiral configuration. Wire fracture was assessed for previously approved EXCLUDER components and IBE Device components for all classes of fracture, but due to varying slice thickness of imaging was considered evaluable if the IBC and IIC

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components could be assessed for class IV and V fractures; the most significant types of fractures in nitinol stents that could have clinical sequelae are usually class IV and V. Further categorization of wire fracture assessment for the IBC and IIC components is presented in Table 12. Wire fracture assessment of the IBC and IIC components was evaluable in 96.7% of subjects in the 1 month study window and 90.2% of subjects in the 6 month study window, with 62.3% of subjects evaluated for all fracture classes in the 1 month and 6 month study windows.

When considering the impact of slice thickness in assessing subclinical device fractures, while slice thickness does impact the ability to identify individual wireform fractures (Class I, Class II, and some Class III), most nitinol stent fractures that could have clinical sequelae progress to Class IV and V, and these can be detected in thicker slice CT imaging. Sequelae of Type III endoleak, migration, and limb occlusion will also be detected in thicker slice CT imaging.

Tables 11 and 12 include subjects eligible for all effectiveness endpoint analyses (Figure 8).

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Table 11. Critical Parameters Evaluated by Independent Core Lab

| Study Period | Eligible for follow-up | IBC Patency Evaluable | IIC Patency Evaluable | Endoleak Evaluable (All Types) | Rupture Evaluable | Migration Evaluable | IBE Wire Fracture Evaluable^{1} | Extrusion /Erosion Evaluable | Lumen Obstruction Evaluable | Device Compression Evaluable | Max Diameters Evaluable |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 Month | 61 | 59 (96.7%) | 59 (96.7%) | 57 (93.4%) | 59 (96.7%) | 60 (98.4%) | 59 (96.7%) | 60 (98.4%) | 59 (96.7%) | 60 (98.4%) | 60 (98.4%) |
| 6 Months | 61 | 55 (90.2%) | 55 (90.2%) | 53 (86.9%) | 55 (90.2%) | 57 (93.4%) | 55 (90.2%) | 57 (93.4%) | 55 (90.2%) | 57 (93.4%) | 57 (93.4%) |
| 12 Months | 60 | 43 (71.7%) | 43 (71.7%) | 43 (71.7%) | 43 (71.7%) | 46 (76.7%) | 46 (76.7%) | 46 (76.7%) | 43 (71.7%) | 46 (76.7%) | 46 (76.7%) |

Study period definitions: 1 Month(15-59 days) 6 Months(60-242 days) 12 Months(243-546 days)

$^{1}$ Wire fracture imaging compliance for IBE Device components (IBC and IIC). Refer to Table 5 below for further categorization. Image considered evaluable if class IV and V fractures could be ruled out, as nitinol stent fractures which could have clinical sequelae usually progress to class IV and V.

Fracture class definitions: 0 (no fracture), I (single tine fracture), II (multiple tine fractures), III (stent fracture with preserved alignment of components), IV (stent fracture with mal-alignment of components), V (stent fracture in a trans-axial spiral configuration).

Table 12. Adequate Imaging to Assess IBC and IIC Wire Fracture

| | Study Period | | |
| --- | --- | --- | --- |
| | 1 Month | 6 Months | 12 Months |
| Eligible for follow-up | 61 | 61 | 60 |
| IBC/IIC Wire Fracture Evaluated | | | |
| Yes | 59 (96.7%) | 55 (90.2%) | 46 (76.7%) |
| All Classes | 38 (62.3%) | 38 (62.3%) | 25 (41.7%) |
| Only Class IV and V (Large Slice Thickness)^{1} | 21 (34.4%) | 17 (27.9%) | 21 (35.0%) |
| No | 2 (3.3%) | 6 (9.8%) | 14 (23.3%) |
| Poor Image Quality | 1 (1.6%) | 2 (3.3%) | 0 |
| Image Not Available | 1 (1.6%) | 4 (6.6%) | 14 (23.3%) |

Study period definitions: 1 Month (15-59 days) 6 Months (60-242 days) 12 Months (243-546 days)

$^{1}$ Class IV and V fractures were ruled out. Class I, II, and some class III fractures could not be ruled out due to large slice thickness of imaging.

Fracture class definitions: 0 (no fracture), I (single tine fracture), II (multiple tine fractures), III (stent fracture with preserved alignment of components), IV (stent fracture with mal-alignment of components), V (stent fracture in a trans-axial spiral configuration).

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### C. Study Population Demographics and Baseline Parameters

The demographics of the study population are typical for an endovascular stent graft study performed in the US.

Baseline assessments of all enrolled IBE 12-04 subjects include demographics and risk factor evaluations, including medical history and comorbidities. **Table 13** provides demographic data. The majority of subjects enrolled were white males with a mean age of 69.6 years. Over 60% of the subjects enrolled into the study had a unilateral CIAA. **Table 14** provides subject medical history, with hypertension, hypercholesterolemia, and cigarette smoking presenting as the most common comorbidities.

**Tables 13 and 14** include the 64 unique subjects enrolled (**Figure 8**).

**Table 13. Subject Demographics**

| | IBE Cohort |
| --- | --- |
| Number of Enrolled Subjects^{1} | 64 |
| Sex at Birth | |
| Male | 63(98.4%) |
| Female | 1(1.6%) |
| Race | |
| White | 59(92.2%) |
| Black | 5(7.8%) |
| Asian | 0(0.0%) |
| American Indian or Alaska Native | 0(0.0%) |
| Hawaiian or Pacific Islander | 0(0.0%) |
| Other | 0(0.0%) |
| Age (yrs) | |
| N | 64 |
| Mean (Std Dev) | 69.6(8.4) |
| Median | 69.5 |
| Range | (51.0,88.0) |
| NYHA Classification | |
| I | 27 (42.2%) |
| II | 13 (20.3%) |
| III | 1 (1.6%) |
| IV | 0 (0.0%) |
| No Cardiac Disease | 23 (35.9%) |
| ASA Classification | |
| I | 4 (6.3%) |
| II | 16 (25.0%) |
| III | 37 (57.8%) |
| IV | 7 (10.9%) |
| V | 0 (0.0%) |
| Summary SVS Risk Score | |
| N | 64 |
| Mean(Std Dev) | 6.0(2.8) |
| Median | 6.0 |

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Table 13. Subject Demographics

| | IBE Cohort |
| --- | --- |
| Range | (0.0,13.0) |
| Iliac Aneurysm Presentation | |
| Bilateral | 25(39.1%) |
| Unilateral | 39(60.9%) |

¹One subject was not included to avoid double-counting in numerators and denominator, as they withdrew as a bilateral subject and re-enrolled as a unilateral subject before the IBE procedure.

Table 14. Subject Medical History

| | IBE Cohort |
| --- | --- |
| Number of Enrolled Subjects¹ | 64 |
| Hypertension | 56 (87.5%) |
| Hypercholesterolemia | 49 (76.6%) |
| Cigarette Smoking | 39 (60.9%) |
| Peripheral Vascular Disease | 27 (42.2%) |
| Cardiac Arrhythmia | 23 (35.9%) |
| Other Concomitant Aneurysm | 19 (29.7%) |
| Cancer | 16 (25.0%) |
| Diabetes Mellitus | 15 (23.4%) |
| Myocardial Infarction | 15 (23.4%) |
| PCI | 15 (23.4%) |
| Chronic Obstructive Pulmonary Disease | 14 (21.9%) |
| Congestive Heart Failure | 14 (21.9%) |
| Cerebrovascular disease | 10 (15.6%) |
| Erectile Dysfunction² | 10 (15.9%) |
| Coronary Artery Bypass Graft | 9 (14.1%) |
| Aneurysm Symptomatic | 7 (10.9%) |
| Thromboembolic Event | 7 (10.9%) |
| Lower Limb Intervention | 4 (6.3%) |
| Renal Insufficiency | 4 (6.3%) |
| Paraplegia | 0 (0.0%) |
| Renal Dialysis | 0 (0.0%) |

¹One subject was not included to avoid double-counting in numerators and denominator, as they withdrew as a bilateral subject and re-enrolled as a unilateral subject before the IBE procedure.
²Males Only

Subjects underwent pre-treatment imaging to assess aortic morphology (Tables 15 and 16). Patient pre-treatment aortic imaging measurements were evaluated in two groups (Table 15): those presenting with abdominal aortic aneurysms (Aortoiliac Aneurysms, aortic diameter ≥ 50 mm) and those presenting without abdominal aortic aneurysms (Isolated Iliac Aneurysms, aortic diameter < 50 mm). Measurements in Table 16 are reported separately for the IBE treated side and the non-IBE side. In both tables,

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information is reported for subjects presenting with unilateral iliac aneurysms and bilateral iliac aneurysms separately as well as combined across the two groups.

Tables 15 and 16 include unique subjects enrolled (Figure 8).

Table 15. Pre-Treatment Imaging Measurements – Abdominal Aorta (Site-Reported)

| | Aortoiliac Aneurysms (aortic diameter > 50 mm) | | | Isolated Iliac Aneurysms (aortic diameter < 50 mm) | | |
| --- | --- | --- | --- | --- | --- | --- |
| All diameters and lengths reported in mm | Unilateral Iliac Aneurysms | Bilateral Iliac Aneurysms | All | Unilateral Iliac Aneurysms | Bilateral Iliac Aneurysms | All |
| Aortic diameter at proximal implantation site | | | | | | |
| n | 15 | 10 | 25 | 24 | 15 | 39 |
| Mean (Std Dev) | 23.5 (2.5) | 22.9 (2.2) | 23.3 (2.4) | 22.6 (2.3) | 23.2 (2.3) | 22.9 (2.3) |
| Median | 23.1 | 22.1 | 22.6 | 22.4 | 23.7 | 23.0 |
| Range | (20.2, 28.3) | (20.9, 28.0) | (20.2, 28.3) | (20.0, 29.0) | (19.8, 27.5) | (19.8, 29.0) |
| Aortic diameter - 15mm distal to proximal implantation site | | | | | | |
| n | 15 | 10 | 25 | 24 | 15 | 39 |
| Mean (Std Dev) | 24.1 (2.9) | 23.8 (2.4) | 24.0 (2.7) | 22.4 (2.4) | 24.0 (2.5) | 23.0 (2.5) |
| Median | 23.0 | 23.2 | 23.0 | 21.9 | 24.9 | 23.0 |
| Range | (20.7, 28.4) | (21.0, 28.0) | (20.7, 28.4) | (19.0, 28.4) | (19.4, 27.5) | (19.0, 28.4) |
| Aortic neck length | | | | | | |
| n | 15 | 10 | 25 | 24 | 15 | 39 |
| Mean (Std Dev) | 36.5 (11.9) | 33.9 (8.4) | 35.5 (10.5) | 43.6 (22.9) | 33.6 (18.0) | 39.7 (21.5) |
| Median | 33.1 | 36.3 | 34.6 | 35.0 | 30.0 | 30.5 |
| Range | (23.0, 60.0) | (15.0, 42.0) | (15.0, 60.0) | (15.0, 105.0) | (20.0, 93.4) | (15.0, 105.0) |
| Maximum aortic diameter | | | | | | |
| n | 15 | 10 | 25 | 24 | 15 | 39 |
| Mean (Std Dev) | 56.1 (5.2) | 58.8 (6.0) | 57.2 (5.5) | 34.9 (7.2) | 41.7 (6.6) | 37.5 (7.6) |
| Median | 56.5 | 60.1 | 57.0 | 34.0 | 43.0 | 38.0 |
| Range | (49.6, 67.1) | (49.7, 67.0) | (49.6, 67.1) | (20.7, 46.8) | (25.0, 49.1) | (20.7, 49.1) |
| Length from lowest renal artery to native aortic bifurcation | | | | | | |
| n | 15 | 10 | 25 | 24 | 15 | 39 |
| Mean (Std Dev) | 123.2 (10.0) | 129.1 (25.1) | 125.6 (17.4) | 106.7 (13.4) | 111.8 (18.0) | 108.7 (15.3) |
| Median | 120.0 | 121.5 | 120.0 | 107.5 | 106.0 | 107.0 |
| Range | (109.0, 140.3) | (106.0, 196.0) | (106.0, 196.0) | (72.0, 136.0) | (75.0, 138.0) | (72.0, 138.0) |
| Distal aortic neck diameter | | | | | | |
| n | 15 | 10 | 25 | 24 | 15 | 39 |
| Mean (Std Dev) | 38.8 (10.0) | 31.9 (7.4) | 36.0 (9.5) | 25.6 (5.2) | 33.8 (7.2) | 28.8 (7.2) |

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**Table 15. Pre-Treatment Imaging Measurements – Abdominal Aorta (Site-Reported)**

| Median | 35.6 | 29.8 | 33.5 | 25.3 | 34.0 | 27.0 |
| --- | --- | --- | --- | --- | --- | --- |
| Range | (28.6, 57.0) | (21.7, 44.0) | (21.7, 57.0) | (18.5, 37.5) | (22.0, 49.0) | (18.5, 49.0) |

**Table 16. Pre-treatment Imaging Measurements – Iliac (Site-Reported)**

| All diameters and lengths reported in mm | IBE Side | | | Non-IBE Side | | |
| --- | --- | --- | --- | --- | --- | --- |
| | Unilateral Iliac Aneurysms | Bilateral Iliac Aneurysms | All | Unilateral Iliac Aneurysms | Bilateral Iliac Aneurysms | All |
| **Length from lowest renal artery to internal iliac artery** | | | | | | |
| n | 39 | 25 | 64 | 39 | 25 | 64 |
| Mean (Std Dev) | 185.9 (18.9) | 192.9 (29.8) | 188.7 (23.8) | 173.3 (22.4) | 193.8 (33.7) | 181.3 (28.9) |
| Median | 185.0 | 190.0 | 186.5 | 170.0 | 191.0 | 178.4 |
| Range | (156.0, 231.0) | (153.0, 275.0) | (153.0, 275.0) | (117.0, 217.0) | (145.0, 288.0) | (117.0, 288.0) |
| **Length from the aortic bifurcation to internal iliac artery** | | | | | | |
| n | 39 | 25 | 64 | - | - | - |
| Mean (Std Dev) | 68.8 (20.3) | 74.9 (27.0) | 71.2 (23.1) | - | - | - |
| Median | 69.7 | 70.0 | 70.0 | - | - | - |
| Range | (25.0, 111.0) | (42.6, 135.0) | (25.0, 135.0) | - | - | - |
| **Minimum common iliac artery diameter within proximal IBE implantation zone** | | | | | | |
| n | 39 | 25 | 64 | - | - | - |
| Mean (Std Dev) | 22.2 (6.1) | 23.1 (5.0) | 22.6 (5.6) | - | - | - |
| Median | 20.5 | 22.2 | 21.3 | - | - | - |
| Range | (17.0, 50.0) | (17.0, 37.7) | (17.0, 50.0) | - | - | - |
| **Common iliac artery diameter at iliac bifurcation** | | | | | | |
| n | 39 | 25 | 64 | - | - | - |
| Mean (Std Dev) | 24.3 (8.0) | 25.2 (7.8) | 24.7 (7.9) | - | - | - |
| Median | 23.3 | 23.0 | 23.2 | - | - | - |
| Range | (14.0, 54.0) | (14.6, 46.0) | (14.0, 54.0) | - | - | - |
| **Maximum common iliac artery diameter** | | | | | | |
| n | 39 | 25 | 64 | - | - | - |
| Mean (Std Dev) | 38.4 (10.0) | 40.2 (11.6) | 39.1 (10.6) | - | - | - |
| Median | 36.3 | 39.0 | 37.0 | - | - | - |
| Range | (25.4, 72.0) | (25.0, 62.0) | (25.0, 72.0) | - | - | - |
| **Common iliac artery diameter at intended landing zone^{1}** | | | | | | |
| n | - | - | - | 39 | 18 | 57 |
| Mean (Std Dev) | - | - | - | 18.8 (4.0) | 32.5 (16.7) | 23.1 (11.7) |
| Median | - | - | - | 19.0 | 27.0 | 21.0 |

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**Table 16. Pre-treatment Imaging Measurements – Iliac (Site-Reported)**

| Range | - | - | - | (10.0, 25.0) | (8.0, 76.0) | (8.0, 76.0) |
| --- | --- | --- | --- | --- | --- | --- |
| **External iliac artery diameter at intended landing zone^{2}** | | | | | | |
| n | 39 | 25 | 64 | 18 | 25 | 43 |
| Mean (Std Dev) | 11.2 (1.9) | 10.8 (1.3) | 11.1 (1.7) | 10.6 (1.8) | 10.7 (1.6) | 10.7 (1.7) |
| Median | 11.0 | 11.0 | 11.0 | 10.0 | 10.8 | 10.4 |
| Range | (6.6, 15.8) | (8.4, 13.0) | (6.6, 15.8) | (6.6, 15.0) | (7.9, 14.0) | (6.6, 15.0) |
| **Internal iliac artery diameter at intended landing zone** | | | | | | |
| n | 39 | 25 | 64 | - | - | - |
| Mean (Std Dev) | 10.2 (1.7) | 10.6 (1.5) | 10.4 (1.6) | - | - | - |
| Median | 10.2 | 10.9 | 10.4 | - | - | - |
| Range | (7.1, 13.1) | (6.5, 13.0) | (6.5, 13.1) | - | - | - |
| **Access vessel diameter** | | | | | | |
| n | 39 | 25 | 64 | 39 | 25 | 64 |
| Mean (Std Dev) | 11.0 (2.2) | 10.1 (1.4) | 10.7 (2.0) | 11.0 (2.1) | 10.0 (1.6) | 10.6 (2.0) |
| Median | 11.0 | 10.1 | 10.5 | 11.0 | 10.0 | 10.3 |
| Range | (6.6, 15.8) | (6.5, 13.0) | (6.5, 15.8) | (6.5, 15.0) | (7.0, 13.0) | (6.5, 15.0) |

$^{1}$Measurement not required on IBE side, or on non-IBE side for subjects with bilateral iliac aneurysms. Any measurements provided are included in this table.

$^{2}$Measurement on non-IBE side not required for subjects with unilateral iliac aneurysm. Any measurements provided are included in this table.

#### **D. Device Usage**

**Table 17** provides device usage for patients implanted with the IBE Device. Diameter distribution of all IBE Devices implanted (IBC and IIC) are presented in **Table 18**. Sixty-three (63) IBCs were implanted in 63 subjects and 68 IICs were implanted in 62 subjects. One subject was not implanted with an IIC due to difficulty in sheath advancement. Multiple IICs were used in five subjects for various reasons including distal extension to gain length and / or address tortuosity, as well as to improve overlap with the IBC. **Table 19** presents the diameter and length distributions of implanted Contralateral Leg components. Seventy-three (73) Contralateral Leg components were implanted in 63 subjects. Multiple Contralateral Leg components were used in 9 subjects to provide an adequate bridge between the Trunk-Ipsilateral Leg Endoprosthesis and the IBE Device.

**Tables 17, 18, and 19** include subjects undergoing IBE Device procedure (**Figure 8**).

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**Table 17. Device Use at Initial Procedure**

| | IBE Cohort |
| --- | --- |
| Number of Subjects with Devices Implanted | 63 |
| IBE Device Components | |
| Subjects with Iliac Branch Components (IBC) Implanted | 63 (100.0%) |
| Subjects with Internal Iliac Components (IIC) Implanted^{1} | 62 (98.4%) |
| EXCLUDER AAA Device Components | |
| Subjects with Trunk-Ipsilateral Legs Implanted | 63 (100.0%) |
| Subjects with Contralateral Legs Implanted | 63 (100.0%) |
| Subjects with Aortic Extenders Implanted | 6 (9.5%) |
| Subjects with Iliac Extenders Implanted | 11 (17.5%) |

$^{1}$One subject underwent the IBE Device procedure with successful placement and deployment of the investigational IBC, but difficulty in sheath advancement resulted in failure to place the IIC. Eventually, a commercially available EXCLUDER AAA Endoprosthesis Iliac Extender was used in place of the investigational IIC.

**Table 18. Number of Implanted Subjects by IBE Device Component Sizes**

| Distal Leg Diameter (mm) | IBC | | IIC | |
| --- | --- | --- | --- | --- |
| | Subjects (N=63) | Devices (N=63) | Subjects (N=62) | Devices (N=68) |
| 10 | 10 (15.9%) | 10 (15.9%) | 17 (27.4%) | 17 (25.0%) |
| 12 | 24 (38.1%) | 24 (38.1%) | 17 (27.4%) | 18 (26.5%) |
| 14.5 | 29 (46.0%) | 29 (46.0%) | 29 (46.8%) | 33 (48.5%)^{1} |

$^{1}$Multiple IICs were used for distal extension to gain length and / or address tortuosity, and also to improve overlap with the IBC.

**Table 19. Number of Implanted Subjects by Contralateral Leg Bridging Component Size**

| Distal Leg Diameter (mm) | Length (cm) | Subjects (N=63) | Devices (N=73) |
| --- | --- | --- | --- |
| 23 | 10 | 3 (4.8%) | 3 (4.1%) |
| 23 | 12 | 5 (7.9%) | 5 (6.9%) |
| 27 | 10 | 27 (42.9%) | 30 (41.1%) |
| 27 | 12 | 22 (34.9%) | 23 (31.5%) |
| 27 | 14 | 12 (19.0%) | 12 (16.4%) |

### **E. Procedural Data**

**Table 20** provides procedure and recovery data for all subjects in which the IBE procedure was attempted. All subjects survived the endovascular procedure. Median hospital stay was 1 day (range of 1 – 11 days). Fourteen (14) subjects required an ICU stay. For subjects with an ICU stay, the median length of ICU stay was 1.1 days. Median time to return to normal daily activities, as reported by subjects, was 27 days.

Additional procedures performed during endovascular treatment included stenting procedure (n=5, 7.9%) and embolization (n=2, 3.2%). Two subjects had additional stents deployed within the external iliac leg of the IBC for

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distal extension and to address vessel tortuosity, and two subjects had an additional stent deployed on the non-IBE side for distal extension to address vessel tortuosity. Additional stents were self-expanding bare metal and nitinol stents. One patient had a bare metal balloon-expandable…