EXCLUDER BIFURCATED ENDOPROSTHESIS

P020004 · W. L. Gore & Associates, Inc. · MIH · Nov 6, 2002 · Cardiovascular

Device Facts

• Record ID: P020004
• Device Name: EXCLUDER BIFURCATED ENDOPROSTHESIS
• Applicant: W. L. Gore & Associates, Inc.
• Product Code: MIH · Cardiovascular
• Decision Date: Nov 6, 2002
• Decision: APPR
• Device Class: Class 3
• Attributes: Therapeutic

Intended Use

The EXCLUDER Bifurcated Endoprosthesis is intended to exclude the aneurysm from the blood circulation in patients diagnosed with infrarenal abdominal aortic aneurysms (AAA) disease and who have appropriate anatomy as described below: - Adequate iliac/femoral access - Infrarenal aortic neck treatment diameter range of 19-26 mm and a minimum aortic neck length of 15 mm. - Proximal aortic neck angulation = 60°. - Iliac artery treatment diameter range of 8-13.5 mm and iliac distal vessel seal zone length of at least 10 mm. The EXCLUDER Extender Endoprostheses (Aortic and Iliac) are intended to be used after deployment of the EXCLUDER Bifurcated Endoprosthesis. These extensions are intended to be used when additional length and/or sealing for aneurysmal exclusion is desired.

Device Story

Endovascular graft system for infrarenal AAA repair; consists of trunk-ipsilateral leg, contralateral leg, and optional aortic/iliac extenders. Graft material is ePTFE/FEP supported by external Nitinol wire. Delivery system uses ePTFE/FEP sleeve for constraint; deployment initiated from leading end. Used in clinical/OR settings by physicians. Radiopaque markers facilitate fluoroscopic visualization and accurate placement. Device excludes aneurysm from circulation, reducing blood loss, ICU stay, and recovery time compared to open surgery. Clinical decision-making supported by pre-operative anatomical assessment (CT/angiography).

Clinical Evidence

Prospective, non-randomized, multi-center study (19 US sites) comparing EXCLUDER (n=235) to open surgical control (n=99). Primary endpoints: major adverse events (MAE) and effectiveness (aneurysm exclusion, absence of endoleak/enlargement) through 1 year. 24-month follow-up provided. Results: EXCLUDER showed significant benefits in secondary outcomes (blood loss, ICU stay, hospital length of stay, recovery time). 24-month survival 87% (EBE) vs 93% (Control); freedom from aneurysm-related death 98% (both). MAE rates significantly lower for EBE at 24 months (47% vs 66%).

Technological Characteristics

Materials: ePTFE/FEP graft, Nitinol wire frame. Dimensions: Trunk 23-28.5mm diameter, 16-18cm length; extenders 3.3-7cm length. Sensing/Actuation: Mechanical deployment via delivery catheter. Connectivity: None. Sterilization: Not specified. Algorithm: None.

Indications for Use

Indicated for patients diagnosed with infrarenal abdominal aortic aneurysms (AAA) requiring exclusion from blood circulation, possessing adequate iliac/femoral access, infrarenal aortic neck diameter 19-26 mm, minimum neck length 15 mm, and proximal neck angulation = 60°. Extenders indicated for additional length/sealing post-bifurcated graft deployment.

Submission Summary (Full Text)

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# Summary of Safety and Effectiveness Data (SSED)
EXCLUDER™ Bifurcated Endoprosthesis

## 1.0 General Information

Device Generic Name
Endovascular Graft

Device Trade Name
EXCLUDER™ Bifurcated Endoprosthesis
(See Pages 11-12 for model numbers)

Applicant's Name and Address
W. L. Gore & Associates, Inc.
1327 Orleans Drive
Sunnyvale, CA 94089

PMA Application Number
P020004

## 2.0 Indications and Usage

### 2.1 Trunk-Ipsilateral Leg Endoprosthesis and Contralateral Leg Endoprosthesis Components

The EXCLUDER Bifurcated Endoprosthesis is intended to exclude the aneurysm from the blood circulation in patients diagnosed with infrarenal abdominal aortic aneurysms (AAA) disease and who have appropriate anatomy as described below:

- Adequate iliac/femoral access
- Infrarenal aortic neck treatment diameter range of 19-26 mm and a minimum aortic neck length of 15 mm.
- Proximal aortic neck angulation = 60°.
- Iliac artery treatment diameter range of 8-13.5 mm and iliac distal vessel seal zone length of at least 10 mm.

### 2.2 Aortic Extender Endoprosthesis and Iliac Extender Endoprosthesis Components

The EXCLUDER Extender Endoprostheses (Aortic and Iliac) are intended to be used after deployment of the EXCLUDER Bifurcated Endoprosthesis. These extensions are intended to be used when additional length and/or sealing for aneurysmal exclusion is desired.

## 3.0 Contraindications

There are no known contraindications for these devices.

## 4.0 Warnings and Precautions

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

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# 5.0 Device Description

# 5.1 Trunk-Ipsilateral Leg Endoprosthesis and Contralateral Leg Endoprosthesis Components

The EXCLUDER Bifurcated Endoprosthesis is comprised of two components, the Trunk-Ipsilateral Leg Endoprosthesis (Trunk) (Figure 1) and the Contralateral Leg Endoprosthesis (Figure 2). The graft material is expanded polytetrafluoroethylene and fluorinated ethylene propylene (ePTFE and FEP), and is supported by Nitinol wire along its external surface. Nitinol anchors and an ePTFE/FEP sealing cuff are located at the aortic end of the trunk (Figure 1). An ePTFE/FEP sleeve is used to constrain the endoprostheses on the leading end of the delivery catheters.

Deployment of both endoprosthesis components initiates from the leading (aortic) end and proceeds toward the trailing (iliac) end of the delivery catheter (Figures 3A, 3B, and 3C). The ePTFE/FEP sleeve remains in situ between the endoprosthesis and the vessel wall.

Figure 1: Trunk-Ipsilateral Leg Endoprosthesis

# Trunk-Ipsilateral Leg Endoprosthesis Radiopaque Markers

Three (3) short markers at the aortic end.
- One (1) long and one (1) short marker at the endoprosthesis bifurcation level. The long marker denotes the contralateral leg side location and orientation.
One (1) marker ring at the opening of the contralateral leg hole.
One (1) short marker at the iliac end of the ipsilateral leg.

Figure 2: Contralateral Leg Endoprosthesis

# Contralateral Leg Endoprosthesis Radiopaque Markers

One (1) marker at each end

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Figure 3A: EXCLUDER Bifurcated Endoprosthesis Delivery Catheter

Figure 3B: Constrained EXCLUDER Bifurcated Endoprosthesis (Trunk-Ipsilateral) on Delivery Catheter with Radiopaque Markers

Figure 3C: Constrained EXCLUDER Bifurcated Endoprosthesis (Contralateral) on Delivery Catheter with Radiopaque Markers

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# 5.2 Aortic Extender Endoprosthesis and Iliac Extender Endoprosthesis Components

# 5.2.1 Aortic Extender Endoprosthesis

The Aortic Extender Endoprosthesis (Aortic Extender) provides an extension of approximately 1.6 cm of the leading (proximal) end of the Trunk-Ipsilateral Leg Endoprosthesis (Trunk). This extension also allows a minimum of approximately 1.6 cm overlap with the Trunk, and can be overlapped with the Trunk at increasing length, until completely seated within the Trunk if necessary. This allows for customization of extender length based on patient anatomy and physician preference. The graft material is expanded polytetrafluoroethylene and fluorinated ethylene propylene (ePTFE and FEP), and is supported by Nitinol wire along its external surface. An ePTFE/FEP sealing cuff is located near the proximal end of the endoprosthesis (Figure 4). An ePTFE/FEP sleeve is used to constrain the endoprosthesis on the leading end of the delivery catheter (Figures 5A and 5B). Deployment of the Aortic Extender initiates from the trailing (trunk) end and proceeds toward the leading (aortic) end of the endoprosthesis and delivery catheter. Following deployment, the ePTFE/FEP sleeve remains in situ between the endoprosthesis and the vessel wall.

Figure 4: Aortic Extender Endoprosthesis*

# Aortic Extender Radiopaque Markers (4 total)

Three (3) long markers at the proximal or top end
One (1) short marker at the distal or bottom end
* Note: All dimensions are nominal.

Figure 5A: EXCLUDER Extender Endoprosthesis Delivery Catheter

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Figure 5B: Constrained EXCLUDER Extender Endoprosthesis (Aortic Extender)

Figure 5C: Constrained EXCLUDER Extender Endoprosthesis (Iliac Extender)

# 5.2.2 Iliac Extender Endoprosthesis

The Iliac Extender Endoprosthesis (Iliac Extender) provides an extension of up to $4\mathrm{cm}$ of either the ipsilateral or contralateral limb. The extender component can be placed at variable extension lengths from $4\mathrm{cm}$ to $0\mathrm{cm}$ for a complete overlap within the iliac leg component allowing customization of extender treatment length based on patient anatomy and physician preference. The graft material is ePTFE/FEP, and is supported by Nitinol wire along its external surface. A radiopaque marker is located $3\mathrm{cm}$ from the proximal or top end (Figures 5C and 6). This marker denotes the recommended minimum overlap with the ipsilateral or contralateral limb of the EXCLUDER Bifurcated Endoprosthesis. An ePTFE/FEP sleeve is used to constrain the endoprosthesis on the leading end of the delivery catheter (Figures 5A and 5C). Deployment of the Iliac Extender initiates from the leading (aortic) end and proceeds toward the trailing (iliac) end of the delivery catheter. Following deployment, the ePTFE/FEP sleeve remains in situ between the endoprosthesis and the vessel wall.

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Figure 6: Iliac Extender Endoprosthesis*

Iliac Extender Radiopaque Markers (3 total)
- Two (2) end markers: One (1) at each end
- One (1) marker located 3 cm below the proximal end
* Note: All dimensions are nominal.

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Table 5.1 Trunk-Ipsilateral Leg Endoprosthesis Sizes

| Part Number | Endoprosthesis Aortic Diameter [mm] | Endoprosthesis Iliac Diameter [mm] | Endoprosthesis Length [cm] |
| --- | --- | --- | --- |
| PCT231216 | 23 | 12 | 16 |
| PCT231218 | 23 | 12 | 18 |
| PCT231416 | 23 | 14.5 | 16 |
| PCT231418 | 23 | 14.5 | 18 |
| PCT261216 | 26 | 12 | 16 |
| PCT261218 | 26 | 12 | 18 |
| PCT261416 | 26 | 14.5 | 16 |
| PCT261418 | 26 | 14.5 | 18 |
| PCT281216 | 28.5 | 12 | 16 |
| PCT281218 | 28.5 | 12 | 18 |
| PCT281416 | 28.5 | 14.5 | 16 |
| PCT281418 | 28.5 | 14.5 | 18 |

Table 5.2 Contralateral Leg Endoprosthesis Sizes

| Part Number | Endoprosthesis Proximal Diameter [mm] | Endoprosthesis Iliac Diameter [mm] | Endoprosthesis Length [cm] |
| --- | --- | --- | --- |
| PCC121000 | 16 | 12 | 10 |
| PCC121200 | 16 | 12 | 12 |
| PCC121400 | 16 | 12 | 14 |
| PCC141000 | 16 | 14.5 | 10 |
| PCC141200 | 16 | 14.5 | 12 |
| PCC141400 | 16 | 14.5 | 14 |

Table 5.3 Aortic Extender Endoprosthesis Sizes

| Part Number | Endoprosthesis Diameter [mm] | Endoprosthesis Lengths [cm] |
| --- | --- | --- |
| PCA230300 | 23 | 3.3 |
| PCA260300 | 26 | 3.3 |
| PCA280300 | 28.5 | 3.3 |

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Table 5.4 Iliac Extender Endoprosthesis Sizes

| Part Numbers | Endoprosthesis Proximal Diameter [mm] | Endoprosthesis Iliac Diameter [mm] | Endoprosthesis Length [cm] |
| --- | --- | --- | --- |
| PCL161007 | 16 | 10 | 7 |
| PCL161207 | 16 | 12 | 7 |
| PCL161407 | 16 | 14.5 | 7 |

## 6.0 Alternative Practices and Procedures

The generally accepted treatment for AAA repairs is surgical repair, which involves dissecting the aneurysm and placing a synthetic graft inside the diseased tissue. AAA diagnosed patients who are considered good or acceptable surgical and anesthetic risk are recommended for elective surgical repair when the aneurysm shows rapid growth, becomes symptomatic, or reaches a maximum diameter generally greater than 4.5 cm.

AAA diagnosed patients who are considered unacceptable surgical or anesthesia risk candidates may be medically managed and closely monitored, or recommended for endovascular repair.

## 7.0 Marketing History

The EXCLUDER Bifurcated Endoprosthesis has been commercially available throughout the world, including Europe, Asia, Latin America and Australia since 1998. The EXCLUDER Bifurcated Endoprosthesis has not been withdrawn from marketing in any country for any reason, including safety or effectiveness.

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# 8.0 Adverse Events

## 8.1 Observed Adverse Events

A US multi-center, prospective study conducted at 19 centers which included 235 test subjects and 99 control subjects provide the basis of the observed adverse event rates presented in Table 8.1.

Table 8.1 Major Adverse Events

| Major Adverse Events | Early (≤ 30 days) | | | Late (> 30 days to 12 months) | | |
| --- | --- | --- | --- | --- | --- | --- |
| | EXCLUDER Bifurcated Endoprosthesis 235 (%) | Control 99 (%) | EXCLUDER Bifurcated Endoprosthesis 231 (%) | Control 97 (%) | Control 97 (%) | |
| Deaths | 3 1% | 0 0% | 14 6% | 5 5% | | |
| Other Adverse Events | | | | | | |
| Aneurysm Size Increase with an Intervention | 0 0% | N/A N/A | 1 0.4% | N/A N/A | | |
| Bleeding^{1,2} | 10 4% | 32 32% | 1 0.4% | 1 1% | | |
| Bowel^{1} | 5 2% | 16 16% | 6 3% | 3 3% | | |
| Cardiac^{1} | 7 3% | 14 14% | 16 7% | 13 13% | | |
| Endoleak with an Intervention | 0 0% | N/A N/A | 13 6% | N/A N/A | | |
| Genitourinary | 1 0.4% | 1 1% | 6 3% | 1 1% | | |
| Neoplasm | 1 0.4% | 0 0% | 3 1% | 1 1% | | |
| Neurologic | 1 0.4% | 2 2% | 7 3% | 1 1% | | |
| Pulmonary^{1} | 3 1% | 12 12% | 10 4% | 4 4% | | |
| Renal | 2 1% | 3 3% | 5 2% | 0 0% | | |
| Vascular^{1} | 3 1% | 6 6% | 7 3% | 5 5% | | |
| Wound | 7 3% | 4 4% | 9 4% | 2 2% | | |
| Other Complications | 0 0% | 2 2% | 12^{3} 5% | 4 4% | | |

Major Adverse Events from Clinical Study

1. Differences between groups are significantly different for Early Adverse Events (≈ 30 days).
2. The major adverse event Bleeding threshold for both EXCLUDER Bifurcated Endoprosthesis and control patients is defined as procedural blood loss > 1000 cc requiring intervention.
3. "Other Complications" in the EXCLUDER Bifurcated Endoprosthesis group were identified by physicians as follows:
1. Reaction to chemotherapy
2. Right axillary hematoma - post transaxillary arteriogram
3. Self inflicted gunshot wound to the head
4. Cholelithiasis with recurrent pancreatitis
5. Recurrent macular pucker, left eye

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6. Fractured left humerus with hospitalization
7. Fractured left wrist, injured shoulder and right wrist (fall in hospital while there for ascites)
8. Thrombosis of known popliteal aneurysm
9. Fractured right femur
10. Bilateral carotid stenosis
11. Gynecomastia
12. Cataract and macular pucker, right eye

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## 8.2 Potential Device or Procedure Related Adverse Events

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

- amputation
- 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
- 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
- neurologic damage, local or systemic (e.g., stroke, paraplegia, paraparesis)
- occlusion of device or native vessel
- pulmonary complications (e.g., pneumonia, respiratory failure)
- renal (e.g., artery occlusion, contrast toxicity, insufficiency, failure)
- surgical conversion
- wound (e.g., infection, dehiscence)
- vascular spasm or vascular trauma (e.g., ilio-femoral vessel dissection, bleeding, rupture, death)

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# 9.0 Summary of Pre-clinical Results

# 9.1 Biocompatibility

Toxicology and biocompatibility testing was conducted for materials in the EXCLUDER Bifurcated Endoprosthesis System. Testing was conducted in accordance with Federal Good Laboratory Practices per 21 CFR §58. The EXCLUDER Bifurcated Endoprosthesis was classified per ISO 10993 as an implant device with permanent contact. The EXCLUDER Bifurcated Endoprosthesis delivery catheter was classified as an externally communicating device with limited exposure ( $\leq$ 24 hr).

Table 9.1 summaries the biocompatibility test results for the implant. Table 9.2 summarizes the biocompatibility test results for the catheter.

Table 9.1 Summary of Biocompatibility Test Results for the Implant

| Test Name | Test Method | Results |
| --- | --- | --- |
| Cytotoxicity | MEM Elution Test – ISO | Non-Cytotoxic |
| Sensitization | Kligman Maximization Study – ISO | Non-Sensitizing |
| Irritation/Intracutaneous Toxicity | Intracutaneous Injection Test - ISO | Negligible Irritant |
| Acute Systemic Toxicity | Systemic Injection Test - ISO | No significantly greater biological reaction than the controls. |
| Pyrogenicity | Rabbit Pyrogen Test (Material Mediated) -ISO | Non-Pyrogenic |
| Hemocompatibility | Hemolysis: Direct Contact-Rabbit Blood – ISO | Non-Hemolytic |
| Subchronic Toxicity | Canine Implant Study | No Systemic Effects Observed |
| Genotoxicity/Mutagenicity | Salmonella typhimurium and Escherichia coli Reverse Mutation Assay –ISO | Non-Mutagenic |
| | CHO/HGPRT Forward Mutation Assay –ISO | Non-Mutagenic |
| | Chromosomal Aberration Assay –ISO | Non-Clastogenic |
| Implantation | Intramuscular Implantation –ISO | Test Article and Negative Control had Comparative Results |
| Chronic Toxicity | Canine Implant Study | No Systemic Effects Observed |

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Table 9.2 Summary of Biocompatibility Test Results for the Catheter

| Test Name | Test Method | Results |
| --- | --- | --- |
| Cytotoxicity | MEM Elution Test – ISO | Non-Cytotoxic |
| Sensitization | Kligman Maximization Study – ISO | Non-Sensitizing |
| Irritation/Intracutaneous Toxicity | Intracutaneous Injection – ISO | Negligible Irritant |
| Acute Systemic Toxicity | Systemic Injection Test – ISO | Non-Toxic |
| Pyrogenicity Test | Rabbit Pyrogen Test (Material Mediated) – ISO | Non-Pyrogenic |
| Hemocompatibility | Hemolysis Rabbit Blood – ISO | Non-Hemolytic |

All test results indicate that the materials and processes used to manufacture the EXCLUDER implant and catheter are biocompatible and suitable for their intended use.

## 9.2 Product Testing

W. L. Gore and Associates, Inc. (GORE), conducted comprehensive pre-clinical bench and analytical testing on the EXCLUDER Bifurcated Endoprosthesis (EBE) implant and delivery system. The express intent of this in vitro testing was to verify that the performance attributes of the EBE system are sufficient to minimize the risk of adverse events under anticipated clinical use conditions. Results obtained from the in vitro test regimen provide evidence substantiating the safety and effectiveness of the EBE system.

A summary of results is presented below for each of the in vitro tests. Table 9.4 summarizes test results associated with the functional requirements of the delivery system, and Table 9.5 summarizes test results related functional requirements of the implant.

The results of the in vitro testing, taken as a whole, demonstrate that the EBE system meets established functional requirements for aortic endovascular devices. Furthermore, these data substantiate the safety and effectiveness of the EBE system, which, consequently, is expected to perform as intended when used in accordance with its labeled indications.

## 9.2.1 Delivery System Test Results Summary

The following table contains test results that were performed to evaluate the ability of the EBE delivery system to access the implant location, accurately deploy the device, safely withdraw the delivery system catheter, maintain hemostasis, and be fluoroscopically visualized.

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Table 9.3 Summary of Test Results Related to the EBE Delivery System Functionality

| In Vitro Test | Relevant Functional Requirement | Summary of Test Results |
| --- | --- | --- |
| Catheter Angular Rotation to Failure Test | ·Ability to access the intended location ·Ability to deploy the implant ·Ability to withdraw the delivery system | Twenty sterilized, finished delivery systems with mounted devices were tested in a 37°C water bath to determine angular rotation to failure. All delivery systems were tested in both clockwise and counter-clockwise rotation of 360° and then to failure noting the failure angle and failure. Based on the results of these tests, the EBE delivery catheters would not be expected to fail in torsion during anticipated clinical use. |
| Catheter Bond Tensile Strength Test | ·Ability to access the intended location ·Ability to deploy the implant ·Ability to withdraw the delivery system | The longitudinal tensile strength of the critical bonds and joints of the EBE delivery catheters were determined. A total of 158 catheter bonds were tested. Results indicate that there is at least 95% confidence level that the minimum tensile strength of each critical catheter junction will exceed the ISO 10555-1 standard of 3.37lbf. |
| Catheter Deployment Knob-Line Assembly Tensile Test | ·Ability to deploy the implant | The tensile strength of the catheter deployment knob/line assembly (n=60) was determined to demonstrate conformance to design requirements. Mean deployment knob/line assembly strength was 4.06 lbf. The data demonstrates that there is at least 95% confidence that there is a 95% probability that any individual deployment knob/line tensile strength exceeds the maximum expected deployment force. |
| Catheter Leak Test | ·Hemostasis of the delivery system | The leak resistance of the delivery catheters was evaluated. No catheter leakage was observed in any of the test samples when tested up to pressures of 20 atmospheres. These data indicate there is a 95% confidence that there is at least a 95% probability that any EBE delivery catheter will meet the minimum design requirement of 1.5 atm. |
| Catheter Length Test | ·Ability to access the intended location ·Ability to deploy the implant | The minimum and maximum expected catheter working lengths for 60 delivery system configurations tested met the established design specifications at a minimum confidence level of 95%. |
| Catheter Profile Test | ·Ability to access the intended location ·Ability to deploy the implant ·Ability to withdraw the delivery system ·Hemostasis of the delivery system | A total of 114 measurements were made on a total of 90 final sterilized delivery catheters. All tested catheter shafts met the design specifications (0.130mm ± 0.002mm) with at least 95% confidence. Compatibility with recommended introducer sheath accessories is expected. |
| Catheter Torsional Bond Strength Test | ·Ability to access the intended location ·Ability to deploy the implant | The torsional strength of the two catheter junctions that will be subjected to the greatest torsional load during deployment were determined to have torsional bond strengths significantly in excess of established |

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| In Vitro Test | Relevant Functional Requirement | Summary of Test Results |
| --- | --- | --- |
| | • Ability to withdraw the delivery system | design specifications. The results show that the catheter junctions can withstand up to 160 inches – ounces of torque without any failures, to a confidence/reliability level of 95%/95%. |
| Delivery System Accessory Compatibility | • Ability to access the intended location
• Ability to deploy the implant
• Ability to withdraw the delivery system
• Hemostasis of the delivery system | A total of 60 sterilized, finished devices were tested for dimensional compatibility; all tested samples successfully passed the guidewire through the lumen and were able to be passed through the appropriately sized sheath. All delivery system configurations were dimensionally compatible with the recommended guidewires and 12F and 18F introducer sheaths per established design specifications. |
| Delivery System Deployment Force Test | • Ability to deploy the implant | The force required to deploy the EBE was determined. The mean peak deployment force of the Trunk-Ipsilateral Leg component was 1.70lbf; the mean peak deployment force of the Contralateral Leg component was 1.23 lbf. Using the Trunk-Ipsilateral Leg as a conservative measure of expected deployment force, the one sided upper bound from the prediction interval for individual peak deployment force is 2.11 lbf. The maximum expected deployment force does not exceed the minimum expected strength of the EBE delivery catheter deployment knob/line tensile strength. |
| Delivery System Deployment Reliability Test | • Ability to access the intended location
• Ability to deploy the implant
• Ability to withdraw the delivery system | A comprehensive evaluation of in vitro deployments was conducted in a clinically relevant model at 37° C. A total of 284 finished sterilized devices including appropriate introducer sheaths, guidewires, and balloon catheters were used and were tested with 100% deployment success. Binomial statistics demonstrate with a 95% confidence level that at least 98% of the EBE will access the intended implant location, safety deploy the implant, and be successfully withdrawn when used in a manner consistent with labeling or under anticipated clinical use. |
| Delivery System Radiopacity Confirmation Test | • Fluoroscopic visualization | Tissue density was simulated by aluminum plates of varying densities: 1.0 cm, 2.0 cm, and 3.0 cm. An Integris V-3000 (Phillips Imaging, Inc.) digital fluoroscope was used for imaging. The results of the in vitro radiopacity testing show that the radiopacity of the EBE delivery systems have sufficient radiopacity for clinical use. |
| Delivery System Torquability Test | • Ability to access the intended location
• Ability to deploy the implant | The torque response of the delivery system and the torque effect on deployment reliability were evaluated. All 130 tested delivery systems exhibited acceptable torque response after being tracked through an in vitro aneurysmal deployment model. |

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| In Vitro Test | Relevant Functional Requirement | Summary of Test Results |
| --- | --- | --- |
| | • Ability to withdraw the delivery system | Acceptable torque response was defined as 360° rotation clockwise and counterclockwise from the neutral position in the Trunk-Ipsilateral Leg component and, for the Contralateral Leg component and extenders, distal tip rotation of at least 90°. All tested delivery systems deployed successfully after being subjected to design-specific torque testing. |
| Sewn Sleeve (Corset) Burst Strength Test | • Ability to access the intended location
• Ability to deploy the implant | The burst strength of representative corsets was characterized (150 – 593 psi) and determined to be adequate to constrain the stent-graft prior to implantation. |

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# 9.2.2 Implant Test Results Summary

The following table contains tests results that were performed to assess the EBE implant's ability to accurately deploy, fixation effectiveness, durability, ability to exclude the aneurysm (permeability considerations), modularity, sizing, patency, and MRI compatibility, and ability to be fluoroscopically visualized.

Table 9.4 Summary of Test Results Related to the EBE Implant Functionality

| In Vitro Test | Relevant Functional Requirement | Summary of Test Result |
| --- | --- | --- |
| Acute Anchoring Test | ·Fixation effectiveness of the implant | Acute resistance to migration of the EBE was demonstrated under simulated physiological conditions when used in a manner consistent with those set forth in the Instructions for Use (over-sizing, appropriate device placement, post-deployment balloon touch-up). For this test, maximum allowable device displacement after deployment was defined as ± 1 mm. A total of 100 final sterilized EBE components were tested with no observed acute migration after exposure to simulated flow conditions. |
| Accelerated Anchor Fatigue Test | ·Durability and integrity of the implanted device | Anchor fatigue resistance was evaluated for 10 years simulated physiological loading (380 million cycles) under “worst-case” test conditions. Samples were subjected to severe loading, far in excess of clinically expected loads. Only one anchor fatigue fracture out of 112 tested anchors was noted at the ten-year equivalent inspection. The fractured anchor was attached to the stent-graft. No compromise of device function was noted. From the data generated from this “worst-case” testing, it is expected that the anchors will survive ten years of pulsatile loading under anticipated physiological conditions without fatigue related anchor fracture or compromise of device fixation. |
| Deployment Accuracy Test | ·Ability to accurately deploy | The Aortic Extender was selected for deployment testing as it is the component most likely to produce deployment inaccuracies. Based on testing in straight and angulated segments of an in vitro test model, the EBE is expected to be deployed no more than 5 mm proximal to the intended implant site at a 95% confidence level. Testing was performed on 39 final sterilized Aortic extenders using a physiological pulsatile pressure and flow model maintained at 37°C. All samples met the acceptance criteria of deployment within 5 mm proximal of the intended location. |
| Endoprosthesis Radiopacity Confirmation Test | ·Fluoroscopic visualization | The radiographic visibility of the EBE was determined to be sufficient for clinical use when compared to clinically validated devices under a range of simulated tissue densifications. Tissue density was simulated by aluminum plates of varying densities: 1.0 cm, 2.0 cm, |
| | | 1.0 cm, 2.0 cm, and 3.0 cm. The EBE is also used to evaluate the ability of the implant to perform a full-simulated motion. |

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| In Vitro Test | Relevant Functional Requirement | Summary of Test Result |
| --- | --- | --- |
| | | and 3.0 cm. An Integris V-3000 (Phillips Imaging, Inc.) digital fluoroscope was used for imaging. The results of the in vitro radiopacity testing show that the radiopacity of the EBE delivery systems have sufficient radiopacity for clinical use. |
| Finite Element Analysis | • Durability and integrity of the implanted device | The location and magnitude of the maximum strains in the EBE Nitinol wire frame were analytically determined as a function of radial compression when subjected to catheter loading and an in vivo pulsatile loading environment. Peak strain magnitudes at simulated catheter loading are predicted to be below the ultimate tensile strain of the Nitinol wire. Maximum strain locations and values determined from the simulated in vivo pulsatile loading were subsequently used as a reference in appropriate in vitro testing including pulsatile fatigue testing and wear and migration testing. |
| Integral Water Permeability | • Fixation effectiveness of the implant
• Permeability considerations
• Testing of the modularity of the endovascular system | The integral water permeability of the EBE modular components was determined. Integral Water Permeability of all EBE components was calculated and shown to be between 0.05 and 1.57 ml/min/cm² using methods defined in AMSI/AAMI VP20 – 1994. The integral water permeability observed in the 129 EBE devices tested is less than the water permeability of polyester materials used in endovascular and vascular applications. |
| Longitudinal Tensile Strength Test | • Durability and integrity of the implanted device | The longitudinal tensile strength of 44 final sterilized EBE devices was characterized and compared to the appropriate ePTFE graft design specifications using the methods as defined in ANSI/AAMI VP20 - 1994. All tensile strengths exceed the established specifications of 4.14 kg. |
| Magnetic Resonance Imaging Safety Test | • MRI compatibility | The EBE is not expected to present an additional hazard or risk when implanted in a patient subjected to MRI at 1.5-Tesla. There were no observable magnetic field interactions, minimal MRI-related heating (<1.0°C), and only minor image artifacts. The device has therefore been determined to be MRI safe under these conditions. |
| Microscopic Determination of Porosity Test | • Permeability considerations
• Patency of the implant | The fibril length of the ePTFE material comprising the luminal surface of the EBE was determined using methods defined in ANSI/AAMI VP20 - 1994. The data from 25 final sterilized EBE devices (10 measurements in 3 regions per sample) ranged from 20.0 - 26.2 μm. The fibril length of the EBE luminal surface is consistent with that of GORE-TEX® Vascular Grafts successfully used in aortic applications. |

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| In Vitro Test | Relevant Functional Requirement | Summary of Test Result |
| --- | --- | --- |
| Nitinol Material Analysis Test | • Durability and integrity of the implanted device | The bulk material and surface of the Nitinol wire used for the EBE were chemically analyzed and quantified, indicating 55 weight percent nickel and 44.5 weight percent titanium, with trace amounts of carbon, oxygen, and hydrogen. The surfaces of the wire were also examined under SEM to detect defects and contamination. The bulk material analysis and surface analysis met design requirements. Surface observations with SEM demonstrated a consistently smooth wire surface with no unacceptable anomalies such as pitting, cracks, or contaminants. |
| Nitinol Stent Corrosion Resistance Test | • Durability and integrity of the implanted device | The corrosion resistance of both the Nitinol wire and the complete EBE was analyzed using potentiodynamic polarization testing in a simulated in-vitro environment (Hanks Balanced Salt Solution pH 7.4 at 37° C). The results of the potentiodynamic polarization tests showed that the average corrosion rate predicted for the base Nitinol wire stent is 343 x 10^{-6} mm/yr, whereas the EBE device is 10 fold less, or 34 x 10^{-6} mm/yr. The finished EBE device has an average predicted corrosion rate less than 316L stainless steel under the test conditions. |
| Nitinol Thermo-mechanical Properties Test | • Durability and integrity of the implanted device. | The thermodynamic and mechanical attributes of the Nitinol wire used in the EBE were assessed for conformance with established design specifications. All test articles had an austenitic finish temperatures (A_{f}) below 35°C, and therefore met the established design specifications. Tensile testing was performed on samples of all wire sizes to characterize the mechanical properties of the material. These properties include tensile strength, mean elongation at break, ultimate tensile loading plateau, and tensile permanent set after deformation. The results demonstrate that the mechanical properties of the processed wire meet or exceed, as appropriate, the established acceptance criteria. Samples of the three diameters of Nitinol wire utilized in device manufactured on tensile testing recorded the following material characteristics: ultimate tensile strength (range 1471 – 1512 MPa), mean elongation at break (range 11.2 – 12.4 %), mean tensile loading plateau (range 535 – 561 MPa), and mean tensile permanent set (0.04 – 0.15%) after initial deformation. |
| Pull Test for Modular Components | • Testing of the modularity of the endovascular system | The force required to separate the modular components of the EBE in an in vitro setting was determined using an Instron mechanical tester at 37° C. Mean peak force to pull the Contralateral Leg from the Trunk Ipsilateral Leg ranged from 0.909 lbf to 1.478 lbf. based on 3cm overlap as described in the IFU. The average |

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| In Vitro Test | Relevant Functional Requirement | Summary of Test Result |
| --- | --- | --- |
| | | longitudinal separation (pull-out) forces are expected to be sufficient for clinical use. |
| Pulsatile Fatigue Test | • Durability and integrity of the implanted device | After 10 years simulated physiological loading of 380 million cycles, tested samples were examined visually and with magnification (30x and SEM). There was no evidence of Nitinol wire pitting or cracking, nor of fatigue related fractures. No wear, abrasion, or migration between the overlapping portion of the trunk-ipsilateral leg and contralateral leg were noted. The device was intact after 10 years simulated in vivo physiological loading of 380 million cycles with no perforation or detachment of the ePTFE graft as a result of pulsatile fatigue testing. |
| Radial Compression Strength Test | • Fixation effectiveness of the implant
• Appropriate Sizing of the implant
• Patency of the implant | The radial compression forces of the EBE components were characterized at the appropriate diameters representative of clinically relevant oversizing. Load data were collected for the 23mm Trunk component, 26mm Trunk component, 28.5mm Trunk component, 12mm Contralateral Leg, 14.5mm Contralateral Leg, the 23mm, 26mm and 28.5mm Aortic Extender, and the 10mm Iliac Extender at both 10 and 20 % oversizing. Load data were collected using a 1cm wide ribbon and are representative of the force to uniformly compress 1cm of device length. Radial compression strength ranged from a mean of 0.212 lbf – 0.754 lbf. The radial compression strengths of the EBE are anticipated to be adequate for clinical use. |
| Sealing Test | • Fixation effectiveness of the implant
• Permeability considerations
• Testing of the modularity of the endovascular system | The overall rate of fluid loss around and through the various modular components of the EBE when deployed in a flow model was characterized in 55 sterilized final devices. The total rate of fluid loss for the worst case EBE configurations, inclusive of the leakage at the modular junctions and the permeability of the graft material, was 234-366 ml/min, approximately the permeability of commercially available polyester materials used in vascular and endovascular applications, which range from 310-800 ml/min. |
| Stent-Graft Bend Radius Test | • Ability to accurately deploy
• Fixation effectiveness of the implant
• Patency of the implant | The bend radii (without kinking) of the various components of EBE were characterized using 71 final sterilized devices. Mean bend radii range from 0.39 inches to 1.00 inches, depending on component tested. Comparison to published literature shows that the EBE System is capable of accommodating typical aorto-iliac anatomy without kinking. |

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| In Vitro Test | Relevant Functional Requirement | Summary of Test Result |
| --- | --- | --- |
| Stent-Graft Burst Strength Test | • Durability and integrity of the implanted device | The burst strength of the EBE components was determined and compared to the appropriate ePTFE graft design specifications per ANSI/AAMI VP:20 – 1994. Mean burst strength ranged from 76.4 psi – 126.4 psi on the 43 components tested (trunk, leg or extender). All burst strengths exceeded the minimum design requirements. |
| Stent-Graft Diameter and Wall Thickness Test | • Testing of the modularity of the endovascular system
• Appropriate sizing of the implant | The outer diameters and wall thickness of the deployed EBE components were characterized and verified in accord with ANSI/AAMI VP:20 – 94. The outer diameter and wall thickness of 120 final sterilized EBE devices were tested. All components tested met the appropriate design requirements of 0.002 – 0.012 inches diameter, and stent graft outer diameter of 10.0 – 29.7mm, depending on component size. |
| Stent-Graft Length Test | • Ability to accurately deploy
• Appropriate sizing of the implant | The length of the 90 EBE components, mounted on the delivery catheters was measured and compared to relevant design specifications in a manner consistent with ANSI/AAMI VP:20-94. Acceptance criteria range from ± 0.3cm - ± 0.6cm from the nominal length. All devices tested met the acceptance criteria. |
| Stent-Graft Profile Test | • Appropriate sizing of the implant | The profiles of 80 final sterilized EBE devices mounted on delivery catheters were assessed to assure dimensional compatibility with recommended introducer sheath sizes per ISO/CD 15539-1 (Draft 2000). All devices were successfully passed through the appropriate hole gauge. |
| Wear and Migration Test | • Fixation effectiveness of the implant
• Durability and integrity of the implant
• Testing of the modularity of the endovascular system | Endoprosthesis integrity was intact after 5 and 10 years simulated physiological loading of 190 million and 380 million cycles, respectively. Test conditions included simulated compliance of 4-7% with pulsatile pressures cycle between approximately 90mm Hg and 130mm Hg. Although test specimens showed artifactual evidence of extensive pulsatile testing, no modular component migration or wire fatigue fracture was noted. Neither significant detachment of the stent-graft, nor wear-induced perforations were noted. There was no obstruction of the graft lumen. |

A robust test and analysis regimen was constructed to characterize the mechanical attributes of the EBE. The results of the in vitro testing, taken as a whole, demonstrate that the EBE system meets established functional requirements for aortic endovascular devices. Furthermore, these data substantiate the safety and effectiveness of the EBE system by providing evidence that the mechanical attributes of the device have met design goals appropriate for the repair of abdominal aortic aneurysms.

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## 9.3 Animal Studies

Three preclinical *in vivo* studies were conducted to evaluate the performance of the EXCLUDER Bifurcated Endoprosthesis. A canine model was used to assess the ability of the delivery system to successfully access the target site, deploy the graft and be withdrawn from the vasculature, to assess device functionality, and to assess the sub-chronic and chronic biological response to the implanted endoprosthesis. A bovine model, in a near human-size animal, was used for acute assessment of the delivery system to successfully access the target site, deploy the graft and be withdrawn from the vasculature, and the ability of the device to resist migration. An additional bovine model was used to evaluate the deployment system and device functionality of Aortic and Iliac Extender Endoprostheses. A summary of these studies follows in Table 9.5.

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Table 9.5 Summary of Preclinical In Vivo Studies

| Animal Study | #/ Type of Animal | Test Article | Methods | Results/ Conclusions |
| --- | --- | --- | --- | --- |
| Sub-chronic and Chronic Study of Bifurcated Endoprosthesis | 15 Canines | Scaled-down, trunk-ipsilateral leg, contralateral leg devices, and delivery catheter. | Catheter delivery and device functionality were assessed sub-chronically and chronically in 15 animals. Two sub-chronic animals were maintained in life for approximately one week. Additionally, three canines were maintained in life for one month, one canine for two months, three canines for three months, and four canines for six months. Two canines in the chronic phase were retrieved within one day post-op. | All devices were successfully delivered and deployed. The functional requirements of the device were met and the devices performed as intended. All devices were patent at retrieval, and the host tissue response was judged to be acceptable at both gross and histological examination. There was no evidence of device/component migration or graft disruption. |
| Acute Study of Bifurcated Endoprosthesis | 6 Bovines | Human size, trunk-ipsilateral leg, contralateral leg devices, and delivery catheter. | Six bovines were assessed for acute delivery catheter and device functionality. | All devices were successfully and accurately deployed. The devices were patent and exhibited normal antegrade flow after deployment. There was no evidence of migration or graft disruption. |
| Acute Study of Aortic and Iliac Extenders | 2 Bovines | Human size, aortic and iliac extender devices. Short trunk endoprosthesis and delivery catheter. | Six aortic extenders on long catheters, six iliac extenders on catheters, and six short trunks were deployed in two bovines. These animal procedures were assessed for acute delivery catheter and device performance of the aortic and iliac extender components. | All devices were successfully deployed. Both aortic and iliac extenders could be accurately placed and deployed within another stent-graft or separately. Radiographic evidence showed that no migration had occurred during the acute phase. Post-deployment angiography showed patency. |

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# 10.0 Summary of Clinical Studies

## 10.1 Objectives

The primary objective of the clinical study was to evaluate the safety and effectiveness of the EXCLUDER Bifurcated Endoprosthesis as an alternative to open surgical repair in the primary treatment of infrarenal abdominal aortic aneurysms. Safety was determined by evaluating whether the EXCLUDER Bifurcated Endoprosthesis subjects would have a total proportion of major adverse events that is less than the subjects treated with open surgical repair as evaluated through one year follow-up. Effectiveness was based on exclusion of the aneurysm including the absence of any endoleak, the absence of aneurysm enlargement (≈ 5 mm), and the absence of major device efficacy adverse events evaluated through one year follow-up. Secondary objectives included an assessment of clinical benefit and quality-of-life measures.

## 10.2 Study Design

This prospective, non-randomized, multi-center clinical study was designed to compare patients treated with endovascular repair to an open surgical repair control group. Nineteen US sites enrolled 235 EXCLUDER Bifurcated Endoprostheses and 99 control subjects. The control group included patients whose vascular anatomy may not have been suitable for endovascular AAA repair. The ratio of EXCLUDER Bifurcated Endoprostheses to control subjects was approximately 2:1. Follow-up evaluations were scheduled for pre-discharge, 1 month, 6 months, 12 months and annually thereafter. Twelve and 24 month data are provided in this summary based on findings from an independent Core Lab facility. An independent Core Lab facility reviewed CT scans and abdominal X-rays to assess aneurysm diameter changes, device and relative component migration, device integrity (wire and graft) and the presence and type of endoleaks.

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Table 10.1 Patient Follow-up and Accountability

| Treatment | EXCLUDER Bifurcated Endoprosthesis (N=235)* | | | Control (N=99)* | | |
| --- | --- | --- | --- | --- | --- | --- |
| Post-Procedure Interval | 1 Month | 12 Month | 24 Month | 1 Month | 12 Month | 24 Month |
| Expired | 3 | 14 | 30 | 0 | 5 | 6 |
| Withdrawn / Lost to Follow-up | 0 | 6 | 17 | 2 | 13 | 20 |
| Available Subjects | 232 | 215 | 188 | 97 | 81 | 73 |
| Actual Visit | 226 | 202 | 177 | 88 | 74 | 67 |
| Site CT Imaging | 223 | 199 | 168 | N/A | 68 | 65 |
| Core Lab CT Imaging | 218 | 196 | 155 | N/A | 64 | 62 |
| Site X-ray Imaging | N/A | 163 | 148 | N/A | N/A | N/A |
| Core Lab X-ray Imaging | N/A | 154 | 129 | N/A | N/A | N/A |
| Site Evaluated for Endoleak | 221 | 199 | 165 | N/A | N/A | N/A |
| Core Lab Evaluated for Endoleak | 180 | 156 | 119 | N/A | N/A | N/A |
| Site Evaluated for Aneurysm Enlargement | N/A | 191 | 158 | N/A | N/A | N/A |
| Core Lab Evaluated for Aneurysm Enlargement | N/A | 181 | 146 | N/A | N/A | N/A |

* Data analysis sample size varies for each of the timepoints above and in the following tables. This variability is due to patients available 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. Another example is images that may have been interpretable by the Core Lab for flow channel narrowing but the same images may not necessarily have been interpretable for trunk migration.

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# 10.3 Patient Demographics

Tables 10.2 and 10.3 compare the subject characteristics and initial aneurysm diameter of the EXCLUDER Bifurcated Endoprosthesis and open surgical population, respectively.

Table 10.2 Comparison of Subject Characteristics

| Characteristic | EXCLUDER Bifurcated Endoprosthesis (N=235) | | Control (N=99) | | P-Value |
| --- | --- | --- | --- | --- | --- |
| | N | (%) | N | (%) | |
| Average Age (range in years) | 73.0 | (48-91) | 70.01 | (51-87) | 0.002 |
| Gender: | | | | | |
| Male | 204 | 87% | 73 | 74% | 0.004 |
| Female | 31 | 13% | 26 | 26% | |
| Aneurysm Symptomatic | 11 | 5% | 15 | 15% | <0.001 |
| Arrhythmia | 56 | 24% | 21 | 21% | 0.591 |
| Bleeding Disorder | 11 | 5% | 1 | 1% | 0.119 |
| Cancer | 59 | 25% | 19 | 19% | 0.243 |
| Congestive Heart Failure | 22 | 9% | 8 | 8% | 0.708 |
| COPD | 62 | 26% | 25 | 25% | 0.830 |
| Coronary Artery Disease | 145 | 62% | 53 | 54% | 0.165 |
| Erectile Dysfunction (males only) | 33 | 16% | 10 | 14% | 0.616 |
| Family History of AAA | 14 | 6% | 9 | 9% | 0.307 |
| Hepatic Dysfunction | 6 | 3% | 1 | 1% | 0.679 |
| Inflammatory AAA | 2 | 1% | 1 | 1% | 1.00 |
| Long-Term Use of Steroids | 8 | 3% | 1 | 1% | 0.290 |
| Other Concomitant Aneurysms | 18 | 8% | 13 | 13% | 0.116 |
| Peripheral Arterial Occlusive Disease | 38 | 16% | 14 | 14% | 0.640 |
| Paraplegia | 0 | 0% | 0 | 0% | N/A |
| Prior Vascular Intervention | 26 | 11% | 10 | 10% | 0.796 |
| Renal Dialysis | 0 | 0% | 0 | 0% | N/A |
| Smoking History | 208 | 89% | 84 | 85% | 0.357 |
| Stroke | 26 | 11% | 10 | 10% | 0.818 |
| Thrombotic Event | 17 | 7% | 4 | 4% | 0.332 |
| Valvular Heart Disease | 18 | 8% | 7 | 7% | 0.852 |

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Table 10.3 Aneurysm Diameter Distribution

| Diameter Range | EXCLUDER Bifurcated Endoprosthesis (N=235) | | Control (N=99) | |
| --- | --- | --- | --- | --- |
| | N | (%) | N | (%) |
| < 30 mm | 0 | 0% | 0 | 0% |
| 30 - 39 mm | 0 | 0% | 0 | 0% |
| 40 - 49 mm | 61 | 26% | 15 | 15.3% |
| 50 - 59 mm | 109 | 46.4% | 46 | 46.9% |
| 60 - 69 mm | 44 | 18.7% | 22 | 22.2% |
| 70 - 79 mm | 15 | 6.4% | 10 | 10.2% |
| 80 - 89 mm | 4 | 1.7% | 5 | 5.1% |
| = 90 mm | 2 | 0.9% | 1 | 1.0% |

# 10.4 Results

Data gathered in Tables 10.4 through 10.15 were collected by the clinical study sites and Core Lab. Table 10.4 describes the types of devices implanted into the clinical study patients. Table 10.5 summarizes longer-term device performance compared to control subjects, and Kaplan-Meier data at both 12 and 24 months. Figures 7 through 10 depict Survival at 24 months (Figure 7), Freedom from Aneurysm Related Mortality (Figure 8), Freedom from First Major Adverse Event (Figure 9), and Cumulative Major Adverse Event Rates (Figure 10). Error bars in Figures 7, 8, 9 and 10 represent a $95\%$ confidence limit.

Table 10.4 Devices Implanted

| | N | (%) |
| --- | --- | --- |
| Number of EXCLUDER Bifurcated Endoprosthesis Subjects | 235 | 100% |
| | | |
| Devices Implanted | | |
| Trunk/Ipsilateral Leg and Contralateral Leg1 | 159 | 67% |
| with Aortic Extender(s)2 | 17 | 7% |
| with Iliac Extender(s)3 | 53 | 23% |
| with Aortic and Iliac Extender(s)4 | 6 | 3% |

$N = 5$ Subjects received one Trunk-Ipsilateral Leg Endoprosthesis and two Contralateral Leg Endoprostheses.
$2$ N = 2 Subjects received two Aortic Extender Endoprostheses.
3 N = 9 Subjects received more than one Iliac Extender Endoprosthesis (2, 3, or 4 Iliac Extenders).
4 N = 2 Subjects received two Iliac Extender Endoprostheses.

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Table 10.5 Summary of Kaplan-Meier Curves to 24 Months

| | Total Number of Patients Reaching Follow-up | | Aneurysm Rupture | | Conversion to Surgical Repair | Death | | Aneurysm Related Death1 | | Major Adverse Event | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | T | C | T | C | T | T | C | T | C | T | C |
| | N | N | N | N | N | N (%) | N (%) | N (%) | N (%) | N (%) | N (%) |
| Intra-operative | 235 | 99 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | n/a2 | n/a2 |
| ≤ 30 Days | 235 | 99 | 0 | 0 | 0 | 3 1% | 0 | 3 1% | 0 | 323 14%3 | 563 57%3 |
| > 30 Days to 12 Months | 232 | 97 | 0 | 0 | 0 | 11 5% | 5 5% | 1 0.4% | 2 2% | 57 27% | 24 25% |
| 12 Months to 24 Months | 214 | 82 | 0 | 0 | 04 | 16 7% | 1 1% | 0 | 0 | 37 17% | 10 12% |
| Total Patients (at 24 Months) | 214 | 82 | 0 | 0 | 0 | 30 | 6 | 4 | 2 | 1103 47% | 653 66% |
| Kaplan-Meier Summaries | | | Freedom from Aneurysm Rupture | | Freedom from Conversion | Probability of Survival | | Freedom from Aneurysm Related Death | | Freedom from Major Adverse Event | |
| 12 Month Kaplan-Meier | 232 | 97 | 100% | 100% | 100% | 94% | 95% | 98% | 98% | 65%3 | 36%3 |
| 24 Month Kaplan-Meier | 214 | 82 | 100% | 100% | 100% | 87% | 93% | 98% | 98% | 52%3 | 33%3 |

T = EXCLUDER Bifurcated Endoprosthesis C = Control
1 Aneurysm related death is defined as all deaths due to aneurysm rupture, a primary or secondary procedure, surgical conversion, or within 30 days of the primary or secondary procedure. (Chaikof; J Vasc Surg 2002;35:1048-60)
Major adverse events during the intraoperative period are reported in the $\leq 30$ day period.
3 Statistically significant, $P &lt; .05$
4 Three elective conversions post 24 months. Three elective conversions occurred $&gt;24$ months post-operative. Two conversions were due to aneurysm enlargement and one conversion was due to aneurysm enlargement with a persistent Type II endoleak. All conversions were elective with no ruptures.
5 Total number of patients with a first adverse event only.

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Figure 7: Survival at 24 Months

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Figure 8: Freedom from Aneurysm Related Mortality

Figure 9: Freedom from First Major Adverse Event

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Figure 10: Cumulative Major Adverse Event Rates

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Tables 10.6 through 10.13 describe results of the EXCLUDER Bifurcated Endoprosthesis subjects as reported by the Core Lab. Device performance factors analyzed by the Core Lab included device integrity (Table 10.6), device patency (Table 10.7), migration (Tables 10.8 and 10.9), and aneurysm exclusion (Tables 10.10-10.13). Device integrity encompasses the structural findings of the wire-form via abdominal X-ray images at the corresponding follow-up timepoints.

Table 10.6 Abdominal X-ray Findings - Device Integrity*

| Device Integrity: Abdominal X-ray | Discharge (N=171) | | 6 Months (N=156) | | 12 Months (N=140) | | 24 Months (N=117) | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | N | (%) | N | (%) | N | (%) | N | (%) |
| Subjects Free from Device Integrity Issues | 170 | 99% | 156 | 100% | 140 | 100% | 117 | 100% |
| - Fracture | 1 | 0.6% | 0 | 0% | 0 | 0% | 0 | 0% |

* None resulted in clinical sequelae.

Table 10.7 CT Findings – Narrowing of the Flow Channel*

| CT - Narrowing | 1 Month (N=212) | | 6 Months (N=193) | | 12 Months (N=185) | | 24 Months (N=148) | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | N | (%) | N | (%) | N | (%) | N | (%) |
| EXCLUDER Endoprosthesis | 3 | 1.5% | 0 | 0% | 2 | 1.1% | 2 | 1.4% |

* None affected device patency.

Table 10.8 CT Findings – Trunk Migration*

| CT – Trunk Migration | 6 Month (N=171) | | 12 Months (N=175) | | 24 Months (N=144) | |
| --- | --- | --- | --- | --- | --- | --- |
| | N | (%) | N | (%) | N | (%) |
| Trunk Migration (≥ 10mm) | 5 | 3.0% | 4 | 2.3% | 2 | 1.4% |

* None resulted in clinical sequelae.

Table 10.9 Abdominal X-ray Findings – Component Migration*

| Abdominal X-ray – Component Migration | 6 Month (N=139) | | 12 Months (N=139) | | 24 Months (N=122) | |
| --- | --- | --- | --- | --- | --- | --- |
| | N | (%) | N | (%) | N | (%) |
| Component Migration (≥ 10mm) | 2 | 1.4% | 1 | 1.0% | 1 | 1.0% |

* None resulted in clinical sequelae.

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Table 10.10 Endoleak Status According to Evaluation Interval

| Type of Endoleak* | Evaluation Interval | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | 1 Month (N=180) | | 6 Month (N=177) | | 12 Month (N=156) | | 24 Month (N=119) |
| | N | (%) | N | (%) | N | (%) | N |
| Type 1 | 7 | 4% | 3 | 2% | 2 | 1% | 3 |
| Type II | 21 | 12% | 19 | 11% | 19 | 12% | 16 |
| Type III | 0 | 0% | 0 | 0% | 0 | 0% | 0 |
| Type IV | 0 | 0% | 0 | 0% | 0 | 0% | 0 |
| Indeterminate | 11 | 6% | 14 | 7% | 6 | 4% | 5 |
| Total | 39 | 22% | 36 | 20% | 27 | 17% | 24 |

*As defined by White GH, et. al. JES 1997 and 1998.

Table 10.11 Change in Aneurysm Size by Interval

| Change in Aneurysm Size | 1 Month to 6 Months (N=182) | | 1 Month to 12 Months (N=181) | | 1 Month to 24 Months (N=146) | |
| --- | --- | --- | --- | --- | --- | --- |
| | N | (%) | N | (%) | N | (%) |
| Increase ≥ 5mm | 5 | 3% | 13 | 7% | 21 | 14% |
| No Change | 159 | 87% | 142 | 79% | 97 | 67% |
| Decrease ≤ 5mm | 18 | 10% | 26 | 14% | 28 | 19% |

Table 10.12 Aneurysm Diameter Change with and without Endoleaks at 12-Months

| Aneurysm Change from 1 to 12 Months* | Patients | | With Endoleak at 12 Months* | | Without Endoleak at 12 Months* | |
| --- | --- | --- | --- | --- | --- | --- |
| | N | (%) | N | (%) | N | (%) |
| Increase (≥ 5mm) | 10 | 7% | 4 | 40% | 6 | 60% |
| No Change | 118 | 81% | 19 | 16% | 99 | 84% |
| Decrease (≥ 5mm) | 18 | 12% | 2 | 11% | 16 | 89% |
| Total | 146 | 100% | 25 | 17% | 121 | 83% |

* Only includes subjects with interpretable films (endoleak) and measurements of aneurysm change from 1 to 12 months.

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Table 10.13 Aneurysm Diameter Change with and without Endoleaks at 24-Months*

| Aneurysm Change from 1 to 24 Months* | Patients | | With Endoleak at 24 Months* | | Without Endoleak at 24 Months* | |
| --- | --- | --- | --- | --- | --- | --- |
| | N | (%) | N | (%) | N | (%) |
| Increase (≥ 5mm) | 15 | 13% | 7 | 47% | 8 | 53% |
| No Change | 74 | 66% | 10 | 14% | 64 | 86% |
| Decrease (≥ 5mm) | 23 | 21% | 2 | 9% | 21 | 91% |
| Total | 112 | 100% | 19 | 17% | 93 | 83% |

* P = 0.004 for aneurysm size change and endoleak.
** Only includes subjects with interpretable films (endoleak) and measurements of aneurysm change from 1 to 24 months.

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Secondary interventions within the first and second year each were performed in 6% of the EXCLUDER Bifurcated Endoprostheses subjects as shown in Table 10.14. All interventions were catheter-based except for one surgical ligation. Subjects may have had a single intervention to address both an endoleak and an aneurysm enlargement. No other interventions were performed for any other reason, e.g., migration, limb occlusion, through 24 months.

Table 10.14 Interventions for Endoleak and Aneurysm Size Increases

| Intervention | Post-procedure to 12 Months (N=235) | | >12 Months to 24 Months (N=203) | |
| --- | --- | --- | --- | --- |
| | N | (%) | N | (%) |
| Number of Subjects with ≥ 1 Intervention | 15 | 6% | 12 | 6% |
| Treat an Endoleak: | | | | |
| Embolization | 15 | 6% | 6 | 4% |
| Ligation | 1 | 0.4% | 0 | 0% |
| Conversion to Open Repair | 0 | 0 | 0* | 0% |
| Treat an Aneurysm Increase: | | | | |
| Embolization | 0 | 0% | 5** | 3% |
| Ligation | 1 | 0.4% | 0 | 0% |
| Conversion to Open Repair | 0 | 0% | 0* | 0% |

* Total of three conversions post 24 months.
** Five also had endoleak.

As described in Table 10.15, treatment of AAA with EXCLUDER Bifurcated Endoprosthesis compared to the control group demonstrated significant benefits in recovery and quality of life measures.

Table 10.15 Secondary Outcomes by Treatment Group

| Secondary Outcomes | EXCLUDER Bifurcated Endoprosthesesis | Control |
| --- | --- | --- |
| Blood Loss (ml) | 310 | 1590 |
| Mean (range)* | (50 – 2160) | (100 – 7000) |
| Procedure Transfusion (%) | 14% | 89% |
| Procedure Time (minutes) | 144 | 196 |
| Mean (range)* | (51 – 320) | (67 – 420) |
| ICU Stay (%) | 24% | 87% |
| Hospital Length of Stay (days) | 2 | 9.8 |
| Mean (range)* | (1 – 11) | (3 – 114) |
| Time to First Oral Intake (days) | 0.5 | 2.6 |
| Mean (range)* | (0 – 2.1) | (0.07 – 9.5) |
| Time to Ambulation (days) | 1.0 | 2.6 |
| Mean (range)* | (0 – 5.0) | (0 – 18) |
| Time to Return to Normal Activities | 42 | 92 |
| Mean (days)* | | |

* Statistically significant (P &lt; .0001).

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# 10.5 Evaluation of Gender Bias

Abdominal aortic aneurysm disease is uncommon in women (male:female disease ratio 3:1 to 6:1). When women have AAAs, they less frequently have surgery. EXCLUDER Bifurcated Endoprosthesis subjects exhibited no significant differences between males and females for survival and freedom from major adverse events.

As shown below in Table 10.16, the results for EBE subjects were comparable between males and females. Women did not have an increased rate of early or late adverse events or mortality in the pivotal study. Various safety and other outcomes were compared for males and females in each of the treatment groups.

Table 10.16 Safety Outcomes According to Gender and Treatment Group

| Treatment Group/12-months Outcome | | | Females | |
| --- | --- | --- | --- | --- |
| | % rate | 95% CI | | 95% CI |
| EBE Subjects: | N= 204 | | N=31 | |
| Survival | 94% | 89 – 96% | 97% | 80 – 99.5% |
| Freedom From Major Adverse Events | 66% | 59 – 72% | 70% | 52 – 84% |
| Cumulative Major Adverse Events (per patient)* | 0.8 | 0.7 – 0.9 | 0.4 | 0.2 – 0.6 |
| Control Subjects: | N=73 | | N=26 | |
| Survival | 97% | 89 – 99% | 87% | 67 – 96% |
| Freedom From Major Adverse Events | 35% | 25 – 47% | 38% | 22 – 58% |
| Cumulative Major Adverse Events (per patient) | 1.7 | 1.3 – 2.1 | 1.8 | 1.3 – 2.4 |

* Statistically significant at P = 0.003

Table 10.17 Additional Outcomes According to Gender and Treatment Group

| Treatment Group/Outcome | Males
N % | | Females
N % | |
| --- | --- | --- | --- | --- |
| EBE: | N = 173 | | N = 28 | |
| Aneurysm enlargement (>5mm) at 1-year | 143 | 83% | 23 | 82% |
| Endoleak at 1-year | 26 | 15% | 5 | 18% |

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# 11.0 Conclusions Drawn from the Studies

As compared to conventional open surgery, the clinical benefits of the EXCLUDER Bifurcated Endoprosthesis are a lower rate of major complications, reduced blood loss and blood replacement volume, reduced need for an ICU stay, shorter hospitalization and faster return to normal activities. The risks include procedure- and/or device-related phenomenon, which include but are not limited to endoleaks and increase in aneurysm size.

# 12.0 Panel Recommendation

The Excluder™ Bifurcated Endoprosthesis was presented to the Circulatory System Device Panel on September 9, 2002. The Panel recommended approving the device with conditions. The first condition was mandatory five-year follow-up on all the patients in the pivotal study cohort to assess the long-term safety and effectiveness of the device. The second condition was to re-review the information on the 40 postoperative CT scans that had been classified as "uninterpretable" at the time of the submission to determine if additional information was available concerning these data. The third condition was that the Instructions for Use should stress the sources of co-morbidities and mortality, and that the patient labeling or brochure should include this information as well to provide further information to the physicians and patients concerning these issues.

# 13.0 FDA Decision

FDA reviewed portions of the premarket approval (PMA) application under the modular PMA process (M000014). All of the modules were incorporated into the review of the PMA (P020004).

FDA concurred with the Circulatory System Devices Panel recommendations of September 9, 2002. To address these conditions, W.L. Gore &amp; Associates submitted: 1) a written concurrence to conduct the mandatory five-year follow-up study; 2) information on the 40 postoperative CT scans, which was reviewed by FDA and found acceptable; and 3) revised labeling to address the concerns raised by the panel, which was reviewed by FDA and found acceptable.

FDA also asked the sponsor to provide a clinical update to physicians 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. The sponsor also provided their written concurrence to provide a clinical update to physicians annually on the performance of the device.

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On March 16, 2001 and May 8, 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 P020004 on November 6, 2002.

## 12.0 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.