INCRAFT(R) AAA STENT GRAFT SYSTEM

P150002 · Cordis US Corporation · MIH · Nov 27, 2018 · Cardiovascular

Device Facts

• Record ID: P150002
• Device Name: INCRAFT(R) AAA STENT GRAFT SYSTEM
• Applicant: Cordis US Corporation
• Product Code: MIH · Cardiovascular
• Decision Date: Nov 27, 2018
• Decision: APWD
• Device Class: Class 3
• Attributes: Therapeutic

Intended Use

The INCRAFT® AAA Stent Graft System (INCRAFT) is intended for the endovascular treatment of patients with infrarenal abdominal aortic aneurysms with the following characteristics: - Adequate, but complex iliac or femoral vessel morphology (e.g., high tortuosity index, heavily calcified, small diameter), that is compatible with vascular access techniques, devices or accessories; - Proximal neck length ≥ 10 mm; - Aortic neck diameters ≥ 17 mm and ≤ 31 mm; - Aortic neck suitable for suprarenal fixation; - Infrarenal and suprarenal neck angulation ≤ 60°; - Iliac fixation length ≥ 15 mm; - Iliac diameters ≥ 7 mm and ≤ 22 mm; and - Minimum overall AAA treatment length (proximal landing location to distal landing location) ≥ 128 mm.

Device Story

Modular bifurcated endovascular stent graft system; treats infrarenal abdominal aortic aneurysms. System includes aortic bifurcate prosthesis and iliac limb prostheses; preloaded into delivery system. Deployed under fluoroscopy; creates new blood flow channel to exclude aneurysm. Aortic bifurcate features flared bare transrenal stent with fixation barbs for suprarenal fixation; iliac limbs provide distal seal. Radiopaque markers (tantalum, platinum-iridium) assist in alignment and deployment. Used in hospital setting by vascular surgeons. Output is physical exclusion of aneurysm sac. Benefits include minimally invasive alternative to open surgery for patients with complex vascular access morphology.

Clinical Evidence

Pivotal prospective, multi-center, single-arm study (INSPIRATION, IDE #G120003) of 190 patients (134 US, 56 Japan). Primary safety endpoint: 30-day Major Adverse Event (MAE) rate (3.2%, 95% CI: <6.1%, goal <20%). Primary effectiveness endpoint: successful aneurysm treatment at 1 year (87.9%, 95% CI: 83.0%+, goal >80%). Follow-up through 4 years showed high rates of transrenal stent fractures (17 patients, 31 fractures) and secondary interventions (17.9% total). No aneurysm ruptures reported. Bench testing and animal studies supported biocompatibility and durability.

Technological Characteristics

Modular bifurcated stent graft. Materials: woven polyester graft, laser-cut self-expanding nitinol stent-rings. Fixation: suprarenal bare transrenal stent with barbs. Radiopaque markers: tantalum, platinum-iridium. Delivery system: 0.035" guidewire compatible, hydrophilic coating, disposable. MRI Conditional (1.5T/3T). Sterilization: 100% Ethylene Oxide (EO).

Indications for Use

Indicated for patients ≥ 20 years with infrarenal abdominal aortic aneurysms (AAA) > 5.0 cm or > 0.5 cm growth in 6 months, meeting specific anatomical criteria (neck length ≥ 10 mm, diameter 17-31 mm, angulation ≤ 60°). Contraindicated in patients with known allergy to nitinol, PET, PTFE, tantalum, or platinum-iridium, or conditions threatening graft infection.

Submission Summary (Full Text)

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SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED)

I. GENERAL INFORMATION

Device Generic Name: Endovascular Graft

Device Trade Name: Cordis INCRAFT® AAA Stent Graft System

Device Procode: MIH

Applicant’s Name and Address: Cordis Corporation
1820 McCarthy Boulevard
Milpitas, CA, 95035 U.S.A

Date of Panel Recommendation: June 12, 2018

Premarket Approval Application (PMA) Number: P150002

Date of FDA Notice of Approval: 11/27/2018

II. INDICATIONS FOR USE

The INCRAFT® AAA Stent Graft System (INCRAFT) is intended for the endovascular treatment of patients with infrarenal abdominal aortic aneurysms with the following characteristics:

- Adequate, but complex iliac or femoral vessel morphology (e.g., high tortuosity index, heavily calcified, small diameter), that is compatible with vascular access techniques, devices or accessories;
- Proximal neck length ≥ 10 mm;
- Aortic neck diameters ≥ 17 mm and ≤ 31 mm;
- Aortic neck suitable for suprarenal fixation;
- Infrarenal and suprarenal neck angulation ≤ 60°;
- Iliac fixation length ≥ 15 mm;
- Iliac diameters ≥ 7 mm and ≤ 22 mm; and
- Minimum overall AAA treatment length (proximal landing location to distal landing location) ≥ 128 mm.

III. CONTRAINDICATIONS

The INCRAFT® AAA Stent Graft System is contraindicated in the following patient populations:

- Patients with a known allergy or intolerance to the device materials [i.e., nickel titanium (nitinol), polyethylene terephthalate (PET), polytetrafluoroethylene (PTFE), tantalum, or platinum-iridium alloy].
- Patients who have a condition that threatens to infect the graft.

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# IV. WARNINGS AND PRECAUTIONS

The warnings and precautions can be found in the Cordis INCRAFT® AAA Stent Graft System labeling.

# V. DEVICE DESCRIPTION

The INCRAFT® AAA Stent Graft System (also referred to as INCRAFT) is a modular bifurcated endovascular stent graft system comprised of two main types of devices: the INCRAFT® Stent Graft implant and the INCRAFT® Delivery System. The stent graft is preloaded into the delivery system and advanced to the intended location under fluoroscopy, where it is deployed to create a new blood flow channel to exclude an aneurysm.

## Stent Graft

The INCRAFT consists of three main components (Figure 1): an aortic bifurcate prosthesis and two iliac limb prostheses. In addition, to extend the implant in a caudal direction, the iliac limb prosthesis can be used as an iliac extension prosthesis. Each prosthesis is constructed of a seamless, woven polyester graft supported by a series of short, laser-cut, electro-polished, self-expanding nitinol stent-rings throughout the entire length. Aortic bifurcate and iliac limb prosthesis sizes, their sizing recommendations and corresponding delivery system profiles are described in Table 1 and Table 2.

Figure 1: INCRAFT Aortic Bifurcate and Iliac Limb/ Iliac Limb Extension


The aortic bifurcate prosthesis is deployed first into the cranial portion of the infrarenal aorta, as well as a small portion of the suprarenal aorta. It has a flared bare transrenal stent with 8 or 10 laser-cut barbs depending on the cranial diameter. The fixation barbs (Figure 1) are located at the cranial end of the transrenal stent and help keep the prosthesis in place.

Distal to the bare transrenal stent, the main trunk of the aortic bifurcate prosthesis has two sealing stents and a taper stent that divides into the ipsilateral and contralateral legs,

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supported by a series of Z-stents. While the diameter of the trunk varies by product code, the lengths of the trunk (49 mm) and legs (45 mm on the ipsilateral side and 37 mm on the contralateral side), as well as the diameters of the legs (11 mm) are constant. The aortic bifurcate prosthesis is manufactured in 4 trunk diameter sizes (22, 26, 30 and 34 mm).

The iliac limb prostheses are deployed into the legs of the aortic bifurcate prosthesis and into the ipsilateral and contralateral iliac vessels. The overlap between the aortic bifurcate prosthesis and the iliac limb prosthesis can vary between 2 cm and 5 cm on the ipsilateral side, and between 2 cm and 4 cm on the contralateral side.

The iliac limb prosthesis has a series of Z-stents cranially, 1 or more taper stents (if other than a straight configuration), and a diamond sealing stent caudally. The cranial diameter is always constant at 13 mm while the length and the caudal diameter of the iliac limb prosthesis could vary by product code. The iliac limb prostheses are available in 5 different caudal diameters (10, 13, 16, 20 and 24 mm) and in 4 different lengths (8, 10, 12, and 14 cm) except for the 24 mm x 8 cm code that does not exist.

The iliac limb prostheses could also be used as iliac extensions by placing one into a previously deployed iliac limb prosthesis to gain additional exclusion length.

Note: The 10 mm iliac limb prosthesis cannot be extended by design as the cranial diameter for all iliac limb prostheses is 13 mm.

Radiopaque markers provide a reference for proper alignment when deploying the prosthesis components (Figure 2). The aortic bifurcate cranial edge markers indicate the location of the cranial edge of the graft material (0.0-1.0 mm below the markers). The cranial edge markers serve as a guide for placement of the bifurcate's cranial edge just the below the lowest renal artery. The contralateral side marker indicates the orientation of the bifurcate's contralateral leg. The bifurcate's maximum and minimum overlap markers indicate the overlap range allowed for the cranial end of the iliac limb prostheses within each leg of the aortic bifurcate. The contralateral gate markers represent the caudal end of the bifurcate's contralateral leg and provide visualization in three dimensions to assist in cannulation of the contralateral leg. Radiopaque markers on the iliac limb protheses are included to indicate cranial and caudal edges of the graft and to assist in placement within the bifurcate leg cranially and iliac landing zone caudally.

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Figure 2: INCRAFT Prothesis Markers


| Marker | Material | Configuration |
| --- | --- | --- |
| 1. Contralateral side marker | Tantalum | Cylindrical marker crimped onto stent strut |
| 2. Bifurcate cranial edge markers | Tantalum | Cylindrical marker crimped onto stent strut. Graft edge begins below and within 1 mm of the bottom edge of the marker. |
| 3. Maximum overlap marker | Platinum-Iridium alloy | Cylindrical markers sewn onto the graft |
| 4. Minimum overlap marker | Platinum-Iridium alloy | Cylindrical markers sewn onto the graft |
| 5. Contralateral leg-gate markers | Platinum-Iridium alloy | Cylindrical markers sewn onto the graft edge |
| 6. Limb cranial edge marker | Tantalum | Cylindrical marker crimped on the stent strut |
| 7. Limb caudal edge marker | Tantalum | Cylindrical marker crimped on the stent strut |

Table 1: INCRAFT Aortic Bifurcate Prosthesis Sizes and Sizing Guide

| Product Code | Bifurcate Main Diameter (mm) | Aortic Vessel Diameter Range Treated (mm) | Delivery System ID (F) | Delivery System OD | | Ipsilateral Length (cm) | Contralateral Length (cm) |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | F | mm | | |
| AB2298US | 22 | 17.0 - 19.9 | 13 | 14 | 4.7 | 9.4 | 8.6 |
| AB2698US | 26 | 20.0 - 22.9 | 13 | 14 | 4.7 | 9.4 | 8.6 |
| AB3098US | 30 | 23.0 - 26.9 | 13 | 14 | 4.7 | 9.4 | 8.6 |
| AB3498US | 34 | 27.0 - 31.0 | 15 | 16 | 5.3 | 9.4 | 8.6 |

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Table 2: Iliac Limb and Limb Extension Prosthesis Sizes and Sizing Guide

| Product Code | Limb Diameter (mm) | Iliac Vessel Diameter Range Treated (mm) | Limb Length (cm) | Delivery System OD | | Ipsilateral Treatment Length (mm) | Contralateral Treatment Length (mm) |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | F | mm | | |
| IL1008US | 10 | 7.0 - 8.9 | 8.2 | 12 | 4.0 | 128-156 | 128-147 |
| IL1010US | 10 | 7.0 - 8.9 | 10.1 | 12 | 4.0 | 147-175 | 147-166 |
| IL1012US | 10 | 7.0 - 8.9 | 12.0 | 12 | 4.0 | 166-194 | 166-185 |
| IL1014US | 10 | 7.0 - 8.9 | 13.8 | 12 | 4.0 | 184-212 | 184-203 |
| IL1308US | 13 | 9.0 - 10.9 | 8.2 | 12 | 4.0 | 128-156 | 128-147 |
| 5IL1310US | 13 | 9.0 - 10.9 | 10.1 | 12 | 4.0 | 147-175 | 147-166 |
| IL1312US | 13 | 9.0 - 10.9 | 12.0 | 12 | 4.0 | 166-194 | 166-185 |
| IL1314US | 13 | 9.0 - 10.9 | 13.8 | 12 | 4.0 | 184-212 | 184-203 |
| IL1608US | 16 | 11.0 - 13.9 | 8.2 | 12 | 4.0 | 128-156 | 128-147 |
| IL1610US | 16 | 11.0 - 13.9 | 10.1 | 12 | 4.0 | 147-175 | 147-166 |
| IL1612US | 16 | 11.0 - 13.9 | 12.0 | 12 | 4.0 | 166-194 | 166-185 |
| IL1614US | 16 | 11.0 - 13.9 | 13.8 | 12 | 4.0 | 184-212 | 184-203 |
| IL2008US | 20 | 14.0 - 17.9 | 8.2 | 12 | 4.0 | 128-156 | 128-147 |
| IL2010US | 20 | 14.0 - 17.9 | 10.1 | 12 | 4.0 | 147-175 | 147-166 |
| IL2012US | 20 | 14.0 - 17.9 | 12.0 | 12 | 4.0 | 166-194 | 166-185 |
| IL2014US | 20 | 14.0 - 17.9 | 13.8 | 12 | 4.0 | 184-212 | 184-203 |
| IL2410US | 24 | 18.0 - 22.0 | 10.1 | 13 | 4.3 | 147-175 | 147-166 |
| IL2412US | 24 | 18.0 - 22.0 | 12.0 | 13 | 4.3 | 166-194 | 166-185 |
| IL2414US | 24 | 18.0 - 22.0 | 13.8 | 13 | 4.3 | 184-212 | 184-203 |

## Delivery System

Each prosthesis is loaded into a delivery system (Figure 3) intended to facilitate controlled deployment of the prosthesis into the intended locations under fluoroscopic guidance. Each delivery system is delivered over a 0.035" (0.89 mm) stiff guide wire and is operated to deploy the prosthesis by rotating the gold handle component (#5 in Figure 3) in a clockwise direction while firmly holding the white handle component (#6 in Figure 3). The deployment of each prosthesis is completed by pulling a secondary release mechanism (#4 in Figure 3).

There are two variations of the delivery system: one for the aortic bifurcate prosthesis, and one for the iliac limb prosthesis. Both variations of the delivery system are disposable and for single use only.

The aortic bifurcate delivery system has an integrated sheath introducer along with a hemostatic valve to facilitate component exchanges during the procedure. The working length of the aortic bifurcate delivery system is approximately 54 cm. The size of the integrated sheath introducer varies depending on the diameter of the prosthesis it contains. For prosthesis diameters of 22, 26, and 30 mm, the inner diameter of the integrated sheath introducer is 13F (outer diameter of 14F). For the prosthesis diameter of 34 mm, the inner diameter of the integrated sheath introducer is 15F (outer diameter of 16F). The outer surface of the integrated sheath introducer has a lubricious (hydrophilic) coating at the distal end to facilitate introduction into the vasculature. The graft is held between the inner and the outer

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catheter of the delivery system, just proximal of the distal catheter tip. The inner catheter is 0.035” guidewire compatible terminating in the tapered catheter tip.

The delivery system of the iliac limb prosthesis is similar to that of the aortic bifurcate except for its size, and that it does not have an integrated sheath introducer. The iliac limb delivery system has a working length of approximately 77 cm and can be delivered through the integrated sheath introducer of the aortic bifurcate system. The iliac limb delivery system has a 12F outer diameter for prosthesis diameters between 10 mm and 20 mm, and a 13F outer diameter for the 24 mm diameter prosthesis. The outer surface of each iliac limb delivery system has a lubricious (hydrophilic) coating at the distal end to facilitate introduction into the vasculature. The graft is held between the inner and the outer catheter of the delivery system, just proximal of the distal catheter tip. The inner catheter is 0.035” guidewire compatible terminating in the tapered catheter tip.

Figure 3. INCRAFT Delivery System Components

1. Manifold assembly (manifold core with guidewire lumen flush connector and manifold shell)
2. Fixation release wire
3. Fixation release wire hemostasis valve
4. Release wire retainer
5. Gold handle component (body)

6. White handle component
7. Sheath hemostasis valve (aortic bifurcate only)
8. Prosthesis location
9. Sheath tip marker
10. Integrated sheath introducer (aortic bifurcate only)

Please refer to the Cordis INCRAFT® AAA Stent Graft System Instructions for Use for additional description on the implants and associated delivery systems.

## VI. ALTERNATIVE PRACTICES AND PROCEDURES

There are several alternatives for the treatment of infrarenal abdominal aortic aneurysms, including endovascular repair using other endovascular grafts, medical management, and open surgical repair. Each alternative has its own advantages and disadvantages. A patient should fully discuss these alternatives with his/her physician to select the method that best meets expectations and lifestyle.

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# VII. MARKETING HISTORY

The INCRAFT is marketed in the European Union (Austria, Belgium, Croatia, Cyprus, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Liechtenstein, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, United Kingdom), the Middle East (Egypt, Israel, Kuwait, Saudi Arabia, United Arab Emirates), Canada, South America (Argentina, Brazil, Colombia, Mexico), and Asia Pacific (Australia, China, Korea). The INCRAFT has not been withdrawn from the market in any country for any reason.

# VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH

In Table 3 below is a list of the potential adverse effects (e.g., complications) associated with the use of the device.

Table 3: Potential Adverse Events

| ·Amputation ·Anesthesia complications ·Aneurysm enlargement ·Aneurysm sac rupture ·Aortic damage (perforation, dissection, bleeding, rupture) ·Aortocaval fistulae ·Aortoenteric fistulae ·Arterial or venous thrombosis ·Bleeding events ·Bowel complications (e.g., ileus, transient ischemia, infarction, necrosis) ·Cardiac arrhythmia ·Cardiac complications ·Cardiac failure or infarction ·Claudication ·Coagulopathy ·Component migration ·Contrast toxicity / anaphylaxis ·Death ·Edema ·Embolism or thrombotic events | ·Endoleaks ·Fever ·Gastrointestinal complications ·Genitourinary complications (e.g., ischemia, erosion, fistula, incontinence, hematuria) ·Graft erosion ·Graft material wear ·Graft puncture ·Graft twisting or kinking ·Hematoma (surgical) ·Hepatic failure ·Impotence ·Improper stent graft placement ·Incomplete stent graft deployment ·Infection ·Insertion and removal difficulties ·Lymphatic complications ·Multiorgan system failure ·Neurological complications (e.g. CVA, transient ischemic attack) | ·Open surgical conversion ·Paralysis or paraparesis ·Perigraft flow ·Post-implant syndrome ·Prosthesis occlusion/stenosis ·Pseudoaneurysm ·Pulmonary complications ·Radiation complications ·Renal failure/renal insufficiency ·Sheath leakage ·Shock ·Stenosis/occlusion of native vessel ·Stent fracture / separation / dislodgement of stent strut ·Suture break (endograft) ·Vascular access site complications occlusion/stenosis ·Vascular spasm/trauma ·Wound complications |
| --- | --- | --- |

For the specific adverse events that occurred in the clinical study, please see Section X below.

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IX. SUMMARY OF NONCLINICAL STUDIES

The following studies were completed to evaluate the INCRAFT device: non-clinical bench testing, biocompatibility, sterilization/packaging/shelf-life, and animal studies. These are discussed in more detail in the subsequent sections.

A. Laboratory Studies

The INCRAFT underwent testing for design verification and validation, including long-term durability and corrosion testing. All testing was conducted in accordance with international standards and guidance documents, specifically ISO 25539-1 "Cardiovascular implants -- Endovascular devices -- Part 1: Endovascular prostheses" and ISO 7198 "Cardiovascular implants and extracorporeal systems -- Vascular prostheses -- Tubular vascular grafts and vascular patches." Testing was conducted on either a subset of device configurations/sizes for each test or worst-case sizes, in order to represent the entire size range available for the INCRAFT.

The testing details provided below include results from baseline, as well as 2 year accelerated aging, as appropriate. An asterisk (*) initiates that testing was performed at both baseline and 2 years accelerated aging. A summary of this testing is provided in Table 4.

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Table 4: Summary of Design Verification and Validation Testing

| Test Name | Test Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Delivery System Testing | | | |
| Dimensional Verification and Component Dimensions Compatibility | To determine the working length of INCRAFT delivery system | All test samples must meet predefined specification for working length (90% of the population with 95% confidence) | Pass* |
| | To confirm that the INCRAFT delivery system is compatible with a 0.035" guide wire | All test samples must accept a typical 0.035" stiff guide wire through the entire length of the delivery system's guide wire lumen | Pass |
| | To confirm compatibility of distal sheath section of bifurcate delivery system with limb delivery system | The inner diameter of the bifurcate distal sheath must be ≥ 4.0 mm and all test samples must meet a limb delivery system compatibility force with the bifurcate distal sheath of ≤ 10.0 lbf (90% of the population with 95% confidence) | Pass* |
| | To confirm luer compatibility with accessory devices | All test samples must meet predefined specification for luer dimensions | Pass* |
| Profile/ Diameter Test | To determine the profile of INCRAFT delivery system | All test samples must meet its nominal labeled profile ≤ 4.8 mm (22, 26 & 30 mm bifurcate) ≤ 5.5 mm (34 mm bifurcate) ≤ 4.2 mm (10, 13, 16 & 20 mm limbs) ≤ 4.5 mm (24 mm limb) (90% of the population with 95% confidence) | Pass* |
| Assessment of Hemostasis | To confirm ability of sheath valve to maintain hemostatic seal | All test samples must meet a maximum leak rate of ≤ 60 ml/min (90% of the population with 95% confidence) | Pass* |
| Simulated Use Models | Design validation tests to evaluate: (a) ability to flush guidewire lumen; (b) accessory compatibility; (c) delivery system chemical compatibility; (d) device deliverability and deployment; (e) prosthesis conformability and kink resistance | All test samples must be able to complete flushing of the guidewire lumen and without incident | Pass |
| | | All test samples must show acceptable balloon compatibility during tracking activities and post deployment shall be assessed | Pass |
| | | All test samples must pass a subjective assessment of the delivery system kink resistance as determined by the test performer. | Pass |
| | | All test samples must not show visible signs of crazing, cracking, blister/ bubble, haze/ cloudiness, pitting, discoloration, precipitate formation or other conditions | Pass |
| | | All test samples must pass a subjective, simulated use assessment of deployment accuracy as determined by the test performer. | Pass |
| | | All test samples must have a deployment initiation torque of ≤ 1.75 rotations of the handle | Pass |
| | | All test samples must meet a handle rotation angle for response of the delivery system tip of ≤ 90 degrees | Pass |
| | | All test samples must meet a peak push force of ≤10.0 lbf | Pass |

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| Test Name | Test Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| | | All samples must pass a subjective, simulated use assessment of the prosthesis kink resistance as assessed by the test performer. | Pass |
| | | All samples must pass a subjective, simulated use assessment of the prosthesis conformability to the vessel as assessed by the test performer. | Pass |
| Gasket Retention | To confirm that gasket remains secure in hemostasis valve after withdrawal of inner member | All test samples must pass a gasket retention assessment to confirm that the gasket remains secure after inner member is withdrawn from distal sheath of bifurcate delivery system | Pass* |
| Residual Retraction Length | To confirm residual travel capability of outer member after prosthesis deployment | All test samples must meet a residual retraction length of ≥ 12.0 mm (bifurcate) / 37.0 mm (limb) (99% of the population with 95% confidence) | Pass* |
| Force to Deploy | To determine the force to deploy the endovascular prosthesis under simulated anatomical conditions. All applicable steps of the deployment process were evaluated | All test samples must meet a peak initiation torque of ≥ 12.0 in-oz (99% of the population with 95% confidence) | Pass* |
| | | All test samples must meet a peak primary deployment torque of ≤ 24.0 in-lb (99% of the population with 95% confidence) | Pass* |
| | | All test samples must meet a primary deployment force of < 26.0 lbf (99% of the population with 95% confidence) | Pass* |
| | | All test samples must meet a secondary release force (Sheathed) of ≥ 1.6 lbf (99% of the population with 95% confidence) | Pass* |
| | | All test samples must meet a secondary release force (Unsheathed) of ≤ 10.0 lbf (99% of the population with 95% confidence) | Pass* |
| Tensile Bond Strength | To confirm adequate tensile bond strengths of delivery system during delivery, deployment and retraction from the vasculature | All test samples must meet an inner member tip to hypotube tensile strength of ≥ 10.0 lbf (99% of the population with 95% confidence) | Pass* |
| | | All test samples must meet an inner member wire guide to hypotube tensile strength of ≥ 25.0 lbf (bifurcate) and ≥ 17.0 lbf (limb) (99% of the population with 95% confidence) | Pass* |
| | | All test samples must meet an eyelet wires to wire holder tensile strength of ≥ 1.3 lbf (99% of the population with 95% confidence) | Pass* |
| | | All test samples must meet a bifurcate release wire to wire holder tensile strength of ≥ 5.0 lbf (99% of the population with 95% confidence) | Pass* |

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| Test Name | Test Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| | | All test samples must meet proximal inner member component joint tensile strength of ≥ 10.0 lbf (95% of the population with 95% confidence) | Pass* |
| | | All test samples must meet an outer member proximal shaft to handle tensile strength of ≥ 26.0 lbf (99% of the population with 95% confidence) | Pass* |
| | | All test samples must meet hemostasis valve tensile strength of ≥ 35.0 lbf (99% of the population with 95% confidence) | Pass* |
| Torsional Bond Strength | To confirm adequate torsional bond strengths of delivery system during delivery, deployment and retraction from the vasculature | All test samples (bifurcate) must meet an inner member to hypotube torque of ≥ 3.5 in-oz (99% of the population with 95% confidence) | Pass* |
| | | All test samples (limb) must meet an inner member to hypotube torque of ≥ 0.9 in-oz (99% of the population with 95% confidence) | Pass* |
| | | All test samples must meet an outer member shaft to handle torque of ≥ 13.0 in-oz (99% of the population with 95% confidence) | Pass* |
| | | All test samples (bifurcate) must meet a haemostasis valve torque of ≥ 13.0 in-oz (99% of the population with 95% confidence) | Pass* |
| | | All test samples (bifurcate) must meet a prosthesis retention torque of ≥ 2.6 in-oz (99% of the population with 95% confidence) | Pass* |
| Coating Lubricity | To confirm adequate lubricity due to coating on delivery system | The tip and outer member of all test samples must have a pull force of ≤ 376 g (90% of the population with 95% confidence) | Pass* |
| Implant Testing | | | |
| Dimensional Verification | To determine the endovascular prosthesis diameter in the deployed state | All test samples (aortic bifurcate) must meet an outer diameter that is +/-5% of the nominal diameter after a 24 hour soak at 37°C (99% of the population with 95% confidence) All test samples (limb) must meet an outer diameter that is between the maximum labeled treatable vessel diameter (immediately after deployment) and +5% of the nominal diameter (for 24 mm limb) or +1.0 mm greater than the nominal diameter for all other limbs after a 24 hour soak at 37°C (99% of the population with 95% confidence) | Pass* |
| Water Permeability | To determine graft permeability | All test samples must have a water permeability of ≤ 700 ml/min/cm2 (95% of the population with 95% confidence) | Pass* |
| Graft Circumferential Strength | To determine the circumferential strength of the graft material | All test samples must meet a circumferential tensile strength of ≥ 2.3 lbf/cm (99% of the population with 95% confidence) | Pass* |

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| Test Name | Test Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Flex/ Kink | To confirm that the endovascular prosthesis can accommodate a minimum radius without kinking | All test samples (bifurcate) must meet a minimum radius of curvature of ≤ 38.1 mm (centerline radius of curvature) | Pass |
| | | All test samples (limb) must meet a minimum radius of curvature of ≤ 25.4 mm (inner line radius of curvature) | Pass |
| Graft Longitudinal Tensile Strength | To determine the longitudinal tensile strength of the graft material | All test samples must meet a maximum graft longitudinal tensile force of ≥ 10.0 lbf (99% of the population with 95% confidence) | Pass* |
| Migration Resistance | To evaluate the ability of the endovascular prosthesis to resist migration when subjected to an axial force or pressure | All test samples must have a displacement of ≤ 10 mm for forces of: 2.24 lbf (22, 26 and 30 mm bifurcates) 2.70 lbf (34 mm bifurcate) (99% of the population with 95% confidence) | Pass* |
| Pull Test for Modular Components (Or Overlapping Endoprostheses) | To determine the force required to separate overlapping modular components (e.g., main body & limbs, limb & limb) in the deployed state | All test samples must meet a peak modular junction force of ≥ 0.6 lbf (99% of the population with 95% confidence) | Pass* |
| Radial Force | To determine the outward force as a function of the diameter of the endovascular prosthesis | All test samples must meet a maximum chronic outward force (COF) of ≤ 3.58 lbf for the smallest labeled vessel diameter after 24 hour exposure to 37°C water | Pass |
| | | All test samples (bifurcate) must meet a minimum COF for the largest label vessel diameter (after 24 hour exposure to 37°C) of ≥ 0.50 lbf (99% of the population with 95% confidence) | Pass* |
| | | All test samples (limb) must meet a minimum COF for the largest label vessel diameter immediately after deployment of ≥ 0.20 lbf | Pass |
| Strength of Graft to Stent/ Attachment System Bond | To determine the strength of the connection(s) between the graft material and discrete implant components | All samples must meet a peak force to complete separation of an internal stent to graft of ≥ 0.02 lbf (99% of the population with 95% confidence) | Pass* |
| | | All test samples must meet a peak force to complete separation of a transrenal stent to graft of ≥ 15.0 lbf (99% of the population with 95% confidence) | Pass* |
| | | All test samples must meet a peak marker band tensile force of ≥ 0.1 lbf (99% of the population with 95% confidence) | Pass* |
| Corrosion Assessment | To evaluate the corrosion resistance properties of the INCRAFT nitinol laser-cut stents | For all test samples the average breakdown potential (Eb) of the INCRAFT samples shall be greater than or equal to that of the comparison AAA device | Pass |
| | | No preference for pitting near dissimilar material contact points in all test units that have dissimilar material contact points for the stents tested for pitting and crevice corrosion | Pass |

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| Test Name | Test Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| MRI Compatibility | To provide the recommended scan conditions for use with the device | Non-clinical tests of the stent-graft prosthesis for MRI compatibility and safety were conducted at worst-case conditions for: displacement and deflection force; torque force; RF heating; and MRI artifact. The testing demonstrated that INCRAFT is MR Conditional. It can be scanned safely in both 1.5 Tesla (T) and 3T magnetic resonance systems under the following conditions: • Static magnetic field of 1.5T or 3T • Spatial gradient field ≤ 2500 Gauss/cm (25T/m) • Maximum whole-body-averaged specific absorption rate (SAR) of 4 W/kg for 15 minutes of scanning (First Level Controlled Mode) | Pass |
| Stress/Strain Analysis and Fatigue Analysis (FEA) | Determine stent strains during crimping and in-vivo cyclic loading conditions (radial fatigue and axial fatigue conditions). Use strain-life data to predict fatigue safety factors | The fatigue safety factor for each stent shall be ≥ 1.0 under both radial fatigue and axial fatigue loading | Pass |
| Fatigue and Durability Testing | Pulsatile Fatigue Testing: Evaluate the long-term durability of stent-graft assembly across 400 million cycles of pulsatile loading | All test samples must meet the following: 1. Stent Fracture: No strut fractures unless analysis of final design negates the impact of specific strut fractures on migration, sealing and/ or embolic events 2. Fabric Holes: No holes or fabric abrasions yielding a hole with a major axis >1.34 mm in length 3. Graft Attachment Separation: No stent or radiopaque marker separation from the graft that can enter the blood stream 4. Suture Breaks: Suture breaks that lead to separation of a stent from the graft will constitute failure | Pass |
| | Migration Durability in a Bent Neck Condition: Evaluate the long-term durability of stent-graft assembly (including fatigue performance of barbs and transrenal stent to graft attachment) under cyclic axial loads | All test samples must meet the following: 1. No point on the cranial graft edge should migrate in excess of 7 mm through the test 2. No separation of any transrenal stent apex from the graft edge 3. The tensile force to remove the transrenal stent from the graft exceeds 15 lbs | Pass |
| | Dynamic Modular Junction Testing: Evaluate the junction between the modular components when subjected to dynamic tensile conditions | The modular junctions include both bifurcate leg to limb junction as well as limb to limb junction. For all test samples, the stabilization of the junction must be demonstrated and there must be no complete modular separation | Pass |

* Testing successfully repeated after shelf life exposure.

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# Fracture Root Cause Investigation

As described below, the INCRAFT was evaluated in the INSPIRATION clinical study. During the clinical study, transrenal stent fractures were observed. An investigation was conducted to identify the root cause for transrenal stent strut fractures observed in the INSPIRATION clinical study and to characterize potential risks associated with these fractures. All stent strut fractures observed in the INSPIRATION study were located at the transrenal stent component, with the majority of the fractures at the stent "Cranial X" location (Figure 6 in Section X.D.2.2.8). Additionally, no transrenal stent strut fractures were observed during design verification and validation tests or the implant durability tests discussed in Table 4.

The root-cause investigation revealed that the primary cause of the strut fractures was likely cardiac-induced cyclic axial deformations (i.e., axial length changes in the transrenal aortic region associated with the cardiac cycle). To support the root cause analysis, a range of axial compression values was determined to use as boundary conditions to input into a finite element analysis (FEA). These values were obtained from literature sources, clinical data of patients with the INCRAFT device (i.e., dynamic CT imaging in one patient after exhibiting fractures for one quantitative measurement, post-procedural imaging for 2 patients who developed a fracture for qualitative observation of cyclic axial deformation), and data from an analysis completed by the sponsor on a competitor's infrarenal AAA device using cardiac-gated CT imaging.

FEA was conducted on the transrenal stent with the physiologically-relevant axial compression range. The calculated device strains exceeded the material constant life line at the cranial "x" location regardless of the applied axial deformation magnitude. Moreover, with increased deformation magnitudes, locations pertaining to the cranial tip, caudal "x" and the cranial strut location also begin to show susceptibility to fracture, suggesting that these locations are secondary fracture locations. This analysis predicted that the most likely location of stent fracture is the cranial "x" with the secondary fracture locations being the cranial tip and the caudal "x" location, which is consistent with the observations in the INSPIRATION clinical study. Bench fatigue tests of the transrenal stent under cyclic axial deformations corroborated the cranial "x" location as the primary fracture location under this deformation mode (Figure 4). However, the FEA and additional testing did not identify clinical conditions specific to patients with fractures as compared to those without fractures.

As implant migration is a risk of transrenal stent fracture, the sponsor completed acute and chronic migration resistance testing on device test samples that represent the worst-case fracture condition. This chronic testing was conducted in a $37^{\circ}\mathrm{C}$ saline bath using a $30\mathrm{mm}$ aortic bifurcate component deployed in a silicone vessel with cyclic loading intended to simulate a $60^{\circ}$ neck angulation with an increasing number of induced fractures. Each chronic test with a given number of induced fractures was conducted to 10 million cycles (or 3 months equivalent). Results indicated that migration (i.e.,

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movement greater than $10\mathrm{mm}$ ) did not occur with 10 out of the 16 stent struts fractured (i.e., only 3 suprarenal barbs remained intact).

The acute migration resistance testing was conducted in air at $37^{\circ}\mathrm{C}$ after the $30\mathrm{mm}$ aortic bifurcate component was deployed into a silicone vessel. The barbs were cut sequentially around the circumference for testing. Results indicated that the aortic bifurcate component did not migrate more than the $10\mathrm{mm}$ specification until more than 12 stent strut fractures were induced.

Figure 4. Summarized root-cause of stent strut fractures depicted by (a) primary fracture location in INSPIRATION study; (b) primary fracture location predicted by computational modeling and (c) primary fracture location predicted by bench fatigue testing.



# B. Animal Studies

In vivo animal study testing was conducted on the INCRAFT to evaluate the safety of the device following implantation in ovine aorta and iliac arteries. The test article consisted of a $22\mathrm{mm}$ aortic bifurcate prosthesis and a shortened $13\mathrm{mm}$ iliac limb prosthesis. One aortic bifurcate prosthesis was placed transrenally in the aorta and one iliac limb prosthesis was placed separately in the right iliac artery of each animal. The tissue response to INCRAFT was evaluated histologically and the sealing capability and integrity of the bifurcate and iliac limb were evaluated angiographically and radiographically, respectively. Migration was evaluated angiographically. The effect of trans-renal implantation of the aortic bifurcate on renal function was also assessed. Results are presented in Table 5. The results demonstrated adequate acute performance, acceptable stent graft integrity and fixation, and appropriate healing characteristics and tissue response.

Table 5: Summary of INCRAFT In-Vivo Studies

| Study | # of Animals | Objectives | Results |
| --- | --- | --- | --- |
| A 30 Day and 180 Day GLP Safety Study to Evaluate | 6 animals in 30-day cohort | To evaluate healing characteristics and tissue response | INCRAFT was interpreted to have appropriate tissue biocompatibility with little to no device related inflammation, rare mural injury, negligible neointima formation, optimal luminal characteristics (e.g., |
| | | | inflammation, and minimal neointima formation) |
| B 30 Day and 180 Day GLP Safety Study to Evaluate | 6 animals in 30-day cohort | To evaluate healing characteristics and tissue response | INCRAFT was interpreted to have appropriate tissue biocompatibility with little to no device related inflammation, rare mural injury, negligible neointima formation, optimal luminal characteristics (e.g., |
| | | | inflammation, minimal neointima formation) |

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| Cordis' INCRAFT™ Abdominal Aortic Aneurysm (AAA) Stent Graft System in a Sheep Model | 7 animals in 180-day cohort | | percent area occlusion) and no device-related mortality. |
| --- | --- | --- | --- |
| | | To evaluate the sealing capability | Some branches appear to be filling following implant and prior to termination. Due to the implant configuration chosen for this study, which is not representative of the clinical application, it appears these branches are filling due to retrograde flow. |
| | | To evaluate stent graft migration | Angiographic images for this were reviewed and based on the post-implant and pre-termination angiography, no gross migration occurred. |
| | | To evaluate the Stent:Artery Ratio | As expected, Stent to artery ratios were high compared to that target human condition. As a result of the high stent:artery ratio it is likely arteries experienced higher amounts of radial force than one would anticipate in a comparable human case. |
| | | To evaluate the structural integrity of the stent graft | There was no radiographic evidence of strut fractures. |
| | | To evaluate the acute performance by a physician | The implanting physician rated all areas of performance as acceptable and performed well above minimal requirements for acceptable rating. |
| | | To evaluate renal function during the study | No clinical or histological indications of renal impairment. |
| | | To evaluate overall animal health during the study | There was no significant trending noted in the clinical pathology or daily observations and the animals were in good general health over the course of the study with no device-related mortality. |

## C. Biocompatibility

The biocompatibility assessment performed for the INCRAFT was based on the matrix for body contact and contact duration included in ISO 10993-1:2009/Cor 1:2010, Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process. For purposes of biocompatibility testing, the stent graft was classified as an implant device, permanent contact (&gt; 30 days), while the delivery system was classified as an external communicating device, circulating blood, limited exposure (&lt; 24 hours). All testing was performed by a qualified contract laboratory in accordance with FDA GLP Regulations, 21 CFR Part 58.

All testing performed met the pre-specified acceptance criteria. The results are summarized in Table 6 for the implant and Table 7 for the delivery system.

Table 6: Biocompatibility Evaluation – INCRAFT Implant

| Biological Effect (Test) | Purpose | Results | Acceptance Criteria Met? |
| --- | --- | --- | --- |
| ISO MEM Elution Cytotoxicity | To determine if stent graft extracts cause cytotoxicity when exposed to mouse L-929 fibroblast cells | Non-cytotoxic: Grade 0 (no reactivity) | Yes |

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| Biological Effect (Test) | Purpose | Results | Acceptance Criteria Met? |
| --- | --- | --- | --- |
| ISO Guinea Pig Maximization Sensitization | To evaluate the allergenic/sensitization potential of stent graft extracts in guinea pigs | Non-sensitizer: All animals scored 0 resulting in 0% sensitization rate | Yes |
| ISO Intracutaneous Reactivity | To evaluate stent graft extracts for potential irritation effects after intracutaneous injection in rabbits | Non-irritant: All injection sites scored 0 | Yes |
| ISO Acute Systemic Toxicity | To evaluate stent graft extracts for potential toxic effects after single-dose systemic injections in mice | Animals treated with stent graft extracts did not exhibit greater biological response than controls | Yes |
| Material Mediated Pyrogenicity | To evaluate the stent graft for the potential of inducing a pyrogenic response in rabbits | Non-pyrogenic: rabbits showed a maximum temperature rise of 0.1, 0.2, and 0.2 °C, respectively over the 3 hour test period | Yes |
| Genotoxicity/ Mutagenicity | | | |
| • Ames Assay | To evaluate the mutagenic potential of the stent graft by measuring its ability to induce back mutations at selected loci of several strains of bacteria | Non-mutagenic: The stent graft did not cause an increase in point mutations, exchanges or deletions | Yes |
| • In vitro Mouse Lymphoma | To evaluate the potential of the stent graft extracts to induce a forward mutation in the TK gene of L5178Y TK+/- cells | Non-genotoxic and non-mutagenic: Mutant frequencies and cloning efficiencies of preparations treated with stent graft were within the limits defined for a negative response | Yes |
| • In vivo Mouse Micronucleus | To evaluate the potential of the stent graft to induce micronuclei formation in immature polychromatic erythrocytes (mPCEs) present in the bone marrow of adult CD-1 mice | Non-genotoxic and non-clastogenic: No statistically significant in the number of mPCEs observed with the stent graft | Yes |
| Hemocompatibility | | | |
| • Hemolysis | To evaluate the potential of the stent graft to cause hemolysis in direct contact or by extraction | Non-hemolytic: percent hemolysis: Direct contact – 0.7% Extract – 0.0% | Yes |
| • Partial Thromboplastin Time (PTT) | To determine the time citrated plasma exposed to stent graft takes to form a clot when exposed to a suspension of phospholipid particles and calcium chloride | Non activator of intrinsic coagulation pathway: The stent graft had an average clotting time of 300 seconds (100% of the negative control) | Yes |

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| Biological Effect (Test) | Purpose | Results | Acceptance Criteria Met? |
| --- | --- | --- | --- |
| • Platelet and Leukocyte Count | To determine if the stent graft exposed to whole blood would adversely affect the make-up of the platelet and leukocyte components of the blood | Leukocyte counts 93% of control; Platelet counts 106% of control | Yes |
| • Complement Activation | To measure complement activation in normal human serum (NHS) when serum is exposed to the stent graft | C3a – 0.6% activation compared to cobra venom factor SC5b-9 – 0.0% activation compared to cobra venom factor | Yes |
| Rabbit Intramuscular Implant (including Chronic Toxicity) | | | |
| • 13 week | To evaluate the potential for local and systemic toxic effects of a test article in direct contact with skeletal muscle of the rabbit for 13 weeks | Non-irritant with an irritant ranking score of 0.7; No biologically significant changes to clinical chemistry or hematology | Yes |
| • 26 week | To evaluate the potential for local and systemic toxic effects of a test article in direct contact with skeletal muscle of the rabbit for 26 weeks | Non-irritant with an irritant ranking score of 1.6; No biologically significant changes to clinical chemistry or hematology | Yes |
| In vivo Thrombogenicity | | N/A* | |

*In vivo thrombogenicity of the implant was assessed in the 30- and 180-day in vivo safety studies.

Table 7: Biocompatibility Evaluation – INCRAFT Delivery System

| Biological Effect (Test) | Purpose | Results | Acceptance Criteria Met? |
| --- | --- | --- | --- |
| ISO MEM Elution Cytoxicity | To determine if delivery system extracts cause cytotoxicity when exposed to mouse L-929 fibroblast cells | Non-cytotoxic: Grade 0 (no reactivity) | Yes |
| ISO Guinea Pig Maximization Sensitization | To evaluate the allergenic/sensitization potential of delivery system extracts in guinea pigs | Non-sensitizer: All animals scored 0 resulting in 0% sensitization rate | Yes |
| ISO Intracutaneous Reactivity | To evaluate delivery system extracts for potential irritation effects after intracutaneous injection in rabbits | Non-irritant: the difference between each test extract overall mean score and corresponding control overall mean score was 0.0 and 0.1 for the 0.9% sodium chloride (SC) and sesame oil (SO) test extracts, respectively | Yes |

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| Biological Effect (Test) | Purpose | Results | Acceptance Criteria Met? |
| --- | --- | --- | --- |
| ISO Acute Systemic Toxicity | To evaluate delivery system extracts for potential toxic effects after single-dose systemic injections in mice | Animals treated with delivery system extracts showed no mortality or evidence of systemic toxicity | Yes |
| Material Mediated Pyrogenicity | To evaluate the delivery system for the potential of inducing a pyrogenic response in rabbits | Non-pyrogenic rabbits showed a maximum temperature rise of 0.0, 0.0, and 0.3 °C, respectively over the 3 hour test period | Yes |
| Genotoxicity/ Mutagenicity | | | |
| • Ames Assay | To evaluate the mutagenic potential of the delivery system by measuring its ability to induce back mutations at selected loci of several strains of bacteria | Non-mutagenic: The delivery system did not cause an increase in point mutations, exchanges or deletions | Yes |
| • In vitro Mouse Lymphoma | To evaluate the potential of the delivery system extracts to induce a forward mutation in the TK gene of L5178Y TK+/- cells | Non-genotoxic and non-mutagenic: Delivery system extracts did not cause a two-fold or greater increase in the mean mutant frequency | Yes |
| • In vivo Mouse Micronucleus | To evaluate the potential of the delivery system to induce micronuclei formation in immature polychromatic erythrocytes present in the bone marrow of adult CD-1 mice | Non-genotoxic and non-clastogenic: Extracts of the delivery system did not induce micronuclei formation in mice | Yes |
| Hemocompatibility | | | |
| • Hemolysis | To evaluate the potential of the delivery system to cause hemolysis in direct contact or by extraction | Non-hemolytic: percent hemolysis: Direct contact – 0.5% Extract – 0.0% | Yes |
| • Partial Thromboplastin Time (PTT) | To determine the time citrated plasma exposed to delivery system takes to form a clot when exposed to a suspension of phospholipid particles and calcium chloride | Minimal activator of intrinsic coagulation pathway: The delivery system had an average clotting time of 195.2 seconds (81% of the negative control) | Yes |
| • Platelet and Leukocyte Count | To determine if the delivery system exposed to whole blood would adversely affect the make-up of the platelet and leukocyte components of the blood | Leukocyte counts 99% of control; Platelet counts 105% of control | Yes |

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| Biological Effect (Test) | Purpose | Results | Acceptance Criteria Met? |
| --- | --- | --- | --- |
| • Complement Activation | To measure complement activation in normal human serum (NHS) when serum is exposed to the delivery system | C3a – 4.0% activation compared to cobra venom factor
SC5b-9 – 3.6% activation compared to cobra venom factor | Yes |
| In vivo Thrombogenicity | To evaluate the thrombogenic potential of the delivery system | Minimal thrombus formation (score =1); similar to slightly better thromboresistance than control | Yes |

## D. Sterilization, Packaging, and Shelf-Life

The INCRAFT is a single-use device that is provided sterile to the end user. The INCRAFT is sterilized using 100% Ethylene Oxide (EO) gas with heated aeration to allow for residual sterilant dissipation. The sterilization process was validated to demonstrate a Sterility Assurance Level (SAL) of 10⁻⁶.

All packaging and shelf life validation testing was performed on sterilized dummy devices that had been environmentally conditioned and transportation tested. All protocol acceptance criteria were met, and the results of the testing demonstrated that the packaging configuration for the INCRAFT is capable of maintaining package and sterile integrity for a two (2) year shelf-life.

Specific engineering testing completed to support shelf life are denoted by an asterisk (*) in Table 4. Accelerated shelf-life product testing conducted on the INCRAFT supports a 2-year shelf-life claim.

## X. SUMMARY OF PRIMARY CLINICAL STUDY

The applicant performed a clinical study to establish a reasonable assurance of safety and effectiveness of endovascular repair of infrarenal abdominal aortic aneurysms with the INCRAFT device in the United States (US) and Japan under IDE #G120003. Data from this clinical study were the basis for the PMA approval decision.

Although the primary effectiveness endpoint was at 1 year, at the time of the data lock for PMA submission, complete 4-year data of the INSPIRATION clinical study were available. A summary of the clinical study is presented below.

## A. Study Design

Patients were treated between July 2012 and August 2013. The database for this original PMA reflected data collected through December 29, 2017 and included 190

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patients (134 in the US and 56 in Japan). There were 32 investigational sites in the United States (27) and Japan (5).

The study was a multi-center, prospective, open label, non-randomized, single arm clinical study. The primary safety endpoint was defined as the proportion of patients with a Major Adverse Event (MAE) within 30 days post index procedure.

$$
\mathrm{H}_0: \mathrm{P}_{\mathrm{MAE}} \geq 20\% \text{ vs. } \mathrm{H}_a: \mathrm{P}_{\mathrm{MAE}} &lt; 20\%
$$

Where, $\mathrm{P}_{\mathrm{MAE}}$ is the proportion of patients who have at least one MAE at 30 days post-procedure among the INCRAFT patients.

The primary effectiveness endpoint was defined as the proportion of patients with aneurysm treatment success within 1 year post index procedure.

$$
\mathrm{H}_0: \mathrm{P}_{\text{Success}} \leq 80\% \text{ vs. } \mathrm{H}_a: \mathrm{P}_{\text{Success}} &gt; 80\%
$$

Where, $\mathrm{P}_{\text{Success}}$ is the proportion of patients with successful aneurysm treatment after the use of the INCRAFT through 1 year post-procedure.

The results were tested against a performance goal derived from the open surgical control group in the Society of Vascular Surgery (SVS) Lifeline Registry for the safety endpoint (herein referred to as the SVS Controls) and a performance goal derived from recent IDE studies for EVAR for the effectiveness endpoint.

The hypothesis of the primary safety endpoint was that the 30-day MAE rate in the INCRAFT™ arm was lower than performance goal of $20\%$. With expected attrition of $5\%$, a final sample size of 190 patients ensured that 180 evaluable patients were available at 30 days for the primary safety analysis. With a sample size of 180, a one-sided exact binomial test using a nominal significance level of 0.05 had at least $95\%$ power to reject the null hypothesis when the 30-day MAE rate is $10\%$.

The hypothesis of the primary effectiveness endpoint was that the proportion of patients with the composite endpoint of successful aneurysm treatment was greater than the performance goal of $80\%$. Assuming a $20\%$ attrition rate over 12 months, the total enrollment was 190 patients. With a sample size of 150, a one-sided exact binomial test using a nominal significance level of 0.05 had approximately $90\%$ power to reject the null hypothesis when the successful aneurysm treatment rate at 12 months was $89\%$.

The INSPIRATION study utilized external evaluation groups, whose roles and responsibilities are described below:

- Independent Reviewers: In order to confirm that only appropriate patients would be enrolled, an independent reviewer reviewed all screening CT imaging to confirm the patients met eligibility criteria prior to enrollment. The

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team of independent reviewers were vascular surgeons, separate from the sponsor, Core Laboratory, and sites. Each independent reviewer was trained to the protocol inclusion and exclusion criteria, the INCRAFT device, and the imaging software.

- Core Laboratory: A Core Laboratory was utilized to evaluate Angiograms, CT scans, and X-ray images from screening through the 5-year follow-up. They assessed the following events: aneurysm enlargement, endoleaks, stent fracture, and stent graft migration. Two Core Laboratories were used in this pivotal study. The first Core Lab evaluated all images through the first year. The second Core Lab reviewed all imaging after the first year. The second Core Lab re-reviewed all x-rays for the detection of fracture(s) and also recalculated the 1-month baseline measurements due to changes in migration measurement process from the first Core Lab. The 1-month aneurysm diameter measurements were not re-evaluated by the second Core Lab as both laboratories used the same definition.
- Clinical Events Committee: The Clinical Events Committee (CEC) reviewed and adjudicated protocol-defined MAEs, endograft occlusions, secondary interventions and Type I, III, and IV endoleaks. Type II endoleaks were reviewed by the CEC only if there was a discrepancy between the Site and Core Lab assessment.
- Data Safety Monitoring Board (DSMB): The Data Safety Monitoring Board (DSMB) served as an independent group of experts that periodically reviewed and evaluated the accumulated study data for patient safety, study conduct, and study progress.

1. Clinical Inclusion and Exclusion Criteria

Enrollment in the INSPIRATION study was limited to patients who met the following inclusion criteria:

- Male or Female age 20-years or older;
- Proximal aortic neck is 17-31 mm in diameter;
- Supra-renal aorta, at 20 mm above the anticipated landing location, is smaller than the nominal diameter of the aortic bifurcate prosthesis to be used;
- Infra-renal aortic neck is ≥ 10 mm in length with supra-renal and infra-renal angulations ≤ 60°;
- Subject has at least one of the following:

- Abdominal aortic aneurysm (AAA) size &gt; 5.0 cm;
- Increase of the AAA diameter of &gt;0.5 cm over the last 6 months;

- Abdominal treatment length (lowest renal artery origin to aortic bifurcation) ≥ 9.4 cm;
- Aortic bifurcation &gt; 18 mm in diameter;
- Iliac landing zone ≥ 15 mm in length;

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- Iliac landing zone 7-22 mm in diameter;
- Minimum access vessel size of ≥ 5 mm;
- Minimum overall AAA treatment length (from lowest renal artery to distal landing zone) of 128 mm;
- Women of child bearing potential must be non-pregnant, non-lactating, and not planning to become pregnant during the course of the trial; and have a negative urine or serum pregnancy test within 7 days prior to index procedure;
- Provide written informed consent and as applicable written HIPAA (Health Insurance Portability and Accountability Act) authorization (for U.S. sites only) prior to initiation of study procedures;
- Willing to comply with the specified follow-up evaluation schedule.

Patients were not permitted to enroll in the INSPIRATION study if they met any of the following exclusion criteria:

- Vascular anatomy in which the placement of the stent-graft will cause occlusion of both internal iliac arteries or necessitates surgical occlusion of both internal iliac arteries;
- Subject has one of the following:
- Aneurysm sac rupture or leaking abdominal aortic aneurysm;
- Mycotic, dissecting, or inflammatory abdominal aortic aneurysm;
- Clinically significant acute vascular injury due to trauma;
- Significant aortic or iliac mural thrombus, plaque or calcification that would compromise fixation and seal of the device;
- A conical aortic neck defined as &gt; 3 mm distal increase over a 10 mm length in the planned seal zone;
- Thoracic aortic aneurysm ≥ 45 mm;
- Any aortic dissection;
- Morbid obesity (BMI &gt; 40.0 kg/m²) or other clinical conditions that limit required imaging studies or visualization of the aorta;
- Renal insufficiency (Creatinine &gt;2.0 mg/dL) or subject on renal dialysis;
- Known allergy or intolerance to nickel titanium (nitinol), Polyethylene terephthalate (PET), or polytetrafluoroethylene (PTFE);
- Known contraindication to undergoing angiography or anticoagulation (e.g. contrast allergies which cannot be treated);
- Connective tissue disorder (such as Marfan’s Syndrome or Ehlers-Danlos Syndrome);
- Coagulopathy, bleeding disorder, or other hypercoagulable state;
- Organ transplant recipient or subject requiring systemic immunosuppressant therapy;
- Cerebral vascular accident (CVA), MI, or intracranial bleeding within 3 months prior to the procedure;
- Active infection or chronic systemic illness at the time of index procedure that may interfere with the study objectives;

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- Major surgical procedure within 1 month prior to the index procedure or pre-planned within 1 month afterwards;
- Co-existing condition with a life expectancy of less than 2-years at time of procedure;
- Current or planned participation in any other investigational drug or medical device clinical study that has not completed primary endpoint(s) evaluation;
- Existing AAA surgical graft and/or a AAA stent-graft system;
- Other medical, social, or psychological issues that in the opinion of the investigator preclude the subjects from receiving this treatment, and the procedures and evaluations pre- and post-treatment.

2. Follow-up Schedule

All patients were scheduled to return for follow-up visits at the investigational site at 1 month, 6 months, 1 year post-procedure and annually through 5 years. A subset of patients (i.e., those with at least one fracture identified within the first 5 years) will be followed for an additional 5 years, for a total of 10 years post index procedure.

Pre-operative assessment included medical history, physical exam, CT scan, patient-reported outcomes questionnaire and laboratory testing as well as a pregnancy test for female patients of childbearing potential.

Post-operatively, the objective parameters measured during the study included clinical utility measures (e.g., post index procedural length of hospital stay (days) and length of Intensive Care Unit (ICU) stay (hours)), acute procedural information, appropriate effectiveness measures, and concomitant medications, with physical examination, CT scans with and without contrast, four-plane X-rays, and patient-reported outcomes questionnaires.

Pre-operative and post-operative parameters measured during the study are described in the Time and Event Schedule, Table 8.

Adverse events and complications were recorded at all visits.

The key timepoints are shown below in the tables summarizing safety and effectiveness.

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Table 8: Time and Event Schedule

| | Screening | Index | Discharge Assessments | 1 month +/- 7 days | 6 months +/- 30 days | 1 year +/- 30 days | 2 – 5 years9 |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Informed Consent | X1 | | | | | | |
| Medical History | X1 | | | | | | |
| Physical examination | X1 | | X | X | X | X | X |
| Verify Inclusion / Exclusion Criteria | X1 | X | | | | | |
| Labs: complete blood count (CBC), serum creatinine | X2 | | | | | | |
| Angiogram | | X | | | | | |
| CT scan w/ & w/o contrast | X3 | | | X4 | X4 | X4 | X4 |
| X-ray (abdominal) | | | | X5 | X5 | X5 | X5 |
| Adverse Event assessment | | X | X | X | X | X | X |
| Patient-Reported Outcomes (PRO) Questionnaire SF36v2 | X6 | | | X6 | X6 | X6 | |
| Conc. Medication at time of visit | X | X7 | X | X | X | X | X |

1 Prior to any study related procedure and within 6 weeks prior to index procedure
2 Labs must be within 6 weeks prior to index procedure
3 CT Reconstructed, a CT-scan (with contrast) performed within 6 months before index procedure is accepted. Screening CT-scan (w/o contrast) is optional and should be submitted to the independent Core Lab.
4 For subjects who develop renal insufficiency after index procedure, a duplex ultrasound (DUS) can replace the contrast CT (CT without contrast remains mandatory)
5 X-rays are required for all four abdominal views (AP, lateral, and 2 oblique views)
6 The SF36v2 PRO questionnaire must be fully completed by the patient prior to receipt of clinical assessments, tests, or study related procedures and can also be fully administered over the phone in the event a patient cannot return for their follow-up visit
7 Medication given to the subject at the time of index procedure
8 This timing convention is used throughout the protocol
9 2 years +/-45 days, 3 years +/-60 days, 4 years +/-75 days and 5 years +/-90 days

# 3. Clinical Endpoints

With regards to safety, the primary safety endpoint was the incidence of major adverse events (MAEs) at 30 days post-procedure. A major adverse event was defined as any of the following:

Death
Stroke
Myocardial infarction
- New onset renal failure (requiring dialysis)
- Respiratory Failure (requiring mechanical ventilation)
- Paralysis/ paraparesis
- Bowel Ischemia (requiring surgical intervention)
- Procedural Blood Loss $(\geq 1,000~\mathrm{cc})$

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This primary safety endpoint was compared to a performance goal of 20%.

With regards to effectiveness, the primary effectiveness endpoint was successful aneurysm treatment, which was a composite endpoint defined as the following.

- Technical success at the conclusion of the index procedure, that is, successful insertion of the delivery system through the vasculature and successful deployment of the device at the intended location. The endovascular graft must be patent, with absence of Types I or III endoleaks or aneurysm sac rupture, at the time of procedure completion as confirmed by angiography or other imaging modality;
- Absence of postoperative aneurysm enlargement (growth &gt; 5 mm), or stent graft migration (&gt; 10 mm), as compared to the 1 month size measurement at any time up to 1 year; and
- Absence of postoperative conversion to open surgery, aneurysm sac rupture, endoleak Type I/ III, or graft occlusion (including unilateral or bilateral limb occlusion) at any time up to 1 year.

This primary effectiveness endpoint was compared to a performance goal of 80%.

With regard to success criteria, the study would be considered successful if the performance goal for the safety and effectiveness primary endpoints were met.

The following secondary analyses were performed using descriptive summary statistics:

- Secondary safety endpoints include the following:
- Major Adverse Events (MAEs) and the individual components at 180 days and 360 days compared with SVS Open Surgical Controls, wherever the appropriate control data is available. These endpoints will be reported annually to 5 years;
- Procedure-related complications through 30 days, 180 days, 360 days and annually to 5 years;

- Secondary effectiveness endpoints include the following:
- Aneurysm-related mortality at 30 days, 180 days, 360 days, and annually through 5 years;
- Technical Success at 30 days as confirmed by CT or other imaging modality;
- Clinical utility measures to be compared with SVS Open Surgical Controls include:
- Length of hospital stay (days) post index procedure;
- Length of Intensive Care Unit (ICU) stay (hours) post index procedure;
- Length of the Index procedure (minutes).
- Incidence of secondary interventions, or the need for secondary interventions, to repair vascular events or malfunctions which are related to

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device and/or peri-graft complications at 1 month, 6 months, 1 year and annually to 5 years. Secondary intervention is any vascular event which requires intervention to repair the AAA or device, Indications for secondary intervention may include endoleaks, stent graft migration, occlusion, or aneurysm sac rupture.

- The incidence of secondary interventions within 1 year post-procedure, needed to prevent the occurrence of a significant event. Significant event being defined as: aneurysm enlargement (growth &gt; 5 mm), stent graft migration (&gt; 10 mm) compared to the 1-month size, endoleak type I / III, graft occlusion, sac rupture.
- Device-related events at 1 month, 6 months, 1 year and annually to 5 years. The device-related event may include:
- Aneurysm Enlargement – defined as an increase in maximum aneurysm cross sectional diameter &gt; 5 mm compared to the 1 month measurement;
- Endoleak(s);
- Aneurysm sac rupture;
- Fracture(s);
- Delivery System Malfunction;
- Device Malfunction;
- Stent Graft Migration – evidence of proximal or distal movement of the stent graft &gt;10 mm relative to fixed anatomic landmarks compared with 1 month;
- Graft Occlusion (including unilateral or bilateral limb occlusion);
- Conversion to open surgery.

## B. Accountability of PMA Cohort

At the time of database lock, of 190 patients enrolled in the PMA study, 100% of patients were available for analysis of the primary safety endpoint at 1 month and 96.3% (183) were available for analysis of the primary effectiveness endpoint at 1 year.

One hundred and ninety patients (190) were implanted with the INCRAFT® AAA Stent Graft System and seen through discharge. Ninety nine percent (99%) of the eligible patients (189/190) completed the 1 month follow-up visit. One patient died 2-days post-operatively. The visit compliance rate was 97% (182/188) at 6 months and 97% (177/183) at 1 year. There was at least 90% imaging compliance up to the 1 year visit with suitability for evaluating endoleaks, aneurysm enlargement, migration, and stent fracture. There were two (2) conversions to open surgery after the 6 month visit but prior to the 1 year visit and the devices were explanted in each case. The patients who underwent conversion did not have follow up imaging post-conversion as the INCRAFT device was no longer present; however, they continue annual clinical follow up. One patient who underwent an axillo-bifemoral bypass procedure to address a patency event at the 4 year timepoint (Stent Graft Patency Section 2.2.9) is continuing to be followed via clinical and imaging follow-up for endovascular graft

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assessment. Beyond the 1-year visit, there was at least 85% imaging compliance at 2 years, at least 82% imaging compliance at 3 years, and at least 70% imaging compliance at 4 years, with suitability for evaluating endoleaks, aneurysm enlargement, migration, and stent fracture. Detailed patient accountability and follow-up are presented in Table 9.

Table 9. Patient Imaging Accountability

| | | Number of Patients (%) | | | | Adequate Imaging to Assess the Parameter6 # (%) (Core Lab data) | | | | Events Occurring before Next Interval # (%) | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Visit | Eligible1 | Clinical data2 | CT3 | KUB XRAY4 | FU pending5 | Endoleak | Aneurysm Expansion | Migration | Fracture | Conversion7 | Death8 | LTF9 | Not due for visit10 |
| Procedure | 190 | 190 | N/A | N/A | 0 | 190/190 (100%)11 | N/A | N/A | N/A | 0 | 0 | 0 | 0 |
| Discharge | 190 | 190 | N/A | N/A | 0 | 190/190 (100%)12 | N/A | N/A | N/A | 0 | 0 | 0 | 0 |
| 1 Month | 190/19013 (100%) | 189/190 (99%) | 188/190 (99%) | 183/190 (96%) | 0 | 186/190 (98%) | 188/190 (99%) | 187/190 (98%) | 183/190 (96%) | 0 | 2/190 (1%) | 0 | 0 |
| 6 Months | 188/190 (99%) | 182/188 (97%) | 178/188 (95%) | 173/188 (92%) | 0 | 175/188 (93%) | 176/188 (94%) | 177/188 (94%) | 172/188 (91%) | 2/188 (1%) | 2/188 (1%) | 3/188 (2%) | 0 |
| 1 Year | 183/190 (96%) | 177/183 (97%) | 173/181 (96%) | 164/181 (91%) | 0 | 167/181 (92%) | 173/181 (96%) | 172/181 (95%) | 163/181 (90%) | 0 | 6/183 (3%) | 5/183 (3%) | 0 |
| 2 Years | 172/190 (91%) | 162/172 (94%) | 155/170 (91%) | 144/170 (85%) | 0 | 149/170 (88%) | 155/170 (91%) | 154/170 (91%) | 144/170 (85%) | 0 | 6/172 (3%) | 5/172 (3%) | 0 |
| 3 Years | 161/190 (85%) | 148/161 (92%) | 142/159 (89%) | 132/159 (83%) | 0 | 131/159 (82%) | 142/159 (89%) | 141/159 (89%) | 132/159 (83%) | 0 | 10/161 (6%) | 3/161 (2%) | 0 |
| 4 Years | 148/190 (78%) | 129/148 (87%) | 113/146 (77%) | 108/146 (74%) | 0 | 102/146 (70%) | 112/146 (77%) | 112/146 (77%) | 108/146 (74%) | 0 | 11/148 (7%) | 5/148 (3%) | 0 |

Visit windows are defined based on imaging windows:
Procedure (day 0), Discharge (1- discharge), 1 Month (discharge - 90 days), 6 Months (91 - 270 days), 1 Year (271 - 540 days), 2 Years (541 - 900 days), 3 Years (901 - 1260 days), 4 Years (1261 - 1620 days), and 5 Years (1621 - 1980 days).
Eligible for follow-up = (previous eligible for follow-up - previous death - previous LTF) - currently not due). Patient(s) not due for a visit are excluded from the denominator.
2Defined as patients with either the scheduled study visit or patients with an unscheduled study visit within the imaging window for the visit.
3Only images that pass QC are listed.
4Only images that pass QC are listed.
Patients still within follow-up window but have not had clinical follow up.
Not the number of subjects with these reported events, but rather, the number with adequate imaging to evaluate the listed outcome.
Patients who converted to open surgery no longer completed imaging follow-up, only clinical follow-up.
Deaths within imaging windows.
Lost to Follow-up (LTF) are those subjects that are either withdrawn or classified as lost to follow-up in the Electronic Data Capture.
10Number of patients who are still alive and participating in the study but have not had the device implanted long enough to be eligible for the follow-up visit. Percent of patients is out of those who are still alive (not dead) and participating in the study (not LTF).

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$^{11}$ Endoleak at procedure determined by angiogram. Adequate imaging count provided by sponsor, angiogram Core Lab data not received by Contract Research Organization (CRO).
$^{12}$ Endoleak at discharge determined by CT. Adequate imaging count provided by sponsor, CT at discharge Core Lab data not received by CRO.
13The denominator for eligibility at 1 month is based on the 1 month imaging window defined as "post-procedure through 90 days." The 2 patients died at 2 days and 78 days within the 1 month imaging window therefore they were included in the denominator.

# C. Study Population Demographics and Baseline Parameters

# Demographics

The demographics of the study population are typical for a pivotal study performed in the US for the evaluation of an endovascular graft system intended for infrarenal abdominal aortic aneurysm repair, with the exception of a higher percentage of nonwhite/Caucasian study patients.

Patient demographics for the INCRAFT cohort and SVS controls are presented in Table 10. The INCRAFT cohort was older (73.8 years vs. 70.1 years SVS) and shorter in stature (172 cm vs. 174 cm SVS) than the SVS controls. In addition, the INCRAFT cohort included more males (90% vs. 83.3% SVS). The INCRAFT cohort was only 68.9% white/Caucasian as compared with the SVS controls (94.9%) because roughly one-third of the patients in the INCRAFT cohort were from Japan while all the patients in SVS controls were from the US.

The patients in the US cohort were slightly older (74.5 vs. 72.1 years) and taller (174.8 vs. 165.8) with a higher body mass index (28.6 vs. 24.6) as compared to the Japanese cohort. The percentage of women enrolled in the study was higher in the US (13.4%) as compared to Japan (1.8%).

Table 10. Patient Demographics

| Patient Characteristics | INCRAFT US (N = 134) | INCRAFT Japan (N = 56) | INCRAFT US & Japan (N = 190) | SVS Controls (N = 323) |
| --- | --- | --- | --- | --- |
| Age (years) | | | | |
| Mean ± SD (N) | 74.5 ± 7.48 (134) | 72.1 ± 7.55 (56) | 73.8 ± 7.56 (190) | 70.1 ± 7.41 (323) |
| Median | 75.0 | 71.0 | 74.0 | 70.7 |
| Range (Min, Max) | 51.0, 89.0 | 56.0, 90.0 | 51.0, 90.0 | 41.2, 86.1 |
| Number of Men (%) | 86.6% (116/134) | 98.2% (55/56) | 90.0% (171/190) | 83.3% (269/323) |
| Height (cm) | | | | |
| Mean ± SD (N) | 174.8 ± 8.96 (134) | 165.8 ± 7.09 (56) | 172.1 ± 9.37 (190) | 174.0 ± 9.26 (315) |
| Median | 177.8 | 166.0 | 172.7 | 175.3 |
| Range (Min, Max) | 150.0, 196.0 | 147.0, 179.5 | 147.0, 196.0 | 135.0, 194.3 |
| Weight (kg) | | | | |
| Mean ± SD (N) | 87.6 ± 15.78 (134) | 67.7 ± 11.87 (56) | 81.7 ± 17.27 (190) | 82.9 ± 17.25 (318) |
| Median | 86.2 | 69.9 | 80.5 | 83.0 |
| Range (Min, Max) | 48.6, 137.8 | 35.9, 96.2 | 35.9, 137.8 | 40.4, 151.5 |

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| Patient Characteristics | INCRAFT US (N = 134) | INCRAFT Japan (N = 56) | INCRAFT US & Japan (N = 190) | SVS Controls (N = 323) |
| --- | --- | --- | --- | --- |
| BMI (kg/m2) | | | | |
| Mean ± SD (N) | 28.6 ± 4.49 (134) | 24.6 ± 3.74 (56) | 27.4 ± 4.66 (190) | 27.3 ± 5.07 (314) |
| Median | 27.9 | 24.9 | 27.1 | 27.1 |
| Range (Min, Max) | 19.7, 40.0 | 15.1, 34.4 | 15.1, 40.0 | 15.8, 63.1 |
| Race | | | | |
| White/Caucasian | 97.8% (131/134) | 0.0% (0/56) | 68.9% (131/190) | 94.9% (244/257) |
| Non-White/Non-Caucasian | 2.2% (3/134) | 100.0% (56/56) | 31.1% (59/190) | 5.1% (13/257) |

# Baseline Medical History

Baseline clinical history for the study patients is summarized in Table 11 according to body system and/or medical condition. The cardiovascular comorbidities that were most commonly observed in the INCRAFT cohort were hypertension (77.9%) and hypercholesterolemia (72.1%).

A larger proportion of patients in the SVS controls had angina (25.5% vs. 15.8%), coronary artery disease (53.3% vs. 40.5%), history of myocardial infarction (32.8% vs. 18.4%), and stroke (13.6% vs. 6.3%). In contrast, a larger proportion of patients in the INCRAFT cohort had diabetes (25.3% vs. 12.7%), and history of cancer (32.6% vs. 23.6%). There was a high prevalence of smoking history in the INCRAFT cohort (92.6%) and the SVS controls (88.2%).

There were differences between the US patient population and the Japanese patient population with respect to their baseline medical histories as summarized in Table 11. The most commonly observed comorbidities were the same in the US and Japan; however, the rates were only similar for hypertension (78.4% vs. 76.8%) and were different for hypercholesterolemia (78.4% vs. 57.1%). The rates of comorbidities at baseline were higher in the US patient population as compared to the Japanese patient population, with the exception of angina (9.0% vs. 32.1%), liver disease (4.5% vs. 8.9%), and percutaneous transluminal coronary angioplasty or stent (22.4% vs. 30.4%).

Table 11. Baseline Medical History

| Body System/Medical Condition | INCRAFT US (N = 134) | INCRAFT Japan (N = 56) | INCRAFT US & Japan (N = 190) | SVS Controls (N = 323) |
| --- | --- | --- | --- | --- |
| Cardiovascular | | | | |
| Number of Patients with at least one cardiovascular comorbidity | 97.0% (130/134) | 87.5% (49/56) | 94.2% (179/190) | 92.6% (287/310)* |
| Angina | 9.0% (12/134) | 32.1% (18/56) | 15.8% (30/190) | 25.5% (54/212) |
| Arrhythmia | 21.6% (29/134) | 10.7% (6/56) | 18.4% (35/190) | 13.9% (45/323) |

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| Body System/Medical Condition | INCRAFT US (N = 134) | INCRAFT Japan (N = 56) | INCRAFT US & Japan (N = 190) | SVS Controls (N = 323) |
| --- | --- | --- | --- | --- |
| Coronary Artery Disease | 47.8% (64/134) | 23.2% (13/56) | 40.5% (77/190) | 53.3% (172/323) |
| Myocardial Infarction | 20.1% (27/134) | 14.3% (8/56) | 18.4% (35/190) | 32.8% (106/323) |
| Hypertension | 78.4% (105/134) | 76.8% (43/56) | 77.9% (148/190) | 70.6% (228/323) |
| Hypercholesterolemia | 78.4% (105/134) | 57.1% (32/56) | 72.1% (137/190) | NA |
| Congestive Heart Failure | 3.7% (5/134) | 0.0% (0/56) | 2.6% (5/190) | 6.5% (21/323) |
| Family History of Aneurysm | 14.2% (19/134) | 5.4% (3/56) | 11.6% (22/190) | 17.9% (38/212) |
| Peripheral Arterial Disease | 18.7% (25/134) | 5.4% (3/56) | 14.7% (28/190) | 18.0% (58/323) |
| Neurological | | | | |
| Stroke | 6.7% (9/134) | 5.4% (3/56) | 6.3% (12/190) | 13.6% (44/323) |
| Endocrine | | | | |
| Diabetes | 26.9% (36/134) | 21.4% (12/56) | 25.3% (48/190) | 12.7% (41/323) |
| Urinary | | | | |
| Moderate Renal Insufficiency | 6.7% (9/134) | 1.8% (1/56) | 5.3% (10/190) | 3.1% (10/323) |
| Pulmonary | | | | |
| Chronic Obstructive Pulmonary Disease | 30.6% (41/134) | 17.9% (10/56) | 26.8% (51/190) | 26.9% (87/323) |
| Other Medical Conditions | | | | |
| Liver Disease | 4.5% (6/134) | 8.9% (5/56) | 5.8% (11/190) | 3.4% (5/146) |
| Cancer | 37.3% (50/134) | 21.4% (12/56) | 32.6% (62/190) | 23.6% (50/212) |
| Alcoholism | 11.2% (15/134) | 1.8% (1/56) | 8.4% (16/190) | 8.5% (18/212) |
| Smoking | 91.0% (122/134) | 96.4% (54/56) | 92.6% (176/190) | 88.2% (285/323) |

* There were 13 patients who reported no other cardiovascular (CV) comorbidities but missing data for a prior history of angina or a family history of aneurysm for these patients, therefore, they were not included in the denominator.

## Baseline Vessel Measurements

Baseline aneurysm and anatomical measurements, as well as access vessel characteristics of the study population, were reported by both the Core Lab and site. Two CT scans were not evaluated by the Core Lab due to imaging quality. Baseline aneurysm characteristics are summarized in Table 12.

All patie…