Gore Carotid Stent

P180010 · W. L. Gore & Associates, Inc. · NIM · Nov 1, 2018 · Cardiovascular

Device Facts

• Record ID: P180010
• Device Name: Gore Carotid Stent
• Applicant: W. L. Gore & Associates, Inc.
• Product Code: NIM · Cardiovascular
• Decision Date: Nov 1, 2018
• Decision: APWD
• Device Class: Class 3
• Attributes: Therapeutic

Indications for Use

The GORE Carotid Stent, used with the GORE Embolic Filter, is indicated for the treatment of carotid artery stenosis in patients deemed at high surgical risk for carotid endarterectomy (CEA) and who meet the criteria below. - Patients with symptomatic carotid artery stenosis, ≥50%, as confirmed by ultrasound or angiography. - Patients with asymptomatic carotid artery stenosis, ≥80%, as confirmed by ultrasound or angiography. - Patients must have a Reference Vessel Diameter of 3.7 mm – 9.0 mm.

Device Story

The GORE Carotid Stent (GCS) is a hybrid, self-expanding nitinol stent featuring an open-cell frame and an expanded polytetrafluoroethylene (ePTFE) lattice (closed-cell component). The device surface is treated with a proprietary covalent heparin coating (CBAS Heparin Surface) to improve hemocompatibility. It is delivered via a catheter-based system (5F or 6F) and used in conjunction with the GORE Embolic Filter to capture distal emboli during carotid artery stenting. The device is intended for use by physicians in a clinical setting to treat carotid artery stenosis in high-surgical-risk patients. By providing mechanical support to the vessel wall, the stent restores luminal patency, while the embolic protection device mitigates the risk of stroke during the procedure. The heparin coating reduces the potential for thrombus formation on the implant surface. Clinical outcomes are monitored via angiography and ultrasound to assess residual stenosis and restenosis, helping to reduce the risk of future ischemic events.

Clinical Evidence

The SCAFFOLD clinical study was a prospective, multicenter, single-arm study (n=312 enrolled, 265 per-protocol) evaluating the GCS in high-surgical-risk patients. The primary endpoint was a composite of Major Adverse Events (MAE: death, stroke, MI) through 30 days and ipsilateral stroke through 1 year. The 1-year MAE rate was 4.5% (95.1% UCL 8.5%), significantly lower than the 16.9% performance goal (p<0.00001). Technical success was 100%. In-stent restenosis rate was 1.8% at 1 year. No unanticipated adverse device effects were reported.

Technological Characteristics

Implant: Laser-cut nitinol (nickel-titanium) frame (ASTM F2063, F2633) with ePTFE lattice. Surface: CBAS Heparin Surface. Delivery: Catheter-based, 5F/6F compatible. Sterilization: Ethylene oxide. MRI: MR Conditional (1.5T and 3.0T). Dimensions: 5.0–10.0 mm diameter, 30–40 mm length. Hybrid open/closed-cell design.

Indications for Use

Indicated for treatment of carotid artery stenosis in patients at high surgical risk for carotid endarterectomy (CEA). Includes symptomatic patients (≥50% stenosis) and asymptomatic patients (≥80% stenosis) with reference vessel diameter 3.7–9.0 mm. Contraindicated in patients with anticoagulant/antiplatelet therapy contraindications, severe vascular tortuosity, nickel-titanium hypersensitivity, uncorrected bleeding disorders, ostium lesions, or heparin hypersensitivity.

Regulatory Classification

Identification

Stent, Carotid -- a metal scaffold placed via a delivery catheter into the carotid artery to maintain the lumen

Reference Devices

• ACCULINK

Submission Summary (Full Text)

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SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED)

I. GENERAL INFORMATION

Device Generic Name: Stent, Carotid Artery
Device Trade Name: GORE Carotid Stent
Device Procode: NIM
Applicant's Name and Address: W.L. Gore &amp; Associates, Inc.
4150 West Kiltie Lane
Flagstaff, AZ 86005
Date(s) of Panel Recommendation: None
Premarket Approval Application (PMA) Number: P180010
Date of FDA Notice of Approval: November 01, 2018

II. INDICATIONS FOR USE

The GORE Carotid Stent, used with the GORE Embolic Filter, is indicated for the treatment of carotid artery stenosis in patients deemed at high surgical risk for carotid endarterectomy (CEA) and who meet the criteria below.

- Patients with symptomatic carotid artery stenosis, ≥50%, as confirmed by ultrasound or angiography.
- Patients with asymptomatic carotid artery stenosis, ≥80%, as confirmed by ultrasound or angiography.
- Patients must have a Reference Vessel Diameter of 3.7 mm – 9.0 mm.

III. CONTRAINDICATIONS

The GORE Carotid Stent is contraindicated for use in

- Patients in whom anticoagulant and/or antiplatelet therapy is contraindicated.
- Patients with severe vascular tortuosity or anatomy that would preclude the safe introduction of the delivery catheter or embolic protection device.
- Patients with a known hypersensitivity to nickel-titanium.
- Patients with uncorrected bleeding disorders.
- Lesions in the ostium of the common carotid artery.
- Patients with known hypersensitivity to heparin, including those patients who have had a previous incident of Heparin-Induced Thrombocytopenia (HIT) type II.

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# IV. WARNINGS AND PRECAUTIONS

The warnings and precautions can be found in the GORE Carotid Stent labeling.

# V. DEVICE DESCRIPTION

The GORE Carotid Stent (GCS) is designed as a "hybrid" stent in that it incorporates open-cell and closed-cell stent features. The GCS is comprised of two sub-systems: a deployment catheter and a self-expanding, deployable stent. The stent integrates a proprietary stable, covalent end-point attached heparin, which is used to create the CBAS Heparin Surface. The device includes 18 part numbers with a diameter range from 5.0 to 10.0 mm, including tapered stents (6/8 mm, 7/9 mm, and 8/10 mm diameters), with lengths of 30 and 40 mm. Table 1 summarizes the device sizes and delivery system compatibility.

Table 1. GORE Carotid Stent Sizing Summary

| GORE Carotid Stent Catalogue Number | Stent Distal Inner Diameter (mm) | Stent Proximal Inner Diameter (mm) | Stent Length (mm) | Delivery System |
| --- | --- | --- | --- | --- |
| GCS5530A | 5 | 5 | 30 | 5 Fr |
| GCS5540A | 5 | 5 | 40 | |
| GCS6630A | 6 | 6 | 30 | |
| GCS6640A | 6 | 6 | 40 | |
| GCS7730A | 7 | 7 | 30 | |
| GCS7740A | 7 | 7 | 40 | |
| GCS8830A | 8 | 8 | 30 | |
| GCS8840A | 8 | 8 | 40 | |
| GCS6830A | 6 | 8 | 30 | |
| GCS6840A | 6 | 8 | 40 | |
| GCS9930A | 9 | 9 | 30 | 6 Fr |
| GCS9940A | 9 | 9 | 40 | |
| GCS0030A | 10 | 10 | 30 | |
| GCS0040A | 10 | 10 | 40 | |
| GCS7930A | 7 | 9 | 30 | |
| GCS7940A | 7 | 9 | 40 | |
| GCS8030A | 8 | 10 | 30 | |
| GCS8040A | 8 | 10 | 40 | |

# A. Stent Component

The implantable stent portion of the GCS is constructed of a self-expanding, laser cut, nitinol (nickel-titanium alloy) stent frame comprising an "open cell" component of the device and with an expanded polytetrafluoroethylene (ePTFE) lattice comprising a "closed cell" component of the device, as shown in Figure 1 below. The CBAS Heparin Surface is subsequently applied to all surfaces of the device prior to loading on the delivery system.

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Figure 1. GORE Carotid Stent

## B. Delivery System

The stent is delivered on the catheter-based delivery system. The stent is radially compressed and placed within a pullback sheath. The pullback sheath is mounted on a 5F or 6F introducer-sheath compatible delivery system as shown in Figure 2.

Figure 2. GCS Delivery System

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# C. Accessory Devices

The system packaging includes a 2.5cc syringe and luer adapter to facilitate system flushing from the hub (syringe only) and distal tip (syringe fitted with luer adapter).

# VI. ALTERNATIVE PRACTICES AND PROCEDURES

There are several other alternatives for the correction of carotid artery disease. Alternate treatments for carotid artery disease are dependent on symptomatic status, patient anatomy and comorbidities, and degree of stenosis. Patients with less severe disease or symptoms are generally treated with medical management including antiplatelet and/or anticoagulant medicine, antihypertensive or antilipidemic drugs. Carotid endarterectomy and carotid artery stenting with other devices are more invasive alternative treatments, particularly with more severe disease. 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.

# VII. MARKETING HISTORY

The GCS is currently approved for use in the European Union, where the CE mark was obtained in April, 2014. These countries include the following: Austria, Belgium, Denmark, Finland, France, Germany, Greece, Iceland, Ireland, Italy, Luxembourg, Monaco, the Netherlands, Norway, Portugal, Spain, Sweden, Switzerland, and the United Kingdom.

# VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH

Table 2 lists the potential adverse effects (e.g., complications) associated with the use of the device.

Table 2. List of Procedure and Device Related Potential Adverse Effects

| Abrupt vessel closure |
| --- |
| Allergic reactions to anti-platelet agents/contrast medium |
| Aneurysm |
| Angina/coronary ischemia |
| Arrhythmia |
| Arterial occlusion/thrombosis at puncture site or remote site |
| Arteriovenous fistula |
| Bacteremia or septicemia |
| Bleeding from anticoagulant or antiplatelet medications |
| Bradycardia/arrhythmia and other conduction disturbances |
| Cerebral edema |
| Cerebral hemorrhage |
| Cerebral ischemia / transient ischemic attack (TIA) |

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| Congestive heart failure (CHF) |
| --- |
| Death |
| Detachment and/or implantation of a component of the system |
| Drug reactions |
| Emboli, distal (air, device, tissue or thrombotic emboli) |
| Emergent or urgent endarterectomy or access vessel surgical or endovascular procedure |
| Fever |
| Filter thrombosis/occlusion |
| Groin hematoma, with or without surgical repair |
| Hemorrhage, with or without transfusion |
| Heparin induced thrombocytopenia (HIT) |
| Hyperperfusion syndrome |
| Hypotension/hypertension |
| Infection and pain at insertion site |
| Ischemia/infarction of tissue/organ |
| Myocardial infarction (MI) |
| Pain (head, neck) |
| Pseudoaneurysm, femoral |
| Renal failure/insufficiency |
| Restenosis of stented segment |
| Seizure |
| Severe unilateral headache |
| Stent/filter entanglement / damage |
| Stent embolization |
| Stent fracture |
| Stent malposition |
| Stent migration |
| Stent thrombosis / occlusion |
| Stroke/cerebrovascular accident (CVA) or other neurological complications (e.g. paralysis, paraplegia or aphasia) |
| Temporary or total occlusion of carotid artery or branch vessels |
| Tissue necrosis |
| Vascular access complications (e.g. bleeding, vessel damage, pseudoaneurysm and infection) |
| Vessel dissection, perforation, or rupture |
| Vessel spasm or recoil |
| Vessel thrombosis |
| Unstable angina pectoris |

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

## IX. SUMMARY OF NONCLINICAL STUDIES

### A. Biocompatibility Studies

Biocompatibility testing was conducted on the GCS in accordance with applicable Good Laboratory Practices (21 CFR §58) and ISO 10993-1: 2009, Biological Evaluation of Medical Devices. Tests were conducted separately on product manufactured, packaged and sterilized using materials and procedures intended for the marketed product for the delivery system and the stent.

The GCS delivery system is classified as an externally-communicating device in limited contact (&lt; 24 hrs) with circulating blood. The stent is classified as an implant device in permanent contact (&gt; 30 days) with blood. A summary of the biocompatibility testing conducted can be found in Table 3 below.

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Table 3. Summary of GORE Carotid Stent Biocompatibility Testing

| Test Performed | Test Description | Stent | Delivery System | Results |
| --- | --- | --- | --- | --- |
| Cytotoxicity | ISO MEM Elution Assay with L-929 Mouse Fibroblast Cells | X | X | Non-cytotoxic |
| Sensitization | ISO Guinea Pig Maximization | X | X | Non-sensitizing |
| Irritation | ISO Intracutaneous Reactivity | X | X | Non-irritating |
| Pyrogenicity | Material-Mediated Pyrogenicity | X | X | Non-pyrogenic |
| Acute Systemic Toxicity | ISO Systemic Toxicity Study | X | X | Non-toxic |
| Subchronic / Subacute Toxicity | 14 Day Repeat Dose Intravascular and Intraperitoneal Toxicity Study | X | N/A | Non-toxic |
| Implantation | Subcutaneous Implantation Study – 4 Weeks | X | N/A | Non-irritant |
| Hemocompatibility | ASTM Hemolysis Study (Direct and Indirect Contact) | X | X | Non-hemolytic |
| | Complement Activation Assay (C3a and SC5b-9) | X | X | Not a complement activator |
| | In Vivo Thrombogenicity Study | X^{a} | X | Non-thrombogenic |
| Genotoxicity | Bacterial Reverse Mutation (Ames) Assay | X | N/A | Non-mutagenic |
| | Mouse Lymphoma Assay | X | N/A | Non- clastogenic |

a Evaluated as part of the animal studies outlined in Section C, below.

Stent thrombogenicity was evaluated as part of other in vivo studies conducted to evaluate safety and effectiveness of the device in a vascular implant location, as described in Section C below. These additional animal studies demonstrated a lack of significant thrombus formation when stents were implanted in a clinically-relevant vascular implant location.

The omission of chronic toxicity and carcinogenicity testing for the stent was supported by information regarding the starting materials, processing of the finished device compared to a marketed device, genotoxicity testing, the GLP animal study, and/or toxicity data from the literature.

The information provided demonstrates that the GCS is biocompatible.

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# B. In Vitro Engineering Testing

In vitro bench testing to support the GCS was developed based on the device risk assessment and is consistent with FDA Non-Clinical Tests and Recommended Labeling of Intravascular Stents and Associated Delivery Systems, April 18, 2010 and its addendum, Select Updates for Non-Clinical Engineering Tests and Recommended Labeling for Intravascular Stents and Associated Delivery Systems, August 30, 2013.

The relevant in vitro tests outlined in the guidance document and included in support of the GORE Carotid Stent devices are summarized in Table 4 below.

Table 4. Summary of in vitro Test Results

| Test | Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Material Composition | Document material composition and characterize the surface oxide of the nitinol frame component. | Characterize Nitinol stent frame via surface analysis. | The stent material conforms to the material specification, ASTM F2633, and ASTM F2063 |
| Shape Memory & Superelasticity | Document the active austenitic finish transformation temperature (At) of the stent component. | Af must be ≤ body temperature. | Each lot of nitinol tubing used for the production of stents is tested for austenitic finish temperature (Af). The stent retains its specified size and shape by superelasticity. |
| Corrosion Resistance | The stent must resist corrosion following implantation. | The deployed stent must exhibit equivalent or superior breakdown potentials as compared to an appropriate reference device per ASTM F2129-15. | GCS devices exhibited statistically higher mean breakdown (Eb) potential than the reference device. |
| Nickel Elution | The stent must have acceptable levels of nickel elution. | The stent must not elute nickel beyond the acute and chronic tolerable intakes. | All stents meet the acceptance criteria for acute and chronic nickel elution. |
| Dimensional Verification (deployed length) | The stent must be within the dimensional specification when implanted. | Stents with a labeled length of 30 mm shall be ≥ 27.0 mm and ≤ 33.0 mm when deployed. Stents with a labeled length of 40 mm shall be ≥ 36.0 mm and ≤ 44.0 mm when deployed. | All measurements passed the applicable requirement for deployed length. |
| Dimensional Verification (deployed stent outer diameter) | The deployed stent outer diameter must be consistent with as-labeled diameter. | The deployed device must be the labeled device diameter ± 0.4 mm. | All measurements pass the applicable requirement for stent outer diameter. |

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| Test | Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Percent Surface Area of Stent | Determine the ratio of the stent/vessel non-contact surface area to the vessel surface area at minimum, nominal, and maximum indicated vessel diameters. | Stents were characterized for information only. | The stent percent contact surface area was calculated and ranges from 29% to 47% depending on device diameter. |
| Foreshortening / Elongation | This test assesses the difference between crushed stent length and deployed stent length for the GCS. | Deployed stent length shall be ± 20% of the crushed stent length. | Foreshortening values range between 0.9% and 8.8% depending on labeled stent length. |
| Crushed Stent Length | This test assesses the crushed stent length for the GCS to provide a baseline for determination of foreshortening/elongation. | Length shall be ± 3 mm for 30mm devices and ± 4 mm for 40mm devices. | Crushed stent length values range between 31.6mm and 32.3mm for 30mm length and 40.8mm and 43.1mm for 40mm length devices. |
| Stent Integrity | To verify the stent has no clinically significant defects or flaws after deployment. | Frame fracture, percent delamination, and lattice breakage shall not be at a clinically relevant level, and there shall be no contamination. | All devices tested met established acceptance criteria. |
| Mechanical Integrity - Radial Outward Force | This test determines the radial pressure of the stent at its minimum and maximum indicated diameters. | The radial outward pressure must be sufficient to withstand clinically relevant forces. | All devices tested met established acceptance criteria. |
| Material Mechanical Properties | Characterize the stent materials mechanical properties to ensure they are acceptable for the intended use. | ASTM F2063 | The stent material conforms to implant material standards ASTM F2063 for material properties. |
| Strain and Fatigue Analysis/Finite Element Analysis | To determine the location and magnitude of the maximum principal strains in the stents, under expected clinical use conditions, through the use of Finite Element Analysis (FEA). | Strains are calculated for: A) radial pulsatile loading conditions when deployed in vessels at maximum and minimum product specification diameters, B) radial compressions due to catheter loading C) flat plate compression and D) multi-modal loading conditions when subjected to pulsatile loading conditions that are combined with bending. | The location and magnitude of the maximum principle strains have been calculated and the strain states are below the endurance limit for the Nitinol material. |

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| Test | Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Accelerated Durability Testing: Pulsatile | The purpose of this test is to evaluate the simulated 10 year durability of stents under expected clinical use conditions as it pertains to fatigue due to pulsatile motion. | The stent must exhibit a design life of at least 10 years through simulated physiological loading without failure that would compromise device function or patient safety. | All devices tested met established acceptance criteria. |
| Particulate Evaluation | This test evaluates particulation during simulated use. | The Finished Good shall not introduce clinically-relevant particulation during delivery, deployment, and retraction. | All devices were within the limits provided in USP <788>. |
| Magnetic Resonance Imaging Compatibility | To evaluate the MRI safety and compatibility of the stent. | The implant must not present additional risk to the patient when exposed to static magnetic field strengths of 1.5 and 3.0 Tesla. | The stent does not pose additional risk to patients and may be labeled MR Conditional. |
| Radiopacity | The purpose of this test is to demonstrate the ability of the stent and delivery system to be visualized adequately under fluoroscopy. | Units must be visible under fluoroscopy and comparable to a commercially available carotid stent and carotid stent system. | All samples were comparable to a commercially available carotid stent system and were all visible under digital radiographic imaging. |
| Crush Resistance | This test evaluates the ability of the GCS to recover its original size and shape from potential external, non-cardiac loads after removal of the load. | The stent must recover its desired shape after application and removal of external loads, deformation, or both. | The stent adequately recovers its diameter and length following deployment from the constrained profile. |
| Kink Resistance | This test determines the smallest radius of curvature the GCS can withstand without kinking, and demonstrates if the GCS recovers its original size and shape after testing. | The GCS shall not kink at bend radius ≤ 19mm. | All stents had kink radii below 19mm. All devices returned to original geometry after testing. |
| Dimensional Verification (Crossing Profile) | This test is to assess the diameter of the GCS delivery system with constrained stent. | The crossing profile for 5 Fr compatible delivery systems shall be ≤ 1.85 mm (0.073 in) diameter. The crossing profile for 6 Fr compatible delivery systems shall be ≤ 2.03 mm (0.080 in) diameter. | The delivery system and constrained stents met the acceptance criteria. |
| Dimensional Verification (Working Length) | Delivery catheter working length enables treatment of the intended site. | The delivery catheter working length must be 135 ± 3 cm. | The delivery catheter meets the acceptance criteria for working length. |

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| Test | Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Delivery, Deployment, and Retraction | This test assesses the ability of the delivery system to: 1) access the target location; 2) deploy the stent; and 3) retract the delivery system without dislodging the stent. | The catheter delivery system must be able to reliably access target location, deploy the stent, and retract without dislodging the stent. | The catheter delivery system meets the established acceptance criteria. |
| Delivery, Deployment, and Retraction (Accessory Compatibility) | The system must be compatible with accessories typical of the procedure. | The system must be flushable with a syringe, compatible with 0.014" guidewires, pass through 5 Fr or 6 Fr introducer sheaths, and be compatible with embolic protection devices (GORE Embolic Filter). | The system is compatible with accessories that would be used in a typical clinical procedure. |
| Delivery Catheter Bond Strength | Evaluate the tensile strength of delivery catheter bonds. | The delivery catheter must maintain its function during access, deployment, and retraction per ISO 10555-1. | Tensile strengths for all delivery catheter samples across all bond locations pass the applicable acceptance criteria. |
| Delivery System Flexibility & Kink | To verify the catheter delivery system is able to reliably track through tortuous, clinically relevant anatomy and deliver the stent to its intended location. | The catheter delivery system must be able to reliably: • Access the target location. • Deploy the stent by withdrawing the tear tube. • Retract the intact catheter without dislodging the stent. | The catheter delivery system meets the established acceptance criteria. |
| Catheter Torque Strength | This test is to assess the torque strength of the catheter. | The catheter must be able to complete at least 1 full rotation without a kink in the body of the delivery system of failure of a bond. | The catheter delivery system meets the established acceptance criteria. |
| Coating Integrity | To characterize the CBAS Heparin Surface of the stent. | Stents were characterized for information only. | Based on the image analysis, the coating integrity of the CBAS Heparin Surface is maintained throughout aging, across device size configurations. There was no apparent gross heterogeneity in the presence or uniformity of the coating. |
| Heparin Surface Activity | To test that heparin surface activity of the CBAS Heparin Surface meets specification requirements throughout the stent shelf-life. | Must meet specification for heparin surface activity through the product shelf-life | The specification was met throughout the product shelf-life. |

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| Test | Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Heparin Surface Concentration | To demonstrate the presence of heparin on the stent surface and characterize the mass of heparin present per unit area. | Testing must demonstrate the presence of heparin on the surface and characterize the mass of heparin present per unit area. | Results of heparin surface concentration testing met the established acceptance criteria. |
| Chemical Residuals | To test chemical residuals on the device surface related to the heparin coating process. | Must be acceptable within the bounds of established allowable limits. | Chemical residuals of the coated stent surface are within allowable limits. |
| Chandler Blood Loop Testing | To characterize the potential thrombogenicity of mechanically induced disruptions of the CBAS Heparin Surface of the stent. | Stents were characterized for information only. | The results of this evaluation did not identify, either grossly or with SEM, observable evidence of thrombus associated with any disruption. Additionally, no evidence of thrombus was observed on the surfaces of control CBAS Heparin Surface-coated GCS devices, which did not contain mechanically induced disruptions, and represents the final device design. |

# C. Animal Studies

The GCS was subjected to two GLP animal studies to evaluate the safety and performance of the device. The GLP in vivo animal studies demonstrated the safety and overall product performance of the GCS in vivo in a total of 14 porcine models. Table 5 summarizes the results of the GLP studies conducted on finished, sterile devices.

Table 5. Summary Results of the GLP Animal Studies

| Study Description | Study Overview | Purpose | Summary of Test Results |
| --- | --- | --- | --- |
| #2103SC GORE Carotid Stent (GCS): A 24 hour In Vivo Compatibility Evaluation with the GORE Embolic Filter (GEF) and GORE Flow Reversal Systems (GFRS) in the Arterial Vasculature of the Porcine Model | -GLP -2 domestic swine -common carotid artery -24 hours -n=2 GCS/GEF -n=2 GCS/GFRS | Assess compatibility of the GCS with the GEF and GFRS | GCS is compatible with GEF and GFRS |

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| Study Description | Study Overview | Purpose | Summary of Test Results |
| --- | --- | --- | --- |
| #2102SC
GORE Carotid Stent (GCS):
An In Vivo Performance
Evaluation in the Carotid
Arteries of Swine | -GLP
-12 Hanford mini-swine
-common carotid artery
-3, 30, 90 days
-n=12 GCS
-n=9 ACCULINK | Assess delivery/deployment, patency, integrity, and tissue response | -Delivery and deployment evaluations received PASS scores.
-All GCS stents patent at each time point.
-Four ACCULINKs migrated; three of four devices could not be analyzed.
-Angiographic stenosis statistically similar between GCS and ACCULINK
-All GCS stents intact at 90 days.
-Tissue response biologically acceptable;
GCS similar to ACCULINK for all histological parameters except vessel injury. |

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

The GCS is sterilized by ethylene oxide. Validation of the sterilization method to ensure a Sterility Assurance Level (SAL) of $10^{-6}$ has been conducted in accordance with ISO 11135-1:2007 Sterilization of health care products- Ethylene oxide-Part 1: Requirements for development, validation and routine control of a sterilization process for medical devices.

Packaging Validation demonstrated the ability of the packaging to protect the product and maintain a sterile barrier through shipping and shelf life. The device is packaged in a backer card, sealed in a foil-Tyvek primary pouch, and a poly-Tyvek secondary pouch. The packaged device is then placed in a carton.

A shelf life of 40 months has been established for the GCS based on product and package shelf life testing. Heparin stability testing was conducted to demonstrate that heparin surface activity and heparin surface concentration requirements will be met for the claimed 40-month shelf-life. The stability characteristics of the drug-related attributes of the GCS will continue to be monitored as part of an established on-going stability program.

## X. SUMMARY OF PRIMARY CLINICAL STUDY

The applicant performed a clinical study (SCAFFOLD) to establish a reasonable assurance of safety and effectiveness of carotid stenting with the GCS in patients at high risk for surgery with symptomatic carotid artery disease and $\geq 50\%$ stenosis or asymptomatic disease and $\geq 80\%$ stenosis by angiography under IDE #G110127. Data from this clinical study were the basis for the PMA approval decision. A summary of the clinical study is presented below.

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## A. Study Design

Patients were treated between August 6, 2013 and December 2, 2016. The database for this PMA reflected data collected through December 5, 2017 and included 312 patients at 35 investigational sites.

The study evaluated the GCS for the treatment of carotid artery stenosis in patients at increased risk for adverse events from carotid endarterectomy. The study was a multicenter, single-arm, prospective study comparing the GCS to a performance goal developed from CEA outcomes used in performance goals for previous carotid stenting studies to evaluate the safety and effectiveness of the GCS for the treatment of carotid artery stenosis in similar patient populations.

The primary endpoint was the Major Adverse Event (MAE) rate, defined as a composite of death, stroke, or myocardial information (MI) through 30 days post-index procedure, and ipsilateral stroke from day 31 through 1 year. The endpoint was compared to a performance goal based on historical carotid stenting literature, reflecting an overall expected event rate derived from separate, weighted expected rates of adverse events in patients with anatomic versus co-morbid high-surgical-risk factors. All primary endpoint events were adjudicated and determined by the study Clinical Events Committee.

The Data Safety Monitoring Board (DSMB) reviewed all study safety data on a regular basis and advised on the continuing safety, validity and scientific merit of the study. Additionally, all vascular imaging required for the study was evaluated and analyzed by a core lab.

### 1. Clinical Inclusion and Exclusion Criteria

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

#### General Inclusion Criteria

- Patient is at least 18 years old at informed consent.
- Patient is willing and capable of complying with all study protocol requirements, including specified follow-up period and can be contacted by telephone.
- Patient is willing to provide written informed consent prior to enrollment in the study.
- Patient has no childbearing potential, or is a non-lactating female of childbearing potential, practicing an acceptable method of birth control with a negative pregnancy test within 10 days of study procedure.
- Patient is either:
- Symptomatic with carotid stenosis ≥ 50% as determined by angiography using NASCET methodology.

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- Symptomatic is defined as amaurosis fugax ipsilateral to the carotid lesion; TIA or non-disabling stroke within 180 days of the procedure within the hemisphere supplied by the target vessel; or
- Asymptomatic with carotid stenosis ≥ 80% as determined by angiography using NASCET methodology.
- Patient has a target lesion located at the carotid bifurcation and / or proximal ICA.
- Patient has a single de novo or restenotic (post-CEA) target lesion that can be covered by a single 40 mm stent.
- Patient has a stent landing zone diameter between 3.7 mm and 9.0 mm

## High Risk Inclusion Criteria

For inclusion in the study, a patient must have qualified in at least one High-Risk condition, as shown below.

### Anatomic Conditions:

- Patient has surgically inaccessible lesions at or above the level of C2 or below the clavicle
- Patient is status / post-radical head or neck surgery or radiation therapy
- Patient has spinal immobility of the neck
- Patient has the presence of tracheostomy stoma
- Patient has laryngeal palsy or laryngectomy
- Patient has contralateral laryngeal nerve paralysis
- Patient has restenosis after a previous CEA

### Co-morbid Conditions:

- Patient is ≥ 75 years of age at time of enrollment
- Patient has NYHA Class III or IV congestive heart failure (CHF)
- Patient has chronic obstructive pulmonary disease (COPD) with FEV &lt; 30%
- Patient has a left ventricular ejection fraction (LVEF) &lt; 30%
- Patient has documented uncontrolled diabetes
- Patient has unstable angina with ECG changes
- Patient has had a recent myocardial infarction (≥ 72 hours, &lt; 30 days)
- Patient has coronary artery disease with two or more vessels with ≥ 70% stenosis
- Patient has planned coronary artery bypass grafting (CABG) or valve replacement surgery between 31-60 days after the carotid artery stenting (CAS) procedure
- Patient has contralateral total occlusion of the internal carotid artery (ICA)

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

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General Exclusion Criteria:

- Patient has life expectancy of less than 1 year.
- Patient is experiencing (or has experienced) an evolving, acute, or recent disabling stroke.
- Patient has anticipated or potential sources of emboli (e.g. atrial fibrillation, known previously symptomatic patent foramen ovale (PFO), mechanical heart valve, or deep vein thrombosis (DVT) treated within 6-months).
- Patient has had an acute myocardial infarction within 72 hours prior to index procedure.
- Patient has had any major surgical procedure (i.e., intraabdominal or intrathoracic surgery or any surgery / interventional procedure involving cardiac or vascular system) within 30 days of the index procedure.
- Patient plans to have a major surgical procedure (i.e., intraabdominal or intrathoracic surgery or any surgery / interventional procedure involving cardiac or vascular system) within 30 days after index procedure.
- Patient has a history of major, disabling ipsilateral stroke with residual deficit that may confound the neurological subject assessments.
- Patient has known severe carotid stenosis contralateral to the target lesion requiring treatment within 30 days following the index procedure.
- Patient has a modified Rankin Scale of &gt; 3 or has another neurological deficit, not due to stroke that may confound the neurological subject assessments.
- Patient has chronic renal insufficiency (serum creatinine ≥ 2.5 mg/dL).
- Patient has platelet count &lt; 100,000 / μL.
- Patient has known sensitivity to heparin or previous incident of Heparin-Induced Thrombocytopenia (HIT) type II.
- Patient has contraindication to standard of care study medications, including antiplatelet therapy.
- Patient has known sensitivity to contrast media that cannot be adequately controlled with pre-medication.
- Patient has known bleeding diathesis or hypercoagulable state or refuses blood transfusions.
- Patient has intracranial pathology that, in the opinion of the investigator, makes the patient inappropriate for study participation (e.g. brain tumor, arteriovenous malformation (AVM), cerebral aneurysm) or would confound neurological evaluation.
- Patient had intracranial hemorrhage within the last 90 days.
- Patient is contraindicated for the GORE Embolic Filter per the criteria outlined in the IFU.
- Patient is currently enrolled in another investigational study protocol that has not completed its primary endpoint or that will confound the current study endpoints.
- Patients who are involved in the long-term surveillance of a clinical study are eligible.

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Angiographic Exclusion Criteria:

- Patient has a total occlusion of the target carotid arteries (i.e., CCA or ICA).
- Patient has a previously placed arterial stent distal to or including the origin of the ipsilateral great vessel (includes a stent anywhere in the ICA, CCA or brachiocephalic artery).
- Patient has severe lesion calcification that may restrict the full deployment of the carotid stent.
- Patient has the presence of filling defect or thrombus in target vessel.
- Patient has occlusion or presence of “string sign” of the target vessel.
- Patient has carotid (intracranial) stenosis located distal to target stenosis that is more severe than target stenosis.
- Patient has ≥ 50% stenosis of the common carotid artery (CCA) proximal to the target lesion.
- Patient has known mobile plaque, thrombus, or excessive calcification in the aortic arch.
- Patient has aneurysmal carotid bifurcation on the ipsilateral side.
- Patient has tortuous anatomy or disease morphology which would prohibit the safe placement of guide catheter, sheaths, embolic protection systems or stent systems within the access or target vessel.

2. Follow-up Schedule

All patients were scheduled to return for follow-up examinations at 30 days (± 7 days), 6 months (± 14 days), 1 year (± 30 days), and 2 and 3 years (± 45 days) postoperatively, as shown in Table 6 below. Adverse events and complications were recorded at all visits. To determine patient eligibility, a screening committee reviewed pre-operative angiography and/or computed tomography angiography (CTA), along with patient medical history, for assessment of entry criteria and approval prior to the study procedure.

The screening committee was comprised of an interdisciplinary team of study investigators with pertinent knowledge in carotid stenting, and operated under prespecified procedures as outlined in the Screening Committee Charter. Prior to a patient being enrolled in the study, the investigational site received confirmation from the screening committee that the patient was eligible to be enrolled. Although patients may have been deemed eligible to be enrolled, it was still the responsibility of the investigator to assess all inclusion and exclusion criteria prior to enrollment.

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

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Table 6: Schedule of Events

| Procedure or Evaluation | Screening | Pre-procedure | Procedure/ Enrollment | Post-Procedure (prior to hospital discharge) | 30 days (±7 days) | 6 months (±14 days) | 1 Year (±30 days) | 2 & 3 Years (±45 days) | Unscheduled | Early Withdrawal |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Informed Consent | X | | | | | | | | | |
| Demographics & Medical History | X | | | | | | | | | |
| Exam & Vital Signs^{7} | X^{6} | | | X | X | X | X | X | X^{5} | X |
| NIH Stroke Scale^{1} | | X | | X | X | X | X | X | X^{5} | X |
| Modified Rankin Scale^{6} | X | | | | X | X | X | X | X^{5} | X |
| CT Scan or MRI | X^{2} | | | | | | | | | |
| Carotid Duplex Ultrasound | X^{3} | | | | X | X | X | X | X^{5} | X |
| Cerebral Angiography | | | X | | | | | | X^{5} | |
| Screening angiogram or CTA | X | | | | | | | | | |
| Screening Committee review | X | | | | | | | | | |
| 12-lead ECG^{6} | X | | | X | | | | | X^{5} | |
| Chemistry^{6} (BUN, Creatinine) | X | | | | | | | | X^{5} | |
| Hematology^{6} (CBC with Platelets) | X | | | X | | | | | X^{5} | |
| Cardiac Enzymes (Troponin) | | X | | X | | | | | X^{5} | |
| Pregnancy Test^{4} | | X | | | | | | | | |
| Assess Concomitant Medications(antiplatelet or anticoagulant therapy) | X | X | X | X | X | X | X | X | X | X |
| Assess Adverse Events | | | X | X | X | X | X | X | X | X |

1 Neurological assessments by a physician certified in the administration of NIHSS or research personnel certified in the administration of NIHSS
2 Required for symptomatic patients only within 180 days prior to index procedure
Obtained within the 60 days preceding the index procedure
Obtained within the 10 days preceding the index procedure. Pregnancy test (via urine or blood) required for females of childbearing potential
To be done when clinically indicated
6 May be obtained at either screening or pre-procedure visit
7 Vital Signs include: Blood Pressure, Pulse, and respirations. Collection of height and weight will be done at screening. Temperature should be collected pre- and post- procedure at a minimum

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3. Clinical Endpoints

The primary endpoint included a composite of major adverse events (MAE): death, any stroke, or myocardial infarction (MI) through 30 days post-index procedure and ipsilateral stroke between 31 days and 1 year. All primary endpoint events were adjudicated and determined by the study Clinical Events Committee.

Secondary endpoints included the following:

- Stent Technical Success: Successful deployment of a GCS.
- Embolic Protection Device (EPD) Technical Success: Device delivered, placed, and retrieved without requiring assisting interventional methods.
- Procedure Success: Successful GCS deployment, &lt; 30% residual angiographic stenosis by visual assessment post-procedure in the target lesion and no in-hospital (pre-discharge) Major Adverse Event.
- 30-day Major Adverse Events: Composite of death, any stroke, or myocardial infarction through 30 days post-index procedure
- In-stent Restenosis: Measured as percent stenosis at follow-up evaluation within the stented lesion or within 5 mm proximal or distal to the stent. Additionally, will assess percent of subjects with stenosis ≥ 50% by ultrasound and ≥ 80% by angiographic evaluation.
- Target Lesion Revascularization (TLR): any clinically driven revascularization procedure of the original treatment site, including angioplasty, stenting, endarterectomy, or thrombolysis, performed to open or increase the luminal diameter inside or within 5 mm of the previously treated lesion.

B. Accountability of PMA Cohort

At the time of database lock, of 312 patients enrolled in the PMA study, 100% (312) patients were available for analysis at the completion of the study, the 1-year post-operative visit.

After the first 100 subjects were enrolled, the screening committee retrospectively reviewed anatomical criteria from angiograms and MR/CT; 38 subjects were deemed ineligible by this review. The most commonly occurring reasons for ineligibility were that the subject did not meet the inclusion criterion of having a target lesion located at the carotid bifurcation and/or proximal ICA, met the angiographic exclusion criteria of having severe lesion calcification that may restrict the full deployment of the carotid stent or tortuous anatomy or disease morphology which would prohibit the safe placement of guide catheter, sheaths, embolic protection systems or stent systems within the access or target vessel, or did not meet the specified high risk exclusion criteria of having surgically inaccessible lesions at or above the level of c2 or below the clavicle. An additional 9 subjects were enrolled in the study and subsequently found to have an inclusion or exclusion eligibility criteria deviation. The most commonly occurring reasons for ineligibility among these 9 subjects were that the subject was enrolled with a history of atrial fibrillation (a general exclusion criterion for the study) or with an asymptomatic stenosis of &lt; 80%. A total of 47 subjects were deemed ineligible for

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inclusion in the study; 265 patients were treated per protocol, and study results will be presented for these subjects below. The intent-to-treat cohort of all 312 subjects enrolled in the study, regardless of the final eligibility determination, was also analyzed; results were consistent with the per-protocol cohort.

Of the 265 per-protocol subjects, two hundred thirty-five (235) subjects have completed the 1-year study interval, 1 subject evaluation was pending and later determined to be missed, 14 visits were missed and 15 subjects discontinued prematurely. A summary of subject disposition is presented in Table 7.

Table 7. Subject Disposition

| All Per-Protocol Subjects (N=265) | Pre-Discharge | 30 Days^{1} | 6 Months | 1 Year |
| --- | --- | --- | --- | --- |
| Discontinued Prior to Interval | NA | 1 | 5 | 10 |
| Not Reached Start of Interval | NA | 0 | 0 | 0 |
| Evaluation Not Expected^{2} | 0 | 0 | 0 | 0 |
| Available for Follow-up^{3} | 265 | 264 | 260 | 255 |
| With Follow-up Evaluation | 265 (100.0%) | 261 (98.9%) | 247 (95.0%) | 235 (92.2%) |
| In Protocol Window | 247 (93.2%) | 225 (85.2%) | 192 (73.8%) | 204 (80.0%) |
| Outside Protocol Window | 18 (6.8%) | 36 (13.6%) | 55 (21.2%) | 31 (12.2%) |
| Pending Evaluation | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 1 (0.4%) |
| Without Evaluation | 0 (0.0%) | 3 (1.1%) | 13 (5.0%) | 19 (7.5%) |
| Discontinued in Interval | 0 (0.0%) | 0 (0.0%) | 1 (0.4%) | 5 (2.0%) |
| Missed Visit | 0 (0.0%) | 3 (1.1%) | 12 (4.6%) | 14 (5.5%) |

Percentages use Subjects Available for Interval Follow-up as the denominator.
NA = Not Applicable
1 Follow-up windows are: 30 Days (30±7 days) 6 Months (180±14 days) 1 Year (365±30 days) and 2 and 3 Years (730 and 1095 ±45 days).
2 For technical failures, follow-up at 30 days is the only evaluation expected.
3 Subjects Available for Interval Follow-up is equal to Total Number of Subjects minus Subjects Discontinued Prior to Interval, Subjects Not Reached Start of Interval, and Evaluation Not Expected.

## C. Study Population Demographics and Baseline Parameters

One hundred seventy-six (176) men and 89 women with a median age of 74 years (range 45 to 92) were enrolled in the study. Subject demographics are summarized in Table 8. The demographics of the study population are typical for a carotid artery stenting study performed in the US.

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Table 8. Subject Demographics

| All Per-Protocol Subjects | |
| --- | --- |
| Number of Subjects | 265 |
| | |
| Sex at Birth | N = 265 |
| Male | 176 (66.4%) |
| Female | 89 (33.6%) |
| | |
| Ethnicity | N = 263 |
| Hispanic or Latino | 5 (1.9%) |
| | |
| Not Hispanic or Latino | 258 (98.1%) |
| | |
| Race | N = 265 |
| American Indian or Alaska Native | 1 (0.4%) |
| Asian | 2 (0.8%) |
| Black | 7 (2.6%) |
| White | 253 (95.5%) |
| Hawaiian | 0 (0.0%) |
| Other Race | 3 (1.1%) |
| | |
| Age at Procedure (years) | N = 265 |
| Mean (Std Dev) | 73.1 (8.8) |
| Median | 74.4 |
| (Min, Max) | (45.8, 92.8) |

1. Subject Medical History

A summary of subject medical history is provided in Table 9. A total of 33 subjects (12.5%) were reported to be symptomatic, 249 (94%) were reported as having hypertension and 107 (40%) were reported as having a history of diabetes.

Table 9. Subject Medical History

| All Per-Protocol Subjects (N = 265) | |
| --- | --- |
| Carotid Disease and Symptoms | |
| Previous carotid disease | 47.2% (125/265) |
| Etiology of current carotid disease | N = 265 |
| Atherosclerosis | 207 (78.1%) |
| Radiation | 9 (3.4%) |
| Restenosis | 43 (16.2%) |
| Other | 1 (0.4%) |
| Unknown | 5 (1.9%) |
| Symptomatic | 12.5% (33/265) |
| Evidence of non-carotid morphology | 6.1% (2/33) |
| History of ischemic stroke | 18.1% (48/265) |
| Location of most recent ischemic stroke | N = 43 |

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| All Per-Protocol Subjects (N = 265) | |
| --- | --- |
| Ipsilateral | 27 (62.8%) |
| Contralateral | 16 (37.2%) |
| History of TIA | 15.1% (40/265) |
| Location of most recent TIA | N = 33 |
| Ipsilateral | 25 (75.8%) |
| Contralateral | 8 (24.2%) |
| Ipsilateral Amaurosis Fugax or TMB | 3.4% (9/265) |
| Endarterectomy | 29.8% (79/265) |
| Location of most recent endarterectomy | N = 79 |
| Ipsilateral | 53 (67.1%) |
| Contralateral | 26 (32.9%) |
| | |
| Vascular and Cardiovascular History | |
| Coronary artery disease | 62.6% (166/265) |
| Peripheral vascular disease | 37.0% (98/265) |
| Myocardial infarction | 26.8% (71/265) |
| Previous Cardiovascular Intervention | |
| PCI | 38.1% (101/265) |
| Aortic / mitral valve surgery | 3.8% (10/265) |
| CABG | 27.2% (72/265) |
| Radiotherapy in cerebral circulation | 3.8% (10/265) |
| General Medical History | |
| Diabetes Mellitus | 40.4% (107/265) |
| Hypertension | 94.0% (249/265) |
| Cigarette Smoking | N = 265 |
| Current or stopped < 12 Months ago | 67 (25.3%) |
| Previous (stopped > 12 Months ago) | 139 (52.5%) |
| Never | 59 (22.3%) |

2. Procedure Characteristics

Procedure characteristics are summarized in Table 10 below. The mean lesion length was 20 mm. The mean target lesion percent stenosis was 84.9%.

Table 10. Procedure Characteristics

| All Per-Protocol Subjects (N = 265) | |
| --- | --- |
| Angiography performed | 100.0% (265/265) |
| Bovine Arch | 15.8% (42/265) |
| Pre-procedure ECA < 50% stenosis | 51.7% (137/265) |
| Pre-dilation required before EPD deploy | 5.7% (15/265) |
| Pre-dilation required before stent deploy | 79.6% (211/265) |
| Post-dilation performed after stent deploy | 92.5% (245/265) |
| | |
| Target Lesion Side | N = 265 |
| Right | 144 (54.3%) |

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| All Per-Protocol Subjects (N = 265) | |
| --- | --- |
| Left | 121 (45.7%) |
| | |
| Arch Type | N = 265 |
| Type I | 133 (50.2%) |
| Type II | 120 (45.3%) |
| Type III | 12 (4.5%) |
| | |
| Arterial Access Site | N = 265 |
| Left femoral | 15 (5.7%) |
| Right femoral | 244 (92.1%) |
| Other | 6 (2.3%) |
| | |
| Target Lesion Location | N = 265 |
| ICA | 235 (88.7%) |
| Bifurcation | 30 (11.3%) |
| | |
| Target vessel reference diameter (mm) | N = 265 |
| Mean (Std Dev) | 5.6 (1.0) |
| Median | 5.5 |
| (Min, Max) | (3.7, 9.0) |
| | |
| Target lesion length (mm) | N = 265 |
| Mean (Std Dev) | 20.0 (9.0) |
| Median | 20.0 |
| (Min, Max) | (1.0, 40.0) |
| | |
| Target lesion % stenosis | N = 265 |
| Mean (Std Dev) | 84.9 (6.3) |
| Median | 85.0 |
| (Min, Max) | (50.0, 99.0) |

3. Procedure Outcomes

A summary of procedure outcomes is provided in Table 11. All study devices (100%) were successfully delivered to the target lesion with a mean residual stenosis of 11.8% at the completion of the study procedure.

Table 11. Procedure Outcomes

| All Per-Protocol Subjects (N = 265) | |
| --- | --- |
| Gore Carotid Stent attempted | 100.0% (265/265) |
| Gore Embolic Filter successfully used | 94.7% (251/265) |
| Additional EPD used | 4.5% (12/265) |
| Gore Carotid Stent successfully implanted | 100.0% (265/265) |
| Other stent implanted | 0.8% (2/265) |
| More than one stent implanted | 3.0% (8/265) |

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| All Per-Protocol Subjects (N = 265) | |
| --- | --- |
| | |
| Gore Embolic Filter total dwell time (minutes) | N = 251 |
| Mean (Std Dev) | 14.2 (9.3) |
| Median | 11.0 |
| (Min, Max) | (1.0, 60.0) |
| | |
| Post-procedure target lesion % stenosis | N = 265 |
| Mean (Std Dev) | 11.8 (9.5) |
| Median | 10.0 |
| (Min, Max) | (0.0, 42.0) |
| | |
| Contrast volume (cc) | N = 265 |
| Mean (Std Dev) | 124.2 (62.2) |
| Median | 120.0 |
| (Min, Max) | (15.0, 400.0) |
| | |
| Total fluoroscopy time (minutes) | N = 263 |
| Mean (Std Dev) | 16.9 (9.5) |
| Median | 14.5 |
| (Min, Max) | (3.8, 60.0) |
| | |
| Total procedure time (minutes) | N = 265 |
| Mean (Std Dev) | 53.7 (23.5) |
| Median | 50.0 |
| (Min, Max) | (17.0, 148.0) |
| | |
| Total hospital time (days) | N = 265 |
| Mean (Std Dev) | 1 (1) |
| Median | 1 |
| (Min, Max) | (1, 13) |

## D. Safety and Effectiveness Results

### 1. Safety and Effectiveness Results

The primary analysis of safety and effectiveness was based on the per-protocol cohort of 265 patients with 244 patients with evaluable endpoint information through 1 year. The primary study endpoint was defined as a composite of Major Adverse Events (MAEs) defined as death, any stroke, or myocardial infarction (MI) through 30 days post-index procedure, and ipsilateral stroke between 31 days and 1 year. Eight (8) subjects (3.0%) had one or more MAEs through 30 days post-index procedure. Of those MAEs, four (1.5%) were due to myocardial infarction, three (1.1%) were due to major stroke, and one (0.4%) was due to death resulting from pulseless electrical activity at day 15. Three subjects (1.2%) had ipsilateral stroke between 31 days and 1 year post-index procedure. All three of the strokes reported were ischemic and minor with one

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occurring at day 50, one at day 249 and one at day 276 post-index procedure. Table 12 lists the MAEs through 30 days post-index procedure and ipsilateral stroke between 31 days and 1 year.

Table 12. Major Adverse Events through 30 Days and 1 year

| All Per-Protocol Subjects (N=265) | | 95% CI3 |
| --- | --- | --- |
| Subjects Evaluable for 30-Day MAE1 | 264 (99.6%) | |
| Not Evaluable for 30-Day MAE | 1 (0.4%) | |
| Unsuccessful Procedure | 0 (0.0%) | |
| Discontinued Early | 0 (0.0%) | |
| Missing or Insufficient Follow-up | 1 (0.4%) | |
| | | |
| Subjects With One or More 30-Day MAE | 8 (3.0%) | [1.3%, 5.9%] |
| Death | 1 (0.4%) | [0.0%, 2.1%] |
| Myocardial Infarction | 4 (1.5%) | [0.4%, 3.8%] |
| Q-Wave MI | 0 (0.0%) | [0.0%, 1.4%] |
| Non-Q-Wave MI | 4 (1.5%) | [0.4%, 3.8%] |
| Stroke | 3 (1.1%) | [0.2%, 3.3%] |
| Major Stroke | 3 (1.1%) | [0.2%, 3.3%] |
| Ischemic Stroke | 2 (0.8%) | [0.1%, 2.7%] |
| Ipsilateral | 2 (0.8%) | [0.1%, 2.7%] |
| Non-ipsilateral | 0 (0.0%) | [0.0%, 1.4%] |
| Hemorrhagic Stroke | 1 (0.4%) | [0.0%, 2.1%] |
| Ipsilateral | 1 (0.4%) | [0.0%, 2.1%] |
| Non-ipsilateral | 0 (0.0%) | [0.0%, 1.4%] |
| Minor Stroke | 0 (0.0%) | [0.0%, 1.4%] |
| Ischemic Stroke | 0 (0.0%) | [0.0%, 1.4%] |
| Ipsilateral | 0 (0.0%) | [0.0%, 1.4%] |
| Non-ipsilateral | 0 (0.0%) | [0.0%, 1.4%] |
| Hemorrhagic Stroke | 0 (0.0%) | [0.0%, 1.4%] |
| Ipsilateral | 0 (0.0%) | [0.0%, 1.4%] |
| Non-ipsilateral | 0 (0.0%) | [0.0%, 1.4%] |
| | | |
| Subjects Evaluable for 1-year MAE2 | 244 (92.1%) | |
| Not Evaluable for 1-year MAE | 21 (7.9%) | |
| Unsuccessful Procedure | 0 (0.0%) | |
| Discontinued Early | 6 (2.3%) | |
| Missing or Insufficient Follow-up | 15 (5.7%) | |
| | | |
| Subjects With One or More 1-year MAE | 11 (4.5%) | [2.3%, 7.9%] |
| 30-Day MAE | 8 (3.3%) | [1.4%, 6.4%] |
| Ipsilateral Stroke (31-365 Days) | 3 (1.2%) | [0.3%, 3.6%] |

1 Experienced MAE within 30 days or MAE-free with at least 23 days clinical follow-up

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$^{2}$ Experienced 30-Day MAE or 31-365-day ipsilateral stroke, or MAE-free with at least 335 days clinical follow-up
3Clopper-Pearson exact confidence interval

The overall weighted MAE proportion was $4.5\%$ , which was identical within rounding error to the overall unweighted proportion of $4.5\%$ (11/244). The $95.1\%$ one-sided upper confidence limit (UCL) for the weighted MAE proportion was $8.5\%$ , which is substantially lower than the pre-specified weighted performance goal of $16.9\%$ , leading to the conclusion of acceptable performance of the test device on the basis of 1-year MAE. The corresponding binomial test versus the $16.9\%$ performance goal produced a significant one-sided $\mathrm{p} &lt; 0.00001$ .

# 2. Secondary Effectiveness Endpoint Results

As described above, secondary endpoints were capture to evaluate performance of the stent and EPD. Results are shown in Tables 13-15. Technical success, as defined as successful deployment of the GCS and successful delivery, placement, and retrieval of the EPD, was for the stent and EPD were $100\%$ and $94.7\%$ respectively. Procedure Success as defined by successful stent deployment, $&lt; 30\%$ residual angiographic stenosis by visual assessment post-procedure in the target lesion and no in-hospital MAEs was $94.3\%$ .

Table 13. Secondary Endpoints

| All Per-Protocol Subjects (N=265) | |
| --- | --- |
| Stent Technical Success1 | 100.0% (265/265) |
| Stent Technical Failure | 0.0% (0/265) |
| | |
| EPD Technical Success2 | 94.7% (251/265) |
| EPD Technical Failure | 5.3% (14/265) |
| | |
| Procedure Success3 | 94.3% (250/265) |
| Procedure Failure | 5.7% (15/265) |
| Stent Technical Failure | 0.0% (0/265) |
| ≥30% Residual Stenosis | 4.2% (11/265) |
| In-hospital MAE | 1.5% (4/265) |

1 Successful deployment of a GORE Carotid Stent
2 GORE Embolic Filter delivered, placed, and retrieved without requiring assisting interventional methods
3 Stent Technical Success, $&lt; 30\%$ residual stenosis and no in-hospital MAE

Kaplan-Meier estimated for in-stent restenosis as measured as percent stenosis ( $\geq 50\%$ by ultrasound and $\geq 80\%$ by angiographic evaluation) at follow-up evaluation within the stented lesion or within $5\mathrm{mm}$ proximal or distal to the stent are shown in Table 14.

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Table 14. Kaplan-Meier Estimates of Probability of Restenosis

| Time from Procedure (Months) | At Risk at Start of Interval | Events During Interval (Cumulative) | Censored During Interval (Cumulative) | Probability of Restenosis | 95% C.I. |
| --- | --- | --- | --- | --- | --- |
| All Per-Protocol Subjects (N=265) | | | | | |
| 0 | 265 | 0 (0) | 0 (0) | 0.0% | (0.0%, 0.0%) |
| 1 | 265 | 0 (0) | 5 (5) | 0.0% | (0.0%, 0.0%) |
| 6 | 260 | 0 (0) | 11 (16) | 0.0% | (0.0%, 0.0%) |
| 12 | 249 | 4 (4) | 104 (120) | 1.8% | (0.7%, 4.7%) |
| Time defined as time from index procedure to restenosis, or last follow-up if censored. Event defined as restenosis (≥80% diameter stenosis by core lab angiographic analysis). | | | | | |

Five subjects underwent a clinically-driven TLR, including angioplasty, stenting, endarterectomy, or thrombolysis, performed to open or increase the luminal diameter inside or within $5\mathrm{mm}$ of the previously treated lesion, as described in Table 15.

Table 15. Freedom from Clinically Driven Target Lesion Revascularization (TLR) Kaplan-Meier Estimates of Probability of Freedom from Clinically Driven TLR

| Time from Procedure (Months) | At Risk at Start of Interval | Events During Interval (Cumulative) | Censored During Interval (Cumulative) | Probability of Freedom from Clinically Driven TLR | 95% C.I. |
| --- | --- | --- | --- | --- | --- |
| All Per-Protocol Subjects (N=265) | | | | | |
| 0 | 265 | 0 (0) | 0 (0) | 100.0% | (100.0%, 100.0%) |
| 1 | 265 | 0 (0) | 5 (5) | 100.0% | (100.0%, 100.0%) |
| 6 | 260 | 0 (0) | 11 (16) | 100.0% | (100.0%, 100.0%) |
| 12 | 249 | 5 (5) | 103 (119) | 97.8% | (94.8%, 99.1%) |
| Time defined as time from index procedure to first clinically driven TLR, or last follow-up if censored. Event defined as any clinically driven target lesion revascularization. Clinically driven defined as core lab angiographic diameter stenosis ≥80%, or diameter stenosis ≥50% with clinical symptoms. | | | | | |

# 3. Adverse Events

Adverse events (AEs) were defined as any untoward medical occurrences (that the investigator feels were reportable events) experienced by a subject whether device related or not. Adverse Device Effects were defined as any adverse events related to the use of an investigational medical device. Serious Adverse Events were defined as any events that:

- led to death
- led to serious deterioration in the health of a subject that:
resulted in a life threatening illness or injury
resulted in a permanent impairment of a body structure or a body function

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- required inpatient hospitalization or prolongation of existing hospitalization
- resulted in medical or surgical intervention to prevent permanent impairment to a body structure or a body function
- led to fetal distress, fetal death or a congenital abnormality or birth defect

i. Adverse Events through the 30-Day Follow-Up

Of 265 subjects, one hundred ten (110) subjects (41.5%) experienced an adverse event through the 30-day follow-up period. Of those subjects, one (0.4%) experienced a stent-related adverse event due to internal carotid partial in-stent thrombus at day 4 post-index procedure and was treated with medication and hospitalization. Sixty-seven (67) subjects (25.3%) experienced one or more procedure-related events. The majority of those events (7.5%) were due to minor episodes of hypotension. Four (4) subjects (1.5%) experienced one or more medication-related events as a result of the antiplatelet therapy regimen required during their participation in the study. Eight (8) subjects (3%) experienced one or more disease-related events; 53 subjects (20%) experienced one or more unrelated events; 14 subjects (5.3%) experienced one or more events of unknown study relationship; and no subjects experienced EPD-related events. Tables 16 and 17 below summarize all adverse events through the 30-day follow-up by seriousness of event.

Table 16. Adverse Events through 30-Day Follow-Up by Study Relationship and Seriousness

| | Seriousness of Event | | |
| --- | --- | --- | --- |
| All Per-Protocol Subjects (N=265) | Non-Serious | Serious¹ | Overall |
| Subjects with Coded Adverse Events | 90 (34.0%) | 37 (14.0%) [3] | 110 (41.5%) |
| | | | |
| Stent Related | 0 (0.0%) | 1 (0.4%) | 1 (0.4%) |
| EPD Related | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Procedure Related | 54 (20.4%) | 18 (6.8%) | 67 (25.3%) |
| Medication Related | 3 (1.1%) | 1 (0.4%) | 4 (1.5%) |
| Disease Related | 7 (2.6%) | 1 (0.4%) | 8 (3.0%) |
| Not Related | 42 (15.8%) | 16 (6.0%) [3] | 53 (20.0%) |
| Relationship Unknown | 9 (3.4%) | 6 (2.3%) | 14 (5.3%) |

¹Number of subject deaths related to a serious adverse event are presented in [ ].

Table 17. Adverse Events through 30-Day Follow-Up by MedDRA SOC, Preferred Term, and Seriousness

| | Seriousness of Event | | |
| --- | --- | --- | --- |
| All Per-Protocol Subjects (N=265) | Non-Serious | Serious | Overall |
| Subjects with Coded Adverse Events | 90 (34.0%) | 37 (14.0%) | 110 (41.5%) |
| | | | |
| Vascular disorders | 27 (10.2%) | 7 (2.6%) | 33 (12.5%) |
| Hypotension | 17 (6.4%) | 6 (2.3%) | 23 (8.7%) |

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| | Seriousness of Event | | |
| --- | --- | --- | --- |
| All Per-Protocol Subjects (N=265) | Non-Serious | Serious | Overall |
| Hypertension | 7 (2.6%) | - | 7 (2.6%) |
| Haematoma | 2 (0.8%) | - | 2 (0.8%) |
| Deep vein thrombosis | 1 (0.4%) | - | 1 (0.4%) |
| Orthostatic hypotension | - | 1 (0.4%) | 1 (0.4%) |
| Peripheral artery stenosis | 1 (0.4%) | - | 1 (0.4%) |
| Thrombosis | 1 (0.4%) | - | 1 (0.4%) |
| Nervous system disorders | 19 (7.2%) | 9 (3.4%) | 26 (9.8%) |
| Headache | 10 (3.8%) | 1 (0.4%) | 11 (4.2%) |
| Carotid artery dissection | 1 (0.4%) | 1 (0.4%) | 2 (0.8%) |
| Cerebrovascular accident | - | 2 (0.8%) | 2 (0.8%) |
| Dizziness | 2 (0.8%) | - | 2 (0.8%) |
| Hypoaesthesia | 2 (0.8%) | - | 2 (0.8%) |
| Seizure | - | 2 (0.8%) | 2 (0.8%) |
| Syncope | 2 (0.8%) | - | 2 (0.8%) |
| Transient ischaemic attack | - | 2 (0.8%) | 2 (0.8%) |
| Aphasia | 1 (0.4%) | - | 1 (0.4%) |
| Ataxia | - | 1 (0.4%) | 1 (0.4%) |
| Carpal tunnel syndrome | 1 (0.4%) | - | 1 (0.4%) |
| Haemorrhage intracranial | - | 1 (0.4%) | 1 (0.4%) |
| Hemiparesis | 1 (0.4%) | - | 1 (0.4%) |
| Presyncope | 1 (0.4%) | - | 1 (0.4%) |
| Visual field defect | 1 (0.4%) | - | 1 (0.4%) |
| Injury, poisoning and procedural complications | 21 (7.9%) | 4 (1.5%) | 25 (9.4%) |
| Incision site haemorrhage | 8 (3.0%) | - | 8 (3.0%) |
| Incision site haematoma | 4 (1.5%) | - | 4 (1.5%) |
| Procedural hypotension | 2 (0.8%) | 1 (0.4%) | 3 (1.1%) |
| Vascular pseudoaneurysm | 1 (0.4%) | 1 (0.4%) | 2 (0.8%) |
| Anaemia postoperative | - | 1 (0.4%) | 1 (0.4%) |
| Autonomic dysreflexia | - | 1 (0.4%) | 1 (0.4%) |
| Incision site complication | 1 (0.4%) | - | 1 (0.4%) |
| Incision site oedema | 1 (0.4%) | - | 1 (0.4%) |
| Incision site pain | 1 (0.4%) | - | 1 (0.4%) |
| Laceration | 1 (0.4%) | - | 1 (0.4%) |
| Limb injury | 1 (0.4%) | - | 1 (0.4%) |
| Muscle strain | 1 (0.4%) | - | 1 (0.4%) |
| Wound | 1 (0.4%) | - | 1 (0.4%) |
| Cardiac disorders | 13 (4.9%) | 7 (2.6%) | 19 (7.2%) |
| Bradycardia | 8 (3.0%) | 1 (0.4%) | 8 (3.0%) |
| Angina pectoris | 3 (1.1%) | 2 (0.8%) | 5 (1.9%) |
| Pulseless electrical activity | - | 2 (0.8%) | 2 (0.8%) |
| Acute myocardial infarction | - | 1 (0.4%) | 1 (0.4%) |
| Angina unstable | 1 (0.4%) | - | 1 (0.4%) |
| Cardiomyopathy | - | 1 (0.4%) | 1 (0.4%) |

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| | Seriousness of Event | | |
| --- | --- | --- | --- |
| All Per-Protocol Subjects (N=265) | Non-Serious | Serious | Overall |
| Sinus arrest | 1 (0.4%) | - | 1 (0.4%) |
| General disorders and administration site conditions | 11 (4.2%) | 4 (1.5%) | 14 (5.3%) |
| Fatigue | 3 (1.1%) | - | 3 (1.1%) |
| Adverse drug reaction | 2 (0.8%) | - | 2 (0.8%) |
| Oedema peripheral | 2 (0.8%) | - | 2 (0.8%) |
| Asthenia | 1 (0.4%) | - | 1 (0.4%) |
| Chest discomfort | 1 (0.4%) | - | 1 (0.4%) |
| Chest pain | - | 1 (0.4%) | 1 (0.4%) |
| Chills | 1 (0.4%) | - | 1 (0.4%) |
| Gait disturbance | - | 1 (0.4%) | 1 (0.4%) |
| Non-cardiac chest pain | - | 1 (0.4%) | 1 (0.4%) |
| Pain | 1 (0.4%) | - | 1 (0.4%) |
| Peripheral swelling | 1 (0.4%) | - | 1 (0.4%) |
| Pyrexia | 1 (0.4%) | - | 1 (0.4%) |
| Swelling | 1 (0.4%) | - | 1 (0.4%) |
| Vascular stent thrombosis | - | 1 (0.4%) | 1 (0.4%) |
| Infections and infestations | 10 (3.8%) | 4 (1.5%) | 14 (5.3%) |
| Urinary tract infection | 4 (1.5%) | 3 (1.1%) | 7 (2.6%) |
| Groin infection | 2 (0.8%) | - | 2 (0.8%) |
| Cellulitis | 1 (0.4%) | - | 1 (0.4%) |
| Kidney infection | 1 (0.4%) | - | 1 (0.4%) |
| Laryngitis | 1 (0.4%) | - | 1 (0.4%) |
| Nasopharyngitis | 1 (0.4%) | - | 1 (0.4%) |
| Pneumonia | - | 1 (0.4%) | 1 (0.4%) |
| Respiratory tract infection | 1 (0.4%) | - | 1 (0.4%) |
| Sinusitis | 1 (0.4%) | - | 1 (0.4%) |
| Musculoskeletal and connective tissue disorders | 8 (3.0%) | 1 (0.4%) | 9 (3.4%) |
| Pain in jaw | 2 (0.8%) | - | 2 (0.8%) |
| Arthralgia | 1 (0.4%) | - | 1 (0.4%) |
| Back pain | 1 (0.4%) | - | 1 (0.4%) |
| Lumbar spinal stenosis | - | 1 (0.4%) | 1 (0.4%) |
| Muscular weakness | 1 (0.4%) | - | 1 (0.4%) |
| Musculoskeletal discomfort | 1 (0.4%) | - | 1 (0.4%) |
| Myalgia | 1 (0.4%) | - | 1 (0.4%) |
| Neck pain | 1 (0.4%) | - | 1 (0.4%) |
| Pain in extremity | 1 (0.4%) | - | 1 (0.4%) |
| Gastrointestinal disorders | 4 (1.5%) | 4 (1.5%) | 8 (3.0%) |
| Nausea | 3 (1.1%) | - | 3 (1.1%) |
| Gastrointestinal haemorrhage | - | 2 (0.8%) | 2 (0.8%) |
| Constipation | 1 (0.4%) | - | 1 (0.4%) |
| Intestinal obstruction | - | 1 (0.4%) | 1 (0.4%) |
| Odynophagia | 1 (0.4%) | - | 1 (0.4%) |

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| | Seriousness of Event | | |
| --- | --- | --- | --- |
| All Per-Protocol Subjects (N=265) | Non-Serious | Serious | Overall |
| Retroperitoneal haemorrhage | - | 1 (0.4%) | 1 (0.4%) |
| Vomiting | 1 (0.4%) | - | 1 (0.4%) |
| Respiratory, thoracic and mediastinal disorders | 6 (2.3%) | 3 (1.1%) | 8 (3.0%) |
| Dyspnoea | 2 (0.8%) | - | 2 (0.8%) |
| Chronic obstructive pulmonary disease | - | 1 (0.4%) | 1 (0.4%) |
| Cough | 1 (0.4%) | - | 1 (0.4%) |
| Dyspnoea exertional | 1 (0.4%) | - | 1 (0.4%) |
| Hypoxia | - | 1 (0.4%) | 1 (0.4%) |
| Pulmonary mass | 1 (0.4%) | 1 (0.4%) | 1 (0.4%) |
| Respiratory failure | - | 1 (0.4%) | 1 (0.4%) |
| Sleep apnoea syndrome | 1 (0.4%) | - | 1 (0.4%) |
| Blood and lymphatic system disorders | 4 (1.5%) | 2 (0.8%) | 6 (2.3%) |
| Anaemia | 4 (1.5%) | 2 (0.8%) | 6 (2.3%) |
| Thrombocytopenia | 1 (0.4%) | - | 1 (0.4%) |
| Renal and urinary disorders | 4 (1.5%) | 2 (0.8%) | 6 (2.3%) |
| Chronic kidney disease | 1 (0.4%) | 1 (0.4%) | 2 (0.8%) |
| Urinary retention | 2 (0.8%) | - | 2 (0.8%) |
| Nephrolithiasis | - | 1 (0.4%) | 1 (0.4%) |
| Neurogenic bladder | 1 (0.4%) | - | 1 (0.4%) |
| Investigations | 4 (1.5%) | 1 (0.4%) | 5 (1.9%) |
| Blood pressure decreased | 2 (0.8%) | - | 2 (0.8%) |
| Blood creatinine increased | - | 1 (0.4%) | 1 (0.4%) |
| Body temperature decreased | 1 (0.4%) | - | 1 (0.4%) |
| Weight decreased | 1 (0.4%) | - | 1 (0.4%) |
| Eye disorders | 3 (1.1%) | 1 (0.4%) | 4 (1.5%) |
| Vision blurred | 2 (0.8%) | - | 2 (0.8%) |
| Conjunctival haemorrhage | 1 (0.4%) | - | 1 (0.4%) |
| Diplopia | - | 1 (0.4%) | 1 (0.4%) |
| Metabolism and nutrition disorders | 3 (1.1%) | - | 3 (1.1%) |
| Hyperglycaemia | 2 (0.8%) | - | 2 (0.8%) |
| Hypoglycaemia | 1 (0.4%) | - | 1 (0.4%) |
| Psychiatric disorders | 2 (0.8%) | - | 2 (0.8%) |
| Depression | 1 (0.4%) | - | 1 (0.4%) |
| Insomnia | 1 (0.4%) | - | 1 (0.4%) |
| Mental status changes | 1 (0.4%) | - | 1 (0.4%) |
| Immune system disorders | 1 (0.4%) | - | 1 (0.4%) |
| Contrast media reaction | 1 (0.4%) | - | 1 (0.4%) |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | - | 1 (0.4%) | 1 (0.4%) |
| Pancreatic carcinoma | - | 1 (0.4%) | 1 (0.4%) |

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ii. Adverse Events through 1-Year Follow-Up

One hundred eighty-six (186) subjects (70.2%) experienced an adverse event through the 1-year follow-up period. Of those subjects, 13 (4.9%) experienced one or more stent-related adverse events:

- Thirteen (13) device-related events were due to in-stent carotid artery restenosis treated with revascularization.
- One (1) device-related event was due to internal carotid partial in-stent thrombus treated with medication and hospitalization.
- One (1) device-related event was an asymptomatic occluded carotid stent with no treatment given.
- One (1) device-related event was for questionable carotid stent fracture reported by the site during revascularization of the in-stent carotid artery restenosis.

Sixty-seven (67) subjects (25.3%) experienced one or more procedure-related events. The majority of those events (7.5%) were due to minor episodes of hypotension. Seven (7) subjects (2.6%) experienced one or more medication-related events as a result of the antiplatelet therapy regimen required during their participation in the study. Twenty-seven (27) subjects (10.2%) experienced one or more disease-related events; 145 subjects (54.7%) experienced one or more unrelated events; 18 subjects (6.8%) experienced one or more events of unknown study relationship; and no subjects experienced EPD-related events. Tables 18 and 19 summarize all adverse events through the 1-year follow-up by seriousness of event.

Table 18. Adverse Events through 1-Year Follow-Up by Study Relationship and Seriousness

| | Seriousness of Event | | |
| --- | --- | --- | --- |
| All Per-Protocol Subjects (N=265) | Non-Serious | Serious¹ | Overall |
| Subjects with Coded Adverse Events | 148 (55.8%) | 104 (39.2%) [12] | 186 (70.2%) |
| Stent Related | 2 (0.8%) | 11 (4.2%) | 13 (4.9%) |
| EPD Related | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Procedure Related | 54 (20.4%) | 18 (6.8%) | 67 (25.3%) |
| Medication Related | 5 (1.9%) | 2 (0.8%) | 7 (2.6%) |
| Disease Related | 15 (5.7%) | 13 (4.9%) | 27 (10.2%) |
| Not Related | 109 (41.1%) | 79 (29.8%) [12] | 145 (54.7%) |
| Relationship Unknown | 13 (4.9%) | 6 (2.3%) | 18 (6.8%) |

¹Number of subject deaths related to a serious adverse event are presented in [ ].

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Table 19. Adverse Events through 1-Year Follow-Up by MedDRA SOC, Preferred Term, and Seriousness

| | Seriousness of Event | | |
| --- | --- | --- | --- |
| All Per-Protocol Subjects (N=265) | Non-Serious | Serious | Overall |
| Subjects with Coded Adverse Events | 148 (55.8%) | 104 (39.2%) | 186 (70.2%) |
| | | | |
| Nervous system disorders | 39 (14.7%) | 32 (12.1%) | 66 (24.9%) |
| Headache | 14 (5.3%) | 1 (0.4%) | 15 (5.7%) |
| Carotid artery stenosis | 1 (0.4%) | 9 (3.4%) | 10 (3.8%) |
| Dizziness | 8 (3.0%) | 2 (0.8%) | 10 (3.8%) |
| Cerebrovascular accident | - | 6 (2.3%) | 6 (2.3%) |
| Hypoaesthesia | 4 (1.5%) | 1 (0.4%) | 5 (1.9%) |
| Syncope | 5 (1.9%) | - | 5 (1.9%) |
| Transient ischaemic attack | - | 4 (1.5%) | 4 (1.5%) |
| Amnesia | 2 (0.8%) | - | 2 (0.8%) |
| Carotid artery dissection | 1 (0.4%) | 1 (0.4%) | 2 (0.8%) |
| Carpal tunnel syndrome | 1 (0.4%) | 1 (0.4%) | 2 (0.8%) |
| Hemiparesis | 1 (0.4%) | 1 (0.4%) | 2 (0.8%) |
| Presyncope | 1 (0.4%) | 1 (0.4%) | 2 (0.8%) |
| Seizure | - | 2 (0.8%) | 2 (0.8%) |
| Aphasia | 1 (0.4%) | - | 1 (0.4%) |
| Ataxia | - | 1 (0.4%) | 1 (0.4%) |
| Balance disorder | 1 (0.4%) | - | 1 (0.4%) |
| Cerebral artery stenosis | 1 (0.4%) | - | 1 (0.4%) |
| Cervical radiculopathy | 1 (0.4%) | - | 1 (0.4%) |
| Dementia Alzheimer's type | - | 1 (0.4%) | 1 (0.4%) |
| Diabetic neuropathy | 1 (0.4%) | - | 1 (0.4%) |
| Dysgraphia | 1 (0.4%) | - | 1 (0.4%) |
| Encephalopathy | - | 1 (0.4%) | 1 (0.4%) |
| Generalised tonic-clonic seizure | - | 1 (0.4%) | 1 (0.4%) |
| Haemorrhage intracranial | - | 1 (0.4%) | 1 (0.4%) |
| Ischaemic stroke | - | 1 (0.4%) | 1 (0.4%) |
| Nerve compression | 1 (0.4%) | - | 1 (0.4%) |
| Parkinson's disease | - | 1 (0.4%) | 1 (0.4%) |
| Post herpetic neuralgia | 1 (0.4%) | - | 1 (0.4%) |
| Radiculopathy | 1 (0.4%) | - | 1 (0.4%) |
| Tremor | 1 (0.4%) | - | 1 (0.4%) |
| Vertebral artery stenosis | 1 (0.4%) | - | 1 (0.4%) |
| Visual field defect | 1 (0.4%) | - | 1 (0.4%) |
| Vascular disorders | 46 (17.4%) | 18 (6.8%) | 61 (23.0%) |
| Hypotension | 24 (9.1%) | 9 (3.4%) | 33 (12.5%) |

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| | Seriousness of Event | | |
| --- | --- | --- | --- |
| All Per-Protocol Subjects (N=265) | Non-Serious | Serious | Overall |
| Hypertension | 9 (3.4%) | - | 9 (3.4%) |
| Haematoma | 5 (1.9%) | - | 5 (1.9%) |
| Aortic aneurysm | 1 (0.4%) | 3 (1.1%) | 4 (1.5%) |
| Intermittent claudication | 2 (0.8%) | 2 (0.8%) | 4 (1.5%) |
| Aortic stenosis | - | 2 (0.8%) | 2 (0.8%) |
| Deep vein thrombosis | 2 (0.8%) | - | 2 (0.8%) |
| Orthostatic hypotension | 1 (0.4%) | 1 (0.4%) | 2 (0.8%) |
| Peripheral arterial occlusive disease | 2 (0.8%) | - | 2 (0.8%) |
| Peripheral artery occlusion | 2 (0.8%) | - | 2 (0.8%) |
| Aortic aneurysm rupture | - | 1 (0.4%) | 1 (0.4%) |
| Labile hypertension | 1 (0.4%) | - | 1 (0.4%) |
| Peripheral artery stenosis | 1 (0.4%) | - | 1 (0.4%) |
| Peripheral vascular disorder | 1 (0.4%) | - | 1 (0.4%) |
| Subclavian artery thrombosis | - | 1 (0.4%) | 1 (0.4%) |
| Thrombosis | 1 (0.4%) | - | 1 (0.4%) |
| Infections and infestations | 35 (13.2%) | 19 (7.2%) | 49 (18.5%) |
| Urinary tract infection | 14 (5.3%) | 3 (1.1%) | 17 (6.4%) |
| Pneumonia | 2 (0.8%) | 10 (3.8%) | 12 (4.5%) |
| Bronchitis | 4 (1.5%) | 1 (0.4%) | 5 (1.9%) |
| Cellulitis | 2 (0.8%) | 2 (0.8%) | 4 (1.5%) |
| Sinusitis | 4 (1.5%) | - | 4 (1.5%) |
| Influenza | 3 (1.1%) | - | 3 (1.1%) |
| Diverticulitis | 1 (0.4%) | 1 (0.4%) | 2 (0.8%) |
| Groin infection | 2 (0.8%) | - | 2 (0.8%) |
| Herpes zoster | 2 (0.8%) | - | 2 (0.8%) |
| Sepsis | - | 2 (0.8%) | 2 (0.8%) |
| Upper respiratory tract infection | 2 (0.8%) | - | 2 (0.8%) |
| Acute sinusitis | 1 (0.4%) | - | 1 (0.4%) |
| Appendicitis | - | 1 (0.4%) | 1 (0.4%) |
| Ear infection | 1 (0.4%) | - | 1 (0.4%) |
| Helicobacter gastritis | 1 (0.4%) | - | 1 (0.4%) |
| Kidney infection | 1 (0.4%) | - | 1 (0.4%) |
| Laryngitis | 1 (0.4%) | - | 1 (0.4%) |
| Localised infection | 1 (0.4%) | - | 1 (0.4%) |
| Nasopharyngitis | 1 (0.4%) | - | 1 (0.4%) |
| Osteomyelitis | - | 1 (0.4%) | 1 (0.4%) |
| Otitis media | 1 (0.4%) | - | 1 (0.4%) |
| Prostate infection | 1 (0.4%) | - | 1 (0.4%) |
| Respiratory tract infection | 1 (0.4%) | - | 1 (0.4%) |

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| | Seriousness of Event | | |
| --- | --- | --- | --- |
| All Per-Protocol Subjects (N=265) | Non-Serious | Serious | Overall |
| Septic shock | - | 1 (0.4%) | 1 (0.4%) |
| Staphylococcal bacteraemia | 1 (0.4%) | - | 1 (0.4%) |
| Tuberculosis | 1 (0.4%) | - | 1 (0.4%) |
| Injury, poisoning and procedural complications | 36 (13.6%) | 10 (3.8%) | 43 (16.2%) |
| Incision site haemorrhage | 8 (3.0%) | - | 8 (3.0%) |
| Laceration | 6 (2.3%) | - | 6 (2.3%) |
| Incision site haematoma | 5 (1.9%) | - | 5 (1.9%) |
| Procedural hypotension | 2 (0.8%) | 1 (0.4%) | 3 (1.1%) |
| Carotid artery restenosis | 1 (0.4%) | 1 (0.4%) | 2 (0.8%) |
| Fall | 1 (0.4%) | 1 (0.4%) | 2 (0.8%) |
| Vascular pseudoaneurysm | 1 (0.4%) | 1 (0.4%) | 2 (0.8%) |
| Anaemia postoperative | - | 1 (0.4%) | 1 (0.4%) |
| Ankle fracture | 1 (0.4%) | - | 1 (0.4%) |
| Autonomic dysreflexia | - | 1 (0.4%) | 1 (0.4%) |
| Comminuted fracture | - | 1 (0.4%) | 1 (0.4%) |
| Contusion | 1 (0.4%) | - | 1 (0.4%) |
| Extradural haematoma | - | 1 (0.4%) | 1 (0.4%) |
| Hand fracture | 1 (0.4%) | - | 1 (0.4%) |
| Head injury | 1 (0.4%) | - | 1 (0.4%) |
| Incision site complication | 1 (0.4%) | - | 1 (0.4%) |
| Incision site oedema | 1 (0.4%) | - | 1 (0.4%) |
| Incision site pain | 1 (0.4%) | - | 1 (0.4%) |
| Joint injury | - | 1 (0.4%) | 1 (0.4%) |
| Ligament rupture | 1 (0.4%) | - | 1 (0.4%) |
| Limb injury | 1 (0.4%) | - | 1 (0.4%) |
| Muscle strain | 1 (0.4%) | - | 1 (0.4%) |
| Skin abrasion | 1 (0.4%) | - | 1 (0.4%) |
| Subdural haematoma | - | 1 (0.4%) | 1 (0.4%) |
| Tendon injury | 1 (0.4%) | - | 1 (0.4%) |
| Upper limb fracture | 1 (0.4%) | - | 1 (0.4%) |
| Wound | 1 (0.4%) | - | 1 (0.4%) |
| Cardiac disorders | 26 (9.8%) | 21 (7.9%) | 40 (15.1%) |
| Angina pectoris | 5 (1.9%) | 5 (1.9%) | 10 (3.8%) |
| Bradycardia | 9 (3.4%) | 1 (0.4%) | 9 (3.4%) |
| Acute myocardial infarction | 2 (0.8%) | 4 (1.5%) | 6 (2.3%) |
| Coronary artery disease | 1 (0.4%) | 5 (1.9%) | 6 (2.3%) |
| Atrial fibrillation | 3 (1.1%) | 1 (0.4%) | 4 (1.5%) |
| Cardiac failure congestive | 1 (0.4%) | 2 (0.8%) | 3 (1.1%) |

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| | Seriousness of Event | | |
| --- | --- | --- | --- |
| All Per-Protocol Subjects (N=265) | Non-Serious | Serious | Overall |
| Pulseless electrical activity | - | 2 (0.8%) | 2 (0.8%) |
| Sinus tachycardia | 1 (0.4%) | 1 (0.4%) | 2 (0.8%) |
| Tachycardia | 2 (0.8%) | - | 2 (0.8%) |
| Angina unstable | 1 (0.4%) | - | 1 (0.4%) |
| Atrial flutter | 1 (0.4%) | - | 1 (0.4%) |
| Atrial tachycardia | - | 1 (0.4%) | 1 (0.4%) |
| Cardiac flutter | 1 (0.4%) | - | 1 (0.4%) |
| Cardiomyopathy | - | 1 (0.4%) | 1 (0.4%) |
| Left ventricular failure | - | 1 (0.4%) | 1 (0.4%) |
| Palpitations | 1 (0.4%) | - | 1 (0.4%) |
| Sinus arrest | 1 (0.4%) | - | 1 (0.4%) |
| Sinus bradycardia | 1 (0.4%) | - | 1 (0.4%) |
| Ventricular tachycardia | - | 1 (0.4%) | 1 (0.4%) |
| General disorders and administration site conditions | 22 (8.3%) | 16 (6.0%) | 36 (13.6%) |
| Vascular stent restenosis | 2 (0.8%) | 10 (3.8%) | 12 (4.5%) |
| Fatigue | 6 (2.3%) | - | 6 (2.3%) |
| Adverse drug reaction | 2 (0.8%) | 2 (0.8%) | 4 (1.5%) |
| Non-cardiac chest pain | 2 (0.8%) | 2 (0.8%) | 4 (1.5%) |
| Peripheral swelling | 4 (1.5%) | - | 4 (1.5%) |
| Asthenia | 2 (0.8%) | - | 2 (0.8%) |
| Gait disturbance | 1 (0.4%) | 1 (0.4%) | 2 (0.8%) |
| Oedema peripheral | 2 (0.8%) | - | 2 (0.8%) |
| Pyrexia | 2 (0.8%) | - | 2 (0.8%) |
| Chest discomfort | 1 (0.4%) | - | 1 (0.4%) |
| Chest pain | - | 1 (0.4%) | 1 (0.4%) |
| Chills | 1 (0.4%) | - | 1 (0.4%) |
| Pain | 1 (0.4%) | - | 1 (0.4%) |
| Swelling | 1 (0.4%) | - | 1 (0.4%) |
| Vascular stent occlusion | 1 (0.4%) | - | 1 (0.4%) |
| Vascular stent thrombosis | - | 1 (0.4%) | 1 (0.4%) |
| Respiratory, thoracic and mediastinal disorders | 21 (7.9%) | 14 (5.3%) | 32 (12.1%) |
| Dyspnoea | 9 (3.4%) | - | 9 (3.4%) |
| Chronic obstructive pulmonary disease | 2 (0.8%) | 3 (1.1%) | 5 (1.9%) |
| Dyspnoea exertional | 3 (1.1%) | 1 (0.4%) | 4 (1.5%) |
| Respiratory failure | - | 4 (1.5%) | 4 (1.5%) |
| Hypoxia | 1 (0.4%) | 2 (0.8%) | 3 (1.1%) |
| Pulmonary mass | 2 (0.8%) | 2 (0.8%) | 3 (1.1%) |
| Acute respiratory failure | 1 (0.4%) | 1 (0.4%) | 2 (0.8%) |

PMA P180010: FDA Summary of Safety and Effectiveness Data

{36}

| | Seriousness of Event | | |
| --- | --- | --- | --- |
| All Per-Protocol Subjects (N=265) | Non-Serious | Serious | Overall |
| Haemoptysis | 1 (0.4%) | 1 (0.4%) | 2 (0.8%) |
| Aspiration | 1 (0.4%) | - | 1 (0.4%) |
| Cough | 1 (0.4%) | - | 1 (0.4%) |
| Pleural effusion | 1 (0.4%) | - | 1 (0.4%) |
| Pneumonia aspir…