EXPONENT SELF-EXPANDING CAROTID STENT SYSTEM WITH OVER-THE-WIRE OR RAPID-EXCHANGE DELIVERY SYSTEM

P070012 · Medtronic Vascular · NIM · Oct 23, 2007 · Cardiovascular

Device Facts

• Record ID: P070012
• Device Name: EXPONENT SELF-EXPANDING CAROTID STENT SYSTEM WITH OVER-THE-WIRE OR RAPID-EXCHANGE DELIVERY SYSTEM
• Applicant: Medtronic Vascular
• Product Code: NIM · Cardiovascular
• Decision Date: Oct 23, 2007
• Decision: APWD
• Device Class: Class 3
• Attributes: Therapeutic

Intended Use

The Medtronic Vascular Exponent® Self-Expanding Carotid Stent System, used in conjunction with a Medtronic Vascular embolic protection system, is indicated for improving carotid luminal diameter in patients at high risk for adverse events from carotid endarterectomy who require carotid revascularization and meet the criteria outlined below. 1. Patients with neurological symptoms and ≥50% stenosis of the common or internal carotid artery by either ultrasound or angiogram OR patients without neurological symptoms and ≥80% stenosis of the common or internal carotid artery by either ultrasound or angiogram, AND 2. Patients having a vessel with reference diameters between 4.5 mm and 9.5 mm at the target lesion.

Device Story

Self-expanding carotid stent system used for percutaneous revascularization of carotid arteries. Stent is laser-cut from nickel-titanium (nitinol) alloy; features open-cell design; exerts outward radial force to maintain vessel patency. Delivered via sheathed catheter (OTW or RX platforms) over 0.014" embolic protection guidewire. Used in clinical settings by physicians; requires fluoroscopic guidance for positioning. Radiopaque markers on delivery system aid placement. Stent remains as permanent scaffold. Benefits include improved luminal diameter in high-surgical-risk patients. Clinical decision-making supported by angiographic/ultrasound assessment of stenosis.

Clinical Evidence

Evidence from two prospective, single-arm, multi-center studies (MAVErIC I, N=99; MAVErIC II, N=399). Primary endpoint: composite of death, MI, stroke (0-30 days) and ipsilateral stroke (31-365 days). MAVErIC I primary event rate: 6.1% at 365 days. MAVErIC II primary event rate: 5.5% at 365 days. Both studies met pre-specified performance goals derived from historical carotid endarterectomy data. No deaths attributed to device malfunction.

Technological Characteristics

Stent material: medical grade nickel-titanium (nitinol) alloy. Design: laser-cut, open-cell, self-expanding. Delivery: OTW or RX sheathed catheter, 5F or 6F, 135cm length. Radiopaque markers for fluoroscopic visualization. Sterilization: E-beam radiation. MRI compatible (3 Tesla or less).

Indications for Use

Indicated for patients ≥18 years, high surgical risk for carotid endarterectomy, requiring carotid revascularization. Includes symptomatic patients with ≥50% stenosis or asymptomatic patients with ≥80% stenosis of common/internal carotid artery. Vessel reference diameters 4.5-9.5 mm. Contraindicated for patients with bleeding disorders, hypersensitivity to Nitinol, severe vascular tortuosity, or lesions in the ostium of the common carotid artery.

Regulatory Classification

Identification

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

Reference Devices

• GuardWire® Temporary Occlusion & Aspiration System

Submission Summary (Full Text)

# SUMMARY OF SAFETY AND EFFECTIVENESS DATA

## 1.0 GENERAL INFORMATION

Device Generic Name: Carotid Stent

Device Trade Name: Exponent® Self-Expanding Carotid Stent with OTW Delivery System
Exponent® Self-Expanding Carotid Stent with RX Delivery System

Applicant Name and Address: Medtronic Vascular Inc.
3576 Unocal Place
Santa Rosa, CA 95403
USA

PMA Number: P070012

Date of Panel Recommendation: None

Date of Notice of Approval to Applicant: October 23, 2007

## 2.0 INDICATIONS FOR USE

The Medtronic Vascular Exponent® Self-Expanding Carotid Stent System, used in conjunction with a Medtronic Vascular embolic protection system, is indicated for improving carotid luminal diameter in patients at high risk for adverse events from carotid endarterectomy who require carotid revascularization and meet the criteria outlined below.

1. Patients with neurological symptoms and ≥50% stenosis of the common or internal carotid artery by either ultrasound or angiogram OR patients without neurological symptoms and ≥80% stenosis of the common or internal carotid artery by either ultrasound or angiogram, AND

2. Patients having a vessel with reference diameters between 4.5 mm and 9.5 mm at the target lesion.

## 3.0 CONTRAINDICATIONS

The Exponent® Self-Expanding Carotid Stent with OTW/RX Delivery System 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 a guide catheter, sheath, embolic protection device, or stent delivery system.
- Patients with known hypersensitivity to Nitinol (nickel-titanium).
- Patients with uncorrected bleeding disorders.
- Lesions in the ostium of the common carotid artery.

## 4.0 WARNINGS, AND PRECAUTIONS

*Warnings and Precautions* can be found in the Instructions for Use for the Exponent® Carotid Stent System.

## 5.0 DEVICE DESCRIPTION

The Exponent® Self-Expanding Carotid Stent System is comprised of two main components:

- Exponent® Self-Expanding Carotid Stent
- Over-the-Wire (OTW) or Rapid Exchange (RX) Delivery System

## 5.1 EXPONENT® SELF-EXPANDING CAROTID STENT

The Exponent® Self-Expanding Carotid Stent is identical for both the OTW and RX delivery system platforms. The stent is laser cut in an open-cell design from a medical grade nickel titanium alloy (nitinol). After manufacture, the stent is compressed and constrained onto the delivery catheter. Upon deployment, the stent expands to its pre-determined diameter and exerts an outward radial force on the arterial wall to establish vessel patency.

The Exponent® Self-Expanding Carotid Stent was developed with two configurations, one for the 6.0 and 7.0mm stent diameters and another for the 8.0, 9.0, and 10.0 mm stent diameters. The two configurations are described in Table 1.

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Table 1: Exponent® Self-Expanding Carotid Stent Dimensional Specifications

| Stent Diameters | 6.0 & 7.0 mm | 8.0, 9.0, & 10.0 mm |
| --- | --- | --- |
| Stent Lengths | 20, 30, & 40 mm | |
| # of Crowns | 12 & 15 crowns alternate along the length of the stent | 16 & 20 crowns alternate through the middle length of the stent, with 18-crown segments at the ends of the stent |
| Nominal Segment Length | 12-crown segments: 2.2 mm (0.086”)
15-crown segments: 2.0 mm (0.078”) | 16-crown segments: 2.0mm (0.078”)
18-crown segments: 1.8 mm (0.071”)
20-crown segments: 1.8 mm (0.071”) |
| Strut Cross-Section | Ellipto-Rectangular
Thickness: 0.005” nominal
Width: 0.005” nominal | Ellipto-Rectangular
Thickness: 0.007” nominal
Width: 0.004” nominal |
| # of Connectors | 6 at stent ends, 3 in stent middle | 6 at stent ends, 5 & 6 alternating in stent middle |
| Foreshortening | 0 – 4% | 0 – 6 % |
| Designs | Alternating crown configuration throughout length for conformability and flexibility

More connectors at ends for proximal and distal "seating" | Fewer connectors and alternating crown configuration for conformability and flexibility

More connectors at end zones for proximal and distal "seating" |

## 5.2 EXPONENT® SELF-EXPANDING CAROTID STENT DELIVERY SYSTEMS

The Medtronic Vascular Exponent® Self-Expanding Carotid Stent Delivery Systems are single use devices that consist of the Exponent® Self-Expanding Carotid Stent mounted on either the OTW stent delivery system or the RX stent delivery system. The Exponent® Self-Expanding Carotid Stent Systems are designed to deliver the stent to the carotid arteries via a sheathed catheter. With the stent pre-mounted and constrained on the catheter with a retractable sheath, the delivery system is inserted through a guide catheter or sheath and tracked over a 0.014” embolic protection device guidewire.

For the RX delivery system, two radiopaque marker bands are located on the inner shaft of the delivery system, one proximal to the stent and one distal to the stent, to aid in positioning of the sheathed stent under fluoroscopy.

The OTW delivery system contains a third radiopaque marker band located at the distal end of the outer sheath, which enables visualization of the distal outer sheath position during stent deployment.

Both the OTW and RX delivery system platforms are provided in two sizes, 5F (for the 6.0 & 7.0 mm stent diameters) and 6F (for the 8.0 – 10.0 mm stent diameters); have a 135cm catheter working length; and are compatible with 0.014” guidewires and embolic protection devices. Each of the delivery system platforms has a retractable outer sheath attached to a slider button inside the handle of the device to deploy the stent. The stent is delivered to the intended lesion site and then expanded by retraction of the protective sheath. The stent then remains as a permanent vessel-scaffolding implant.

The Exponent® Self-Expanding Carotid Stent Systems are available in stent diameter of 6.0, 7.0, 8.0, 9.0 and 10.0mm and lengths of 20mm, 30mm, and 40mm. Table 2 lists the available sizes and part number for the Exponent® Self-Expanding Carotid Stent Systems.

Table 2: Exponent® Self-Expanding Carotid Stent with OTW and RX Model Numbers

| Stent Diameter (mm) | Stent Length (mm) | Exponent® Self-Expanding Carotid Stent with OTW Delivery System Model Numbers | Exponent® Self-Expanding Carotid Stent with RX Delivery System Model Numbers |
| --- | --- | --- | --- |
| 6.0 | 20 | 620SOCG | 620SXCG |
| 7.0 | 20 | 720SOCG | 720SXCG |
| 8.0 | 20 | 820SOCG | 820SXCG |
| 9.0 | 20 | 920SOCG | 920SXCG |
| 10.0 | 20 | 1020SOCG | 1020SXCG |
| 6.0 | 30 | 630SOCG | 630SXCG |
| 7.0 | 30 | 730SOCG | 730SXCG |
| 8.0 | 30 | 830SOCG | 830SXCG |
| 9.0 | 30 | 930SOCG | 930SXCG |
| 10.0 | 30 | 1030SOCG | 1030SXCG |
| 6.0 | 40 | 640SOCG | 640SXCG |
| 7.0 | 40 | 740SOCG | 740SXCG |
| 8.0 | 40 | 840SOCG | 840SXCG |
| 9.0 | 40 | 940SOCG | 940SXCG |
| 10.0 | 40 | 1040SOCG | 1040SXCG |

## 6.0 ALTERNATIVE PRACTICES AND PROCEDURES

Alternative practices and procedures for treatment of atherosclerotic disease of the carotid arteries currently include lifestyle modifications, endovascular intervention using other FDA-approved carotid stents and embolic protection systems, carotid endarterectomy, medical therapy, or a combination of these treatments. Lifestyle modifications include measures such as cessation of smoking and changes to diet and alcohol usage. Medical therapy includes use of antiplatelet and/or anticoagulant medicine (aspirin, clopidogrel or ticlopidine) as well as pharmacological treatment of hypertension and hyperlipidemia. The primary treatment used to prevent stroke in

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patients with carotid artery disease is surgical removal of the plaque from the stenotic artery by means of an endarterectomy.

## 7.0 MARKETING HISTORY

The Exponent® Self-Expanding Carotid Stent with OTW and RX Delivery System were approved for commercial sale in the European Economic Area (EEA) in August 2003 and subsequently in additional countries. Only the Exponent® Self-Expanding Carotid Stent with RX Delivery System has been sold outside the United States. Medtronic Vascular elected to perform a voluntary market withdrawal of the Exponent® Self-Expanding Carotid Stent with RX Delivery System from Europe in February 2005, due to field complaints related to stent deployment. The root cause of these failures was identified, and a corrective action was implemented through minor design changes to the device. The Exponent® Self-Expanding Carotid Stent with RX Delivery System with design modifications was returned to the market outside the United States in April 2006. The Exponent® Self-Expanding Carotid Stent with RX Delivery System that is the subject of this PMA is identical to the version currently marketed outside the United States.

## 8.0 POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH

### 8.1 OBSERVED ADVERSE EVENTS

The Exponent® Self-Expanding Carotid Stent with Over-the-Wire (OTW) Delivery System was evaluated for the treatment of high surgical risk patients with lesions in the common and/or internal carotid artery that are amenable to percutaneous treatment with stenting. A total of 498 patients were enrolled into two separate single-arm trials as follows:

- MAVErIC I, a feasibility study, evaluated the Over-the-Wire (OTW) Exponent® Self-Expanding Carotid Stent System with the GuardWire® Temporary Occlusion & Aspiration System and included 99 patients. The primary objective of this study was to evaluate the safety and efficacy in treating carotid stenosis in patients at high risk for carotid endarterectomy (CEA) in the population under evaluation.

- MAVErIC II, a pivotal study, evaluated the Over-the-Wire (OTW) Exponent® Self-Expanding Carotid Stent System and the GuardWire® Temporary Occlusion & Aspiration System and included 399 patients. The primary objective of the study was the same as MAVErIC I in treating carotid stenosis in patients at high risk for CEA. High-risk patients were defined as having anatomical and/or co-morbidity risk factors as defined in the clinical protocols.

The major adverse events that were reported in both studies within the first 30 and 365 days after stenting are provided in Table 3 below. Table 4 includes all other adverse

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events. All patient deaths are described in Table 5. No deaths were attributed to device malfunction or failure. All events are patient-based.

Table 3: Major Adverse Events Summary¹

| | Events to 30 Days | | Events to 365 Days | |
| --- | --- | --- | --- | --- |
| | MAVErIC I
N = 99
n (%) | MAVErIC II
N = 399
n (%) | MAVErIC I
N = 99
n (%) | MAVErIC II
N = 399
n (%) |
| Primary endpoint event: (Death, Myocardial Infarction [MI], Stroke to 30 days and Ipsilateral Stoke from 31 – 365 Days) | 6 (6.1%) | 21 (5.3%) | 6 (6.1%) | 22 (5.5%) |
| Any Major Adverse Event (Death, MI, Stroke from 0 – 30 Days) | 6 (6.1%) | 21 (5.3%) | N/A | N/A |
| All-cause death² | 1 (1.0%) | 4 (1.0%) | 1 (1.0%) | 37 (9.3%) |
| Neurological | 1 (1.0%) | 2 (0.5%) | 1 (1.0%) | 4 (1.0%) |
| Cardiac | 0 (0.0%) | 2 (0.5%) | 0 (0.0%) | 20 (5.0%) |
| Other | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 13 (3.3%) |
| Myocardial Infarction (Q Wave and Non-Q Wave) | 1 (1.0%) | 6 (1.5%) | 1 (1.0%) | 9 (2.3%) |
| Q Wave MI | 0 (0.0%) | 2 (0.5%) | 0 (0.0%) | 2 (0.5%) |
| Non-Q Wave MI | 1 (1.0%) | 4 (1.0%) | 1 (1.0%) | 8 (2.0%) |
| Stroke | 5 (5.1%) | 16 (4.0%) | 5 (5.1%) | 18 (4.5%) |
| Ipsilateral | 4 (4.0%) | 13 (3.3%) | 4 (4.0%) | 14 (3.5%) |
| Major Ischemic | 3 (3.0%) | 6 (1.5%) | 3 (3.0%) | 7 (1.8%) |
| Minor Ischemic | 1 (1.0%) | 5 (1.3%) | 1 (1.0%) | 6 (1.5%) |
| Major Hemorrhagic | 1 (1.0%) | 3 (0.8%) | 1 (1.0%) | 3 (0.8%) |
| Minor Hemorrhagic | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Non-ipsilateral (to 30 days) | 1 (1.0%) | 4 (1.0%) | 1 (1.0%) | 4 (1.0%) |
| Non-ipsilateral (31 - 365 days) | N/A | N/A | 0 (0.0%) | 1 (0.3%) |
| Non-ipsilateral (All) | 1 (1.0%) | 4 (1.0%) | 1 (1.0%) | 5 (1.3%) |
| Major Ischemic | 0 (0.0%) | 3 (0.8%) | 0 (0.0%) | 4 (1.0%) |
| Minor Ischemic | 1 (1.0%) | 0 (0.0%) | 1 (1.0%) | 0 (0.0%) |
| Major Hemorrhagic | 0 (0.0%) | 1 (0.3%) | 0 (0.0%) | 1 (0.3%) |
| Minor Hemorrhagic | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |

¹ All data based on ITT (intent-to-treat) population, which includes all subjects enrolled in the study regardless of whether they received a stent.
² Death: The Clinical Events Committee (CEC) adjudicated all deaths to determine if the death was defined as neurological (death due to a stroke, a complication of the procedure including bleeding, vascular repair or surgery or any death in which a neurological cause could not be excluded), or non-neurological (defined as death due to either a cardiac-related cause or due to another [other] cause).

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Table 4: Other Adverse Events Summary¹

| | Events to 30 Days | | Events to 365 Days | |
| --- | --- | --- | --- | --- |
| | MAVErIC I
N = 99
n (%) | MAVErIC II
N = 399
n (%) | MAVErIC I
N = 99
n (%) | MAVErIC II
N = 399
n (%) |
| Target Lesion Revascularization (TLR)² | 0 (0.0) | 0 (0.0) | 2 (2.0) | 5 (1.3) |
| Surgery | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (0.3) |
| Percutaneous | 0 (0.0) | 0 (0.0) | 2 (2.0) | 4 (1.0) |
| Target Vessel Revascularization (not TLR)³ | 0 (0.0) | 0 (0.0) | 2 (2.0) | 2 (0.5) |
| Surgery | 0 (0.0) | 0 (0.0) | 1 (1.0) | 0 (0.0) |
| Percutaneous | 0 (0.0) | 0 (0.0) | 1 (1.0) | 2 (0.5) |
| Blood and Lymphatic System Disorders⁴ | 0 (0.0) | 14 (3.5) | 0 (0.0) | 31 (7.8) |
| Cardiac Disorders⁵ | 2 (2.0) | 27 (6.8) | 7 (7.1) | 72 (18.0) |
| Congenital, Familial and Genetic Disorders⁶ | 0 (0.0) | 1 (0.3) | 0 (0.0) | 2 (0.5) |
| Ear and Labyrinth Disorders⁷ | 0 (0.0) | 1 (0.3) | 0 (0.0) | 1 (0.3) |
| Eye Disorders⁸ | 3 (3.0) | 0 (0.0) | 3 (3.0) | 2 (0.5) |
| Gastrointestinal Disorders⁹ | 0 (0.0) | 13 (3.3) | 2 (2.0) | 38 (9.5) |
| General Disorders and Administration Site Conditions¹⁰ | 0 (0.0) | 15 (3.8) | 2 (2.0) | 55 (13.8) |
| Hepatobiliary Disorders¹¹ | 0 (0.0) | 0 (0.0) | 0 (0.0) | 2 (0.5) |
| Infections and Infestations¹² | 0 (0.0) | 18 (4.5) | 3 (3.0) | 33 (8.3) |
| Injury, Poisoning and Procedural Complications¹³ | 0 (0.0) | 6 (1.5) | 3 (3.0) | 22 (5.5) |
| Investigations¹⁴ | 1 (1.0) | 23 (5.8) | 5 (5.1) | 34 (8.5) |
| Metabolism and Nutrition Disorders¹⁵ | 0 (0.0) | 1 (0.3) | 1 (1.0) | 11 (2.8) |
| Musculoskeletal and Connective Tissue Disorders¹⁶ | 0 (0.0) | 2 (0.5) | 1 (1.0) | 5 (1.3) |
| Neoplasms Benign, Malignant and Unspecified (incl Cysts and Polyps)¹⁷ | 1 (1.0) | 5 (1.3) | 3 (3.0) | 11 (2.8) |
| Nervous System Disorders¹⁸ | 5 (5.1) | 30 (7.5) | 9 (9.1) | 50 (12.5) |
| Psychiatric Disorders¹⁹ | 0 (0.0) | 6 (1.5) | 0 (0.0) | 9 (2.3) |
| Renal and Urinary Disorders²⁰ | 0 (0.0) | 8 (2.0) | 3 (3.0) | 24 (6.0) |
| Reproductive System and Breast Disorders²¹ | 0 (0.0) | | 0 (0.0) | 1 (0.3) |
| Respiratory, Thoracic and Mediastinal Disorders²² | 1 (1.0) | 8 (2.0) | 3 (3.0) | 28 (7.0) |
| Skin and Subcutaneous Tissue Disorders²³ | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (0.3) |
| Surgical and Medical Procedures²⁴ | 2 (2.0) | 9 (2.3) | 16 (16.2) | 47 (11.8) |
| Vascular Disorders²⁵ | 5 (5.1) | 28 (7.0) | 10 (10.1) | 70 (17.5) |

¹ All data based on ITT population
² Target Lesion Revascularization: Any ‘clinically driven’ repeat percutaneous intervention (including angioplasty, stenting, endarterectomy, or thrombolysis) or carotid endarterectomy performed to open or increase the luminal diameter of the previously treated lesion.
³ Target Vessel Revascularization: Any ‘clinically driven’ repeat percutaneous intervention (including angioplasty, stenting, endarterectomy or thrombolysis) or carotid endarterectomy of the previously treated vessel.
⁴ Blood and Lymphatic System Disorders include: anemia, blood dyscrasia, coagulopathy, iron deficiency anemia, aggravated neutropenia, secondary anemia, thrombocytopenia
⁵ Cardiac Disorders include: Angina pectoris (includes unstable), bradycardia (includes sinus), aortic valve stenosis, atrial fibrillation, atrioventricular block (includes complete), cardiac arrest, coronary artery disease, congestive heart failure, cardiac failure (includes congestive), cardiac tamponade, cardio-respiratory arrest, cardiomyopathy, cardiopulmonary failure, mitral valve incompetence, MI, myocardial ischemia, pulmonary edema (includes acute), coronary artery insufficiency, sick sinus syndrome, tachycardia (includes supraventricular and ventricular), asystole (includes ventricular), ventricular fibrillation
⁶ Congenital, Familial and Genetic Disorders include: Arterio-venous malformation, congenital atrial septal defect
⁷ Ear and Labyrinth Disorders include: Labyrinthitis

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8 Eye Disorders include: Transient blindness, blindness (unilateral), blurred vision, reduced visual acuity, visual disturbances

9 Gastrointestinal Disorders include: Abdominal hernia, abdominal pain, small intestinal perforation, colonic perforation, diverticulitis, diverticulum intestinal, duodenal ulcer (hemorrhage), esophageal obstruction, gastric ulcer (hemorrhage), gastritis, gastroduodenal ulcer, gastrointestinal hemorrhage, hematemesis, lower gastrointestinal hemorrhage, melena, mesenteric artery stenosis, discolored feces, nausea, pancreatitis, rectal hemorrhage, retroperitoneal hemorrhage, stomatitis, vomiting

10 General Disorders and Administration Site Conditions include: Injection site hemorrhage, peripheral edema, adverse drug reaction, cardiac death, chest pain, death, fall, fatigue, migration of implant, multi-organ failure, peripheral edema, pyrexia, weakness

11 Hepatobiliary Disorders include: cholecystitis, hepatic failure

12 Infections and Infestations include: Bacteremia, cellulitis, colitis pseudomembranous, Infection, pneumonia, urinary tract infection, bacterial endocarditis, genitourinary tract infections, groin infection, herpes zoster, klebsiella infection, pseudomonas infection, sepsis, upper respiratory tract infection, urosepsis, West Nile viral infection

13 Injury, Poisoning and Procedural Complications include: Accidental overdose, coronary artery restenosis, fracture (includes femur, hip, humerus, lower limb, radius, upper limb), wound evisceration, hemothorax, intraoperative hypotension, postoperative anemia, postoperative hypotension, post-procedure diarrhea, post-procedure hemorrhage, road traffic accident, stent occlusion,

14 Investigations include: Decreased hematocrit, decreased hemoglobin, coronary arteriogram, increased cardiac enzymes, abnormal cardiac stress test, increased blood creatinine, decreased blood pressure, increased blood pressure, positive fecal occult blood, prolonged coagulation time, increased intraocular pressure, medical observation, abnormal thoracic cavity drainage test

15 Metabolism and Nutrition Disorders include: anorexia, dehydration, diabetes mellitus (includes inadequately controlled), diabetic ketoacidosis, electrolyte imbalance. Hyperglycemia, hyperkalemia, hyponatremia

16 Musculoskeletal and Connective Tissue Disorders include: Pain in limb, back pain (includes aggravated), groin pain, peripheral swelling

17 Neoplasms Benign, Malignant and Unspecified (incl Cysts and Polyps) include: cancer (includes bladder, breast, colon, gastric, liver, renal cell, pharyngeal, thyroid, ureteric, metastasis), lymphoma, carcinoid tumor, pharyngeal neoplasm

18 Nervous System Disorders include: cerebrovascular accident, carotid artery aneurysm, carotid artery stenosis, hemanopia, loss of consciousness, parathesis, convulsions, dizziness, memory impairment, neurological symptoms, aphasia, cerebral hemorrhage, cerebral infarction, clonic convulsion, coma, dementia of the Alzheimers type, dysarthria, embolic stroke, hemorrhagic transformation stroke, hemiparesis, hemiplegia, intraventricular hemorrhage, hypoesthesia, intracranial hemorrhage, ischemic stroke, spinal stenosis (includes lumbar), monoplegia, somnolence, subarachnoid hemorrhage, subdural hematoma, syncope, TIA, vasovagal attack, visual field defect

19 Psychiatric Disorders include: Agitation, anxiety (includes aggravated), confusion, disorientation, mental status change

20 Renal and Urinary Disorders include: Renal calculus, renal colic, renal failure (acute, aggravated and chronic), renal impairment, renal nephropathy, renal artery stenosis, urinary retention

21 Reproductive System and Breast Disorders include: Uterovaginal prolapse

22 Respiratory, Thoracic and Mediastinal Disorders include: Dyspnea, pulmonary hemorrhage, respiratory failure (includes acute), asthma (includes aggravated), chronic obstructive airway disease (includes aggravated), dyspnea (includes exertional) pleural effusion, aspiration pneumonia, pneumothorax, pulmonary embolism, pulmonary hypertension, respiratory arrest

23 Skin and Subcutaneous Tissue Disorders include: Chronic skin ulcer

24 Surgical and Medical Procedures include: Aortic aneurysm repair, aortic valve repair, aortic valve replacement, arterial bypass operation, cardiac pacemaker replacement, carotid endarterectomy, cerebrovascular surgery, cervical operation, colon surgery, coronary artery bypass grafting (CABG), coronary artery surgery, coronary revascularization, detached retina repair, endarterectomy, hernia repair, arthroplasty (includes hip, knee), hip surgery, malignant neoplasm excision, malignant breast lump removal, mitral valve replacement, mastectomy (partial), percutaneous transluminal coronary angioplasty (PTCA), percutaneous transluminal angioplasty (PTA), polypectomy, renal vascularization surgery, shoulder surgery, spinal laminectomy, hospitalization, tracheostomy, cardiac valvuloplasty, vascular bypass grafts, whole blood transfusion

25 Vascular Disorders include: Aortic aneurysm, arterial restenosis, arterial rupture, arterial stenosis, diabetic peripheral angiopathy, femoral arterial stenosis, femoral artery occlusion, gangrene, hematoma, hemorrhage, hypertension (includes aggravated), hypotension (includes aggravated, orthostatic), iliac artery stenosis, intermittent claudication, peripheral artery dissection, peripheral ischemia, peripheral vascular disorder, peripheral revascularization, poor peripheral circulation, vascular pseudoaneurysm, venous thrombosis (deep limb).

Table 5: Cause of Death¹,²

| | MAVErIC I
n (%) | MAVErIC II
n (%) |
| --- | --- | --- |
| 0 - 30 days | n = 99 | n = 399 |
| Neurological | 1 (1.0%) | 2 (0.5%) |
| Cardiac | 0 | 2 (0.5%) |
| Other | 0 | 0 |
| Total (0- 30 days) | 1 (1.0%) | 4 (1.0%) |
| 31 - 365 days | n = 99 | n = 399 |
| Neurological | 0 | 2 (0.5) |
| Cardiac | 0 | 18 (4.5%) |
| Other: | 0 | 13 (3.3%) |
| Infection | | 2 |
| Respiratory | | 4 |
| Cancer | | 4 |
| Renal Failure | | 2 |
| Stroke³ | | 1 |
| Total (31 - 365 days) | 0 | 33 (8.3) |
| Total (0 - 365 days) | 1 (1.0%) | 37 (9.3%) |

¹ All data based on ITT population.
² No reported deaths due to device malfunction or failure.
³ Death due to progression of arteriosclerosis; does not meet study definition for neurological death.

## 8.2 POSSIBLE ADVERSE EVENTS

As reported in the literature and the Instructions for Use, the following adverse events are potentially associated with use of carotid stents and embolic protection systems:

- Abrupt closure
- Acute myocardial infarction
- Allergic reaction (contrast medium; drug; stent or filter material)
- Amaurosis fugax
- Aneurysm or pseudoaneurysm in vessel or at vascular access site
- Angina/ Coronary ischemia
- Arrhythmia (including premature beats, bradycardia, atrial and/or ventricular tachycardia, atrial and/or ventricular fibrillation [VF])
- Asystole or bradycardia requiring placement of a temporary pacemaker
- Arteriovenous fistula
- Bleeding complications from anticoagulant or antiplatelet medication requiring transfusion or surgical intervention
- Cerebral edema
- Cerebral hemorrhage
- Cerebral ischemia
- Congestive heart failure (CHF)
- Death
- Detachment and/or implantation of a component of the system
- Dissection of blood vessel
- Distal embolic protection device thrombosis/ occlusion
- Emboli, distal (air, tissue, plaque, thrombotic material, stent)

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- Emergent or urgent surgery (Carotid Endarterectomy [CEA])
- Emergent surgery to remove stent or distal embolic protection device
- Fever
- Hematoma at vascular access site, with or without surgical repair
- Hemorrhagic event, with or without transfusion
- Hyperperfusion syndrome
- Hypotension/Hypertension
- Infection, local or systemic including bacteremia or septicemia
- Ischemia/ infarction of tissue/ organ
- Pain (head/ neck)/ severe unilateral headache
- Pain at catheter insertion site
- Renal failure/ insufficiency secondary to contrast medium
- Restenosis of vessel in stented segment
- Seizure
- Stent/ distal embolic protection device entanglement/ damage
- Stent/ distal embolic protection device collapse or fracture
- Stent malapposition/ migration
- Stent thrombosis/ occlusion
- Stroke / cerebrovascular accident (CVA) / transient ischemic attack (TIA)
- Total occlusion of the carotid artery
- Vascular thrombosis/ occlusion at puncture site, treatment site, or remote site
- Vessel dissection, perforation or rupture
- Vessel spasm or recoil

## 9.0 SUMMARY OF NON-CLINICAL STUDIES

Non-clinical studies involving the Exponent® Self-Expanding Carotid Stent with OTW and RX Delivery Systems are provided below. These sections cover bench testing, *in vivo* studies, biocompatibility, sterilization, packaging, and shelf-life.

## 9.1 IN VITRO STUDIES

*In vitro* bench testing to support the Exponent® Self-Expanding Carotid Stent with OTW and RX Delivery Systems was developed based on internal device guidelines and is consistent with the FDA guidances, *Non-Clinical Tests and Recommended Labeling for Intravascular Stents and Associated Delivery Systems* (January 2005), and *Guidance for the Submission of Research and Marketing Applications for Interventional Cardiology Devices: PTCA Catheters, Atherectomy Catheters, Lasers, Intravascular Stents* (May 1995), and applicable American Society for Testing and Materials International (ASTM) Standards. Because the Exponent® stent is self-expanding, tests specifically recommended for balloon-expandable stents were not conducted.

The specific *in vitro* tests conducted are described below in Tables 6 and 7. All test units were sterilized by E-Beam radiation prior to testing.

Table 6: Summary of In Vitro Testing of the Exponent® Stent

| Test | Objective | Summary of Methods and Results |
| --- | --- | --- |
| Material Analysis | Ensure conformance of stent material composition to required specifications | The composition of the nitinol material used to manufacture the stents was chemically analyzed to determine conformance with material specifications. Certificates of conformance for each incoming material lot are provided by the vendor. The stent material composition is appropriately characterized. |
| Ar Temperature Testing | Determine the shape memory properties of the stent | The austenitic finish temperature for the stent was measured by chilling the stents and measuring the temperature at which they regained their nominal diameter. The results show that the stent demonstrates acceptable shape memory characteristics. |
| Mechanical Properties | Ensure acceptable mechanical performance and establish baseline properties for future comparisons | The mechanical properties of the raw nitinol material were measured to ensure conformance with specification. Certificates of conformance are also provided for each incoming material lot. In addition, mechanical properties of processed stent material were calculated. The properties all met established specifications and are similar to historical values for nitinol. |
| Stent-Free Surface Area | Determine the amount of vessel area in contact with the stent | The amount of vessel area in contact with the stent was calculated using the known stent geometry. The surface areas range from 83 – 89% of the stented area, which does not raise any concerns. |
| Corrosion Resistance | Evaluate the compatibility of the stent material in the simulated chemical and mechanical service environment | Stents were subjected to potentiodynamic corrosion testing to measure pitting and crevice corrosion. Fretting corrosion was assessed by subjecting overlapping stents to conditions intended to simulate ten years of implant life, followed by visual inspection for signs of wear. The results demonstrate no evidence of corrosion, indicating satisfactory corrosion resistance and acceptably low levels of nickel leaching. |
| Stent Integrity | Ensure that the stent is free of surface defects | Stent surfaces were examined at 45 – 80X magnification for signs of cracks or defects after expansion. No defects were observed, indicating satisfactory stent integrity. |
| Kink Resistance | Ensure that the stent is resistant to permanent deformations that may affect patency | Expanded stents were bent around a 1” cylinder to simulate worst-case anticipated bend diameters. None of the stents displayed any protruding struts, suggesting that deployment of the stent in tortuous anatomy is not likely to result in permanent stent deformation. |
| Dimensional Verification | Ensure stent dimensions meet specifications and are uniform along the stent length and diameter | Stent length and diameter were measured after expansion. Measurements were performed at multiple locations along and around the stent to assess dimensional uniformity. The distance between two successive crowns was also measured. The results demonstrate that stent dimensions after expansion meet the specifications and that they do not significantly vary as a |

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20

| Test | Objective | Summary of Methods and Results |
| --- | --- | --- |
| | | function of location. |
| Crush Resistance | Ensure that the stent is resistant to large externally-applied deformations | Stents were subjected to flat-plate compression. Samples recovered to their nominal diameter after removal of the applied load, indicating sufficient resistance to external crushing. |
| Foreshortening | Evaluate the extent of length decrease after expansion | The length of the stent was measured before and after deployment. The extent of foreshortening due to stent expansion met specifications, and is recorded in the device labeling to ensure accurate device placement. |
| Radial Stiffness and Outward Force | Ensure that the stent can withstand uniformly radially-applied loads without compression. Ensure that the outward expansion force provided by the stent is capable of maintaining patency without provoking injury. | The effect of stent diameter on the magnitude of the applied inwardly-directed radial force was measured. In addition, the magnitude of the radial force exerted by the stent during expansion was measured. The results suggest that the stent is resistant to collapse and capable of providing sufficient radial force to the vessel wall. |
| Stress and Fatigue Analysis | Calculate the anticipated stresses within the stent and ensure sufficient stent durability | Finite element analysis methods were used to simulate stent manufacture, compression onto the delivery catheter, stent expansion after deployment, and compression to the simulated vessel diameter. Maximum radial stresses resulting from this strain history were calculated. The safety factors for the stents under these conditions all exceeded 1.0, suggesting sufficient durability under clinically anticipated conditions. |
| Accelerated Pulsatile Durability | Determine whether stents fracture when subjected to physiologically relevant radial fatigue loads | Stents were deployed in flexible tubing, and subjected to a total of 420 million physiologically relevant radial deformations to simulate ten years of implant life. No stent fractures, cracks, or other defects were observed during or after the durability test, suggesting satisfactory durability to anticipated radial loads. |
| Magnetic Resonance Imaging (MRI) Compatibility | Ensure that the stented area can be safely imaged using MRI | Stent deflection, torque, heating and imaging artifacts resulting from a 15-minute exposure to a 3 Tesla MRI system were measured. The results suggest satisfactory performance in MR fields of 3 Tesla or less, spatial gradient field strengths of 720 Gauss/cm or less, and a maximum whole-body-averaged specific absorption rate of 3.0 W/kg for 15 minutes of scanning. The device labeling states that the stent is “MR Compatible” under these conditions. Image quality in the area near the stented location may be compromised. |
| Radiopacity | Ensure that deployed stents can be observed under fluoroscopy | The visibility of the stent under fluoroscopy was assessed during animal studies. The radiopacity of the radiopaque markers of the delivery system was also assessed. The results demonstrated that deployed stents and the delivery system are sufficiently radiopaque. |

Table 7: Summary of In Vitro Testing of the OTW and RX Systems

| Test | Objective | Summary of Methods and Results |
| --- | --- | --- |
| Stent Deployment Force | Ensure that excessive force is not required to deploy the stent | Stents were deployed in a fixture simulating challenging target anatomy. The force required to retract the sheath and deploy the stent was measured and met specifications. The results indicate appropriate ease of deployment. |
| Stent Deployment Accuracy | Ensure that stents can be deployed in the target region | Stents were deployed in a fixture simulating challenging target anatomy. The distance between the stent and the target location was measured and met specifications. The results demonstrate that the stent can be deployed at the intended location with sufficient accuracy. |
| Delivery System Dimensions | Ensure delivery system dimensions meet specifications and are compatible with accessory devices | The key delivery system dimensions, including working length, guidewire lumen length, tip internal diameter, and proximal shaft outer diameter, were measured and evaluated against specifications. All dimensions measured met the specification requirements. |
| Crossing Profile | Ensure that the stent system can cross lesions without interaction | The maximum diameter, or crossing profile, of the stent system was measured and evaluated against specifications. The crossing profile met the specification requirements, indicating sufficient ability to cross lesions. This information is incorporated in the device labeling. |
| Sheath/Guide Catheter Compatibility | Demonstrate compatibility between the stent system and sheaths and guide catheters used to deliver the stent | The force needed to insert a stent system through representative introducer sheaths and guide catheters was measured and evaluated against specifications. The stent system was able to pass through all tested devices using forces below the specified limits, suggesting adequate device compatibility. |
| Embolic Protection Device Compatibility | Demonstrate compatibility between the stent system and the Medtronic GuardWire embolic protection device | GuardWire devices were back-loaded through the guidewire lumen of stent systems and passed through the entire length of the catheter without difficulty. The results suggest that the Exponent and GuardWire systems are compatible. |
| Tensile Strength | Ensure the durability of the stent system | The tensile strength of key bond joints in the stent system was measured using a pull tester. All bond joint tensile strengths met the specification requirements, indicating sufficient resistance to tensile forces. |
| Air Entrainment and Embolization | Assess the potential for air entrainment and embolization during stent system introduction | Following stent system flushing, stents were deployed under water, and the presence and size of air bubbles was recorded. The volume of air released was comparable between the OTW and RX systems, which were comparable to the air released during the deployment of a currently marketed carotid stent. The results suggest that the amount of air liberated during deployment does not raise any concerns. |

The in vitro test results support adequate performance of the device.

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# 9.2 ANIMAL STUDIES

Five *in vivo* studies were performed to evaluate the acute and chronic safety of the Exponent® Self-Expanding Carotid Stent with OTW and RX Delivery Systems. All studies were conducted in accordance with Good Laboratory Practices (GLP) per 21 CFR §58. These studies are summarized in Table 8.

| Study | Number of Animals, Time Points, Devices Tested, and Implant Sites | Relevant Findings |
| --- | --- | --- |
| FS40: Acute delivery, mechanical performance and vascular response versus a control in normal porcine peripheral arteries | 8 animals (porcine)
28 days
8 test articles, 5 controls
Carotid and iliac arteries | All stent delivery and deployment procedures were rated well. Vascular injury and neointimal thickness scores were low. |
| FS41: Acute delivery, mechanical performance and chronic vascular response versus a control in normal porcine peripheral arteries | 8 animals (porcine)
6 months
13 test articles, 6 controls
Carotid and iliac arteries | All stent delivery and deployment procedures were rated well. Vascular injury and neointimal thickness scores were low. |
| FS55: Acute performance compatibility of the Self-Expanding Carotid Stent with the GuardWire Temporary Occlusion and Aspiration System in carotid swine arteries | 1 animal (porcine)
Acute
4 stents, 2 embolic protection devices
Carotid arteries | The Exponent and GuardWire devices were used together as a system without observed difficulty. Device compatibility, trackability, stent crossing, and device retrieval were all rated well. |
| FS70: Vascular response and mechanical performance in the swine iliac and carotid arteries. | 10 animals (porcine)
28 days
20 test articles, 10 controls
Carotid and iliac arteries | All stent delivery and deployment procedures were rated well. Vascular injury scores were generally low. One animal experienced severe in-stent granulomas, which is a known potential reaction with nickel-titanium stents. |
| FS139: Mechanical performance of the RX delivery system versus the OTW delivery system, and compatibility with embolic protection systems in target vessels. | 2 animals (ovine)
Acute
8 RX systems and 4 OTW systems, plus the GuardWire® Temporary Occlusion and Aspiration System | Acute performance of the RX system, including both mechanical performance and compatibility with embolic protection systems, was acceptable and equivalent to the performance of the OTW system. No complications were reported. |

The animal study results suggest satisfactory device safety *in vivo*.

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# 9.3 BIOCOMPATIBILITY

The Exponent® Self-Expanding Carotid Stent Systems were tested for biocompatibility in accordance with International Organization for Standardization (ISO) 10993-1, “Biological Evaluation of Medical Devices Part 1: Evaluation of Testing,” FDA’s Blue Book Memorandum dated May 1, 1995, and FDA 21 CFR Part 58. All testing was conducted using finished, sterilized stent systems in accordance with FDA/ISO guidelines for blood contact/implant materials.

The stent is considered an implant with permanent blood contact (> 30 days). Both the OTW and RX delivery systems are categorized as external communicating devices that contact circulating blood for less than 24 hours. The biocompatibility test regimen is outlined in Table 9.

Table 9: Summary of Biocompatibility Testing

| Test Performed | Test Result |
| --- | --- |
| Cytotoxicity (MEM elution) | Pass |
| In vitro hemolysis | Pass |
| Acute intracutaneous reactivity | Pass |
| Acute systemic toxicity | Pass |
| Material-mediated pyrogenicity | Pass |
| Sensitization (Maximization) | Pass |
| In vivo thromboresistance | Pass |
| C3a complement activation | Pass |
| Plasma recalcification/ coagulation time | Pass |
| Muscle implantation | Pass |

Evaluation of chronic toxicity and carcinogenicity was not necessary due to the extensive clinical history of the device materials and their well-characterized long-term safety profile.

The test results demonstrate that both the stent and delivery systems are biocompatible and non-pyrogenic.

# 9.4 STERILIZATION

The Medtronic Vascular Exponent® Self-Expanding Carotid Stent Systems are E-beam sterilized in compliance with AAMI/ISO 11137:1995 (Sterilization of health care products: requirements for validation and routine control: radiation sterilization). Quarterly sterilization dose audits and monitoring of bioburden levels are performed to confirm that the sterilization process is effective in eradicating viable microorganisms. The audit results indicate that the carotid system will maintain a Sterility Assurance Level of $10^{-6}$ when sterilized at a minimum dose of $25\mathrm{kGy}$.

Limulus Amoebocyte Lysate (LAL) testing of finished lot demonstrates acceptable levels of pyrogenicity.

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# 9.5 PACKAGING AND SHELF LIFE

A three-year shelf life has been substantiated for the Exponent® Self-Expanding Carotid Stent with OTW Delivery System, and a one-year shelf-life has been substantiated for the Exponent® Self-Expanding Carotid Stent with RX Delivery System. Shelf-life values were based on demonstration of acceptable packaging integrity and device performance using sterilized samples subjected to real-time and accelerated aging.

# 10.0 SUMMARY OF CLINICAL STUDIES

The MAVErIC (Evaluation of the Medtronic AVE Self-Expanding Carotid Stent System with Distal Protection in the Treatment of Carotid Stenosis) I and II studies were two prospective, single-arm, multi-center, consecutively enrolling clinical studies performed in the United States to demonstrate the safety and efficacy of the Medtronic Exponent® Self-Expanding Carotid Stent with OTW Delivery System in conjunction with the GuardWire® Temporary Occlusion and Aspiration System. In both studies, the devices were used to treat subjects with occlusive disease of the common or internal carotid artery who were either symptomatic (≥ 50% stenosis) or asymptomatic (≥ 80% stenosis), and possessed anatomic and/or co-morbidity risk factors for surgical revascularization. MAVErIC I enrolled a total of 99 patients at 16 U.S. clinical sites and MAVErIC II enrolled 399 patients at 34 U.S. clinical sites in the U.S. An overview of the MAVErIC I & II studies is presented in Table 10.

Table 10: Overview of MAVErIC I and II Studies

| | MAVErIC I | MAVErIC II |
| --- | --- | --- |
| Products Evaluated | Exponent® Self-Expanding Carotid Stent with Over-the-Wire (OTW) Delivery System and the GuardWire® Temporary Occlusion & Aspiration System | |
| Study Design | Non-randomized, multi-center, single-arm, prospective clinical trials | |
| Sample Size | 99 patients | 399 patients |
| Number of Sites | 16 in the U.S. | 34 in the U.S. |
| Primary Endpoint | Any death, MI, stroke to 30 days and ipsilateral stroke from 31 – 365 days | |
| Secondary Endpoints | **Safety:**
• Freedom from any stroke, MI or death at 30 days
• Freedom from target lesion revascularization at one year

**Efficacy:**
• Acute success defined by:
• lesion¹
• device (stent delivery system and distal protection device)²
• procedure³ | **Safety:**
• Major Adverse Events at 30 days post procedure, defined as any stroke, MI, and/or death

**Efficacy:**
• Acute success defined by:
• lesion¹
• device (stent delivery system and distal protection device)²
• procedure³
• Freedom from stroke at one year |
| Study Hypothesis | Results meet the performance goal (PG) derived from historical carotid endarterectomy data | |
| Patient Follow-Up | • Neurological evaluation by an independent neurologist at 30 days, 6 months, and 365 days
• Clinical assessment via telephone call at 14 days and physical assessment (office visit) at 30 days, 6 months, and 365 days, and annually for 3 years thereafter
• Carotid duplex scans performed at 2 weeks and 365 days | • Neurological evaluation by an independent neurologist or NIHSS stroke-certified surrogate at 30 days, 6 months, and 365 days
• Physical assessment (office visit) at 30 days, 6 months, and 365 days, and annually for 3 years thereafter
• Carotid duplex scans performed at 4 weeks and 365 days |

¹ Attainment of <30% residual in-stent stenosis of the target lesion; if in-stent measurements not available, then in-lesion measurements were used; if in-lesion measurements not available, then visual estimates were used.
² Attainment of <30% residual in-stent stenosis of the target lesion using the study devices; this measure is a union of stent and embolic protection device success.
³ Attainment of residual in-stent stenosis of the target lesion and no in-hospital major adverse events. If in-stent measurements not available, then in-lesion measurements were used; if in-lesion measurements not available, then visual estimates were used.

The protocol required regular patient follow-up by the treating physician and follow-up neurological assessment by either an independent neurologist or an NIH Stroke Scale (NIHSS)-certified evaluator. Core laboratories provided independent assessments for angiographic, ultrasound, and eletrocardiogram results. Medical monitors reviewed all safety data to ensure appropriate reporting of adverse events. A Clinical Events Committee adjudicated suspected primary endpoint events. A Data Safety Monitoring Board monitored adverse events to ensure patient safety.

## Statistical Methods

The statistical analyses of MAVErIC I and II were designed to demonstrate that the primary endpoint event rates were significantly less than a performance goal derived

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from available carotid endarterectomy (CEA) literature, which represented the standard of care for carotid revascularization at the time of study initiation.

The one-year major event rate from CEA was estimated as $\omega_{\mathrm{A}} \times 11\% + \omega_{\mathrm{C}} \times 14\%$, where $\omega_{\mathrm{C}} =$ the proportion of subjects with co-morbidity risk factors and $\omega_{\mathrm{A}} =$ the proportion of subjects with anatomic risk factors. Based on this estimate, the study hypotheses were established as:

$$
\begin{array}{l}
\mathrm{H}_{0}: \pi_{\text{Medtronic AVE}} \geq \omega_{\mathrm{A}} \times 11\% + \omega_{\mathrm{C}} \times 14\% + 4\% \\
\mathrm{H}_{\mathrm{A}}: \pi_{\text{Medtronic AVE}} < \omega_{\mathrm{A}} \times 11\% + \omega_{\mathrm{C}} \times 14\% + 4\%,
\end{array}
$$

where $\pi_{\text{Medtronic AVE}} =$ the one-year primary endpoint event rate and where $\omega_{\mathrm{A}}$ and $\omega_{\mathrm{C}}$ are based on the observed mix of subjects enrolled with each type of surgical risk factor. With a one-sided type I error of $5\%$ and a type II error of $20\%$, the upper bound of the one-sided $95\%$ confidence interval for the primary endpoint event rate must be less than the calculated performance goal for the null hypothesis to be rejected.

## Eligibility Requirements

The study population included male and female subjects of at least 18 years of age, with a lesion located between the origin of the common carotid artery and the intracranial segment of the internal carotid artery.

Key inclusion criteria included:

- Neurological symptoms and $\geq 50\%$ stenosis of the common or internal carotid artery by either ultrasound or angiogram, or absence of neurological symptoms and $\geq 80\%$ stenosis of the common or internal carotid artery by either ultrasound or angiogram, and
- Reference diameters between $5.5\,\mathrm{mm}$ and $9.5\,\mathrm{mm}$ at the target lesion.

Symptomatic patients were defined as having:

- sudden numbness or weakness of face, arm or leg – especially on one side of the body,
- sudden confusion, trouble speaking or understanding,
- sudden trouble seeing in one or both eyes,
- sudden trouble walking, dizziness, loss of balance or coordination, or
- sudden severe headache with no known cause.

Patients were excluded from eligibility if they had an occurrence of non-disabling stroke, disabling stroke within 4 weeks of the index procedure or symptoms of a TIA or amaurosis fugax within 24 hours of the index procedure.

26

Each subject must have been considered at high risk for adverse events from carotid endarterectomy, as evidenced by the presence of at least one anatomic or co-morbidity risk factors. These risk factors and their prevalence in the enrolled population are identified in Table 11 below.

Table 11: Surgical High Risk Criteria

| RISK FACTORS | MAVErIC I
(N=99 Patients) | MAVErIC II
(N=399 Patients) |
| --- | --- | --- |
| ANATOMIC | | |
| Previous Carotid Endarterectomy | 59.6% (59/99) | 28.6% (114/399) |
| Contralateral Carotid Artery Occlusion | 5.1% (5/99) | 8.5% (34/399) |
| Previous Radical Neck Dissection Or Radiation Therapy To Neck Region | 11.1% (11/99) | 9.3% (37/399) |
| Target Lesion Above C-2 (Level Of Jaw) | 7.1% (7/99) | 10.3% (41/399) |
| Low Cervical Carotid Lesions | 1.0% (1/99) | 1.0% (4/399) |
| Dissection | 1.0% (1/99) | 0.0% (0/399) |
| Inability To Extend Neck (I.E. Cervical Osteoarthritis, Mobility Limitations) | 8.1% (8/99) | 7.3% (29/399) |
| Tandem Lesions ≥ 70% Stenosis | 2.0% (2/99) | 1.3% (5/399) |
| Contralateral Laryngeal Palsy | 1.0% (1/99) | 1.3% (5/399) |
| At Risk For Wound Infection | 5.1% (5/99) | 3.3% (13/399) |
| Tracheostomy | 1.0% (1/99) | 1.5% (6/399) |
| CO-MORBIDITY | | |
| Patients > 80 Years Of Age | 10.1% (10/99) | 35.3% (141/399) |
| Two Or More Major Diseased Coronary Arteries With >70% Stenosis At The Time Of Index Procedure In Patients With A History Of Angina^{1} | N/A | 15.3% (61/399) |
| Myocardial Infarction Within Previous 6 Weeks | 0.0% (0/99) | 0.8% (3/399) |
| NYHA Class III Or IV Heart Failure | 15.2% (15/99) | 12.8% (51/399) |
| Unstable Angina (Defined As Resting Pain With ECG Changes) | 3.0% (3/99) | 3.3% (13/399) |
| History Of Liver Failure With Elevated Prothrombin Time | 0.0% (0/99) | 0.3% (1/399) |
| Requires Concurrent CABG, AAA Repair Or Peripheral Vascular Surgery | 0.0% (0/99) | 0.0% (0/399) |
| COPD With FEV1 < 30% Predicted | 3.0% (3/99) | 1.8% (7/399) |

1 Part of the MAVErIC II clinical protocol but not a co-morbidity risk factor for the MAVErIC I clinical protocol.

## Description of Subjects Evaluated

Table 12 summarizes patient follow-up compliance at the endpoint evaluation time points.

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Table 12: Subject Follow-up Compliance

| | MAVErIC I
(N = 99)
% (n/N) | MAVErIC II
(N = 399)
% (n/N) |
| --- | --- | --- |
| 30 Days | | |
| Patients Enrolled | 100.0% (99/99) | 100.0% (399/399) |
| Cumulative Death | 1.0% (1/99) | 1.0% (4/399) |
| Cumulative Withdrawn/Lost to Follow-Up (LTF) | 0.0% (0/99) | 1.5% (6/399) |
| Patients Evaluable | 99.0% (98/99) | 97.5% (389/399) |
| Patients Evaluated^{1} | 97.0% (96/99) | 94.5% (377/399) |
| Neurological Evaluation^{2} | 88.9% (88/99) | 89.0% (355/399) |
| Ultrasound Evaluation^{3} | 90.9% (90/99) | 86.4% (345/399) |
| Other Clinical Evaluation Only^{4} | 8.1% (8/99) | 5.5% (22/399) |
| 365 Days | | |
| Cumulative Death | 1.0% (1/99) | 9.3% (37/399) |
| Cumulative Withdrawn or LTF | 1.0% (1/99) | 7.5% (30/399) |
| Patients Evaluable | 98.0% (97/99) | 83.2% (332/399) |
| Patients Evaluated^{1} | 96% (95/99) | 79.7% (318/399) |
| Neurological Evaluation^{2} | 78.8% (78/99) | 72.7% (290/399) |
| Ultrasound Evaluation^{3} | 79.8% (79/99) | 73.2% (292/399) |
| Other Clinical Evaluation Only^{4} | 17.2% (17/99) | 7.0% (28/399) |

1 Patients evaluated defined as a complete 30 or 365 day contact form
2 Neurological assessment defined as a complete NIH Stroke Scale form
3 Ultrasound evaluation took place at 14 days for MAVErIC I
4 Other Clinical Evaluation Only defined as a complete 30 or 365 day contact form with no neurological evaluation

## Description of Patient Demographics

Table 13 summarizes demographic information for the MAVErIC I and II subjects.

Table 13: MAVErIC I and II Subject Demographics

| Subject Characteristics | MAVErIC I | MAVErIC II |
| --- | --- | --- |
| Age (yrs) | | |
| Mean ± SD (N) | 69.26 ± 10.20 (99) | 74.08 ± 9.39 (399) |
| Range (Min, Max) | 43, 89 | 41, 95 |
| Gender, % (n/N)^{1} | | |
| Male | 57.6% (57/99) | 58.6% (234/399) |
| Female | 42.4% 42/99 | 41.4% (165/399) |
| Race, % (n/N)^{1} | | |
| White | 89.9% (89/99) | 91.2% (364/399) |
| Black | 5.1% (5/99) | 3.8% (15/399) |
| Hispanic | 3.0% (3/99) | 3.0% (12/399) |
| Asian | 1.0% (1/99) | 0.8% (3/399) |
| Other | 1.0% (1/99) | 1.3% (5/399) |
| Medical History, % (n/N)^{1} | | |
| Left Ventricular Function | | |
| Normal (ejection fraction >55%) | 45.0% (27/60) | 51.6% (126/244) |
| Mildly Impaired (ejection fraction 46% to 55%) | 25.0% (15/60) | 12.3% (30/244) |
| Moderately Impaired (ejection fraction 30% to 45%) | 15.0% (9/60) | 22.1% (54/244) |
| Severely Impaired (ejection fraction <30%) | 15.0% (9/60) | 13.9% (34/244) |
| Clinical Congestive Heart Failure | 26.5% (26/98) | 24.8% (96/387) |
| Peripheral Vascular Disease | 52.6% (51/97) | 44.0% (171/389) |

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| Subject Characteristics | MAVErIC I | MAVErIC II |
| --- | --- | --- |
| Gastrointestinal/Genitourinary Bleeding | 8.2% (8/97) | 5.3% (21/397) |
| Diabetes Mellitus | 27.3% (27/99) | 34.1% (136/399) |
| History of Liver Failure | 0.0% (0/97) | 0.3% (1/386) |
| Dyslipidemia Requiring Medication | 68.7% (68/99) | 70.8% (281/397) |
| History of Hypertension | 91.8% (90/98) | 87.9% (350/398) |
| Uncontrolled Systemic Hypertension | 2.2% (2/91) | 1.5% (6/393) |
| Cigarette Smoking (Ever) | 72.7% (72/99) | 67.3% (266/395) |
| Family History of Premature Atherosclerosis | 41.9% (26/62) | Not Captured |
| Significant Aortic Arch Atherosclerosis | 1.1% (1/93) | Not Captured |
| History of Cardiac arrhythmia | 17.7% (17/96) | Not Captured |
| Severe Aortic/Mitral Valvular Disease | 7.4% (7/95) | Not Captured |
| Renal Insufficiency | 11.1% (11/99) | Not Captured |
| Clinical COPD | 3.4% (3/88) | Not Captured |
| Coronary Artery Disease | 66.3% (63/95) | Not Captured |
| Unstable Angina | 3.1% (3/98) | Not Captured |
| Current Smoking | 19.4% (19/98) | Not Captured |
| Previous Q wave or Non-Q wave MI | 28.0% (26/93) | 27.8% (107/385) |
| Prior Cardiovascular Procedures, % (n/N)^{1} | | |
| Previous PTCA (coronary) | 23.5% (23/98) | Not Captured |
| Previous Atrial Valve Repair (AVR) | 3.0% (3/99) | Not Captured |
| Previous Mitral Valve Repair (MVR) | 1.0% (1/99) | Not Captured |
| Previous CABG | 33.3% (33/99) | Not Captured |
| Neurological History, % (n/N)^{1} | | |
| Previous PTA (Carotid) | 0.0% (0/97) | 2.3% (9/399) |
| Previous CEA | 60.6% (60/99) | 33.6% (134/399) |
| History of TIA | 23.5% (23/98) | 29.3% (115/392) |
| History of Stroke | 21.9% (21/96) | 22.5% (89/396) |
| Target Lesion Location, % (n/N)^{1} | | |
| Right Carotid | | |
| Common | 6.2% (6/97) | 3.1% (12/389) |
| Internal | 44.3% (43/97) | 48.3% (188/389) |
| Left Carotid | | |
| Common | 11.% (11/97) | 4.9% (19/389) |
| Internal | 38.1% (37/97) | 43.7% (170/389) |
| Baseline Target Lesion Characteristics, % (n/N)^{1} | | |
| Lesion location, % | | |
| Contiguous | 43.3% (42/97) | 50.1% (194/387) |
| Remote | 48.5% (47/97) | 37.7% (146/387) |
| Sequential | 8.2% (8/97) | 12.1% (47/387) |
| Distance from Ostium (mm) | | |
| Mean±SD (N) | 6.01±7.87 (97) | 3.63±5.73 (387) |
| Minimum, maximum | 0.00, 42.40 | 0.00, 34.40 |
| Lesion Length (mm) | | |
| Mean±SD (N) | 14.71±6.99 (96) | 15.17±6.83 (387) |
| Minimum, maximum | 2.29, 33.71 | 4.56, 39.73 |

| Subject Characteristics | MAVErIC I | MAVErIC II |
| --- | --- | --- |
| Discrete (<10 mm), % (n/N) | 26.0% (25/96) | 25.1% (97/387) |
| Tubular (10 to 20 mm), % (n/N) | 53.1% (51/96) | 54.0% (209/387) |
| Diffuse (≥20 mm), % (n/N) | 20.8% (20/96) | 20.9% (81/387) |
| Lesion Eccentricity, % (n/N) | 35.1% (34/97) | 29.2% (113/387) |
| Thrombus, % (n/N) | | |
| None | 93.8% (91/97) | 94.3% (365/387) |
| Possible | 6.2% (6/97) | 5.7% (22/387) |
| Mild | 0.0% (0/97) | 0.0% (0/387) |
| Moderate | 0.0% (0/97) | 0.0% (0/387) |
| Large | 0.0% (0/97) | 0.0% (0/387) |
| Total occlusion | 0.0% (0/97) | 0.0% (0/387) |
| Access tortuosity (any), % (n/N) | 2.1% (2/97) | 3.9% (15/387) |
| Distal tortuosity (any), % (n/N) | 33.0% (32/97) | 34.9% (135/387) |
| Calcification (unilateral or bilateral), % (n/N) | 49.5% (48/97) | 53.7% (208/387) |
| Ulceration, % (n/N) | 23.7% (23/97) | 27.4% (106/387) |
| Aneurysm, % (n/N) | 6.2% (6/97) | 3.1% (12/387) |
| Baseline TIMI flow, % (n/N) | | |
| 0, 1 | 0.0% (0/59) | 0.0% (0/221) |
| 2 | 3.4% (2/59) | 5.9% (13/221) |
| 3 | 96.6% (57/59) | 94.1% (208/221) |

¹Denominators indicate the total number of patients with available data for the related parameter.

Table 14 summarizes quantitative angiographic findings for the MAVErIC I trial.

Table 14: Quantitative Angiographic Findings, MAVErIC I

| Parameter | Pre-procedure | Final Assessment |
| --- | --- | --- |
| Reference diameter | | |
| Common carotid (mm) | | |
| Mean ± SD (N¹) | 6.64±1.33 (97) | 6.65±1.33 (96) |
| Minimum, maximum | 3.60, 10.00 | 3.66, 10.00 |
| Internal carotid (mm) | | |
| Mean ± SD (N¹) | 4.56±0.88 (97) | 4.70±0.93 (96) |
| Minimum, maximum | 2.78, 6.51 | 3.02, 7.75 |
| RVD (mm) | | |
| Mean ± SD (N¹) | 4.99±1.32 (97) | 5.12±1.31 (96) |
| Minimum, maximum | 2.78, 9.17 | 3.02, 8.89 |
| MLD (mm) | | |
| Mean ± SD (N¹) | 1.48±0.76 (97) | 3.81±0.75 (96) |
| Minimum, maximum | 0.21, 3.30 | 1.57, 5.59 |
| % Diameter stenosis | | |
| Mean ± SD (N¹) | 70.59±12.30 (97) | 23.41±13.51 (96) |
| Minimum, maximum | 38.93, 94.05 | 2.58, 63.99 |

¹Denominators indicate the total number of patients with available data for the related parameter.

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Table 15 summarizes quantitative angiographic findings for the 399 patients enrolled into the MAVErIC II trial.

Table 15: Quantitative Angiographic Findings, MAVErIC II

| Parameter | Pre-procedure | Final Assessment |
| --- | --- | --- |
| Reference diameter | | |
| Common carotid (mm) | | |
| Mean±SD (n)^{1} | 6.51±1.19 (387) | 6.48±1.19 (385) |
| Minimum, maximum | 4.11, 10.45 | 4.03, 10.73 |
| Internal carotid (mm) | | |
| Mean±SD (n)^{1} | 4.25±0.79 (387) | 4.32±0.74 (385) |
| Minimum, maximum | 2.22, 6.83 | 2.66, 6.82 |
| RVD (mm) | | |
| Mean ±SD (n)^{1} | 4.40±0.93 (387) | 4.46±0.89 (385) |
| Minimum, maximum | 2.38, 9.55 | 2.66, 9.25 |
| MLD (mm) | | |
| Mean±SD (n)^{1} | 1.34±0.54 (387) | 3.64±0.72 (385) |
| Minimum, maximum | 0.34, 3.62 | (1.79,5.84) |
| % Diameter stenosis | | |
| Mean±SD (n)^{1} | 69.60±9.88 (387) | 17.45±12.42 (385) |
| Minimum, maximum | 36.07, 90.96 | -25.54, 60.98 |

1Denominators indicate the total number of patients with available data for the related parameter.

## Clinical Results Summary

Primary endpoint events (defined as any death, MI, or stroke reported from 0 to 30 days and any ipsilateral stroke reported from 31 – 365 days) occurred in 6 patients in the MAVErIC I clinical trial, for a rate of 6.1% at both 30 days and 365 days. In the MAVErIC II trial, primary endpoint events occurred in 21 patients at 30 days, for a rate of 5.3%, and occurred in 22 patients from 0 - 365 days for a rate of 5.5%. No deaths were attributed to device malfunction or failure. Table 16 summarizes the safety and effectiveness measures for both studies.

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Table 16: Safety and Efficacy Measures¹

| Safety and Efficacy Measures | MAVErIC I
(N = 99)
% (n/N) | MAVErIC II
(N = 399)
% (n/N) |
| --- | --- | --- |
| Primary Endpoint | | |
| Death, MI, Stroke to 30 days and Ipsilateral Stroke from 31-365 Days | 6.1% (6/99) | 5.5% (22/399) |
| 30 Day Death | 1.0% (1/99) | 1.0% (4/399) |
| 30 Day MI | 1.0% (1/99) | 1.5% (6/399) |
| 30 Day Stroke | 5.1% (5/99) | 4.0% (16/399) |
| 31-365 Day Ipsilateral Stroke | 0.0% (0/99) | 0.3% (1/399) |
| Secondary Endpoint | | |
| Any MAE to 30 days (Death, MI, Stroke) | 6.1% (6/99) | 5.3% (21/399) |
| Target Lesion Revascularization (TLR) | 2.0% (2/99) | 1.3% (5/399) |
| Target Vessel Revascularization (TVR) | 2.0% (2/99) | 0.5% (2/399) |
| Primary Patency at 1 year | 85.9% (85/99) | 92.1% (363/394) |
| Technical Success | 80.8% (80/99) | 87.0% (347/399) |
| Acute Procedure Success | 81.8% (81/99) | 88.6% (350/395) |

¹ All data based on ITT population

Table 17 includes the results of primary endpoint event hypothesis testing for the MAVErIC I and II studies. The 95% one-sided upper confidence interval of the MAVErIC primary endpoint event rate is less than the hypothesized value (ωA×11% + ωC×14% + 4%), demonstrating that the MAVErIC study results met the pre-specified performance goal.

Table 17. MAVErIC I and II Statistical Analysis for Primary Endpoint Events

| | Primary Endpoint Events to 365 days¹ | Weighted PG | Weighted PG + 0.04 | Upper Bound of 1-Sided 95% CI |
| --- | --- | --- | --- | --- |
| MAVErIC I | 6.1% (6/98) | 11.765% | 15.765% | 11.73% |
| MAVErIC II | 5.9% (22/375) | 12.728% | 16.728% | 8.27% |

¹ Data based on analysis population (AP), defined as ITT population minus patients lost to follow-up. A primary endpoint event is defined as death, MI, stroke to 30 days and ipsilateral stroke from 31 - 365 days. In MAVErIC I, the PG (performance goal) for the AP population was based on 25 patients with co-morbid risk factors and 73 patients with anatomic risk factors. In MAVErIC II, the PG was based on 216 patients with co-morbid risk factors and 159 patients with anatomic risk factors (2 patients with missing high-risk data were considered to have anatomic risk factors). One-year complication rates of 11% for patients with anatomic risk factors and 14% For patients with co-morbid risk factors were used to calculate the weighted PG for both studies.

The Kaplan-Meier estimates for freedom-from-primary endpoint events to 365 days for the MAVErIC I &amp; II trials for all subjects, symptomatic subjects, and asymptomatic subjects are provided in Tables 18 - 23. All analyses are based on the intent-to-treat population.

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Table 18. MAVErIC I Kaplan-Meier Estimate for Freedom-from-Primary Endpoint Events to 365 Days For All Subjects

| | Time Intervals (Days) | | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | 0* | 1-30 | 31-60 | 61-120 | 121-150 | 151-180 | 181-240 | 241-270 | 271-300 | 301-330 | 331-365 |
| # Entered | 99 | 96 | 93 | 93 | 93 | 93 | 93 | 92 | 92 | 92 | 92 |
| # Censored | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 2 |
| # Incomplete | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| # Events | 3 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Cumulative % Event-Free | 97.0% | 93.9% | 93.9% | 93.9% | 93.9% | 93.9% | 93.9% | 93.9% | 93.9% | 93.9% | 93.9% |
| SE | 1.7% | 2.4% | 2.4% | 2.4% | 2.4% | 2.4% | 2.4% | 2.4% | 2.4% | 2.4% | 2.4% |

* Peri-procedural events
# Entered: The number of patients entering the interval
# Censored: The number of patients who prematurely withdrew without an event in the interval
# Incomplete: The number of patients who died in the interval without event
# Events: The number of patients with event in the interval
Cumulative % Event-Free: Kaplan-Meier estimate of percentage of patients without an event at the end of the specified interval
SE: Kaplan-Meier estimate of standard error


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Table 19. MAVErIC I Kaplan-Meier Estimate for Freedom-from-Primary Endpoint Events to 365 Days for Symptomatic Subjects

| | Time Intervals (Days) | | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | 0* | 1-30 | 31-60 | 61-120 | 121-150 | 151-180 | 181-240 | 241-270 | 271-300 | 301-330 | 331-365 |
| # Entered | 38 | 35 | 33 | 33 | 33 | 33 | 33 | 33 | 33 | 33 | 33 |
| # Censored | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| # Incomplete | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| # Events | 3 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Cumulative % Event-free | 92.1% | 86.8% | 86.8% | 86.8% | 86.8% | 86.8% | 86.8% | 86.8% | 86.8% | 86.8% | 86.8% |
| SE | 4.4% | 5.5% | 5.5% | 5.5% | 5.5% | 5.5% | 5.5% | 5.5% | 5.5% | 5.5% | 5.5% |

* Peri-procedural events
# Entered: The number of patients entering the interval
# Censored: The number of patients who prematurely withdrew without an event in the interval
# Incomplete: The number of patients who died in the interval without event
# Events: The number of patients with event in the interval
Cumulative % Event-Free: Kaplan-Meier estimate of percentage of patients without an event at the end of the specified interval
SE: Kaplan-Meier estimate of standard error


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Table 20. MAVErIC I Kaplan-Meier Estimate for Freedom-from-Primary Endpoint Events to 365 Days for Asymptomatic Subjects

| | Time Intervals (Days) | | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | 0* | 1-30 | 31-60 | 61-120 | 121-150 | 151-180 | 181-240 | 241-270 | 271-300 | 301-330 | 331-365 |
| # Entered | 59 | 59 | 58 | 58 | 58 | 58 | 58 | 57 | 57 | 57 | 57 |
| # Censored | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 |
| # Incomplete | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| # Events | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Cumulative % Event-free | 100% | 98.3% | 98.3% | 98.3% | 98.3% | 98.3% | 98.3% | 98.3% | 98.3% | 98.3% | 98.3% |
| SE | 0.0% | 1.7% | 1.7% | 1.7% | 1.7% | 1.7% | 1.7% | 1.7% | 1.7% | 1.7% | 1.7% |

* Peri-procedural events
# Entered: The number of patients entering the interval
# Censored: The number of patients who prematurely withdrew without an event in the interval
# Incomplete: The number of patients who died in the interval without event
# Events: The number of patients with event in the interval
Cumulative % Event-Free: Kaplan-Meier estimate of percentage of patients without an event at the end of the specified interval
SE: Kaplan-Meier estimate of standard error


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Table 21. MAVErIC II Kaplan-Meier Estimate for Freedom-from-Primary Endpoint Events to 365 Days for All Subjects

| | Time Intervals (Days) | | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | 0* | 1-30 | 31-60 | 61-120 | 121-150 | 151-180 | 181-240 | 241-270 | 271-300 | 301-330 | 331-365 |
| # Entered | 399 | 390 | 369 | 367 | 361 | 359 | 353 | 341 | 336 | 333 | 326 |
| # Censored | 0 | 9 | 2 | 2 | 0 | 3 | 4 | 3 | 0 | 1 | 9 |
| # Incomplete | 0 | 0 | 0 | 4 | 2 | 3 | 7 | 2 | 3 | 6 | 2 |
| # Events | 9 | 12 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Cumulative % Event-free | 97.7% | 94.7% | 94.7% | 94.7% | 94.7% | 94.7% | 94.4% | 94.4% | 94.4% | 94.4% | 94.4% |
| SE | 0.7% | 1.1% | 1.1% | 1.1% | 1.1% | 1.1% | 1.2% | 1.2% | 1.2% | 1.2% | 1.2% |

* Peri-procedural events
# Entered: The number of patients entering the interval
# Censored: The number of patients who prematurely withdrew without an event in the interval
# Incomplete: The number of patients who died in the interval without event
# Events: The number of patients with event in the interval
Cumulative % Event-Free: Kaplan-Meier estimate of percentage of patients without an event at the end of the specified interval
SE: Kaplan-Meier estimate of standard error

Time After Initial Procedure (days)

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Table 22. MAVErIC II Kaplan-Meier Estimate for Freedom-from-Primary Endpoint Events to 365 Days for Symptomatic Subjects

| | Time Intervals (Days) | | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | 0* | 1-30 | 31-60 | 61-120 | 121-150 | 151-180 | 181-240 | 241-270 | 271-300 | 301-330 | 331-365 |
| # Entered | 175 | 171 | 158 | 157 | 153 | 153 | 150 | 145 | 142 | 142 | 139 |
| # Censored | 0 | 5 | 1 | 1 | 0 | 1 | 3 | 2 | 0 | 0 | 5 |
| # Incomplete | 0 | 0 | 0 | 3 | 0 | 2 | 2 | 1 | 0 | 3 | 0 |
| # Events | 4 | 8 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Cumulative % Event-free | 97.7% | 93.1% | 93.1% | 93.1% | 93.1% | 93.1% | 93.1% | 93.1% | 93.1% | 93.1% | 93.1% |
| SE | 1.1% | 1.9% | 1.9% | 1.9% | 1.9% | 1.9% | 1.9% | 1.9% | 1.9% | 1.9% | 1.9% |

* Peri-procedural events
# Entered: The number of patients entering the interval
# Censored: The number of patients who prematurely withdrew without an event in the interval
# Incomplete: The number of patients who died in the interval without event
# Events: The number of patients with event in the interval
Cumulative % Event-Free: Kaplan-Meier estimate of percentage of patients without an event at the end of the specified interval
SE: Kaplan-Meier estimate of standard error


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Table 23. MAVErIC II Kaplan-Meier Estimate for Freedom-from-Primary Endpoint Events to 365 Days for Asymptomatic Subjects

| | Time Intervals (Days) | | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | 0* | 1-30 | 31-60 | 61-120 | 121-150 | 151-180 | 181-240 | 241-270 | 271-300 | 301-330 | 331-365 |
| MAVErIC II | | | | | | | | | | | |
| # Entered | 219 | 214 | 207 | 206 | 204 | 202 | 199 | 192 | 190 | 187 | 183 |
| # Censored | 0 | 3 | 1 | 1 | 0 | 2 | 1 | 1 | 0 | 1 | 4 |
| # Incomplete | 0 | 0 | 0 | 1 | 2 | 1 | 5 | 1 | 3 | 3 | 2 |
| # Events | 5 | 4 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Cumulative % Event-free | 97.7% | 95.9% | 95.9% | 95.9% | 95.9% | 95.9% | 95.4% | 95.4% | 95.4% | 95.4% | 95.4% |
| SE | 1.0% | 1.3% | 1.3% | 1.3% | 1.3% | 1.3% | 1.4% | 1.4% | 1.4% | 1.4% | 1.4% |

* Peri-procedural events
# Entered: The number of patients entering the interval
# Censored: The number of patients who prematurely withdrew without an event in the interval
# Incomplete: The number of patients who died in the interval without event
# Events: The number of patients with event in the interval
Cumulative % Event-Free: Kaplan-Meier estimate of percentage of patients without an event at the end of the specified interval
SE: Kaplan-Meier estimate of standard error

Time After Initial Procedure (days)

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38

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# 11.0 CONCLUSIONS DRAWN FROM CLINICAL STUDIES

Pre-clinical studies indicate that the Exponent® Self-Expanding Carotid Stent with OTW and RX Delivery Systems meet or exceed safety and performance specifications. The Exponent® Self-Expanding Carotid Stent with RX Delivery System is expected to perform similarly to the OTW stent system in clinical use based on similarities in design and non-clinical performance between the two systems. The multi-center clinical studies indicate that the Exponent® Self-Expanding Carotid Stent with OTW Delivery System, used with the GuardWire® Temporary Occlusion and Aspiration System, is safe and effective as a treatment for carotid artery disease in the population indicated.

Results from the pre-clinical and clinical evaluations provide valid scientific evidence and reasonable assurance that the devices are safe and effective when used in accordance with their labeling.

# 12.0 PANEL RECOMMENDATION

In accordance with provisions of section 515(c)(2) of the act as amended by the Safe Medical Devices Act of 1990, this PMA was not referred to the Circulatory System Devices Panel, an FDA advisory committee, for review and recommendation because the information in the PMA substantially duplicates information previously reviewed by this panel.

# 13.0 CDRH DECISION

FDA issued an approval order on October 23, 2007. The conditions of approval require a post-approval study of 1,500 new patients to be evaluated at 30 days and 365 days post-procedure, as well as the continued follow-up of the existing cohort of patients from the MAVErIC II study for a total of three years. The results of these studies will be evaluated to determine whether any changes should be made to the device labeling to ensure that the information available to physicians is complete, appropriate, and up-to-date.

The applicant's manufacturing facility was inspected and was found to be in compliance with the Quality System Regulation (21 CFR 820).

# 14.0 APPROVAL SPECIFICATIONS

Instructions for Use: See labeling.

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

Post-Approval Requirements and Restrictions: See approval order.