Safety and Efficacy of the CGuard™ Carotid Stent System in Carotid Artery Stenting (C-Guardians)

A Multicenter, Single-Arm, Pivotal Study to Evaluate the Safety and Efficacy of the CGuard™ Carotid Stent System When Used to Treat Symptomatic and Asymptomatic Carotid Artery Stenosis in Patients Undergoing Carotid Artery Stenting

The objective of this pivotal study is to evaluate the safety and efficacy of the CGuard™ Carotid Stent System in the treatment of carotid artery stenosis in symptomatic and asymptomatic patients undergoing carotid artery stenting (CAS) to a performance goal developed from published CAS literature.

Study Overview

• Status: Recruiting
• Conditions: Carotid Artery Stenosis
• Intervention / Treatment: Device: CGuard Carotid Stent implantation

• Study Type: Interventional
• Enrollment (Anticipated): 315
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christina Brennan; Phone Number: 888-776-6804; Email: christinab@inspiremd.com

Study Locations

• Poland
  • Katowice, Poland
    • Recruiting
    • Leszek Leic Upper-Silesian Medical Centre of the Silesian Medical University
    • Contact: Professor Kuzmick; Email: wkuczmik@interia.pl
    • Principal Investigator: Professor Kuzmick
  • Kraków, Poland
    • Recruiting
    • John Paul II Hospital
    • Contact: Adam Mazurek, MD; Email: mazurekadam@yahoo.pl
    • Principal Investigator: Piotr Musialek, MD
• United States
  • Florida
    • Jacksonville, Florida, United States, 32209
      • Recruiting
      • University of Florida
      • Principal Investigator: Daniel Soffer, MD
      • Contact: Andrea Burton; Email: Andrea.Burton@jax.ufl.edu
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Recruiting
      • Oschner Health
      • Contact: Steve Jenkins, MD; Email: sjenkins@oschner.org
      • Principal Investigator: Steve Jenkins, MD
  • Michigan
    • Detroit, Michigan, United States, 48236
      • Recruiting
      • Ascension, St. John Hospital
      • Principal Investigator: Thomas Davis, MD
      • Contact: Rhonda Beauchemin; Email: beauchemin@ascension.org
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Recruiting
      • Mercy Hospital
      • Principal Investigator: Anish Thomas, MD
      • Contact: Carol Mechem; Email: carol.mechem@mercy.net
  • New York
    • Buffalo, New York, United States, 14203
      • Recruiting
      • University of Buffalo
      • Principal Investigator: Adnan Siddiqui, MD
      • Contact: Shelby Halm; Email: shalm@ubns.com
    • Stony Brook, New York, United States, 11794
      • Recruiting
      • Stony Brook University Hospital
      • Principal Investigator: David Fiorella, MD
      • Contact: Dawn Madigan; Email: dawn.madigan@stonybrookmedicine.edu
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Recruiting
      • Novant Health
      • Principal Investigator: Donald Heck, MD
      • Contact: Carla Perez; Email: crperez@novanthealth.org
  • Ohio
    • Cleveland, Ohio, United States, 44103
      • Recruiting
      • Cleveland Clinic
      • Principal Investigator: Sean Lyden, MD
      • Contact: Carmen Czich, RN, BSN, CCRP; Email: czichc@ccf.org
  • Pennsylvania
    • Harrisburg, Pennsylvania, United States, 17101
      • Recruiting
      • UPMC-Pinnacle
      • Principal Investigator: William Bachinsky, MD
      • Contact: Gretchen Meise, RN, BSN, CCRC; Email: meisegc@upmc.edu
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Recruiting
      • Miriam Hospital
      • Principal Investigator: Peter Soukas, MD
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Recruiting
      • Prisma Health-Upstate
      • Contact: Diane Blain; Email: diane.blain@prismahealth.org
      • Principal Investigator: Bruce Gray, DO
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57108
      • Recruiting
      • Avera Heart Hospital
      • Principal Investigator: Michael Bacharach, MD
      • Contact: Robin Farley, RN; Email: rfarley@ncheart.com
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Recruiting
      • Ballad CVA Heart Institute
      • Principal Investigator: Chris Metzger, MD
      • Contact: Josh Lester, LPN, CCRC; Email: joshua.lester@balladhealth.org
    • Knoxville, Tennessee, United States, 37934
      • Recruiting
      • Turkey Creek Medical Center
      • Contact: Constance Bales, RN, CCRC; Email: constance.bales@tennova.com
  • Texas
    • Austin, Texas, United States, 78705
      • Recruiting
      • Ascension Seton, Seton Heart Institute
      • Principal Investigator: Peter Monteleone, MD
      • Contact: Aimee Shadrach, MSN; Email: aimee.blake@ascension.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject is willing and able to provide appropriate study-specific informed consent, follow protocol procedures, and comply with follow-up visit requirements.
2. Subject is willing and able to take dual antiplatelet therapy for a minimum of 30 days.
3. Life expectancy ≥ 24 months from the date of the index procedure.
4. Females who are not pregnant or lactating and not planning to become pregnant for the duration of the study.
5. Subject has a modified Rankin Score of ≤ 2at the time of informed consent.

6. Subject is diagnosed with carotid artery disease treatable with carotid artery stenting and is considered high risk for carotid endarterectomy (CEA) as evidenced by:

   1. Symptomatic carotid stenosis ≥ 50%. Symptomatic is defined as amaurosis fugax, transient ischemia attack (TIA) or stroke within the last 6 months ipsilateral to the side of the stenosis.

      Or

   2. Asymptomatic carotid stenosis ≥ 80%

7. Co-Morbidity High Risk Conditions for CEA, i.e., meets one or more of the following criteria:

   1. Age ≥ 70 (maximum 80 years)
   2. CCS angina class 3-4 or unstable angina
   3. Congestive Heart Failure (CHF) NYHA class III-IV
   4. Left ventricular ejection fraction (LVEF) ≤ 35%
   5. MI ≥ 72 hours and < 6 weeks pre-procedure
   6. Multi-vessel CAD (≥ 2 vessels >70% stenosis) and history of angina
   7. Chronic Obstructive Pulmonary Disease (COPD) with FEV1<50
   8. Permanent contralateral cranial nerve injury/paralysis
   9. Restenosis from previous carotid endarterectomy (CEA)
   10. Planned coronary artery bypass grafting (CABG) or valve replacement surgery between 31-60 days after CAS
   11. Abdominal aortic aneurysm repair or peripheral vascular surgery is planned between 31 to 60 days after CAS.

   OR

8. High Anatomical Risk for CEA, i.e., meets one or more of the following criteria:

   1. Occlusion of the contralateral CCA or ICA.
   2. Prior radiation treatment to the neck or a radical neck dissection.
   3. Severe bilateral ICA stenosis requiring treatment.
   4. Target lesion at or above the level of the jaw (C2) or below the clavicle.
   5. Severe tandem lesions
   6. Inability to extend the hear due to cervical disorders.
   7. Laryngeal palsy or laryngectomy.
   8. Prior head and neck surgery in the region of the carotid artery.
   9. Tracheostomy or tracheostoma.
   10. Spinal immobility of the neck.
   11. Hostile neck or surgically inaccessible lesion.

10. Angiographic General Inclusion Criteria, i.e., meets all the following criteria:

1. Target lesion location at the carotid bifurcation and/or proximal internal carotid artery (ICA)
2. Vessel distal to target lesion can accommodate a distal embolic protection device (EPD), and EPD is compatible with CGuard™ device (refer to CGuard™ System IFU for specific EPDs).
3. Target vessel reference diameter at stent landing zone is 4.8 mm to 9.0 mm.
4. Target lesion length ≤ 36 mm, that can be covered by a single CGuard™ stent.

Exclusion Criteria:

1. Planned interventional procedure or surgery of the carotid, coronary or peripheral arteries within 30 days before or after the index carotid procedure.
2. Severe vascular anatomy that would preclude safe sheath insertion, deliverability of stent or embolic protection device.
3. Type III or bovine aortic arch.
4. Total occlusion of the target vessel.
5. Presence of "String sign" of the target lesion.
6. In-tandem lesions with >= 50% or >= 80% diameter stenosis for symptomatic or asymptomatic patients, respectively, which cannot be covered by a single CGuard™ stent.
7. History of bleeding diatheses or coagulopathy or inability to accept blood transfusions.
8. Bilateral carotid stenosis requiring treatment on both sides within 30 days prior to or following planned index procedure.
9. Subject is on renal replacement therapy or has Stage 4 or 5 Chronic Kidney Disease (CKD).
10. Known reason for potential stroke other than carotid artery stenosis, including history of atrial fibrillation or other sources of thromboemboli within the past 12 months.
11. History of thrombophilia.
12. Known sensitivity or allergy to nitinol, titanium, heparin, aspirin or other anticoagulant/ antiplatelet therapies.
13. Contrast media sensitivity or allergy that cannot be pre-treated.
14. Previous stent placement in the target vessel.
15. Evolving stroke or intracranial hemorrhage, or history of previous intracranial hemorrhage or brain surgery within the past 12 months.
16. Major neurologic deficit with NIHSS of ≥ 15.
17. Dementia or other neurologic condition confounding the neurologic assessment.
18. Clinical condition that, in the opinion of the investigator, makes endovascular therapy impossible or hazardous.
19. Subject previously enrolled in this clinical trial.
20. Possible / probable non-compliance of subject with protocol required follow up or medication.
21. Subject is currently participating in another clinical trial that has not completed its primary endpoint assessment or would confound this C-GUARDIANS Pivotal IDE Clinical Study.
22. SARS-CoV2 (COVID-19) active infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CGuard group; Single experimental arm compared vs. objective performace goal	Device: CGuard Carotid Stent implantation; Implantation of CGuard carotid stent in the eligible patients; Other Names: Carotid stenting

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of DSMI through 30 days or ipsilateral stroke 31 - 365 days post-index procedure	The primary endpoint is the composite of the following: Incidence of the following Major Adverse Events: Death (allcause mortality), all Stroke, and Myocardial Infarction (DSMI) through 30-days post-index procedure, based on Clinical Events Committee (CEC) adjudication OR; Ipsilateral stroke from 31-365 day follow-up, based on Clinical Events Committee (CEC) adjudication.	From index procedure to 1 year follow up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of DSMI through discharge, 30 days, 6 months, and yearly follow ups till 3 years	Incidence of the following composite of Major Adverse Events: Death (all-cause mortality), all Stroke, and Myocardial Infarction (DSMI) through discharge, 30-days, 6-months, and 1-,2-,3-year follow-up, based on Clinical Events Committee (CEC) adjudication.	From index procedure to 3 years follow up
Incidence of particular components of DSMI through discharge, 30 days, 6 months, and yearly follow ups till 3 years	Incidence of each individual component of the Major Adverse Events: Death (all-cause mortality), all Stroke, and Myocardial Infarction (DSMI) through discharge, 30-days, 6-months, and 1-,2-,3-year follow-up, based on Clinical Events Committee (CEC) adjudication.	From index procedure to 3 years follow up
Incidence of ipsilateral stroke through discharge, 30 days, 6 months and 1-, 2-, 3-year follow-up.	Ipsilateral stroke through discharge, 30 days, 6 months and 1-, 2-, 3-year follow-up.	From index procedure to 3 years follow up
Incidence of major ipsilateral stroke through discharge, 30 days, 6 months and 1-, 2-, 3-year follow-up.	Major ipsilateral stroke through discharge, 30 days, 6 months and 1-, 2-, 3-year follow-up.	From index procedure to 3 years follow up
Incidence of In-stent Restenosis (ISR) > 70% in ultrasound evaluation	Incidence of In-stent Restenosis (ISR) > 70%. ISR > 70% is defined as PSV > 300 cm/s associated with stent, or vessel occlusion based on transcervical duplex ultrasound through 1-, 2-, 3-year follow-up. Based on Imaging Core Laboratory assessment.	At 1-, 2-, 3-year post-index procedure follow-up
Incidence of In-stent Restenosis (ISR) > 50% in ultrasound evaluation	Incidence of In-stent Restenosis (ISR) > 50%. ISR > 50% is defined as PSV > 220 cm/s associated with stent, or vessel occlusion based on transcervical duplex ultrasound through 1-, 2-, 3-year follow-up. Based on Imaging Core Laboratory assessment.	At 1-, 2-, 3-year post-index procedure follow-up
Incidence of target lesion revascularization	Incidence of Target Lesion Revascularization (TLR) through 1-,2,3-year follow-up. TLR is defined as clinically driven revascularization procedure of the original treatment site, including angioplasty, stenting, endarterectomy, or thrombolysis, performed to open or increase the luminal diameter within the stented lesion or within 5 mm proximal or distal to the index stent.	At 1-, 2-, 3-year post-index procedure follow-up
Composite of Ipsilateral stroke, stent thrombosis, cardiovascular death or other device related clinical events	Ipsilateral stroke, stent thrombosis, cardiovascular death or other device related clinical events from discharge up to 1-,2- and 3-year follow-up.	From index procedure to 3 years follow up
Composite of DSMI through 30 days or ipsilateral stroke 31 - 365 days post-index procedure for subjects that adhere to antiplatelet pharmacology.	Primary endpoint for subjects that adhere to antiplatelet pharmacology.	From index procedure to 1 year follow up

Collaborators and Investigators

• Sponsor: InspireMD
• Investigators: Principal Investigator: Chris Metzger, MD, Ballad Health; Principal Investigator: Piotr Musialek, MD DPhil, John Paul II Hospital, Krakow, Poland

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2021
• Primary Completion (Anticipated): July 1, 2022
• Study Completion (Anticipated): October 1, 2025

Study Registration Dates

• First Submitted: May 20, 2021
• First Submitted That Met QC Criteria: May 20, 2021
• First Posted (Actual): May 25, 2021

Study Record Updates

• Last Update Posted (Actual): June 21, 2022
• Last Update Submitted That Met QC Criteria: June 16, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Carotid Stenosis; Prospective study; Cerebrovascular Disorders; Stenting; Carotid Artery Diseases; Embolic Protection Device (EPD); Constriction, Pathologic
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arterial Occlusive Diseases; Pathological Conditions, Anatomical; Carotid Artery Diseases; Carotid Stenosis; Constriction, Pathologic
• Other Study ID Numbers: PRO-9017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes