Clinical trial NCT00106938: Carotid Angioplasty and Stenting Versus Endarterectomy in Asymptomatic Subjects Who Are at Standard Risk for Carotid Endarterectomy With Significant Extracranial Carotid Stenotic Disease (ACT I)
Official title: Carotid Angioplasty and Stenting Versus Endarterectomy in Asymptomatic Subjects Who Are at Standard Risk for Carotid Endarterectomy With Significant Extracranial Carotid Stenotic Disease (ACT I)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Carotid Artery Disease
Carotid Stenosis
Stroke
Atherosclerosis
Keywords: Carotid stenting
Carotid endarterectomy
Carotid artery disease with severe narrowing of the artery
Stroke prevention
Lead sponsor: Abbott Medical Devices
Sponsor class: INDUSTRY
First posted: 2005-04-04
Enrollment: 1663
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The study is being conducted to demonstrate the non-inferiority of carotid artery stenting (CAS) using the Emboshield® Embolic Protection System with the Xact® Carotid Stent System to carotid endarterectomy (CEA) for the treatment of asymptomatic extracranial carotid atherosclerotic disease.

Detailed description: Randomization for ACT 1 employs a 3:1 ratio of CAS versus CEA. A lead-in phase of up to 400 carotid stent subjects will provide investigators experience with the study devices prior to pivotal enrollment.

Eligibility criteria: Inclusion Criteria:

1. The subject must be \> 18 and \< 80 years of age.
2. Female subjects of child bearing potential must have a documented negative pregnancy test within 30 days prior to the study procedure.
3. Subject must be asymptomatic, defined as no stroke or Transient Ischemic Attack \[(TIA);(hemispheric or ocular)\] within the 180 days prior to the procedure. Subjects who have experienced these neurological symptoms prior to the 180 day pre-procedure window will be eligible for enrollment. An independent study neurologist or independent study neurosurgeon must confirm the subject's neurological status.
4. Subjects taking warfarin may be included if their dosage is reduced before the procedure to result in an International Normalized Ratio (INR) of 1.5 or less. Warfarin may be restarted after the procedure.
5. The subject must sign a written informed consent prior to the procedure, using a form that is approved by the local institutional review board (IRB).
6. The subject must agree to return for all required follow-up visits.
7. Subject has a discrete lesion located in the internal carotid artery (ICA); the contiguous common carotid artery (CCA) may be involved.
8. Carotid stenosis ≥ 70% and ≤ 99% by carotid ultrasound or ≥ 70% and ≤ 99% stenosis (visual estimate) by angiography, without significant (\> 60% by ultrasound or angiography) ICA/CCA contralateral stenosis.
9. Target ICA vessel diameter must be visually estimated to be:

   \> 2.5 mm and \< 7.0 for the Emboshield Pro or for the Emboshield NAV6, \> 2.8 mm and \< 6.2 for the Emboshield Gen 3 And \> 4.0 mm and \< 9.0 mm for the Xact stent treatment segment. An untreated contralateral ICA may be used for visual estimation when a highly stenosed lesion makes measurement of the target vessel inaccurate.
10. Based on the subject's anatomy, the Investigator should expect to successfully deliver the stent to the target lesion (absence of extreme tortuosity, etc.).
11. De novo target lesion that can be treated with a single stent.

Exclusion Criteria:

Each potential subject must be screened to ensure that they do not meet any of the following exclusion criteria. This screening is to be based on known medical history and data available at the time of eligibility determination and enrollment.

1. Subject is symptomatic and has had a stroke or exhibited TIA (hemispheric or ocular) within 180 days prior to randomization, which has been confirmed by an independent study neurologist or independent study neurosurgeon.
2. Subject is participating in another drug or device trial (IND or IDE) that has not completed the primary endpoint or that may potentially confound the results of this trial. Subject may be enrolled only once in this trial and may not participate in any other clinical trial during a 1-year period post-index procedure.
3. Subject has inability to understand and cooperate with study procedures or provide informed consent.
4. Subject has had an intracranial hemorrhage or hemorrhagic stroke within 1-year prior the index procedure.
5. Subject has dementia or has a neurological illness that may confound the neurological evaluation.
6. Subject has had a known untoward reaction to anesthesia or contrast media not able to be overcome by pre-treatment with medications.
7. Subject has history of intolerance or allergic reaction to any of the study medications including aspirin, Clopidogrel bisulfate (Plavix®) or Ticlopidine (Ticlid®), heparin or Bivalirudin (Angiomax™). Subjects must be able to tolerate a combination of aspirin and Clopidogrel/Ticlopidine.
8. Subject has Hemoglobin (Hgb) less than 10 gm/dL, platelet count \<100,000/mm3 or \>500,000/mm3, or known heparin associated thrombocytopenia.
9. Subject has an active bleeding diathesis or coagulopathy, or will refuse blood transfusions.
10. Subject has had a GI bleed that would interfere with antiplatelet therapy.
11. Subject has known cardiac sources of emboli, including paroxysmal or sustained atrial fibrillation (treated or untreated).
12. Subject has had an myocardial infarction (MI) within the previous 30 days.
13. Subject has any condition that limits their anticipated survival to less than 3 years.
14. Subject is a high risk surgical candidate defined as the presence of any one or more of a following medical conditions:

    1. Two or more proximal diseased coronary arteries of \> 70% stenosis that have not or cannot be revascularized or \< 30 days since revascularization.
    2. Ejection fraction \< 30% or New York Heart Association (NYHA) heart failure functional class 3 or higher.
    3. Unstable angina, defined as angina at rest with ECG changes.
    4. On a list for major organ transplant or is being evaluated for such.
    5. Known history of respiratory insufficiency, forced expiratory volume (FEV1) \< 30% (predicted).
    6. Chronic renal insufficiency (serum creatinine \>2.5 mg/dL).
    7. Uncontrolled diabetes defined as fasting glucose \> 400 mg/dL.
    8. Concurrent requirement for any invasive procedure 30 days pre- or post-procedure.
    9. Age ≥ 80 years.
15. Subject may be considered a non-surgical candidate for CEA as a result of one or more anatomic conditions or features which preclude normal surgical access or a high surgical risk because of the presence of any one or more anatomic conditions that present an increased potential for adverse events. These subjects are not eligible for enrollment.

    1. Subject has had radiation treatment to the neck.
    2. Subject has had a radical neck dissection.
    3. Surgically inaccessible lesions (i.e., lesions extending above the level of C2).
    4. Spinal immobility - inability to flex neck beyond neutral or kyphotic deformity.
    5. Presence of carotid artery dissection, aneurysm, pseudoaneurysm, arteritis or fibromuscular dysplasia (FMD) in the target vessel.
    6. Hemodynamically significant (\>60%) stenosis of the right or left common carotid artery (LCCA/RCCA) below the clavicle.
    7. Presence of tracheostomy stoma.
    8. Contralateral laryngeal nerve paralysis.
    9. Previous carotid endarterectomy, extracranial-intracranial or carotid subclavian bypass procedure ipsilateral to the carotid stenosis.
    10. Severe hypertension (defined as blood pressure \> Systolic of 180 mm Hg and/or a diastolic of 110 mm Hg) not adequately controlled by anti-hypertensive therapy at the time of study entry.
16. Severe vascular disease including tortuosity and/or occlusive disease that would preclude the safe introduction of a guiding catheter/sheath, cerebral protection device, balloon catheter, stent delivery system or stent placement. Severe tortuosity is defined as 2 or more \>90 degree bend points within 3cm of the target stenosis. One of these bends will be considered to be present if the ICA branches from the CCA at a 90 degree angle. This includes aortic arch anatomy that is unacceptable for carotid stent placement.
17. Intraluminal filling defect thought to represent thrombus.
18. Excessive calcification: defined as fluoroscopic evidence of calcium that extends circumferentially around the target lesion and includes the majority of the atherosclerotic plaque.
19. Occlusion (TIMI 0 flow), or string sign of the ipsilateral common or internal carotid artery.
20. The target lesion requires treatment with a device other than percutaneous transluminal angioplasty (PTA) prior to stent placement.
21. Significant (\> 60%) stenosis proximal or distal to the target lesion that might require revascularization or impede run off.
22. Presence of a previously placed intravascular stent in the ipsilateral carotid distribution.
23. Cerebral aneurysm (symptomatic or \> 10 mm) or arteriovenous malformation (AVM) of the cerebral vasculature.
24. Bilateral carotid stenosis (ICA/CCA contralateral stenosis \> 60% by ultrasound or angiography).

Primary outcomes:
measure: Composite of Death, Stroke (Ipsilateral or Contralateral; Major or Minor) and Myocardial Infarction (DSMI) Through 30 Days Post-procedure, Plus Ipsilateral Stroke 31 to 365 Days.
timeFrame: 0 to 365 days
Secondary outcomes:
measure: Acute Device Success: Xact Carotid Stent
timeFrame: On day 0 after index procedure
measure: Acute Device Success: Embolic Protection Device System
timeFrame: On day 0 after index procedure
measure: Procedural Success
timeFrame: 0 to 30 days post procedure
measure: Composite Morbidity Measure
timeFrame: 0 to 30 Days Post-procedure
measure: Freedom From Clinically Indicated Target Lesion Revascularization(CI-TLR)
timeFrame: 0 to 180 days
measure: Freedom From Clinically Indicated Target Lesion Revascularization
timeFrame: 0 to 365 days
measure: Freedom From Clinically Indicated Target Lesion Revascularization
timeFrame: 0 to 730 days
measure: Freedom From Clinically Indicated Target Lesion Revascularization
timeFrame: 0 to 1095 days
measure: Freedom From Clinically Indicated Target Lesion Revascularization
timeFrame: 0 to 1460 days
measure: Freedom From Clinically Indicated Target Lesion Revascularization
timeFrame: 0 to 1825 days
measure: Freedom From Ipsilateral Stroke
timeFrame: 31 to 365 days
measure: Freedom From Ipsilateral Stroke
timeFrame: 31 to 730 days
measure: Freedom From Ipsilateral Stroke
timeFrame: 31 to 1095 days
measure: Freedom From Ipsilateral Stroke
timeFrame: 31 to 1460 days
measure: Freedom From Ipsilateral Stroke
timeFrame: 31 to 1825 days
measure: Freedom From Mortality
timeFrame: 0 to 365 days
measure: Freedom From Mortality
timeFrame: 0 to 730 days
measure: Freedom From Mortality
timeFrame: 0 to 1095 days
measure: Freedom From Mortality
timeFrame: 0 to 1460 days
measure: Freedom From Mortality
timeFrame: 0 to 1825 days
measure: Freedom From All Stroke
timeFrame: 0 to 365 days
measure: Freedom From All Stroke
timeFrame: 0 to 730 days
measure: Freedom From All Stroke
timeFrame: 0 to 1095 days
measure: Freedom From All Stroke
timeFrame: 0 to 1460 days
measure: Freedom From All Stroke
timeFrame: 0 to 1825 days
measure: Death (Non-Hierarchical)
timeFrame: ≤ 30 Days Post Index Procedure
measure: All Stroke (Non-Hierarchical)
timeFrame: ≤ 30 Days Post Index Procedure
measure: Myocardial Infarction (MI) (Non-Hierarchical)
timeFrame: ≤ 30 Days Post Index Procedure
measure: Death, Stroke or Myocardial Infarction (MI) (Hierarchical)
timeFrame: ≤ 30 Days Post Index Procedure
measure: Death or Stroke (Hierarchical)
timeFrame: ≤ 30 Days Post Index Procedure
measure: Death or Major Stroke (Hierarchical)
timeFrame: ≤ 30 Days Post Index Procedure
measure: Freedom From Death, Stroke and MI Within 30 Days and Ipsilateral Stroke From 31 Days to 5 Years
timeFrame: 0 to 5 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: St. Luke's Hospital-Phoenix
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: Mountain View
country: United States
facility: Fogarty Clinical Research Inc./El Camino Hospital
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital
state: California
city: Orange
country: United States
facility: St. Joseph Hospital
state: California
city: San Diego
country: United States
facility: Kaiser Foundation Hospital-San Diego
state: California
city: Washington, D.C.
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Miami
country: United States
facility: Baptist Cardiac and Vascular Institute
state: Florida
city: Atlanta
country: United States
facility: Piedmont Hospital
state: Georgia
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center
state: Georgia
city: Honolulu
country: United States
facility: Hawaii Permanente Medical Group - Kaiser
state: Hawaii
city: Chicago
country: United States
facility: Northwestern University Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Springfield
country: United States
facility: St. John's Hospital and Memorial Medical Center/ Prairie Heart Cooperative
state: Illinois
city: Fort Wayne
country: United States
facility: Parkview Hospital
state: Indiana
city: Lexington
country: United States
facility: Central Baptist Hospital
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Lafayette
country: United States
facility: Cardiovascular Institute of the South
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Bayview Medical Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Harper University Hospital/Detroit Medical Center
state: Michigan
city: Flint
country: United States
facility: McLaren Regional Medical Center
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Saint Louis
country: United States
facility: St. John's Mercy Medical Center
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Camden
country: United States
facility: Our Lady of Lourdes Medical Center
state: New Jersey
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: Buffalo
country: United States
facility: Millard Fillmore Hospital
state: New York
city: New York
country: United States
facility: NYU Medical Center
state: New York
city: New York
country: United States
facility: Columbia Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Lenox Hill Hospital
state: New York
city: Rochester
country: United States
facility: University of Rochester-Strong Memorial Hospital
state: New York
city: Roslyn
country: United States
facility: St. Francis Hospital
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Raleigh
country: United States
facility: WakeMed Health and Hospital
state: North Carolina
city: Winston-Salem
country: United States
facility: Forsyth Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Riverside Methodist Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University Stroke Center
state: Oregon
city: Beaver
country: United States
facility: Heritage Valley Health System
state: Pennsylvania
city: Harrisburg
country: United States
facility: Harrisburg Hospital / Pinnacle Health
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center (UPMC)
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Physicians Division of Vascular Surgery/Shadyside Medical
state: Pennsylvania
city: Washington
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Wyomissing
country: United States
facility: St. Joseph's Medical Center/Berks Cardiologists
state: Pennsylvania
city: Columbia
country: United States
facility: Providence Hospital-SC
state: South Carolina
city: Sioux Falls
country: United States
facility: North Central Heart Institute
state: South Dakota
city: Germantown
country: United States
facility: The Stern Cardiovascular Center/Methodist Germantown Hospital
state: Tennessee
city: Kingsport
country: United States
facility: Wellmont Holston Valley Medical Center
state: Tennessee
city: Knoxville
country: United States
facility: Mercy Medical West/Turkey Creek Medical Center
state: Tennessee
city: Austin
country: United States
facility: Westlake Medical Center/Seton Heart Institute
state: Texas
city: Austin
country: United States
facility: Heart Hospital of Austin
state: Texas
city: Dallas
country: United States
facility: Dallas Veteran's Administration Medical Center
state: Texas
city: Dallas
country: United States
facility: Presbyterian Hospital of Dallas
state: Texas
city: Houston
country: United States
facility: St. Luke's Episcopal Hospital
state: Texas
city: Norfolk
country: United States
facility: Chesapeake General Hospital/Sentara Norfolk General Hospital
state: Virginia
city: Richmond
country: United States
facility: St. Mary's Hospital / Virginia Cardiovascular Specilists
state: Virginia
city: Spokane
country: United States
facility: Deaconess Medical Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: St. Luke's Medical Center - Milwaukee
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Jon Matsumura, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Massachusetts General Hospital
name: Kenneth Rosenfield, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Weinberg I, Beckman JA, Matsumura JS, Rosenfield K, Ansel GM, Chaturvedi S, Gray W, Metzger DC, Riles T, Shu Y, Wechsler L, Jaff MR. Carotid Stent Fractures Are Not Associated With Adverse Events: Results From the ACT-1 Multicenter Randomized Trial (Carotid Angioplasty and Stenting Versus Endarterectomy in Asymptomatic Subjects Who Are at Standard Risk for Carotid Endarterectomy With Significant Extracranial Carotid Stenotic Disease). Circulation. 2018 Jan 2;137(1):49-56. doi: 10.1161/CIRCULATIONAHA.117.030030. Epub 2017 Oct 5.
citation: Rosenfield K, Matsumura JS, Chaturvedi S, Riles T, Ansel GM, Metzger DC, Wechsler L, Jaff MR, Gray W; ACT I Investigators. Randomized Trial of Stent versus Surgery for Asymptomatic Carotid Stenosis. N Engl J Med. 2016 Mar 17;374(11):1011-20. doi: 10.1056/NEJMoa1515706. Epub 2016 Feb 17.