Protected Carotid Artery Stenting in Subjects at High Risk for Carotid Endarterectomy (CEA) (PROTECT)

• Sponsor: Abbott Medical Devices (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00402740
• Collaborator: (none)
• Enrollment: 322
• Locations: 38
• Duration (Months): 59
• Patients Per Site: 8.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the long-term safety and efficacy of the Xact™ Rapid Exchange Carotid Stent System used in conjunction with the Emboshield® Pro Rapid Exchange Embolic Protection System (Generation 5) and the Emboshield® BareWire™ Rapid Exchange Embolic Protection System (Generation 3), in the treatment of atherosclerotic carotid artery disease in high-surgical risk subjects.

Condition or Disease	Intervention/Treatment	Phase
Carotid Artery Disease	Device: Xact Stent with either Emboshield Pro (Gen 5) or Emboshield (Gen 3)	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 322 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Protected Carotid Artery Stenting in Subjects at High Risk for Carotid Endarterectomy (CEA)
• Study Start Date: Nov 1, 2006
• Actual Primary Completion Date: Jun 1, 2011
• Actual Study Completion Date: Oct 1, 2011

Outcome Measures

Primary Outcome Measures

1. Kaplan-Meier Estimate of Freedom From the Composite of Any Death, Stroke and MI During the 30 Day Post Procedural Period (DSMI), Plus Fatal and Non-fatal Ipsilateral Stroke From 31-365 Days and Annually Thereafter for a Total of 3 Years. [3 years]

   Freedom from DSMI to 30 days or ipsilateral stroke from 31 days to 3 years. KM event free (%) curve.

Secondary Outcome Measures

1. Acute Device Success [Post-procedure]

   Defined by the attainment of <50% residual stenosis covering an area no longer than the original lesion treated with the stent.

2. Procedural Success [30 Days]

   Defined as the attainment of less than 50% residual stenosis (per angiographic core lab) of the target lesion and the absence of DSMI at 30 days post-index procedure.

3. Composite of Any Transient Ischemic Attack (TIA) and Amaurosis Fugax [≤30 days]

   Includes only each subject's first occurrence of each event.

4. Kapan-Meier Estimate of Freedom From Clinically Driven Target Lesion Revascularization Through Three Years. [3 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria Subject must be ≥ 18 years of age.

Subject has the ability to cooperate with study procedures and agrees to return for all required follow-up visits, tests and exams.

Female subjects of childbearing potential must have a documented negative pregnancy test within 30 days prior to the index procedure.

Subjects taking warfarin may be included if their dosage is reduced before the index procedure to result in an INR of 1.5 or less. Warfarin may be restarted to therapeutic dose after the index procedure.

The subject must sign a written informed consent prior to the initiation of any study procedures, using a form that is approved by the Institutional Review Board (IRB) or Medical Ethics Committee (EC).

The life expectancy of the subject is at least two years.

The subject has a lesion located in the internal carotid artery (ICA); the carotid bifurcation may be involved.

The target lesion is intended to be treated with a single stent.

Target ICA vessel diameter must be visually estimated to be:

• ≥2.5 mm and ≤7.0 for the Emboshield Pro (Gen 5)

• ≥ 2.8 mm and ≤6.2 for the Emboshield (Gen 3)

And

• ≥4.0 mm and ≤9.0 mm for the Xact Stent treatment area.

The subject has a carotid artery stenosis determined by ultrasound or angiography (visual estimate) to be:

• ≥50% for symptomatic subjects

Or

• ≥80% for asymptomatic subjects

High-risk inclusion criteria for either anatomical or co-morbid risk factors are present. The subject must fulfill at least one of the criteria, Category I or II risk factors, listed below to meet the inclusion criteria.

Category I Anatomic Risk Factors

• Previous radiation treatment to the neck or radical neck dissection

• Target lesion is at or above the second vertebral body C2 (level of jaw)

• Inability to extend the head due to cervical arthritis or other cervical disorders

• Tracheostomy or tracheal stoma

• Laryngectomy

• Contralateral laryngeal nerve palsy

• Severe tandem lesions

Category II Co-morbid Risk Factors

• Previous CEA with significant restenosis (as defined for symptomatic or asymptomatic subjects)

• Total occlusion of the contralateral carotid artery

• Left ventricular ejection fraction < 35%

• Congestive Heart failure New York Heart Association (NYHA) Functional Class III or higher

• Dialysis dependent renal failure

• Canadian Cardiovascular Society Angina Classification III or higher or unstable angina

• Requires coronary artery bypass surgery, cardiac valve surgery, peripheral vascular surgery, or abdominal aortic aneurysm repair within 60 days

•≥80 years of age

• Myocardial infarction within previous 6 weeks

• Abnormal stress test. Treadmill, thallium or dobutamine echo are acceptable. The stress tests should be sufficiently abnormal to place the subject at increased risk for CEA. This includes subjects with two or more proximal diseased coronary arteries of >70% stenosis that have not or cannot be revascularized or <30 days since revascularization.

• Severe pulmonary disease, including at least one of the following: requires chronic O2 therapy; resting PO2 ≤60 mm Hg, Hematocrit ≥50%, FEV₁ or DLCO ≤50% of normal.

Exclusion Criteria

• The subject is participating in another investigational trial that would interfere with the conduct or result of this study.

• The subject has dementia or a neurological illness that may confound the neurological evaluation.

• Total occlusion of the target vessel.

• There is an existing, previously placed stent in the target artery.

• The subject has a known life-threatening allergy to the contrast media that cannot be treated.

• 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 or aspirin and Ticlopidine.

• The subject has a GI bleed that would interfere with antiplatelet therapy.

• The subject has known cardiac sources of emboli, including but not limited to current or past history of paroxysmal or sustained atrial fibrillation (treated or untreated), valve replacement, etc.

• Subject has Hemoglobin (Hgb) less than 8 gm/dL (unless on dialysis), platelet count <50,000/mm3, or known heparin associated thrombocytopenia.

• The subject has a history of bleeding diathesis or coagulopathy including thrombocytopenia or an inability to receive heparin or Bivalirudin (Angiomax™) in amounts sufficient to maintain an ACT of >250, or will refuse blood transfusion.

• The subject has atherosclerotic disease involving adjoining vessels that precludes safe placement of the guiding catheter or sheath.

• The subject has other abnormal angiographic findings that indicate the subject is at risk for a stroke due to a problem other than that of the target lesion, such as: ipsilateral arterial stenosis greater in severity than the target lesion, cerebral aneurysm, or arteriovenous malformation of the cerebral vasculature.

• There is evidence of a carotid artery dissection prior to the initiation of the index procedure.

• There is an angiographically visible thrombus.

• There is any condition that precludes proper angiographic assessment, placement of the cerebral protective system or makes percutaneous arterial access unsafe, e.g. morbid obesity, sustained systolic blood pressure >180 mm Hg, tortuosity, occlusive disease, vessel anatomy, or aortic arch anatomy.

• Occlusion (TIMI 0 flow), or string sign of the ipsilateral common or internal carotid artery.

• There is evidence of bilateral carotid stenosis that would require intervention within 30 days of the index procedure.

• There is evidence of a stroke within the previous 30 days of the index procedure.

• There is a planned treatment of a non-target lesion within 30 days post-index procedure.

• There is a history of intracranial hemorrhage within the previous 3 months, including hemorrhagic transformation of an ischemic stroke.

• There is a history of an ipsilateral stroke with fluctuating neurologic symptoms within one year of the index procedure.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington Hospital	Fremont	California	United States	94538
2	El Camino Hospital	Mountain View	California	United States	94040
3	Hoag Memorial Hospital Presbyterian	Newport Beach	California	United States	92663
4	Stanford University Medical Center	Stanford	California	United States	94305
5	University of Connecticut Health Center	Farmington	Connecticut	United States	06030
6	Memorial Hospital Jacksonville	Jacksonville	Florida	United States	32216
7	Lakeland Regional Medical Center	Lakeland	Florida	United States	33805
8	Munroe Regional Medical Center	Ocala	Florida	United States	34475
9	Hawaii Permanente Medical Group-Kaiser Foundation Hospital	Honolulu	Hawaii	United States	96819
10	Northwestern University Memorial Hospital	Chicago	Illinois	United States	60611
11	St. John's Hospital / Memorial Medical Center	Springfield	Illinois	United States	62701
12	Parkview Hospital	Fort Wayne	Indiana	United States	46805
13	St. Vincent Hospital and Health Care Center	Indianapolis	Indiana	United States	46260
14	Terrebonne General Medical Center	Houma	Louisiana	United States	70360
15	Washington Adventist Hospital	Takoma Park	Maryland	United States	20912
16	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
17	St. Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106
18	McLaren Regional Medical Center	Flint	Michigan	United States	48532
19	Genesys Regional Medical Center	Grand Blanc	Michigan	United States	48439
20	William Beaumont Hospital	Royal Oak	Michigan	United States	48073
21	Our Lady of Lourdes Medical Center	Camden	New Jersey	United States	08103
22	St. Michael's Medical Center	Newark	New Jersey	United States	07102
23	Millard Fillmore Hospital-Kaleida Health Systems	Buffalo	New York	United States	14209
24	Lenox Hill Hospital	New York	New York	United States	10021
25	WakeMed Hospital	Raleigh	North Carolina	United States	27610
26	Oregon Health & Science University	Portland	Oregon	United States	97239
27	Lehigh Valley Hospital	Allentown	Pennsylvania	United States	18105
28	Pinnacle Health Hospital	Harrisburg	Pennsylvania	United States	17110
29	St. Joseph's Medical center	Wyomissing	Pennsylvania	United States	19610
30	Greenville Memorial Medical Center	Greenville	South Carolina	United States	29605
31	Holston Valley Medical Center	Kingsport	Tennessee	United States	37660
32	Mercy Medical Center West / Baptist Hospital of East Tennessee	Knoxville	Tennessee	United States	37934
33	Austin Heart P.A.	Austin	Texas	United States	78756
34	Presbyterian Heart Institute	Dallas	Texas	United States	75231
35	St. Luke's Episcopal Hospital	Houston	Texas	United States	77030
36	Chesapeake General Hospital	Norfolk	Virginia	United States	23507
37	Bon Secours St. Mary's Hospital	Richmond	Virginia	United States	23226
38	St. Luke's Medical Center	Milwaukee	Wisconsin	United States	53215

Sponsors and Collaborators

• Abbott Medical Devices

Investigators

• Study Chair: Seemant Chaturvedi, MD, Wayne State University Stroke Program
• Study Chair: William A Gray, MD, Columbia University
• Study Chair: Jon Matsumura, MD, University of Wisconsin, Madison

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Results of carotid artery stenting with distal embolic protection with improved systems: Protected Carotid Artery Stenting in Patients at High Risk for Carotid Endarterectomy (PROTECT) trial.

Publications

None provided.

• Responsible Party: Abbott Medical Devices
• ClinicalTrials.gov Identifier: NCT00402740
• Other Study ID Numbers: 640-0071
• First Posted: Nov 22, 2006
• Last Update Posted: Jun 20, 2012
• Last Verified: May 1, 2012

• Keywords provided by Abbott Medical Devices: Carotid; Artery; Disease; Stent; PROTECT; XACT; EMBOSHIELD
• Additional relevant MeSH terms: Carotid Artery Diseases

Study Results

Participant Flow

Recruitment Details	A total of 322 subjects were enrolled in the PROTECT study at 38 clinical sites in the United States. The first subject was enrolled on November 29, 2006, and enrollment was completed on June 18, 2008.

Arm/Group Title	Group 1
Arm/Group Description
Period Title: Overall Study
STARTED	322
COMPLETED	242
NOT COMPLETED	80

Baseline Characteristics

Arm/Group Title	Group 1
Arm/Group Description
Overall Participants	322
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	71 22%
>=65 years	251 78%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	72.7 (9.8)
Sex: Female, Male (Count of Participants)
Female	115 35.7%
Male	207 64.3%
Region of Enrollment (participants) [Number]
United States	322 100%

Outcome Measures

1. Primary Outcome

Title	Kaplan-Meier Estimate of Freedom From the Composite of Any Death, Stroke and MI During the 30 Day Post Procedural Period (DSMI), Plus Fatal and Non-fatal Ipsilateral Stroke From 31-365 Days and Annually Thereafter for a Total of 3 Years.
Description	Freedom from DSMI to 30 days or ipsilateral stroke from 31 days to 3 years. KM event free (%) curve.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT)

Arm/Group Title	Group 1
Arm/Group Description	Includes only the most serious event for each subject and includes only each subject's first occurrence of the event.
Measure Participants	322
Number [Event-free percentage]	95.5

2. Secondary Outcome

Title	Acute Device Success
Description	Defined by the attainment of <50% residual stenosis covering an area no longer than the original lesion treated with the stent.
Time Frame	Post-procedure

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Xact Stent	Emboshield Pro Gen 5	Emboshield Gen 3
Arm/Group Description	The Xact stent success were counted per subject	Participants receiving Emboshield Pro Gen 5. Emboshield Pro success were counted per filter.	Participants receiving Emboshield Gen 3 Emboshield Gen3 success were counted per filter.
Measure Participants	317	222	101
Number (95% Confidence Interval) [percentage of participants]	98.7 30.7%	97.3 NaN	97.0 NaN

3. Secondary Outcome

Title	Procedural Success
Description	Defined as the attainment of less than 50% residual stenosis (per angiographic core lab) of the target lesion and the absence of DSMI at 30 days post-index procedure.
Time Frame	30 Days

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Group 1
Arm/Group Description
Measure Participants	322
Number (95% Confidence Interval) [percentage of participants]	95.30 29.6%

4. Secondary Outcome

Title	Composite of Any Transient Ischemic Attack (TIA) and Amaurosis Fugax
Description	Includes only each subject's first occurrence of each event.
Time Frame	≤30 days

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Group 1
Arm/Group Description
Measure Participants	322
Number (95% Confidence Interval) [percentage of participants]	2.8 0.9%

5. Secondary Outcome

Title	Kapan-Meier Estimate of Freedom From Clinically Driven Target Lesion Revascularization Through Three Years.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Group 1
Arm/Group Description
Measure Participants	317
Number [Event-free percentage]	98.2

Adverse Events

Time Frame	Three years post-procedure
Adverse Event Reporting Description	Organ systems designations were chosen to match Abbott Categories coding as closely as possible and may differ from other coding systems.
Arm/Group Title	Group 1
Arm/Group Description
All Cause Mortality
	Group 1
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Group 1
	Affected / at Risk (%)	# Events
Total	221/313 (70.6%)
Blood and lymphatic system disorders
Anemia	27/313 (8.6%)	27
Leukopenia	1/313 (0.3%)	1
Anemia	8/313 (2.6%)	8
Cardiac disorders
Abnormal lab test	1/313 (0.3%)	1
Angina	10/313 (3.2%)	15
Arrhythmia	30/313 (9.6%)	46
Cardiac arrest	11/313 (3.5%)	11
Congestive heart failure	30/313 (9.6%)	41
Coronary artery diseasee	39/313 (12.5%)	51
Hypertensive cardiovascular disease	1/313 (0.3%)	1
Myocardial infarctionsee	13/313 (4.2%)	13
Structural heart disease	14/313 (4.5%)	15
Hypotension	6/313 (1.9%)	6
Myocardial infarction Non Q wave	2/313 (0.6%)	2
Arrhythmia	8/313 (2.6%)	8
Cardiac arrest	1/313 (0.3%)	1
Gastrointestinal disorders
Gastrointestinal	14/313 (4.5%)	15
Gastrointestinal	32/313 (10.2%)	50
General disorders
Presyncope /syncope	3/313 (1%)	3
Syncope	6/313 (1.9%)	8
Urinary retention	1/313 (0.3%)	1
Allergic reaction	1/313 (0.3%)	1
Miscellaneous	5/313 (1.6%)	5
Infections and infestations
Infection	26/313 (8.3%)	33
Injury, poisoning and procedural complications
Hematoma	2/313 (0.6%)	2
Occlusion	2/313 (0.6%)	2
Other	3/313 (1%)	3
Dissection	1/313 (0.3%)	1
Fluid overload	1/313 (0.3%)	1
Hypertension	1/313 (0.3%)	1
Hypotension	26/313 (8.3%)	26
Pain	1/313 (0.3%)	1
Dissection	1/313 (0.3%)	2
Instent restenosis	7/313 (2.2%)	9
Metabolism and nutrition disorders
Metabolic	14/313 (4.5%)	18
Musculoskeletal and connective tissue disorders
Musculoskeletal	29/313 (9.3%)	33
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer	26/313 (8.3%)	32
Nervous system disorders
Amaurosis fugax	1/313 (0.3%)	1
Confusion	2/313 (0.6%)	2
Hyperperfusion syndrome	1/313 (0.3%)	1
Neurologic other	21/313 (6.7%)	26
Seizure	3/313 (1%)	4
Transient Ischemic Attack	11/313 (3.5%)	12
Visual disturbance	2/313 (0.6%)	4
Ipsilateral major	3/313 (1%)	3
Ipsilateral minor	8/313 (2.6%)	8
Psychiatric disorders
Mental health related	1/313 (0.3%)	1
Trauma	5/313 (1.6%)	6
Renal and urinary disorders
Hypertension	9/313 (2.9%)	9
Genitourinarynal	26/313 (8.3%)	34
Respiratory, thoracic and mediastinal disorders
Respiratory	55/313 (17.6%)	91
Skin and subcutaneous tissue disorders
Subdural hematoma	1/313 (0.3%)	1
Surgical and medical procedures
Epistaxis	5/313 (1.6%)	5
Hematuria	3/313 (1%)	3
Oropharyngeal	1/313 (0.3%)	1
Vascular disorders
Aneurysm	3/313 (1%)	3
Deep vein thrombosis	4/313 (1.3%)	4
Peripheral vascular disease	23/313 (7.3%)	30
Pseudoaneurysm	1/313 (0.3%)	1
Restenosis	1/313 (0.3%)	1
Stenosis	11/313 (3.5%)	12
Thrombosis	2/313 (0.6%)	2
Non-ipsilateral major	5/313 (1.6%)	5
Non-ipsilateral minor	4/313 (1.3%)	5
Other (Not Including Serious) Adverse Events
	Group 1
	Affected / at Risk (%)	# Events
Total	236/313 (75.4%)
Blood and lymphatic system disorders
Anemia	20/313 (6.4%)	23
Cardiac disorders
Arrhythmia	25/313 (8%)	27
Arrhythmia	22/313 (7%)	24
Hypotension	43/313 (13.7%)	45
Gastrointestinal disorders
Other: Gastrointestinal	48/313 (15.3%)	98
General disorders
Headache	17/313 (5.4%)	18
Nausea/vomiting	17/313 (5.4%)	17
Other: Genitourinary	43/313 (13.7%)	63
Other: Metabolic	28/313 (8.9%)	36
Other: Miscellaneous	63/313 (20.1%)	118
Other: Trauma	16/313 (5.1%)	17
Infections and infestations
Other: Infection	31/313 (9.9%)	52
Injury, poisoning and procedural complications
Pain	30/313 (9.6%)	36
Musculoskeletal and connective tissue disorders
Other: Musculoskeletal	67/313 (21.4%)	122
Nervous system disorders
Neurologic other	37/313 (11.8%)	51
Respiratory, thoracic and mediastinal disorders
Other: Respiratory	55/313 (17.6%)	80
Vascular disorders
Peripheral vascular disease	28/313 (8.9%)	34

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Principal Investigator (PI), Institute, and Research Site (RS) acknowledge this is a multi-center study. An independent, joint publication is anticipated from investigators in the study, including the PI. Therefore, the PI, Institute, and RS agree not to publish or present the results before the publication of the multi-center investigator paper, but in no event shall PI, Institute, and/or RS be so restricted after the expiration of twelve months from completion of the Study at all sites.