SAMMPRIS: Stenting vs. Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis

• Sponsor: Medical University of South Carolina (Other)
• Overall Status: Completed
• CT.gov ID: NCT00576693
• Collaborator: National Institutes of Health (NIH) (NIH), National Institute of Neurological Disorders and Stroke (NINDS) (NIH)
• Enrollment: 451
• Locations: 50
• Arms: 2
• Duration (Months): 54
• Patients Per Site: 9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

PRIMARY HYPOTHESIS:

Compared with intensive medical therapy alone, intracranial angioplasty and stenting combined with intensive medical therapy will decrease the risk of the primary endpoint by 35% over a mean follow-up of two years in high-risk patients patients with 70% - 99% intracranial stenosis who had a transient ischemic attack (TIA) or stroke within 30 days prior to enrollment) with symptomatic stenosis of a major intracranial artery.

SUMMARY:

The best treatment for prevention of another stroke or TIA in patients with narrowing of one of the arteries in the brain is uncertain. A common treatment is the use of anti-clotting medications to prevent blood clots from forming in the narrowed vessel. There are a variety of medicines used for this purpose. These medications are usually taken for the rest of a patient's life.

However, a treatment that has been used successfully together with anti-clotting medications in patients with narrowing of the blood vessels of the heart is now being studied in the blood vessels of the brain. This treatment is called stenting.

Recent research has also indicated a benefit in prevention of recurring stroke by Intensive Medical Therapy, which is defined as treating risk factors for stroke like high blood pressure, elevated LDL (low density lipids - the "bad" form of cholesterol) and diabetes. The purpose of this study is to compare the safety and effectiveness of either Intensive Medical Therapy PLUS Stenting or Intensive Medical Therapy ONLY in preventing stroke, heart attacks or death.

The study will enroll patients over a 5 year period. Each participant will be involved in the study for a minimum of 1 year and a maximum of 3 years.

Fifty different medical centers in the United States are part of this study. Both the Clinical Coordinating Center and the Statistical Coordinating Center for the entire study will be located at Emory University.

Condition or Disease	Intervention/Treatment	Phase
Ischemic Stroke	Device: intracranial angioplasty and stenting; Other: intensive medical management	Phase 3

Detailed Description

This will be an investigator initiated and designed Phase III multicenter trial in which patients with TIA or non-disabling stroke within 30 days prior to enrollment that is caused by 70% - 99% stenosis of a major intracranial artery (MCA, carotid, vertebral, or basilar) will be randomized (1:1) at approximately 50 sites to:

intensive medical therapy alone (aspirin 325 mg / day for entire follow-up, clopidogrel 75mg per day for 90 days after enrollment unless cardiologist recommends continuing clopidogrel beyond 90 days for a cardiac indication, and aggressive risk factor management primarily targeting blood pressure < 140 / 90 mm Hg (< 130 / 80 if diabetic) and LDL < 70 mg / dl)

OR

intracranial angioplasty and stenting using the Gateway balloon and Wingspan self-expanding nitinol stent (or any future FDA approved iterations of the balloon, stent, or the delivery systems) plus intensive medical therapy (aspirin 325 mg / day for entire follow-up, clopidogrel 75mg per day for 90 days after enrollment unless cardiologist recommends continuing clopidogrel beyond 90 days for a cardiac indication, and aggressive risk factor management primarily targeting blood pressure < 140 / 90 mm Hg (< 130 / 80 if diabetic) and LDL < 70 mg / dl).

Risk factor management will be performed by the study neurologist at each site who will be assisted by an innovative, evidence-based, educational, lifestyle modification program (INTERxVENT) that will be administered at regularly scheduled times to all patients throughout the study.

All patients enrolled in the trial will be followed until the first of the following: 90 days after a primary endpoint, death, or the close-out visit in the trial, which will occur within a window from 60 days before March 31, 2012 to 30 days after March 31, 2013. Patients who do not die or have a primary endpoint during follow-up will be followed for 2-4.5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 451 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Stenting vs. Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis
• Study Start Date: Oct 1, 2008
• Actual Primary Completion Date: Apr 1, 2013
• Actual Study Completion Date: Apr 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: intensive medical management plus stenting intracranial angioplasty and stenting using the Gateway balloon and Wingspan self-expanding nitinol stent (or any future FDA approved iterations of the balloon, stent, or the delivery systems) plus intensive medical therapy (aspirin 325 mg / day for entire follow-up, clopidogrel 75mg per day for 90 days after enrollment unless cardiologist recommends continuing clopidogrel beyond 90 days for a cardiac indication, and aggressive risk factor management primarily targeting blood pressure < 140 / 90 mm Hg (< 130 / 80 if diabetic) and LDL < 70 mg / dl).	Device: intracranial angioplasty and stenting; intracranial angioplasty and stenting using the Gateway balloon and Wingspan self-expanding nitinol stent (or any future FDA approved iterations of the balloon, stent, or the delivery systems) plus intensive medical therapy (aspirin 325 mg / day for entire follow-up, clopidogrel 75mg per day for 90 days after enrollment unless cardiologist recommends continuing clopidogrel beyond 90 days for a cardiac indication, and aggressive risk factor management primarily targeting blood pressure < 140 / 90 mm Hg (< 130 / 80 if diabetic) and LDL < 70 mg / dl).; Other Names: Wingspan stent Gateway balloon
Experimental: intensive medical management alone Intensive medical therapy alone (aspirin 325 mg / day for entire follow-up, clopidogrel 75mg per day for 90 days after enrollment unless cardiologist recommends continuing clopidogrel beyond 90 days for a cardiac indication, and aggressive risk factor management primarily targeting blood pressure < 140 / 90 mm Hg (< 130 / 80 if diabetic) and LDL < 70 mg / dl)	Other: intensive medical management; intensive medical therapy alone (aspirin 325 mg / day for entire follow-up, clopidogrel 75mg per day for 90 days after enrollment unless cardiologist recommends continuing clopidogrel beyond 90 days for a cardiac indication, and aggressive risk factor management primarily targeting blood pressure < 140 / 90 mm Hg (< 130 / 80 if diabetic) and LDL < 70 mg / dl)

Outcome Measures

Primary Outcome Measures

1. Any Stroke or Death Within 30 Days of Enrollment or Any Revascularization Procedure OR an Ischemic Stroke in the Territory of the Symptomatic Intracranial Artery Beyond 30 Days After Enrollment. [Mean length of follow-up was 2.4 years]

   Any stroke (ischemic, parenchymal brain hemorrhage, subarachnoid or intraventricular hemorrhage) or death within 30 days after enrollment OR any stroke (ischemic, parenchymal brain hemorrhage, subarachnoid or intraventricular hemorrhage) or death within 30 days of any revascularization procedure of the qualifying symptomatic intracranial artery done during follow-up, OR an ischemic stroke in the territory of the symptomatic intracranial artery from day 31 after study entry to completion of follow-up.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

INCLUSION CRITERIA

1. Transient ischemic attack (TIA) or non-severe stroke within 30 days of enrollment attributed to 70-99% stenosis of a major intracranial artery (carotid artery, MCA stem (M1), vertebral artery, or basilar artery)

• may be diagnosed byTranscranial Doppler (TCD), Magnetic Resonance Angiogram (MRA), or computed tomography angiography (CTA) to qualify for angiogram performed as part of the study protocol but must be confirmed by catheter angiography for enrollment in the trial

1. Modified Rankin score of ≤ 3

2. Target area of stenosis in an intracranial artery that has a normal diameter of 2.00 mm to 4.50 mm

3. Target area of stenosis is less than or equal to 14 mm in length

4. Age ≥ 30 years and ≤ 80 years.

• Patients 30-49 years are required to meet at least one additional criteria (i-vi) provided in the table below to qualify for the study. This additional requirement is to increase the likelihood that the symptomatic intracranial stenosis in patients 30-49 years is atherosclerotic.

1. insulin dependent diabetes for at least 15 years ii. at least 2 of the following atherosclerotic risk factors: hypertension (BP > 140/90 or on antihypertensive therapy); dyslipidemia (LDL > 130 mg /dl or HDL < 40 mg/dl or fasting triglycerides > 150 mg/dl or on lipid lowering therapy); smoking; non-insulin dependent diabetes or insulin dependent diabetes of less than 15 years duration; family history of any of the following: myocardial infarction, coronary artery bypass, coronary angioplasty or stenting, stroke, carotid endarterectomy or stenting, peripheral vascular surgery in parent or sibling who was < 55 years of age for men or < 65 for women at the time of the event ii. history of any of the following: myocardial infarction, coronary artery bypass, coronary angioplasty or stenting, carotid endarterectomy or stenting, or peripheral vascular surgery for atherosclerotic disease iv. any stenosis of an extracranial carotid or vertebral artery, another intracranial artery, subclavian artery, coronary artery, iliac or femoral artery, other lower or upper extremity artery, mesenteric artery, or renal artery that was documented by non-invasive vascular imaging or catheter angiography and is considered atherosclerotic v. aortic arch atheroma documented by non-invasive vascular imaging or catheter angiography vi. any aortic aneurysm documented by non-invasive vascular imaging or catheter angiography that is considered atherosclerotic

1. Negative pregnancy test in a female who has had any menses in the last 18 months

2. Patient is willing and able to return for all follow-up visits required by the protocol

3. Patient is available by phone

4. Patient understands the purpose and requirements of the study, can make him/herself understood, and has provided informed consent

EXCLUSION CRITERIA

1. Tandem extracranial or intracranial stenosis (70%-99%) or occlusion that is proximal or distal to the target intracranial lesion (NOTE: an exception is allowed if the occlusion involves a single vertebral artery proximal to a symptomatic basilar artery stenosis and the contralateral vertebral artery is supplying the basilar artery)

2. Bilateral intracranial vertebral artery stenosis of 70%-99% and uncertainty about which artery is symptomatic (e.g. if patient has pontine, midbrain, or temporal - occipital symptoms)

3. Stenting, angioplasty, or endarterectomy of an extracranial (carotid or vertebral artery) or intracranial artery within 30 days prior to expected enrollment date

4. Previous treatment of target lesion with a stent, angioplasty, or other mechanical device, or plan to perform staged angioplasty followed by stenting of target lesion

5. Plan to perform concomitant angioplasty or stenting of an extracranial vessel tandem to an intracranial stenosis

6. Presence of intraluminal thrombus proximal to or at the target lesion

7. Any aneurysm proximal to or distal to stenotic intracranial artery

8. Intracranial tumor (except meningioma) or any intracranial vascular malformation

9. CT or angiographic evidence of severe calcification at target lesion

10. Thrombolytic therapy within 24 hours prior to enrollment

11. Progressive neurological signs within 24 hours prior to enrollment

12. Brain infarct within previous 30 days of enrollment that is of sufficient size (> 5 cms) to be at risk of hemorrhagic conversion during or after stenting

13. Any hemorrhagic infarct within 14 days prior to enrollment

14. Any hemorrhagic infarct within 15 - 30 days that is associated with mass effect

15. Any history of a primary intracerebral (parenchymal) hemorrhage (ICH)

16. Any other intracranial hemorrhage (subarachnoid, subdural, epidural) within 30 days

17. Any untreated chronic subdural hematoma of greater than 5 mm in thickness

18. Intracranial arterial stenosis due to arterial dissection, Moya Moya disease; any known vasculitic disease; herpes zoster, varicella zoster or other viral vasculopathy; neurosyphilis; any other intracranial infection; any intracranial stenosis associated with Cerebrospinal fluid (CSF) pleocytosis; radiation induced vasculopathy; fibromuscular dysplasia; sickle cell disease; neurofibromatosis; benign angiopathy of central nervous system; post-partum angiopathy; suspected vasospastic process, suspected recanalized embolus

19. Presence of any of the following unequivocal cardiac sources of embolism: chronic or paroxysmal atrial fibrillation, mitral stenosis, mechanical valve, endocarditis, intracardiac clot or vegetation, myocardial infarction within three months, dilated cardiomyopathy, left atrial spontaneous echo contrast, ejection fraction less than 30%

20. Known allergy or contraindication to aspirin, clopidogrel, heparin, nitinol, local or general anesthesia

21. History of life-threatening allergy to contrast dye. If not life threatening and can be effectively pretreated, patient can be enrolled at physician's discretion

22. Active peptic ulcer disease, major systemic hemorrhage within 30 days, active bleeding diathesis, platelets < 100,000, hematocrit < 30, International normalized ratio (INR)

1.5, clotting factor abnormality that increases the risk of bleeding, current alcohol or substance abuse, uncontrolled severe hypertension (systolic pressure > 180 mm Hg or diastolic pressure > 115 mm Hg), severe liver impairment Aspartate Transaminase (AST) or Alanine transaminase (ALT) > 3 x normal, cirrhosis, creatinine > 3.0 (unless on dialysis)

1. Major surgery (including open femoral, aortic, or carotid surgery) within previous 30 days or planned in the next 90 days after enrollment

2. Indication for warfarin or heparin beyond enrollment (NOTE: exceptions allowed for use of systemic heparin during stenting procedure or subcutaneous heparin for deep vein thrombosis (DVT) prophylaxis while hospitalized)

3. Severe neurological deficit that renders the patient incapable of living independently

4. Dementia or psychiatric problem that prevents the patient from following an outpatient program reliably

5. Co-morbid conditions that may limit survival to less than 3 years

6. Pregnancy or of childbearing potential and unwilling to use contraception for the duration of this study

7. Enrollment in another study that would conflict with the current study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UAB Medical Center	Birmingham	Alabama	United States	35294
2	Barrow Neurological Institute - St. Joseph's Hospital and Medical Center	Phoenix	Arizona	United States	85013
3	Mayo	Phoenix	Arizona	United States	85054
4	Glendale Adventist	Glendale	California	United States	91203
5	Cedars Sinai	Los Angeles	California	United States	90048
6	UCLA	Los Angeles	California	United States	90095
7	UCSF	San Francisco	California	United States	94143
8	Washington Hospital	Washington	District of Columbia	United States	20010
9	University of Florida - Shands	Gainesville	Florida	United States	32611
10	University of Miami	Miami	Florida	United States	33136
11	Florida Hospital	Winter Park	Florida	United States	32789
12	Emory University	Atlanta	Georgia	United States	30388
13	Rush University Medical Center	Chicago	Illinois	United States	60612
14	Central DuPage Hospital	Winfield	Illinois	United States	60190
15	Johns Hopkins	Baltimore	Maryland	United States	21287
16	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
17	Wayne State	Detroit	Michigan	United States	48201
18	Henry Ford Medical Center	Detroit	Michigan	United States	48202
19	Providence St. John	Southfield	Michigan	United States	48075
20	University of Mississippi	Jackson	Mississippi	United States	39216
21	University of Buffalo	Buffalo	New York	United States	14209
22	NYU Medical Center	New York	New York	United States	10016
23	Columbia University Medical Center	New York	New York	United States	10032
24	Cornell Medical College	New York	New York	United States	10065
25	Stony Brook University Medical Center	Stony Brook	New York	United States	11790
26	Carolinas Medical Center	Charlotte	North Carolina	United States	28204
27	Duke University Medical Center	Durham	North Carolina	United States	27710
28	Moses Cone Medical Center	Greensboro	North Carolina	United States	27401
29	Forsyth Medical Center	Winston-Salem	North Carolina	United States	27103
30	University of Cincinnati	Cincinnati	Ohio	United States	45219
31	University Hospitals Case Medical Center	Cleveland	Ohio	United States	44106
32	Cleveland Clinic	Cleveland	Ohio	United States	44195
33	Riverside Methodist	Columbus	Ohio	United States	43214
34	Oregon Health Sciences University	Portland	Oregon	United States	97239
35	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
36	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19170
37	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
38	Medical University of South Carolina	Charleston	South Carolina	United States	29425
39	Erlanger Medical Center	Chattanooga	Tennessee	United States	37403
40	Baylor University Medical Center	Dallas	Texas	United States	75246
41	UT Southwestern	Dallas	Texas	United States	75390
42	Baylor St. Luke's	Houston	Texas	United States	77030
43	Methodist Hospital	Houston	Texas	United States	77030
44	Scott & White - Texas A&M	Temple	Texas	United States	76508
45	Inova Fairfax Hospital	Falls Church	Virginia	United States	22042
46	Sentera	Norfolk	Virginia	United States	23507
47	Sacred Heart Medical Center	Spokane	Washington	United States	99204
48	MultiCare	Tacoma	Washington	United States	98405
49	West Virginia University	Morgantown	West Virginia	United States	26506
50	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226

Sponsors and Collaborators

• Medical University of South Carolina
• National Institutes of Health (NIH)
• National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

• Principal Investigator: Marc I Chimowitz, MBChB, Medical University of South Carolina

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Clinical Alert

Publications

None provided.

• Responsible Party: Marc Chimowitz, Full Professor, Medical University of South Carolina
• ClinicalTrials.gov Identifier: NCT00576693
• Other Study ID Numbers: R01NS058728-01A1; NINDS; CRC; 1U01NS058728-01A1
• First Posted: Dec 19, 2007
• Last Update Posted: May 30, 2018
• Last Verified: Apr 1, 2018

• Keywords provided by Marc Chimowitz, Full Professor, Medical University of South Carolina: ischemic stroke; intracranial stenting; vascular risk factor management
• Additional relevant MeSH terms: Stroke; Ischemic Stroke

Study Results

Participant Flow

Arm/Group Title	Intensive Medical Management Plus Stenting	Intensive Medical Management Alone
Arm/Group Description	intracranial angioplasty and stenting using the Gateway balloon and Wingspan self-expanding nitinol stent plus intensive medical therapy (aspirin 325 mg / day for entire follow-up, clopidogrel 75mg per day for 90 days after enrollment unless cardiologist recommends continuing clopidogrel beyond 90 days for a cardiac indication, and aggressive risk factor management primarily targeting blood pressure < 140 / 90 mm Hg (< 130 / 80 if diabetic) and LDL < 70 mg / dl). intracranial angioplasty and stenting: intracranial angioplasty and stenting using the Gateway balloon and Wingspan self-expanding nitinol stent (or any future FDA approved iterations of the balloon, stent, or the delivery systems) plus intensive medical therapy (aspirin 325 mg / day for entire follow-up, clopidogrel 75mg per day for 90 days after enrollment unless cardiologist recommends continuing clopidogrel beyond 90 days for a cardia	Intensive medical therapy alone (aspirin 325 mg / day for entire follow-up, clopidogrel 75mg per day for 90 days after enrollment unless cardiologist recommends continuing clopidogrel beyond 90 days for a cardiac indication, and aggressive risk factor management primarily targeting blood pressure < 140 / 90 mm Hg (< 130 / 80 if diabetic) and LDL < 70 mg / dl) intensive medical management: intensive medical therapy alone (aspirin 325 mg / day for entire follow-up, clopidogrel 75mg per day for 90 days after enrollment unless cardiologist recommends continuing clopidogrel beyond 90 days for a cardiac indication, and aggressive risk factor management primarily targeting blood pressure < 140 / 90 mm Hg (< 130 / 80 if diabetic) and LDL < 70 mg / dl)
Period Title: Overall Study
STARTED	224	227
COMPLETED	214	203
NOT COMPLETED	10	24

Baseline Characteristics

Arm/Group Title	Intensive Medical Management Plus Stenting	Intensive Medical Management Alone	Total
Arm/Group Description	intracranial angioplasty and stenting using the Gateway balloon and Wingspan self-expanding nitinol stent plus intensive medical therapy (aspirin 325 mg / day for entire follow-up, clopidogrel 75mg per day for 90 days after enrollment unless cardiologist recommends continuing clopidogrel beyond 90 days for a cardiac indication, and aggressive risk factor management primarily targeting blood pressure < 140 / 90 mm Hg (< 130 / 80 if diabetic) and LDL < 70 mg / dl). intracranial angioplasty and stenting: intracranial angioplasty and stenting using the Gateway balloon and Wingspan self-expanding nitinol stent (or any future FDA approved iterations of the balloon, stent, or the delivery systems) plus intensive medical therapy (aspirin 325 mg / day for entire follow-up, clopidogrel 75mg per day for 90 days after enrollment unless cardiologist recommends continuing clopidogrel beyond 90 days for a cardia	Intensive medical therapy alone (aspirin 325 mg / day for entire follow-up, clopidogrel 75mg per day for 90 days after enrollment unless cardiologist recommends continuing clopidogrel beyond 90 days for a cardiac indication, and aggressive risk factor management primarily targeting blood pressure < 140 / 90 mm Hg (< 130 / 80 if diabetic) and LDL < 70 mg / dl) intensive medical management: intensive medical therapy alone (aspirin 325 mg / day for entire follow-up, clopidogrel 75mg per day for 90 days after enrollment unless cardiologist recommends continuing clopidogrel beyond 90 days for a cardiac indication, and aggressive risk factor management primarily targeting blood pressure < 140 / 90 mm Hg (< 130 / 80 if diabetic) and LDL < 70 mg / dl)	Total of all reporting groups
Overall Participants	224	227	451
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.0 (10.7)	59.5 (11.8)	60.2 (11.3)
Sex: Female, Male (Count of Participants)
Female	97 43.3%	82 36.1%	179 39.7%
Male	127 56.7%	145 63.9%	272 60.3%
Race/Ethnicity, Customized (participants) [Number]
Black	55 24.6%	49 21.6%	104 23.1%
White	160 71.4%	162 71.4%	322 71.4%
Other	9 4%	16 7%	25 5.5%
History of Hypertension (participants) [Number]
Yes	200 89.3%	203 89.4%	403 89.4%
No	24 10.7%	24 10.6%	48 10.6%
History of Lipid Disorder (participants) [Number]
Yes	195 87.1%	202 89%	397 88%
No	29 12.9%	25 11%	54 12%
Smoking (participants) [Number]
Never	90 40.2%	78 34.4%	168 37.3%
Previously	79 35.3%	80 35.2%	159 35.3%
Currently	54 24.1%	69 30.4%	123 27.3%
Diabetes (participants) [Number]
Yes	105 46.9%	103 45.4%	208 46.1%
No	119 53.1%	124 54.6%	243 53.9%
Systolic Blood Pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	143.9 (20.6)	146.8 (21.8)	145.4 (21.3)
Low Density Lipoprotein Cholesterol (mg/dl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dl]	96.2 (38.4)	97.7 (36.6)	97.0 (37.5)
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	30.3 (6.2)	30.7 (6.3)	30.5 (6.3)
History of Coronary Artery Disease (participants) [Number]
Yes	47 21%	59 26%	106 23.5%
No	177 79%	168 74%	345 76.5%
History of Stroke (Not Qualifying Event) (participants) [Number]
Yes	60 26.8%	58 25.6%	118 26.2%
No	164 73.2%	169 74.4%	333 73.8%
Qualifying Event (participants) [Number]
Stroke	142 63.4%	152 67%	294 65.2%
TIA	82 36.6%	75 33%	157 34.8%
On Antithrombotic Therapy at Qualifying Event (participants) [Number]
Yes	144 64.3%	140 61.7%	284 63%
No	80 35.7%	87 38.3%	167 37%
Time from Qualifying Event to Randomization (days) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [days]	7	7	7
Symptomatic Qualifying Artery (participants) [Number]
Internal Carotid Artery	45 20.1%	49 21.6%	94 20.8%
Middle Cerebral Artery	92 41.1%	105 46.3%	197 43.7%
Vertebral Artery	38 17%	22 9.7%	60 13.3%
Basilar Artery	49 21.9%	51 22.5%	100 22.2%
Percent Stenosis of Symptomatic Qualifying Artery (% of the diameter the artery) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [% of the diameter the artery]	80 (7)	81 (7)	81 (7)

Outcome Measures

1. Primary Outcome

Title	Any Stroke or Death Within 30 Days of Enrollment or Any Revascularization Procedure OR an Ischemic Stroke in the Territory of the Symptomatic Intracranial Artery Beyond 30 Days After Enrollment.
Description	Any stroke (ischemic, parenchymal brain hemorrhage, subarachnoid or intraventricular hemorrhage) or death within 30 days after enrollment OR any stroke (ischemic, parenchymal brain hemorrhage, subarachnoid or intraventricular hemorrhage) or death within 30 days of any revascularization procedure of the qualifying symptomatic intracranial artery done during follow-up, OR an ischemic stroke in the territory of the symptomatic intracranial artery from day 31 after study entry to completion of follow-up.
Time Frame	Mean length of follow-up was 2.4 years

Outcome Measure Data

Analysis Population Description

All patients enrolled in the study were included in the primary outcome analysis.

Arm/Group Title	Intensive Medical Management Plus Stenting	Intensive Medical Management Alone
Arm/Group Description	intracranial angioplasty and stenting using the Gateway balloon and Wingspan self-expanding nitinol stent plus intensive medical therapy (aspirin 325 mg / day for entire follow-up, clopidogrel 75mg per day for 90 days after enrollment unless cardiologist recommends continuing clopidogrel beyond 90 days for a cardiac indication, and aggressive risk factor management primarily targeting blood pressure < 140 / 90 mm Hg (< 130 / 80 if diabetic) and LDL < 70 mg / dl). intracranial angioplasty and stenting: intracranial angioplasty and stenting using the Gateway balloon and Wingspan self-expanding nitinol stent (or any future FDA approved iterations of the balloon, stent, or the delivery systems) plus intensive medical therapy (aspirin 325 mg / day for entire follow-up, clopidogrel 75mg per day for 90 days after enrollment unless cardiologist recommends continuing clopidogrel beyond 90 days for a cardia	Intensive medical therapy alone (aspirin 325 mg / day for entire follow-up, clopidogrel 75mg per day for 90 days after enrollment unless cardiologist recommends continuing clopidogrel beyond 90 days for a cardiac indication, and aggressive risk factor management primarily targeting blood pressure < 140 / 90 mm Hg (< 130 / 80 if diabetic) and LDL < 70 mg / dl) intensive medical management: intensive medical therapy alone (aspirin 325 mg / day for entire follow-up, clopidogrel 75mg per day for 90 days after enrollment unless cardiologist recommends continuing clopidogrel beyond 90 days for a cardiac indication, and aggressive risk factor management primarily targeting blood pressure < 140 / 90 mm Hg (< 130 / 80 if diabetic) and LDL < 70 mg / dl)
Measure Participants	224	227
Number [participants]	52 23.2%	34 15%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intensive Medical Management Plus Stenting, Intensive Medical Management Alone
	Comments	The statistical analysis was based on a comparison of the of the two treatment groups with respect to the time to a primary outcome using the logrank test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0252
	Comments
	Method	Log Rank
	Comments

Adverse Events

Time Frame	Mean length of follow-up was 2.4 years
Adverse Event Reporting Description	The prespecified study outcomes were explicitly requested on the adverse event form. Any other adverse event was to be reported if it was either serious or related to a study intervention according to prespecified criteria and classified on the adverse event form using the Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0.
Arm/Group Title	Intensive Medical Management Plus Stenting		Intensive Medical Management Alone
Arm/Group Description	intracranial angioplasty and stenting using the Gateway balloon and Wingspan self-expanding nitinol stent plus intensive medical therapy (aspirin 325 mg / day for entire follow-up, clopidogrel 75mg per day for 90 days after enrollment unless cardiologist recommends continuing clopidogrel beyond 90 days for a cardiac indication, and aggressive risk factor management primarily targeting blood pressure < 140 / 90 mm Hg (< 130 / 80 if diabetic) and LDL < 70 mg / dl). intracranial angioplasty and stenting: intracranial angioplasty and stenting using the Gateway balloon and Wingspan self-expanding nitinol stent (or any future FDA approved iterations of the balloon, stent, or the delivery systems) plus intensive medical therapy (aspirin 325 mg / day for entire follow-up, clopidogrel 75mg per day for 90 days after enrollment unless cardiologist recommends continuing clopidogrel beyond 90 days for a cardia		Intensive medical therapy alone (aspirin 325 mg / day for entire follow-up, clopidogrel 75mg per day for 90 days after enrollment unless cardiologist recommends continuing clopidogrel beyond 90 days for a cardiac indication, and aggressive risk factor management primarily targeting blood pressure < 140 / 90 mm Hg (< 130 / 80 if diabetic) and LDL < 70 mg / dl) intensive medical management: intensive medical therapy alone (aspirin 325 mg / day for entire follow-up, clopidogrel 75mg per day for 90 days after enrollment unless cardiologist recommends continuing clopidogrel beyond 90 days for a cardiac indication, and aggressive risk factor management primarily targeting blood pressure < 140 / 90 mm Hg (< 130 / 80 if diabetic) and LDL < 70 mg / dl)
All Cause Mortality
	Intensive Medical Management Plus Stenting		Intensive Medical Management Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Intensive Medical Management Plus Stenting		Intensive Medical Management Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	146/224 (65.2%)		121/227 (53.3%)
Blood and lymphatic system disorders
Blood / Bone Marrow	4/224 (1.8%)		3/227 (1.3%)
Coagulation	0/224 (0%)		1/227 (0.4%)
Lymphatics	1/224 (0.4%)		0/227 (0%)
Hemorrhage / Bleeding	1/224 (0.4%)		0/227 (0%)
Cardiac disorders
Myocardial Infarction	5/224 (2.2%)		9/227 (4%)
Cardiac Arrhythmia	13/224 (5.8%)		7/227 (3.1%)
Cardiac General	14/224 (6.3%)		18/227 (7.9%)
Ear and labyrinth disorders
Auditory / Ear	1/224 (0.4%)		1/227 (0.4%)
Endocrine disorders
Endocrine	3/224 (1.3%)		2/227 (0.9%)
Eye disorders
Ocular / Visual	3/224 (1.3%)		5/227 (2.2%)
Gastrointestinal disorders
Gastrointestinal	13/224 (5.8%)		12/227 (5.3%)
General disorders
Systemic Hemorrhage	15/224 (6.7%)		8/227 (3.5%)
Constitutional Symptoms	2/224 (0.9%)		2/227 (0.9%)
Pain	9/224 (4%)		9/227 (4%)
Death	13/224 (5.8%)		13/227 (5.7%)
Hepatobiliary disorders
Hepatobiliary / Pancreas	3/224 (1.3%)		3/227 (1.3%)
Immune system disorders
Allergy / Immunology	3/224 (1.3%)		0/227 (0%)
Infections and infestations
Infection	10/224 (4.5%)		5/227 (2.2%)
Metabolism and nutrition disorders
Metabolic / Laaboratory	10/224 (4.5%)		14/227 (6.2%)
Musculoskeletal and connective tissue disorders
Musculoskeletal / Soft Tissue	8/224 (3.6%)		6/227 (2.6%)
Nervous system disorders
Ischemic Stroke in the Territory of Qualifying Symptomatic Artery	40/224 (17.9%)		30/227 (13.2%)
Ischemic Stroke Not in the Territory of the Qualifying Symptomatic Artery	5/224 (2.2%)		10/227 (4.4%)
Symptomatic Intracranial Hemorrhage	12/224 (5.4%)		1/227 (0.4%)
Intracranial Hematoma	0/224 (0%)		1/227 (0.4%)
Transient Ischemic Attack / Cerebral Infarct with Temporary Signs	30/224 (13.4%)		29/227 (12.8%)
Neurology	26/224 (11.6%)		19/227 (8.4%)
Asymptomatic Intracranial Hemorrhage	1/224 (0.4%)		0/227 (0%)
Renal and urinary disorders
Renal / Genitourinary	10/224 (4.5%)		5/227 (2.2%)
Reproductive system and breast disorders
Sexual / Reproductive	2/224 (0.9%)		1/227 (0.4%)
Respiratory, thoracic and mediastinal disorders
Pulmonary / Upper Respiratory	7/224 (3.1%)		6/227 (2.6%)
Skin and subcutaneous tissue disorders
Dermatology / Skin	3/224 (1.3%)		1/227 (0.4%)
Surgical and medical procedures
Surgery / Intraoperative Injury	4/224 (1.8%)		3/227 (1.3%)
Vascular disorders
Vascular	10/224 (4.5%)		6/227 (2.6%)
Pulmonary Embolus	0/224 (0%)		2/227 (0.9%)
Cerebral Venous Thrombosis	1/224 (0.4%)		1/227 (0.4%)
Deep Vein Thrombosis	2/224 (0.9%)		2/227 (0.9%)
Complications of Acute Ischemia of a Limb or Internal Organ	4/224 (1.8%)		2/227 (0.9%)
Other (Not Including Serious) Adverse Events
	Intensive Medical Management Plus Stenting		Intensive Medical Management Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	117/224 (52.2%)		118/227 (52%)
Cardiac disorders
Cardiac General	39/224 (17.4%)		35/227 (15.4%)
Gastrointestinal disorders
Gastrointestinal	5/224 (2.2%)		15/227 (6.6%)
General disorders
Systemic Hemorrhage	29/224 (12.9%)		24/227 (10.6%)
Pain	14/224 (6.3%)		11/227 (4.8%)
Metabolism and nutrition disorders
Metabolic / Laboratory	17/224 (7.6%)		13/227 (5.7%)
Musculoskeletal and connective tissue disorders
Musculoskeletal / Soft Tissue	21/224 (9.4%)		9/227 (4%)
Nervous system disorders
Transient Ischemic Attack / Cerebral Infarct with Temporary Signs	27/224 (12.1%)		34/227 (15%)
Neurology	25/224 (11.2%)		25/227 (11%)
Respiratory, thoracic and mediastinal disorders
Pulmonary / Upper Respiratory	12/224 (5.4%)		10/227 (4.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.