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

NCT00576693 | Completed Phase 3 Results DMC

• 4 other identifiers: R01NS058728-01A1NINDSCRC1U01NS058728-01A1
• Study Type: interventional
• Target: 451
• Locations: 1 country
• Sites: 50

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.

Conditions

Ischemic Stroke

Keywords

ischemic stroke; intracranial stenting; vascular risk factor management

Outcome Measures

Primary Outcomes (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.

  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.

  Mean length of follow-up was 2.4 years

Study Arms (2)

intensive medical management plus stenting

EXPERIMENTAL

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

intensive medical management alone

EXPERIMENTAL

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

Interventions

intracranial angioplasty and stenting DEVICE

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).

Also known as: Wingspan stent, Gateway balloon

intensive medical management plus stenting

intensive medical management OTHER

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 alone

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Modified Rankin score of ≤ 3
• Target area of stenosis in an intracranial artery that has a normal diameter of 2.00 mm to 4.50 mm
• Target area of stenosis is less than or equal to 14 mm in length
• 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.
• i. 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
• Negative pregnancy test in a female who has had any menses in the last 18 months
• Patient is willing and able to return for all follow-up visits required by the protocol
• Patient is available by phone
• Patient understands the purpose and requirements of the study, can make him/herself understood, and has provided informed consent

You may not qualify if:

• 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)
• 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)
• Stenting, angioplasty, or endarterectomy of an extracranial (carotid or vertebral artery) or intracranial artery within 30 days prior to expected enrollment date
• 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
• Plan to perform concomitant angioplasty or stenting of an extracranial vessel tandem to an intracranial stenosis
• Presence of intraluminal thrombus proximal to or at the target lesion
• Any aneurysm proximal to or distal to stenotic intracranial artery
• Intracranial tumor (except meningioma) or any intracranial vascular malformation
• CT or angiographic evidence of severe calcification at target lesion
• Thrombolytic therapy within 24 hours prior to enrollment
• Progressive neurological signs within 24 hours prior to enrollment
• 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
• Any hemorrhagic infarct within 14 days prior to enrollment
• Any hemorrhagic infarct within 15 - 30 days that is associated with mass effect
• Any history of a primary intracerebral (parenchymal) hemorrhage (ICH)

Sponsors & Collaborators

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

Study Sites (50)

UAB Medical Center

Birmingham, Alabama, 35294, United States

Location

Barrow Neurological Institute - St. Joseph's Hospital and Medical Center

Phoenix, Arizona, 85013, United States

Location

Mayo

Phoenix, Arizona, 85054, United States

Location

Glendale Adventist

Glendale, California, 91203, United States

Location

Cedars Sinai

Los Angeles, California, 90048, United States

Location

UCLA

Los Angeles, California, 90095, United States

Location

UCSF

San Francisco, California, 94143, United States

Location

Washington Hospital

Washington D.C., District of Columbia, 20010, United States

Location

University of Florida - Shands

Gainesville, Florida, 32611, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Florida Hospital

Winter Park, Florida, 32789, United States

Location

Emory University

Atlanta, Georgia, 30388, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Central DuPage Hospital

Winfield, Illinois, 60190, United States

Location

Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Wayne State

Detroit, Michigan, 48201, United States

Location

Henry Ford Medical Center

Detroit, Michigan, 48202, United States

Location

Providence St. John

Southfield, Michigan, 48075, United States

Location

University of Mississippi

Jackson, Mississippi, 39216, United States

Location

University of Buffalo

Buffalo, New York, 14209, United States

Location

NYU Medical Center

New York, New York, 10016, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Cornell Medical College

New York, New York, 10065, United States

Location

Stony Brook University Medical Center

Stony Brook, New York, 11790, United States

Location

Carolinas Medical Center

Charlotte, North Carolina, 28204, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Moses Cone Medical Center

Greensboro, North Carolina, 27401, United States

Location

Forsyth Medical Center

Winston-Salem, North Carolina, 27103, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Riverside Methodist

Columbus, Ohio, 43214, United States

Location

Oregon Health Sciences University

Portland, Oregon, 97239, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19170, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Erlanger Medical Center

Chattanooga, Tennessee, 37403, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

UT Southwestern

Dallas, Texas, 75390, United States

Location

Baylor St. Luke's

Houston, Texas, 77030, United States

Location

Methodist Hospital

Houston, Texas, 77030, United States

Location

Scott & White - Texas A&M

Temple, Texas, 76508, United States

Location

Inova Fairfax Hospital

Falls Church, Virginia, 22042, United States

Location

Sentera

Norfolk, Virginia, 23507, United States

Location

Sacred Heart Medical Center

Spokane, Washington, 99204, United States

Location

MultiCare

Tacoma, Washington, 98405, United States

Location

West Virginia University

Morgantown, West Virginia, 26506, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (16)

• Derdeyn CP, Fiorella D, Lynn MJ, Barnwell SL, Zaidat OO, Meyers PM, Gobin YP, Dion J, Lane BF, Turan TN, Janis LS, Chimowitz MI; SAMMPRIS Trial Investigators. Impact of operator and site experience on outcomes after angioplasty and stenting in the SAMMPRIS trial. J Neurointerv Surg. 2013 Nov;5(6):528-33. doi: 10.1136/neurintsurg-2012-010504. Epub 2012 Sep 12.

  PMID: 22977278 RESULT

• Turan TN, Lynn MJ, Nizam A, Lane B, Egan BM, Le NA, Lopes-Virella MF, Hermayer KL, Benavente O, White CL, Brown WV, Caskey MF, Steiner MR, Vilardo N, Stufflebean A, Derdeyn CP, Fiorella D, Janis S, Chimowitz MI; SAMMPRIS Investigators. Rationale, design, and implementation of aggressive risk factor management in the Stenting and Aggressive Medical Management for Prevention of Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial. Circ Cardiovasc Qual Outcomes. 2012 Sep 1;5(5):e51-60. doi: 10.1161/CIRCOUTCOMES.112.966911. No abstract available.

  PMID: 22991350 RESULT

• Fiorella D, Derdeyn CP, Lynn MJ, Barnwell SL, Hoh BL, Levy EI, Harrigan MR, Klucznik RP, McDougall CG, Pride GL Jr, Zaidat OO, Lutsep HL, Waters MF, Hourihane JM, Alexandrov AV, Chiu D, Clark JM, Johnson MD, Torbey MT, Rumboldt Z, Cloft HJ, Turan TN, Lane BF, Janis LS, Chimowitz MI; SAMMPRIS Trial Investigators. Detailed analysis of periprocedural strokes in patients undergoing intracranial stenting in Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS). Stroke. 2012 Oct;43(10):2682-8. doi: 10.1161/STROKEAHA.112.661173. Epub 2012 Sep 13.

  PMID: 22984008 RESULT

• Chimowitz MI, Lynn MJ, Derdeyn CP, Turan TN, Fiorella D, Lane BF, Janis LS, Lutsep HL, Barnwell SL, Waters MF, Hoh BL, Hourihane JM, Levy EI, Alexandrov AV, Harrigan MR, Chiu D, Klucznik RP, Clark JM, McDougall CG, Johnson MD, Pride GL Jr, Torbey MT, Zaidat OO, Rumboldt Z, Cloft HJ; SAMMPRIS Trial Investigators. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med. 2011 Sep 15;365(11):993-1003. doi: 10.1056/NEJMoa1105335. Epub 2011 Sep 7.

  PMID: 21899409 RESULT

• Derdeyn CP, Chimowitz MI, Lynn MJ, Fiorella D, Turan TN, Janis LS, Montgomery J, Nizam A, Lane BF, Lutsep HL, Barnwell SL, Waters MF, Hoh BL, Hourihane JM, Levy EI, Alexandrov AV, Harrigan MR, Chiu D, Klucznik RP, Clark JM, McDougall CG, Johnson MD, Pride GL Jr, Lynch JR, Zaidat OO, Rumboldt Z, Cloft HJ; Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis Trial Investigators. Aggressive medical treatment with or without stenting in high-risk patients with intracranial artery stenosis (SAMMPRIS): the final results of a randomised trial. Lancet. 2014 Jan 25;383(9914):333-41. doi: 10.1016/S0140-6736(13)62038-3. Epub 2013 Oct 26.

  PMID: 24168957 RESULT

• Siegler JE, Badillo Goicoechea E, Yaghi S, Morsi RZ, Arevalo A, Smith MM, Kothari S, Desai H, Sehgal N, Rana R, Kellogg CA, Jhaveri A, de Havenon A, Dunne T, Cameron K, Chaturvedi S, Ghannam M, Prabhakaran S, Coleman E, Brorson JR, Mehendale R, Kass-Hout T. Estimated Theoretical Benefit of Aggressive LDL Lowering in Patients With Symptomatic Intracranial Atherosclerosis. Neurology. 2025 Jul 8;105(1):e213768. doi: 10.1212/WNL.0000000000213768. Epub 2025 May 30.

  PMID: 40446174 DERIVED

• Wang T, Luo J, Li T, Almallouhi E, Gao P, Gong H, Zhang X, Wang J, Lu T, Yang Y, Yang R, Xing Z, Wang H, Derdeyn CP, Jiao L. Stenting versus medical treatment alone for symptomatic intracranial artery stenosis: a preplanned pooled individual patient data analysis. J Neurointerv Surg. 2025 Sep 12;17(10):1032-1039. doi: 10.1136/jnis-2024-022189.

  PMID: 39147573 DERIVED

• Yaghi S, Khatri P, de Havenon A, Yeatts S, Chang AD, Cutting S, Mac Grory B, Burton T, Jayaraman MV, McTaggart RA, Fiorella D, Derdeyn C, Zaidat OO, Dehkharghani S, Amin-Hanjani S, Furie K, Prahbakaran S, Liebeskind D. Peri-procedural stroke or death in stenting of symptomatic severe intracranial stenosis. J Neurointerv Surg. 2020 Apr;12(4):374-379. doi: 10.1136/neurintsurg-2019-015225. Epub 2019 Sep 4.

  PMID: 31484697 DERIVED

• Wabnitz AM, Derdeyn CP, Fiorella DJ, Lynn MJ, Cotsonis GA, Liebeskind DS, Waters MF, Lutsep H, Lopez-Cancio E, Turan TN, Montgomery J, Janis LS, Lane B, Chimowitz MI; SAMMPRIS Investigators. Hemodynamic Markers in the Anterior Circulation as Predictors of Recurrent Stroke in Patients With Intracranial Stenosis. Stroke. 2019 Jan;50(1):143-147. doi: 10.1161/STROKEAHA.118.020840. Epub 2018 Dec 11.

  PMID: 30580705 DERIVED

• Derdeyn CP, Fiorella D, Lynn MJ, Turan TN, Cotsonis GA, Lane BF, Montgomery J, Janis LS, Chimowitz MI; SAMMPRIS Investigators. Nonprocedural Symptomatic Infarction and In-Stent Restenosis After Intracranial Angioplasty and Stenting in the SAMMPRIS Trial (Stenting and Aggressive Medical Management for the Prevention of Recurrent Stroke in Intracranial Stenosis). Stroke. 2017 Jun;48(6):1501-1506. doi: 10.1161/STROKEAHA.116.014537. Epub 2017 Apr 28.

  PMID: 28455321 DERIVED

• Turan TN, Nizam A, Lynn MJ, Egan BM, Le NA, Lopes-Virella MF, Hermayer KL, Harrell J, Derdeyn CP, Fiorella D, Janis LS, Lane B, Montgomery J, Chimowitz MI. Relationship between risk factor control and vascular events in the SAMMPRIS trial. Neurology. 2017 Jan 24;88(4):379-385. doi: 10.1212/WNL.0000000000003534. Epub 2016 Dec 21.

  PMID: 28003500 DERIVED

• Waters MF, Hoh BL, Lynn MJ, Kwon HM, Turan TN, Derdeyn CP, Fiorella D, Khanna A, Sheehan TO, Lane BF, Janis S, Montgomery J, Chimowitz MI; Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) Trial Investigators. Factors Associated With Recurrent Ischemic Stroke in the Medical Group of the SAMMPRIS Trial. JAMA Neurol. 2016 Mar;73(3):308-15. doi: 10.1001/jamaneurol.2015.4315.

  PMID: 26747792 DERIVED

• Kwon HM, Lynn MJ, Turan TN, Derdeyn CP, Fiorella D, Lane BF, Montgomery J, Janis LS, Rumboldt Z, Chimowitz MI; SAMMPRIS Investigators. Frequency, Risk Factors, and Outcome of Coexistent Small Vessel Disease and Intracranial Arterial Stenosis: Results From the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) Trial. JAMA Neurol. 2016 Jan;73(1):36-42. doi: 10.1001/jamaneurol.2015.3145.

  PMID: 26618534 DERIVED

• Lutsep HL, Lynn MJ, Cotsonis GA, Derdeyn CP, Turan TN, Fiorella D, Janis LS, Lane BF, Montgomery J, Chimowitz MI; SAMMPRIS Investigators. Does the Stenting Versus Aggressive Medical Therapy Trial Support Stenting for Subgroups With Intracranial Stenosis? Stroke. 2015 Nov;46(11):3282-4. doi: 10.1161/STROKEAHA.115.009846. Epub 2015 Sep 17.

  PMID: 26382173 DERIVED

• Chaturvedi S, Turan TN, Lynn MJ, Derdeyn CP, Fiorella D, Janis LS, Chimowitz MI; SAMMPRIS Trial Investigators. Do Patient Characteristics Explain the Differences in Outcome Between Medically Treated Patients in SAMMPRIS and WASID? Stroke. 2015 Sep;46(9):2562-7. doi: 10.1161/STROKEAHA.115.009656. Epub 2015 Aug 6.

  PMID: 26251251 DERIVED

• Lutsep HL, Barnwell SL, Larsen DT, Lynn MJ, Hong M, Turan TN, Derdeyn CP, Fiorella D, Janis LS, Chimowitz MI; SAMMPRIS Investigators. Outcome in patients previously on antithrombotic therapy in the SAMMPRIS trial: subgroup analysis. Stroke. 2015 Mar;46(3):775-9. doi: 10.1161/STROKEAHA.114.007752. Epub 2015 Jan 15.

  PMID: 25593135 DERIVED

Related Links

• Clinical Alert

MeSH Terms

Conditions

Ischemic Stroke

Interventions

Stents

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Prostheses and Implants; Equipment and Supplies

Results Point of Contact

• Title: Marc I. Chimowitz, MBChB
• Organization: Medical University of South Carolina

mchimow@musc.edu

843-792-3020

Study Officials

• Marc I Chimowitz, MBChB

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor

Study Record Dates

• First Submitted: December 7, 2007
• First Posted: December 19, 2007
• Study Start: October 1, 2008
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: May 30, 2018
• Results First Posted: July 11, 2014

Record last verified: 2018-04

Locations

US (50)