Atherosclerotic stenosis of the major intracranial arteries is an important cause of stroke, accounting for approximately 50,000 strokes per year in the USA at a cost of $750,000,000 in year 1 and $4.5 billion over the life time of these patients. A previous NIH funded clinical trial (WASID) performed by our study group showed that aspirin was as effective and safer than warfarin for preventing stroke in patients with intracranial stenosis, and that patients with 70%-99% intracranial stenosis had a high risk of stroke despite antithrombotic therapy and usual management of vascular risk factors. The high risk of stroke in these patients suggests the need for alternative therapies such as intensive management of vascular risk factors and intracranial stenting. In this application we are proposing a randomized clinical trial to address the following primary aim: To determine whether intracranial stenting (using the Wingspan self-expanding nitinol stent) and intensive medical therapy is superior to intensive medical therapy alone for preventing the primary endpoint (any stroke or death within 30 days after enrollment or stroke in the territory of the symptomatic intracranial artery beyond 30 days) during a mean follow-up of two years in high-risk patients with symptomatic stenosis of a major intracranial artery. Intensive medical therapy in both arms of the study will consist of aspirin 325 mg / day for entire follow-up, clopidogrel 75mg per day for 90 days after enrollment, and aggressive risk factor management primarily targeting blood pressure <130 / 80 mm Hg and low density cholesterol <70 mg / dl. The Primary Hypothesis is that compared with intensive medical therapy alone, intracranial 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 with symptomatic stenosis of a major intracranial artery. The sample size required to detect a 35% reduction in the rate of the primary endpoint from stenting based on the logrank test with an alpha of 0.05, 80% power, and adjusting for a 2% loss to follow-up and a 5% crossover from the medical to the stenting arm is 382 patients per group. Patients will be evaluated by study neurologists every 4 months to determine the occurrence of endpoints and by study internists who will manage the vascular risk factors of all study patients. It is expected that the results of this study, which is the first secondary prevention stroke trial to incorporate intensive management of multiple risk factors in the study design, and is also the first Phase III intracranial stenting trial, will lead to more effective therapies for this common cerebrovascular disorder that is associated with a poor prognosis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01NS058728-03
Application #
7858317
Study Section
Special Emphasis Panel (ZNS1-SRB-W (26))
Program Officer
Moy, Claudia S
Project Start
2008-05-01
Project End
2013-04-30
Budget Start
2010-05-01
Budget End
2011-04-30
Support Year
3
Fiscal Year
2010
Total Cost
$4,200,000
Indirect Cost
Name
Medical University of South Carolina
Department
Neurosciences
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425
Derdeyn, Colin P; Fiorella, David; Lynn, Michael J et al. (2017) 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 48:1501-1506
Turan, Tanya N; Smock, Alison; Cotsonis, George et al. (2017) Is There Benefit from Stenting on Cognitive Function in Intracranial Atherosclerosis? Cerebrovasc Dis 43:31-35
Banerjee, Chirantan; Chimowitz, Marc I (2017) Stroke Caused by Atherosclerosis of the Major Intracranial Arteries. Circ Res 120:502-513
Kwon, Hyung-Min; Lynn, Michael J; Turan, Tanya N et al. (2016) 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 73:36-42
Waters, Michael F; Hoh, Brian L; Lynn, Michael J et al. (2016) Factors Associated With Recurrent Ischemic Stroke in the Medical Group of the SAMMPRIS Trial. JAMA Neurol 73:308-15
Lutsep, Helmi L; Lynn, Michael J; Cotsonis, George A et al. (2015) Does the Stenting Versus Aggressive Medical Therapy Trial Support Stenting for Subgroups With Intracranial Stenosis? Stroke 46:3282-4
Chiu, David; Klucznik, Richard P; Turan, Tanya N et al. (2015) Enrollment volume effect on risk factor control and outcomes in the SAMMPRIS trial. Neurology 85:2090-7
Liebeskind, David S; Kosinski, Andrzej S; Lynn, Michael J et al. (2015) Noninvasive fractional flow on MRA predicts stroke risk of intracranial stenosis. J Neuroimaging 25:87-91
Parikh, Neal; Merkler, Alexander E; Cheng, Natalie T et al. (2015) Clinical reasoning: an unusual case of subacute encephalopathy. Neurology 84:e33-7
Lutsep, Helmi L; Barnwell, Stanley L; Larsen, Darren T et al. (2015) Outcome in patients previously on antithrombotic therapy in the SAMMPRIS trial: subgroup analysis. Stroke 46:775-9

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