Trial of Cilostazol in Symptomatic Intracranial Arterial Stenosis II

Study Overview
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Brief Summary
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This study will recruit 480 acute stroke patients with symptomatic intracranial stenosis (M1 segment of Middle cerebral artery (MCA) or basilar artery). They will be randomly assigned into cilostazol group or clopidogrel group. Every patients will take 100mg of aspirin a day additionally. The primary outcome variable of this study is Progression rate of symptomatic intracranial stenosis on magnetic resonance angiogram (MRA).

Detailed Description
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[Goal] To Reveal the Effect and Safety of Cilostazol Compared with Clopidogrel on the Prevention of the Progression of Symptomatic Intracranial Arterial Stenosis. [Trial Design] Double-Blind, Active-Controlled, Randomized, Multicenter Trial [Participants] Acute ischemic stroke patients with symptomatic intracranial arterial stenosis [Methods] Double-Blind, Active-Controlled, Randomized, Multicenter Trial Investigational product (Double Dummy Method): Cilostazol 200mg (100mg twice per day) versus clopidogrel 75mg Concomitant medication: Aspirin 100 (75-150) mg per day Medication Duration: 7 months [Outcome Variables] Primary Outcome Variable: Progression rate of symptomatic intracranial arterial stenosis Secondary outcome variables: The occurrence of new MRI (magnetic resonance image) lesion on follow-up MRI Stroke events Overall cardiovascular events: stroke, acute coronary syndrome, vascular death Ipsilateral ischemic stroke rate Fatal or major bleeding complications

Official Title
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Trial for Efficacy and Safety of Cilostazol on the Progression of Symptomatic Intracranial Stenosis Comparing Clopidogrel

Conditions
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Cerebral Infarction, Atherosclerosis

Intervention / Treatment
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* Drug: clopidogrel
* Drug: Cilostazol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cerebral infarction within 2 weeks from the onset or TIA with corresponding acute ischemic brain lesions on MRI within 2 weeks from the onset Age: more than 35 years of age Patient with significant focal stenosis in the M1 segment of middle cerebral artery (MCA) or basilar artery (BA) with acute ischemic lesions on magnetic resonance imaging (MRI) within the vascular territory of the stenosed artery. Exclusion Criteria: Patients with any contraindications to the treatment with antiplatelet therapy Patients with potential cardiac embolic source; prosthetic valve, atrial fibrillation, atrial flutter, left atrial/atrial appendage thrombus, sick sinus syndrome, left ventricular thrombus, dilated cardiomyopathy, akinetic or hypokinetic left ventricular segment, atrial myxoma, Infective endocarditis, mitral valve stenosis or prolapse, mitral annuls calcification, left atrial turbulence, nonbacterial endocarditis, congestive heart failure, recent myocardial infarction (within 4 weeks) Patients with more than 50% stenosis in the parent artery of symptomatic stenosis Bleeding diathesis Chronic liver disease (ALT > 100 or AST > 100) or chronic renal disease (creatinine > 3.0mg/dl) Anemia (hemoglobin < 10mg/dl) or thrombocytopenia (platelet count less than 100,000/mm3) Nonatherosclerotic vasculopathy; patients with clinical characteristics suggesting arterial dissection, moyamoya disease, Takayasu's arteritis, radiation associated angiopathy, and other vasculitis. Severe stroke: NIH stroke scale : more than 16 Pregnant or lactating patients Chronic user of NSAIDs Thrombolytic therapy for the symptomatic stenosis Symptomatic stenosis scheduled for angioplasty Patients with pacemaker or any other contraindications to MRI

Ages Eligible for Study
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Minimum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cilostazol<br>cilostazol 100mg bid plus placebo of clopidogrel | Drug: Cilostazol<br>* Cilostazol 100mg twice a day plus placebo of clopidogrel once a day<br>* Other names: cilostazol produced by Korea Otsuka Pharmaceutical;|
| Active Comparator: Clopidogrel<br>clopidogrel 75mg qd and matching placebo of cilostazol | Drug: clopidogrel<br>* Clopidogrel 75mg once a day plus placebo of cilostazol twice a day<br>* Other names: Plavix, produced by Sanofi-Aventis.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Progression of Symptomatic Intracranial Stenosis | Blind reviewers classified the presence and severity of stenosis on middle cerebral arteries and basilar artery on magnetic resonance angiogram (MRA) into 5 grades; normal, mild, moderate, severe and occlusion. Progression was defined as worsening of stenosis by 1 or more grades on final MRA as compared with the baseline MRA. The progression of symptomatic stenosis is defined as 1 or more grade worsening of the stenosis on the symptomatic artery on MRA. | 7 months after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With New MRI (Magnetic Resonance Image) Lesions on Follow-up MRI | number of patients with new ischemic lesions on FLAIR (Fluid attenuation inversion recovery) images of follow-up MRI, which were determined by slice to slice comparison with baseline MRI. | 7 months after treatment | 
| Number of Participants With Stroke Events | including nonfatal ischemic stroke, nonfatal hemorrhagic stroke and fatal stroke | upto 7 months after randomization | 
| Number of Participants With Overall Cardiovascular Events | including nonfatal stroke, nonfatal myocardial infarction and vascular death. | upto 7 months after randomization | 
| Number of Patients With Ipsilateral Ischemic Stroke Rate | ischemic stroke event which occured in the vascular territory of initial symptomatic stenosis | upto 7 months after randomization | 
| Numbers of Fatal or Major Bleeding Complications | life-threatening or fatal bleeding was defined as any fatal bleeding event, a drop in hemoglobin of ≥ 50g/L, or significant hypotension with need for inotropic agents, symptomatic intracranial hemorrhage, or transfusion of ≥ 4 units of red-blood cells or equivalent amount of whole blood. Major bleeding was defined as significantly disabling bleedings, intraocular bleeding leading to significant visual loss, or bleeding requiring transfusion of ≤ 3 units of red-blood cells or equivalent amount of whole blood | upto 7 months after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infarction, Cerebral, cilostazol, stenosis, atherosclerosis, clopidogrel