Trial of Cilostazol in Symptomatic Intracranial Arterial Stenosis II

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

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).

[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

Intervention(s) in this Clinical Trial

• Drug: clopidogrel
  • Clopidogrel 75mg once a day plus placebo of cilostazol twice a day
• Drug: Cilostazol
  • Cilostazol 100mg twice a day plus placebo of clopidogrel once a day

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: cilostazol
  • cilostazol 100mg bid plus placebo of clopidogrel
• Active Comparator: Clopidogrel
  • clopidogrel 75mg qd and matching placebo of cilostazol

Primary Measures

• Number of Participants With Progression of Symptomatic Intracranial Stenosis
  • Time Frame: 7 months after treatment
    Safety Issue?: No

Secondary Measures

• Number of Participants With New MRI (Magnetic Resonance Image) Lesions on Follow-up MRI
  • Time Frame: 7 months after treatment
    Safety Issue?: No
• Number of Participants With Stroke Events
  • Time Frame: upto 7 months after randomization
    Safety Issue?: No
• Number of Participants With Overall Cardiovascular Events
  • Time Frame: upto 7 months after randomization
    Safety Issue?: No
• Number of Patients With Ipsilateral Ischemic Stroke Rate
  • Time Frame: upto 7 months after randomization
    Safety Issue?: No
• Numbers of Fatal or Major Bleeding Complications
  • Time Frame: upto 7 months after randomization
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 35 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Asan Medical Center Other

Overall Clinical Trial Officials and Contacts

Sun U. Kwon, MD, PhD Principal Investigator Asan Medical Center, Univsersity of Ulsan, Medical College  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00130039

Study ID Number: TOSS-2

ClinicalTrials.gov Identifier: NCT00130039

Health Authority: South Korea: Korea Food and Drug Administration (KFDA)