Trial of Cilostazol in Symptomatic Intracranial Arterial Stenosis II

Phase 4

Completed

Brief Summary: 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: \[Goal\] 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

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
cilostazol	Cilostazol	cilostazol 100mg bid plus placebo of clopidogrel
Clopidogrel	clopidogrel	clopidogrel 75mg qd and matching placebo of cilostazol

Primary Outcome Measures

Name	Time	Method
Number of Participants With Progression of Symptomatic Intracranial Stenosis	7 months after treatment	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With New MRI (Magnetic Resonance Image) Lesions on Follow-up MRI	7 months after treatment	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.
Number of Participants With Stroke Events	upto 7 months after randomization	including nonfatal ischemic stroke, nonfatal hemorrhagic stroke and fatal stroke
Number of Participants With Overall Cardiovascular Events	upto 7 months after randomization	including nonfatal stroke, nonfatal myocardial infarction and vascular death.
Number of Patients With Ipsilateral Ischemic Stroke Rate	upto 7 months after randomization	ischemic stroke event which occured in the vascular territory of initial symptomatic stenosis
Numbers of Fatal or Major Bleeding Complications	upto 7 months after randomization	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

Locations (19): Inje University Ilsan Paik Hospital
🇰🇷
Goyang, Gyeonggi-do, Korea, Republic of
Dongguk University International Hospital
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Goyang, Kyoungki-do, Korea, Republic of
Hallym University Sacred Heart Hospital
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Anyang, Kyunggi, Korea, Republic of
Inha University Hospital
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Inchon, Korea, Republic of
Kangdong Sacred Heart Hospital, Hallym University
🇰🇷
Seoul, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷
Seongnam, Korea, Republic of
Samsung Medical Center
🇰🇷
Seoul, Korea, Republic of
Asan Medical Center
🇰🇷
Seoul, Korea, Republic of
Soonchunhyang University Hospital
🇰🇷
Seoul, Korea, Republic of
Seoul National University Boramae Hospital
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Seoul, Korea, Republic of
Eulji Hospital
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Seoul, Korea, Republic of
University of Santo Tomas Hospital
🇵🇭
Manila, Philippines
Philippine General Hospital
🇵🇭
Manila, Philippines
Siriraj Hospital
🇹🇭
Bangkok, Thailand
Ramathibodi Hospital
🇹🇭
Bangkok, Thailand
Konkuk Univ. Hospital
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Seoul, Gwangjin-gu Hwayang-dong, Korea, Republic of
Seoul National University Hospital
🇰🇷
Seoul, Korea, Republic of
Prince of Wales Hospital
🇭🇰
Hong Kong, Hong Kong
Queen Mary Hospital
🇭🇰
Hong Kong, Hong Kong