Trial of Cilostazol in Symptomatic Intracranial Arterial Stenosis II

NCT ID: NCT00130039

Last Updated: 2010-01-12

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

457 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-08-31

Study Completion Date

2009-01-31

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

Conditions

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Cerebral Infarction Atherosclerosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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cilostazol

cilostazol 100mg bid plus placebo of clopidogrel

Group Type EXPERIMENTAL

Cilostazol

Intervention Type DRUG

Cilostazol 100mg twice a day plus placebo of clopidogrel once a day

Clopidogrel

clopidogrel 75mg qd and matching placebo of cilostazol

Group Type ACTIVE_COMPARATOR

clopidogrel

Intervention Type DRUG

Clopidogrel 75mg once a day plus placebo of cilostazol twice a day

Interventions

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clopidogrel

Clopidogrel 75mg once a day plus placebo of cilostazol twice a day

Intervention Type DRUG

Cilostazol

Cilostazol 100mg twice a day plus placebo of clopidogrel once a day

Intervention Type DRUG

Other Intervention Names

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Plavix, produced by Sanofi-Aventis. cilostazol produced by Korea Otsuka Pharmaceutical

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
Minimum Eligible Age

35 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Korea Otsuka International Asia Arab

INDUSTRY

Sponsor Role collaborator

Asan Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Asan Medical Center

Principal Investigators

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Sun U. Kwon, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Asan Medical Center, Univsersity of Ulsan, Medical College

Locations

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Prince of Wales Hospital

Hong Kong, , Hong Kong

Site Status

Queen Mary Hospital

Hong Kong, , Hong Kong

Site Status

Philippine General Hospital

Manila, , Philippines

Site Status

University of Santo Tomas Hospital

Manila, , Philippines

Site Status

Konkuk Univ. Hospital

Seoul, Gwangjin-gu Hwayang-dong, South Korea

Site Status

Inje University Ilsan Paik Hospital

Goyang-si, Gyeonggi-do, South Korea

Site Status

Dongguk University International Hospital

Goyang, Kyoungki-do, South Korea

Site Status

Hallym University Sacred Heart Hospital

Anyang, Kyunggi, South Korea

Site Status

Soonchunhyang University Hospital

Seoul, Seoul, South Korea

Site Status

Inha University Hospital

Inchon, , South Korea

Site Status

Seoul National University Bundang Hospital

Seongnam, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Kangdong Sacred Heart Hospital, Hallym University

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Seoul National University Boramae Hospital

Seoul, , South Korea

Site Status

Eulji Hospital

Seoul, , South Korea

Site Status

Ramathibodi Hospital

Bangkok, , Thailand

Site Status

Siriraj Hospital

Bangkok, , Thailand

Site Status

Countries

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Hong Kong Philippines South Korea Thailand

References

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Park TH, Lee JS, Park SS, Ko Y, Lee SJ, Lee KB, Lee J, Kang K, Park JM, Choi JC, Kim DE, Cho YJ, Kim JT, Kim DH, Cha JK, Han MK, Lee J, Oh MS, Yu KH, Lee BC, Bae HJ, Hong KS. Safety and efficacy of intravenous recombinant tissue plasminogen activator administered in the 3- to 4.5-hour window in Korea. J Stroke Cerebrovasc Dis. 2014 Aug;23(7):1805-12. doi: 10.1016/j.jstrokecerebrovasdis.2014.04.027. Epub 2014 Jun 21.

Reference Type DERIVED
PMID: 24957314 (View on PubMed)

Kim BJ, Rha JH, Kim SR, Kim DE, Kim HY, Lee JH, Bae HJ, Han MK, Kang DW, Ratanakorn D, Kim JS, Kwon SU. The effect of cilostazol on carotid intima-media thickness progression in patients with symptomatic intracranial atherosclerotic stenosis. J Stroke Cerebrovasc Dis. 2014 May-Jun;23(5):1164-70. doi: 10.1016/j.jstrokecerebrovasdis.2013.10.007. Epub 2013 Dec 6.

Reference Type DERIVED
PMID: 24315720 (View on PubMed)

Jung JM, Kang DW, Yu KH, Koo JS, Lee JH, Park JM, Hong KS, Cho YJ, Kim JS, Kwon SU; TOSS-2 Investigators. Predictors of recurrent stroke in patients with symptomatic intracranial arterial stenosis. Stroke. 2012 Oct;43(10):2785-7. doi: 10.1161/STROKEAHA.112.659185. Epub 2012 Aug 21.

Reference Type DERIVED
PMID: 22910894 (View on PubMed)

Kim DE, Kim JY, Jeong SW, Cho YJ, Park JM, Lee JH, Kang DW, Yu KH, Bae HJ, Hong KS, Koo JS, Lee SH, Lee BC, Han MK, Rha JH, Lee YS, Kim GM, Chae SL, Kim JS, Kwon SU. Association between changes in lipid profiles and progression of symptomatic intracranial atherosclerotic stenosis: a prospective multicenter study. Stroke. 2012 Jul;43(7):1824-30. doi: 10.1161/STROKEAHA.112.653659. Epub 2012 Apr 26.

Reference Type DERIVED
PMID: 22539545 (View on PubMed)

Kwon SU, Hong KS, Kang DW, Park JM, Lee JH, Cho YJ, Yu KH, Koo JS, Wong KS, Lee SH, Lee KB, Kim DE, Jeong SW, Bae HJ, Lee BC, Han MK, Rha JH, Kim HY, Mok VC, Lee YS, Kim GM, Suwanwela NC, Yun SC, Nah HW, Kim JS. Efficacy and safety of combination antiplatelet therapies in patients with symptomatic intracranial atherosclerotic stenosis. Stroke. 2011 Oct;42(10):2883-90. doi: 10.1161/STROKEAHA.110.609370. Epub 2011 Jul 28.

Reference Type DERIVED
PMID: 21799173 (View on PubMed)

Other Identifiers

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TOSS-2

Identifier Type: -

Identifier Source: org_study_id

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