Clinical trial NCT00130039: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cerebral Infarction
Atherosclerosis
Keywords: Infarction, Cerebral
cilostazol
stenosis
atherosclerosis
clopidogrel
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
Collaborators: name: Korea Otsuka International Asia Arab
First posted: 2005-08-15
Enrollment: 457
Sex: ALL
Minimum age (years): 35
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Progression of Symptomatic Intracranial Stenosis
timeFrame: 7 months after treatment
Secondary outcomes:
measure: Number of Participants With New MRI (Magnetic Resonance Image) Lesions on Follow-up MRI
timeFrame: 7 months after treatment
measure: Number of Participants With Stroke Events
timeFrame: upto 7 months after randomization
measure: Number of Participants With Overall Cardiovascular Events
timeFrame: upto 7 months after randomization
measure: Number of Patients With Ipsilateral Ischemic Stroke Rate
timeFrame: upto 7 months after randomization
measure: Numbers of Fatal or Major Bleeding Complications
timeFrame: upto 7 months after randomization
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Seoul
country: Korea, Republic of
facility: Konkuk Univ. Hospital
state: Gwangjin-gu Hwayang-dong
city: Goyang
country: Korea, Republic of
facility: Inje University Ilsan Paik Hospital
state: Gyeonggi-do
city: Goyang
country: Korea, Republic of
facility: Dongguk University International Hospital
state: Kyoungki-do
city: Anyang
country: Korea, Republic of
facility: Hallym University Sacred Heart Hospital
state: Kyunggi
city: Inchon
country: Korea, Republic of
facility: Inha University Hospital
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Kangdong Sacred Heart Hospital, Hallym University
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Soonchunhyang University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Boramae Hospital
city: Seoul
country: Korea, Republic of
facility: Eulji Hospital
city: Manila
country: Philippines
facility: Philippine General Hospital
city: Manila
country: Philippines
facility: University of Santo Tomas Hospital
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital
city: Bangkok
country: Thailand
facility: Siriraj Hospital
Study officials:
affiliation: Asan Medical Center, Univsersity of Ulsan, Medical College
name: Sun U. Kwon, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.