Trial of Cilostazol in Symptomatic Intracranial Arterial Stenosis II

Atherosclerosis Clinical Trial

— TOSS-2  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00130039
• Other study ID #: TOSS-2
• Status: Completed
• Phase: Phase 4
• First received: August 11, 2005
• Last updated: January 4, 2010
• Start date: August 2005
• Est. completion date: January 2009

Study information

• Verified date: November 2009
• Source: Asan Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Korea: Korea Food and Drug Administration (KFDA)
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 457
• Est. completion date: January 2009
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 35 Years and older

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atherosclerosis
• Cerebral Infarction
• Infarction

Intervention

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

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Asan Medical Center	Korea Otsuka International Asia Arab

Countries where clinical trial is conducted

Hong Kong,  Korea, Republic of,  Philippines,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Progression of Symptomatic Intracranial Stenosis		7 months after treatment	No
Secondary	Number of Participants With New MRI (Magnetic Resonance Image) Lesions on Follow-up MRI		7 months after treatment	No
Secondary	Number of Participants With Stroke Events		upto 7 months after randomization	No
Secondary	Number of Participants With Overall Cardiovascular Events		upto 7 months after randomization	No
Secondary	Number of Patients With Ipsilateral Ischemic Stroke Rate		upto 7 months after randomization	No
Secondary	Numbers of Fatal or Major Bleeding Complications		upto 7 months after randomization	Yes