The Effect and Safety of Combined Anti-platelet Treatment in Acute Ischemic Stroke Due to Large Artery Atherosclerosis

• Aspirin (Drug): Aspirin 100mg qd (21days) * In case of stenting, aspirin will be added to cilostazol and clopidogrel until 90 days after stenting. * Route: per oral. IMP can be taken with or without food. * Frequency: once daily (qd)
• Clopidogrel (Drug): Clopidogrel 75mg qd (180days) * Route: per oral. IMP can be taken with or without food. * Frequency: once daily (qd)
• Cilostazol (Drug): Cilostazol SR 100mg x 2cap (180days) * Route: per oral. IMP can be taken with or without food. * Frequency: once daily (qd)
• Placebo (Drug): Placebo x 2cap (180days) * Route: per oral. IMP can be taken with or without food. * Frequency: once daily (qd)

Primary outcomes

• Proportion of occurrence of composite endpoint [during admission (within 14 days) and within 180 days after stroke]: *Composite endpoint: Neurologic deterioration† during admission (within 14 days) or recurrence of ischemic stroke‡ within 180 days after stroke †Neurologic deterioration: Increment of 2 or more in total NIHSS(National Institutes of Health Stroke Scale) score or one or more in the motor NIHSS score. ‡Recurrence of ischemic stroke: A newly developed neurological deficit corresponding to a new ischemic lesion confirmed by neuro-imaging.

Secondary outcomes

• Proportion of participants with good functional outcome (mRS(modified Rankin Scale) 0-2) [at 180 days]
• mRS score collected at 180 days [at 180 days]
• Proportion of participants with Neurologic Deterioration(ND) during admission [during admission(within 14days)]
• Proportion of participants with good functional outcome (mRS 0-2) [at 90 days]
• Proportion of participants with ischemic stroke recurrence [at 90 days]
• Proportion of participants with ischemic stroke recurrence [at 180 days]
• Proportion of participants with MI(Myocardial Infarction), ischemic stroke recurrence, haemorrhagic stroke and vascular death [within 180 days]
• Proportion of participants with haemorrhagic stroke [within 180 days]
• Proportion of participants with myocardial infarction [within 180 days]
• Proportion of participants with vascular death [within 180 days]
• mRS score collected at 90 days [at 90 days]

Other outcomes

• Preplanned subgroup analysis [during admission (within 14 days), within 180days]: For the primary endpoint, analyses will be performed in the following subgroups: Proportion of occurrence of composite endpoint* in patients with 1. Intracranial atherosclerosis 2. Extracranial atherosclerosis 3. Stent insertion 4. CYP2C19 poor metabolizers * Composite endpoint: Neurologic deterioration during admission (within 14 days) or recurrence of ischemic stroke within 180 days after stroke
• Time to recurrence of ischemic stroke [within 180days]

Sex: All, ages: 20 Years to any

Inclusion Criteria:

1. Age of 20 years or older
2. Acute ischemic stroke due to large artery atherosclerosis (both including Intra and extracranial atherosclerosis) which may be defined by a ischemic lesion confirmed at diffusion-weighted image and a corresponding significant stenosis (more than 50% of diameter reduction) proximal to the ischemic lesion confirmed by MR angiography or CT angiography.
3. Informed consent obtained within 72h from stroke onset
4. Acquisition of written informed consent prior to study entry

Exclusion Criteria:

1. Large infarction unable to start antiplatelet treatment
2. Combined with acute intracranial haemorrhage
3. With initial haemorrhagic transformation
4. Previous mRS higher than 2
5. Indicated for anticoagulation
6. Contraindication for aspirin, clopidogrel or cilostazol
7. Requirement of long term NSAID
8. Pre-planned for surgery
9. Unable to withdraw consent
10. Unavailable to participate based on judgement of the investigator
11. Participants of reproductive potential (PORP)/ Participants of childbearing potential (POCBP) who do not agree to practice methods of birth control or remain fully abstinent from sexual activity with the potential for conception.