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

Phase 4

Not yet recruiting

• Conditions: Cerebral Infarction; Stenosis Artery
• Interventions: Drug: Aspirin; Drug: Clopidogrel; Drug: Cilostazol; Drug: Placebo

• Registration Number: NCT06757764
• Lead Sponsor: Asan Medical Center

Brief Summary

Currently, aspirin plus clopidogrel is considered as a standard acute treatment of ischemic stroke, based on results of CHANCE and POINT trial. However, still a considerable portion of patients showed early stroke recurrence, especially in those with stroke due to large artery atherosclerosis. Cilostazol may have benefit in reducing early stroke recurrence of neurologic deterioriation. The post-hoc analysis of CSPS.com showed that use of cilostazol after 15 days of stroke was effective for preventing subsequent stroke. The effect of adding cilostazol was more effective in those with large artery atherosclerosis and those receiving clopidogrel than aspirin.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-12-26
• Study First Submitted QC: 2024-12-26
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-02
• Study First Posted: 2025-01-03
• Last Update Posted: 2025-01-06
• Study Start: 2025-03-15
• Primary Completion: 2028-03-31
• Study Completion: 2028-03-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 2340

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 or CT angiography.
3. Able to start IMP 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CA group	Aspirin	Aspirin 100mg qd (21days), clopidogrel 75mg qd (180days), Cilostazol SR 100mg x 2cap (180days). In case of stenting, aspirin will be added to cilostazol and clopidogrel until 90 days after stenting.
CA group	Clopidogrel	Aspirin 100mg qd (21days), clopidogrel 75mg qd (180days), Cilostazol SR 100mg x 2cap (180days). In case of stenting, aspirin will be added to cilostazol and clopidogrel until 90 days after stenting.
CA group	Cilostazol	Aspirin 100mg qd (21days), clopidogrel 75mg qd (180days), Cilostazol SR 100mg x 2cap (180days). In case of stenting, aspirin will be added to cilostazol and clopidogrel until 90 days after stenting.
PA group	Aspirin	Aspirin 100mg (21days), clopidogrel 75mg qd (180days), Placebo x 2cap (180days). In case of stenting, aspirin will be added to placebo and clopidogrel until 90 days after stenting.
PA group	Clopidogrel	Aspirin 100mg (21days), clopidogrel 75mg qd (180days), Placebo x 2cap (180days). In case of stenting, aspirin will be added to placebo and clopidogrel until 90 days after stenting.
PA group	Placebo	Aspirin 100mg (21days), clopidogrel 75mg qd (180days), Placebo x 2cap (180days). In case of stenting, aspirin will be added to placebo and clopidogrel until 90 days after stenting.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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 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