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

NCT06757764 | Recruiting Phase 4 DMC

• 1 other identifier: CHANGE
• Study Type: interventional
• Target: 2,340
• Locations: 1 country
• Sites: 24

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.

Conditions

Cerebral Infarction; Stenosis Artery

Outcome Measures

Primary Outcomes (1)

• Proportion of occurrence of composite endpoint

  \*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.

  during admission (within 14 days) and within 180 days after stroke

Secondary Outcomes (11)

• 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

Other Outcomes (2)

• Preplanned subgroup analysis

  during admission (within 14 days), within 180days

• Time to recurrence of ischemic stroke

  within 180days

Study Arms (2)

CA group

EXPERIMENTAL

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.

Drug: Aspirin; Drug: Clopidogrel; Drug: Cilostazol

PA group

PLACEBO COMPARATOR

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.

Drug: Aspirin; Drug: Clopidogrel; Drug: Placebo

Interventions

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)

CA group; PA group

Clopidogrel DRUG

Clopidogrel 75mg qd (180days) * Route: per oral. IMP can be taken with or without food. * Frequency: once daily (qd)

CA group; PA group

Cilostazol DRUG

Cilostazol SR 100mg x 2cap (180days) * Route: per oral. IMP can be taken with or without food. * Frequency: once daily (qd)

CA group

Placebo DRUG

Placebo x 2cap (180days) * Route: per oral. IMP can be taken with or without food. * Frequency: once daily (qd)

PA group

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age of 20 years or older
• 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.
• Informed consent obtained within 72h from stroke onset
• Acquisition of written informed consent prior to study entry

You may not qualify if:

• Large infarction unable to start antiplatelet treatment
• Combined with acute intracranial haemorrhage
• With initial haemorrhagic transformation
• Previous mRS higher than 2
• Indicated for anticoagulation
• Contraindication for aspirin, clopidogrel or cilostazol
• Requirement of long term NSAID
• Pre-planned for surgery
• Unable to withdraw consent
• Unavailable to participate based on judgement of the investigator
• 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.

Sponsors & Collaborators

• Asan Medical Center: lead
• Korea Otsuka Pharmaceutical Co., Ltd.: collaborator

Study Sites (24)

Asan Medical Center

Seoul, Songpa-gu, 05505, South Korea

RECRUITING

Pusan National University Hospital

Busan, South Korea

RECRUITING

Chungbuk National University Hospital

Cheongju-si, South Korea

RECRUITING

Kyungpook National University Chilgok Hospital

Daegu, South Korea

RECRUITING

Chungnam National University Hospital

Daejeon, South Korea

RECRUITING

Eulji University Hospital

Daejeon, South Korea

RECRUITING

Chonnam National University Hospital

Gwangju, South Korea

RECRUITING

Seoul National University Bundang Hospital

Gyeonggi-do, 13620, South Korea

RECRUITING

Hallym University Medical Center

Gyeonggi-do, South Korea

RECRUITING

Hanyang University Guri Hospital

Gyeonggi-do, South Korea

RECRUITING

Korea University Ansan Hospital

Gyeonggi-do, South Korea

RECRUITING

Gachon University Gil Medical Center

Incheon, 21565, South Korea

RECRUITING

Inha University Hospital

Incheon, South Korea

RECRUITING

Jeju National University Hospital

Jeju City, South Korea

RECRUITING

Jeonbuk National University Hospital

Jeonju, South Korea

RECRUITING

Ewha Womans University Seoul Hospital

Seoul, South Korea

RECRUITING

Hanyang University Seoul Hospital

Seoul, South Korea

RECRUITING

Korea University Guro Hospital

Seoul, South Korea

RECRUITING

Kyung Hee University Hospital at Gangdong

Seoul, South Korea

RECRUITING

Kyung Hee University Hospital

Seoul, South Korea

RECRUITING

Samsung Medical Center

Seoul, South Korea

RECRUITING

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, South Korea

RECRUITING

Yonsei University Health System, Gangnam Severance Hospital

Seoul, South Korea

NOT YET RECRUITING

Pusan National University Yangsan Hospital

Yangsan, South Korea

RECRUITING

MeSH Terms

Conditions

Cerebral Infarction

Interventions

Aspirin; Clopidogrel; Cilostazol

Condition Hierarchy (Ancestors)

Brain Infarction; Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Vascular Diseases; Cardiovascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tetrazoles; Azoles; Quinolines

Central Study Contacts

Bum Joon Kim, Professor

CONTACT

+82-2- 3010-3981; bj.kim@amc.seoul.kr

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 26, 2024
• First Posted: January 3, 2025
• Study Start: July 10, 2025
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2028
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

KR (24)