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

The Effect and Safety of Therapy Adding Cilostazol in Acute Ischemic Stroke Due to Large Artery Atherosclerosis: CHANGE Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Cerebral Infarction; Stenosis Artery
• Intervention / Treatment: Drug: Aspirin; Drug: Clopidogrel; Drug: Cilostazol; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 2340
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Bum Joon Kim, Professor; Phone Number: +82-2- 3010-3981; Email: bj.kim@amc.seoul.kr

Study Locations

• South Korea
  • Busan, South Korea
    • Recruiting
    • Pusan National University Hospital
    • Contact: Hanjun Cho; Phone Number: +82-51-240-7000; Email: chohj75@gmail.com
  • Cheongju-si, South Korea
    • Recruiting
    • Chungbuk National University Hospital
    • Contact: Hee-yoon Chae, MD, PhD; Phone Number: +82-1533-0075; Email: chy4142@gmail.com
  • Daegu, South Korea
    • Recruiting
    • Kyungpook National University Chilgok Hospital
    • Contact: Mi-Yeon Eun, MD, PhD; Phone Number: +82-1533-8888; Email: eunmiyn@gmail.com
  • Daejeon, South Korea
    • Recruiting
    • Chungnam National University Hospital
    • Contact: Jong Wook Shin, MD, PhD; Phone Number: +82-1599-7123; Email: jeonghs1028@gmail.com
  • Daejeon, South Korea
    • Recruiting
    • Eulji University Hospital
    • Contact: Jae Guk Kim, MD, PhD; Phone Number: +82-1899-0001; Email: jgkim@eulji.ac.kr
  • Gwangju, South Korea
    • Recruiting
    • Chonnam National University Hospital
    • Contact: Kang-Ho Choi, MD, PhD; Phone Number: +82-1899-0000; Email: ckhchoikang@hanmail.net
  • Gyeonggi-do, South Korea
    • Recruiting
    • Korea University Ansan Hospital
    • Contact: Jin-Man Jung, MD, PhD; Phone Number: +82-31-412-5114; Email: sodium75@hanmail.net
  • Gyeonggi-do, South Korea, 13620
    • Recruiting
    • Seoul National University Bundang Hospital
    • Contact: Beom Joon Kim, MD, PhD; Phone Number: +82-1588-3369; Email: kim.bj.stroke@gmail.com
  • Gyeonggi-do, South Korea
    • Recruiting
    • Hallym University Medical Center
    • Contact: Minwoo Lee, MD, PhD; Phone Number: +82-1577-1801; Email: minwoo.lee.md@gmail.com
  • Gyeonggi-do, South Korea
    • Recruiting
    • Hanyang University Guri Hospital
    • Contact: Hyuk Sung Kwon, MD, PhD; Phone Number: +82-1644-9118; Email: hamohamo1318@gmail.com
  • Incheon, South Korea, 21565
    • Recruiting
    • Gachon University Gil Medical Center
    • Contact: SangHee Ha, MD, PhD; Phone Number: +82-1577-2299; Email: shha31@naver.com
  • Incheon, South Korea
    • Recruiting
    • Inha University Hospital
    • Contact: Cindy W Yoon, MD, PhD; Phone Number: +82-1600-8114; Email: cindywyoon1981@gmail.com
  • Jeju City, South Korea
    • Recruiting
    • Jeju National University Hospital
    • Contact: Joong Goo Kim, MD, PhD; Phone Number: +82-64-717-1114; Email: lilis1118@naver.com
  • Jeonju, South Korea
    • Recruiting
    • Jeonbuk National University Hospital
    • Contact: Hyun Goo Kang, MD, PhD; Phone Number: +82-1577-7877; Email: hgkang@jbnu.ac.kr
  • Seoul, South Korea
    • Recruiting
    • Samsung Medical Center
    • Contact: Woo Keun Seo, MD, PhD; Phone Number: +82-1599-3114; Email: mcastenosis@gmail.com
  • Seoul, South Korea
    • Recruiting
    • Korea University Guro Hospital
    • Contact: Chi Kyung Kim, MD, PhD; Phone Number: +82-1577-9966; Email: ckkim7@gmail.com
  • Seoul, South Korea
    • Recruiting
    • The Catholic University of Korea, Seoul St. Mary's Hospital
    • Contact: Minhwan Lee, MD, PhD; Phone Number: +82-1588-1511; Email: prelee01@naver.com
  • Seoul, South Korea
    • Recruiting
    • Ewha Womans University Seoul Hospital
    • Contact: Tae-Jin Song, MD, PhD; Phone Number: +82-1522-7000; Email: knstar@hanmail.net
  • Seoul, South Korea
    • Recruiting
    • Hanyang University Seoul Hospital
    • Contact: Youngseo Kim, MD, PhD; Phone Number: +82-2-2290-8114; Email: aescula@hanmail.net
  • Seoul, South Korea
    • Recruiting
    • Kyung Hee University Hospital
    • Contact: Hogeol Woo, MD, PhD; Phone Number: +82-2-958-8114; Email: nr85plasma@gmail.com
  • Seoul, South Korea
    • Recruiting
    • Kyung Hee University Hospital at Gangdong
    • Contact: Kyung Chul Noh, MD, PhD; Phone Number: +82-1577-5800; Email: kyungchulnoh85@gmail.com
  • Seoul, South Korea
    • Not yet recruiting
    • Yonsei University Health System, Gangnam Severance Hospital
    • Contact: Yo Han Jung, MD, PhD; Phone Number: +82-1599-6114; Email: yhjung@yuhs.ac
  • Yangsan, South Korea
    • Recruiting
    • Pusan National University Yangsan Hospital
    • Contact: Sungho Ahn, MD, PhD; Phone Number: +82-1577-7512; Email: caesar-ahn@hanmail.net
  • Songpa-gu
    • Seoul, Songpa-gu, South Korea, 05505
      • Recruiting
      • Asan Medical Center
      • Contact: Bum Joon Kim, MD, PhD; Phone Number: +82-2-3010-3981; Email: medicj80@hanmail.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CA group; 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; 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); Drug: Clopidogrel; Clopidogrel 75mg qd (180days); Route: per oral. IMP can be taken with or without food.; Frequency: once daily (qd); Drug: Cilostazol; Cilostazol SR 100mg x 2cap (180days); Route: per oral. IMP can be taken with or without food.; Frequency: once daily (qd)
Placebo Comparator: PA group; 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; 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); Drug: Clopidogrel; Clopidogrel 75mg qd (180days); Route: per oral. IMP can be taken with or without food.; Frequency: once daily (qd); Drug: Placebo; Placebo x 2cap (180days); Route: per oral. IMP can be taken with or without food.; Frequency: once daily (qd)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preplanned subgroup analysis	For the primary endpoint, analyses will be performed in the following subgroups: Proportion of occurrence of composite endpoint* in patients with; Intracranial atherosclerosis; Extracranial atherosclerosis; Stent insertion; CYP2C19 poor metabolizersComposite endpoint: Neurologic deterioration during admission (within 14 days) or recurrence of ischemic stroke within 180 days after stroke	during admission (within 14 days), within 180days
Time to recurrence of ischemic stroke		within 180days

Collaborators and Investigators

• Sponsor: Asan Medical Center
• Collaborators: Korea Otsuka Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2025
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2028

Study Registration Dates

• First Submitted: December 26, 2024
• First Submitted That Met QC Criteria: December 26, 2024
• First Posted (Actual): January 3, 2025

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 25, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Brain Infarction; Brain Ischemia; Infarction; Necrosis; Ischemia; Stroke; Pathological Conditions, Signs and Symptoms; Cerebral Infarction; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Azoles; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Phenols; Benzene Derivatives; Quinolines; Thiophenes; Salicylates; Hydroxybenzoates; Tetrazoles; Ticlopidine; Thienopyridines; Clopidogrel; Cilostazol; Aspirin
• Other Study ID Numbers: CHANGE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No