Combined antiplatelet treatment for acute ischemic stroke due to large artery atherosclerosis

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

This trial sees if adding cilostazol to aspirin and clopidogrel for adults who recently had an ischemic stroke caused by large artery atherosclerosis lowers the risk of early recurrent stroke.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 2340 (estimated)
• Ages: 20 Years and up
• Sex: All
• Sponsor: Asan Medical Center (Academic / other)
• Locations: 24 sites (Seoul, Songpa-gu and 23 other locations)
• Trial ID: NCT06757764 on ClinicalTrials.gov

What this trial studies

This Phase 4 randomized interventional trial enrolls adults within 72 hours of an acute ischemic stroke attributed to large artery atherosclerosis confirmed by diffusion-weighted MRI and ≥50% stenosis on MR or CT angiography. All participants receive standard aspirin plus clopidogrel and are randomized to receive either cilostazol or placebo in addition to dual antiplatelet therapy. Outcomes include early recurrent ischemic stroke, neurological deterioration, and safety endpoints such as hemorrhagic complications. The trial aims to determine whether adding cilostazol reduces early recurrence compared with placebo when combined with aspirin and clopidogrel.

Who should consider this trial

Good fit: Adults aged 20 or older with an acute ischemic stroke due to intra- or extracranial large artery atherosclerosis (DWI-confirmed lesion and ≥50% stenosis on MR/CT angiography) who can give informed consent within 72 hours of symptom onset are the ideal candidates.

Not a fit: Patients with large infarctions preventing antiplatelet start, acute intracranial hemorrhage or hemorrhagic transformation, those indicated for anticoagulation, with contraindications to aspirin/clopidogrel/cilostazol, pre-stroke disability (mRS >2), planned surgery, or otherwise judged unable to participate are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, adding cilostazol could lower early recurrent strokes and reduce neurological deterioration in patients with large-artery atherosclerotic ischemic stroke.

How similar studies have performed: Prior trials (CHANCE, POINT) support short-term aspirin plus clopidogrel, and post-hoc analyses of CSPS.com suggest cilostazol may reduce subsequent stroke—particularly after 15 days and in large-artery disease—but randomized data combining cilostazol with clopidogrel in the acute phase are limited.

Eligibility criteria

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.

Where this trial is running

Seoul, Songpa-gu and 23 other locations

• Asan Medical Center — Seoul, Songpa-gu, 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, 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, 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)

Study contacts

• Study coordinator: Bum Joon Kim, Professor

Conditions Cerebral Infarction; Stenosis Artery