Long-Term Sequential Dual Antiplatelet Therapy Based on Cilostazol in Symptomatic Intracranial Arterial Stenosis (SPDACSIS-RCT)

The Secondary Preventive Effect of Long-term Sequential Dual Antiplatelet Therapy Based on Cilostazol in Cerebral Infarction Patients With Symptomatic Moderate to Severe Intracranial Arterial Stenosis: A Single-Center, Randomized, Open-Label, Blinded-Endpoint Clinical Trial (SPDACSIS-RCT)

This study aims to evaluate whether long-term dual antiplatelet therapy (DAPT) with cilostazol reduces the risk of recurrent symptomatic ischemic stroke or all-cause mortality compared with single antiplatelet therapy (SAPT) in patients with symptomatic moderate-to-severe intracranial arterial stenosis, following the completion of standard DAPT.

Study Overview

• Status: Recruiting
• Conditions: Ischemic Stroke; Symptomatic Intracranial Atherosclerotic Stenosis
• Intervention / Treatment: Drug: Cilostazol; Drug: Aspirin; Drug: Clopidogrel; Drug: Ticagrelor

Detailed Description

Patients with symptomatic intracranial arterial stenosis remain at high risk of recurrent stroke despite standard medical treatment. Although short-term DAPT is recommended, the optimal long-term antiplatelet strategy following standard treatment remains uncertain. Cilostazol-based DAPT may provide additional protection against recurrent ischemic events with an acceptable bleeding risk. Therefore, this study aims to evaluate whether long-term cilostazol-based DAPT reduces the risk of recurrent symptomatic ischemic stroke or all-cause mortality compared to SAPT in patients with symptomatic moderate-to-severe intracranial arterial stenosis.

• Study Type: Interventional
• Enrollment (Estimated): 480
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Yongjun Cao, M.D, PhD; Phone Number: +86 512 67784789; Email: yongjuncao@126.com

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215004
      • Recruiting
      • Second Affiliated Hospital of Soochow University
      • Contact: Yongjun Cao, M.D, PhD; Phone Number: +86 512 67784789; Email: yongjuncao@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age: 18-80 years old.
2. Acute mild non-cardioembolic stroke.
3. Ischemic stroke or transient ischemic attack (TIA) occurring 2 to 4 weeks prior to enrollment.
4. NIHSS score ≤15 at enrollment and pre-stroke mRS score ≤2.
5. Ischemic stroke or TIA attributable to the territory of the qualifying intracranial artery.
6. Symptomatic 70%-99% intracranial atherosclerotic stenosis confirmed by DSA, CTA, or MRA.
7. Completion of 3 months of standard dual antiplatelet therapy (DAPT).
8. Medication adherence ≥80% during the 3 months of standard DAPT.
9. High risk for recurrent stroke (defined by at least one prespecified high-risk feature) at the second screening after 3 months of standard DAPT.
10. No intracranial endovascular or surgical revascularization within the preceding 3 months.
11. No newly developed contraindications to cilostazol-based DAPT or single antiplatelet therapy.
12. Signed informed consent by the patient or legally authorized representative.

Exclusion Criteria:

1. High-risk cardioembolic source requiring or potentially requiring long-term anticoagulation, including persistent or paroxysmal atrial fibrillation, mechanical heart valve or severe valvular disease, intracardiac thrombus, recent myocardial infarction with significant wall-motion abnormality, or severe cardiomyopathy.
2. Stroke or TIA caused by nonatherosclerotic disease, including moyamoya disease, vasculitis, arterial dissection, or other definite nonatherosclerotic causes.
3. Known allergy or serious adverse reaction to cilostazol, aspirin, clopidogrel, ticagrelor, or other antiplatelet agents.
4. Current or previous severe heart failure.
5. Severe bleeding event within the previous 6 months, including spontaneous intracranial hemorrhage, major gastrointestinal bleeding, or other bleeding requiring blood transfusion.
6. Significant bleeding tendency or coagulation abnormality.
7. Medical condition requiring long-term oral anticoagulation.
8. Active malignancy or other serious illness with a life expectancy of less than 1 year.
9. Severe cognitive impairment or psychiatric illness that would prevent adherence to study treatment or long-term follow-up.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cilostazol-Based Dual Antiplatelet Therapy; Participants will receive cilostazol 50 mg twice daily in combination with one antiplatelet agent: aspirin 100 mg once daily, clopidogrel 75 mg once daily, or ticagrelor 90 mg twice daily, for 12 months.	Drug: Cilostazol; Cilostazol 50 mg twice daily for 12 months. Cilostazol is administered in the experimental arm in combination with one antiplatelet agent: aspirin, clopidogrel, or ticagrelor.; Drug: Aspirin; Aspirin 100 mg once daily for 12 months. Aspirin may be administered in combination with cilostazol in the experimental arm or as single antiplatelet therapy in the active comparator arm.; Drug: Clopidogrel; Clopidogrel 75 mg once daily for 12 months. Clopidogrel may be administered in combination with cilostazol in the experimental arm or as single antiplatelet therapy in the active comparator arm.; Drug: Ticagrelor; Ticagrelor 90 mg twice daily for 12 months. Ticagrelor may be administered in combination with cilostazol in the experimental arm or as single antiplatelet therapy in the active comparator arm.
Active Comparator: Single Antiplatelet Therapy; Participants will receive single antiplatelet therapy with aspirin 100 mg once daily, clopidogrel 75 mg once daily, or ticagrelor 90 mg twice daily, for 12 months.	Drug: Aspirin; Aspirin 100 mg once daily for 12 months. Aspirin may be administered in combination with cilostazol in the experimental arm or as single antiplatelet therapy in the active comparator arm.; Drug: Clopidogrel; Clopidogrel 75 mg once daily for 12 months. Clopidogrel may be administered in combination with cilostazol in the experimental arm or as single antiplatelet therapy in the active comparator arm.; Drug: Ticagrelor; Ticagrelor 90 mg twice daily for 12 months. Ticagrelor may be administered in combination with cilostazol in the experimental arm or as single antiplatelet therapy in the active comparator arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First Recurrent Symptomatic Ischemic Stroke or All-Cause Death	Time from Day 90 randomization to the first occurrence of recurrent symptomatic ischemic stroke or death from any cause.	From randomization through 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Any Stroke	Occurrence of any ischemic or hemorrhagic stroke during follow-up.	12 months
Incidence of Hemorrhagic Stroke	Occurrence of symptomatic intracranial hemorrhage or subarachnoid hemorrhage.	12 months
Incidence of Ischemic Stroke or Transient Ischemic Attack	Occurrence of ischemic stroke or transient ischemic attack during follow-up.	Time Frame
Modified Rankin Scale Score	Functional outcome assessed using the Modified Rankin Scale (mRS), ranging from 0 to 6. A score of 0 indicates no symptoms, whereas a score of 6 indicates death. Higher scores represent greater disability and worse functional outcomes.(0 = no symptoms; 1 = no significant disability despite symptoms; 2 = slight disability, unable to perform all previous activities but able to manage personal affairs without assistance; 3 = moderate disability, requiring some help but able to walk without assistance; 4 = moderately severe disability, unable to walk without assistance and unable to attend to bodily needs without assistance; 5 = severe disability, bedridden, incontinent, and requiring constant nursing care and attention; and 6 = death.)	12 months
Incidence of All Vascular Events	Composite vascular events including stroke, myocardial infarction, and other vascular events such as aortic dissection, aortic rupture, pulmonary embolism, hospitalization for heart failure, angina or peripheral artery disease, and coronary, aortic, cervicocephalic, or peripheral arterial revascularization.	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Bleeding	Number and proportion of participants who experience bleeding classified as Bleeding Academic Research Consortium (BARC) grade 3 or higher during follow-up.	12 months
Incidence of Adverse Events	Occurrence of any adverse event during the 12-month treatment and follow-up period.	12 months
Incidence of Cilostazol-Related Adverse Events Leading to Treatment Discontinuation	Number and proportion of participants in the cilostazol-based dual antiplatelet therapy group who discontinue cilostazol because of cilostazol-related adverse events, including headache, diarrhea, abnormal stools, palpitations, tachycardia, dizziness, or other adverse reactions considered related to cilostazol.	12 months

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2026
• Primary Completion (Estimated): February 28, 2029
• Study Completion (Estimated): June 30, 2029

Study Registration Dates

• First Submitted: November 2, 2026
• First Submitted That Met QC Criteria: November 8, 2026
• First Posted (Actual): November 12, 2026

Study Record Updates

• Last Update Posted (Actual): November 12, 2026
• Last Update Submitted That Met QC Criteria: November 8, 2026
• Last Verified: November 1, 2026

More Information

Terms related to this study

• Keywords: Ischemic Stroke; Cilostazol; Dual Antiplatelet Therapy; Secondary Prevention
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Ischemic Stroke; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Azoles; Nucleic Acids, Nucleotides, and Nucleosides; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Purines; Phenols; Benzene Derivatives; Nucleosides; Ribonucleosides; Quinolines; Thiophenes; Salicylates; Hydroxybenzoates; Adenosine; Purine Nucleosides; Tetrazoles; Ticlopidine; Thienopyridines; Ticagrelor; Clopidogrel; Cilostazol; Aspirin
• Other Study ID Numbers: LK2026004; SYW2026005 (Other Grant/Funding Number: SuZhou Municipal Health Commission)

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