Cilostazol Stroke Prevention Study for Antiplatelet Combination

Study Overview
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Brief Summary
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To examine the efficacy and safety of dual antiplatelet therapy (DAPT) including cilostazol (Pletaal OD Tablet ®) in comparison with antiplatelet monotherapy (excluding cilostazol) for secondary prevention of ischemic stroke in high-risk patients for stroke

Official Title
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Cilostazol Stroke Prevention Study for Antiplatelet Combination

Conditions
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Noncardioembolic Cerebral Infarction

Intervention / Treatment
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* Drug: aspirin
* Drug: clopidogrel
* Drug: cilostazol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a diagnosis of noncardioembolic IS that developed between 8 and 180 days before the start of the protocol treatment Patients with a responsible lesion identified by MRI Patients aged 20 to 85 years old when providing informed consent Patients taking clopidogrel or aspirin alone as antiplatelet therapy when providing informed consent Patients meeting at least one of the following criteria a-c: at least 50% stenosis of a major intracranial artery (to the level of A2, M2, or P2) at least 50% stenosis of an extracranial artery (the common carotid artery，internal carotid artery，vertebral artery，brachiocephalic artery，or subclavian artery) Two or more of the following risk factors Aged 65 years or more Diabetes mellitus Hypertension Peripheral arterial disease Chronic kidney disease History of IS (excluding the index IS for this study) History of ischemic heart disease Smoking (only current smokers) Patients considered to be able to visit the study site for ambulatory care throughout the observation period Patients who provided written informed consent Exclusion Criteria: Patients with emboligenic heart disease Patients taking any anticoagulant agents Patients who cannot undergo MRI examination for reasons such as claustrophobia and implanted pacemaker Patients scheduled to undergo any surgery, such as percutaneous angioplasty, stent placement, and bypass grafting, during the study period Patients with a drug-eluting coronary stent implanted within one year Patients with a history of symptomatic non-traumatic intracranial hemorrhage, any other hemorrhagic disease (eg, active peptic ulcer), bleeding predisposition, or blood clotting disorders Patients with a history of hypersensitivity to cilostazol Patients with congestive heart failure or uncontrolled angina pectoris Patients with thrombocytopenia (platelet count ≦ 100,000/mm3) Patients with severe liver or renal dysfunction Women who are pregnant, breast-feeding, or of child-bearing potential Patients with a malignant tumor requiring treatment Patients who are taking aspirin, and meet any of the following criteria: History of hypersensitivity to aspirin or salicylic acid analogues Current peptic ulcer Aspirin-induced asthma or its history Patients who are taking clopidogrel, and meet the following criterion: ・History of hypersensitivity to clopidogrel Patients who are participating in any other clinical studies Patients considered by the investigator/subinvestigator to be unsuitable for participating in this study

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Monotherapy group<br>Aspirin (81mg or 100mg) or clopidogrel (50mg or 75mg) will be orally administered once daily. The treatment period will begin with the first visit of the first subject and end one year after the first visit of the last subject. | Drug: aspirin<br>* Aspirin (81mg or 100mg) will be orally administered once daily.The treatment period will begin with the first visit of the first subject and end one year after the first visit of the last subject.<br>* Other names: Bayaspirin;Drug: clopidogrel<br>* Clopidogrel (50mg or 75mg) will be orally administered once daily.The treatment period will begin with the first visit of the first subject and end one year after the first visit of the last subject.<br>* Other names: Plavix;|
| Experimental: DAPT group<br>Cilostazol (100mg twice daily) will be orally administered in combination with aspirin (81 or 100mg once daily) or clopidogrel (50 or 75mg once daily). The treatment period will begin with the first visit of the first subject and end one year after the first visit of the last subject. | Drug: aspirin<br>* Aspirin (81mg or 100mg) will be orally administered once daily.The treatment period will begin with the first visit of the first subject and end one year after the first visit of the last subject.<br>* Other names: Bayaspirin;Drug: clopidogrel<br>* Clopidogrel (50mg or 75mg) will be orally administered once daily.The treatment period will begin with the first visit of the first subject and end one year after the first visit of the last subject.<br>* Other names: Plavix;Drug: cilostazol<br>* Cilostazol (100mg twice daily) will be orally administered. The treatment period will begin with the first visit of the first subject and end one year after the first visit of the last subject.<br>* Other names: Pletaal OD Tablet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence of symptomatic ischemic stroke, with the symptoms lasting for at least 24 hours | An ischemic stroke hereafter indicates a symptomatic ischemic stroke. | every 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Any stroke [ischemic stroke (IS), intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH)] |  | every 6 months | 
| SAH or ICH |  | every 6 months | 
| IS or transient ischemic attack (TIA) |  | every 6 months | 
| Death from any cause |  | every 6 months | 
| Stroke (IS，ICH，SAH), myocardial infarction (MI), or vascular death |  | every 6 months | 
| All vascular events: stroke, MI, and other vascular events |  | every 6 months | 
| Adverse events and adverse drug reactions |  | every 6 months | 
| Severe or life-threatening hemorrhage (GUSTO Criteria) |  | every 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clopidogrel, Noncardioembolic cerebral infarction, Dual antiplatelet therapy (DAPT), Cilostazol, Aspirin