Cilostazol for Prevention of Recurrent Stroke Trial

• Cilostazol 100 mg Tablets (Drug): The standard dosing regimen is an initial 2-week period during which participants take one tablet of cilostazol (100 mg) orally once daily followed by a maintenance phase in which they take one tablet twice daily. For participants who are on certain interacting drugs or who experience adverse reactions on the standard dosing regimen, the dose is reduced to half a tablet twice daily.
• Placebo (Drug): The standard dosing regimen is an initial 2-week period during which participants take one placebo tablet, which matches cilostazol 100 mg tablets, orally once daily followed by a maintenance phase in which they take one tablet twice daily. For participants who are on certain interacting drugs or who experience adverse reactions on the standard dosing regimen, the dose is reduced to half a tablet twice daily.

Primary outcomes

• Time to first occurrence of any component of the composite of ischemic stroke, acute myocardial infarction, or ischemic vascular death (MACE). [Up to 5 years after randomization]: Major Adverse Cardiovascular Events (MACE) is a composite outcome. MACE is any one of the following: ischemic stroke, acute myocardial infarction (heart attack), or ischemic vascular death (death caused by a lack of blood flow). In this study, the measure is the time from randomization to a particpant's first MACE.

Secondary outcomes

• Time to first occurrence of ischemic stroke [Up to 5 years after randomization]: Ischemic stroke is a stroke caused by a blocked blood vessel in the brain. The measure is the time from randomization to the first ischemic stroke
• Time to first occurrence of major hemorrhage [Up to 5 years after randomization]: Major hemorrhage is defined as the composite of 'major intracranial hemorrhage' and 'major extracranial hemorrhage', based on the International Society on Thrombosis and Haemostasis (ISTH) criteria. The measure is the time from randomization to the first major hemorrhage.

Sex: All, ages: 40 Years to any

Inclusion Criteria:

1. ≥40 years
2. Ischemic stroke or high-risk TIA (ABCD2 score ≥6)
3. Can be randomized within 180 days after ischemic stroke or high-risk TIA
4. Treatment with single or dual antithrombotic therapy with aspirin, clopidogrel and/or ticagrelor per international and/or national guidelines
5. Two or more of the following risk factors: age 65 years or older, hypertension, diabetes mellitus, history of ischemic stroke other than the qualifying event for this trial, currently smoking, peripheral arterial disease, coronary artery disease including prior MI, aortic atherosclerotic plaque ≥4 mm, ≥50% stenosis or occlusion of a major intracranial artery (ICA, M1, M2, A1, P1, vertebral, or basilar) or extracranial artery (ICA or vertebral)
6. In the opinion of the site investigator, patient is medically stable, capable of participating in the trial, and willing and able to attend follow-up
7. Able to receive study drug by mail and able to begin taking study drug promptly after receipt
8. Provision of signed and dated informed consent form by patient or legally authorized representative

Exclusion Criteria:

1. Atrial fibrillation, mechanical heart valve, or left ventricular assist device
2. Use of prohibited medication (as specified in the MOP)
3. Modified Rankin Scale 5
4. Planned cardiac surgery, percutaneous coronary intervention, carotid endarterectomy or stenting (patients are eligible post-procedure)
5. History of symptomatic non-traumatic intracerebral hemorrhage within last 2 years
6. Known thrombocytopenia (platelet count ≤100,000 per microliter (µL))
7. Severe liver dysfunction (active hepatitis or hepatic insufficiency with Child-Pugh score B or C)
8. Pregnant, breast-feeding, or of child-bearing potential but not on birth control
9. Confirmed diagnosis of heart failure with current or prior symptoms or signs (e.g. paroxysmal nocturnal dyspnea, reduced exercise tolerance, ankle swelling, elevated jugular venous pressure)
10. Hypersensitivity to cilostazol or any component of the formulation (e.g. anaphylaxis, angioedema)
11. Currently enrolled in an investigational intervention study
12. Life expectancy less than 6 months
13. Participant does not allow contacting of their surrogate (e.g. family member or friend) or health care practitioner to obtain health information should participant become unwilling or unable to follow the study schedule.
14. Participants who are incarcerated, including prisoners or participants compulsorily detained for treatment of psychiatric disease.

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• Maarten Lansberg, MD, PhD, Principal investigator, Stanford University

NIH grants: 1UG3NS133209-01A1