Cilostazol for Prevention of Recurrent Stroke (CLARITY)

/ABSTRACT In recent years, clinical trials have demonstrated that ischemic stroke recurrence can be reduced during the first weeks after stroke or TIA with a short course of dual antiplatelet therapy (DAPT). These trials, however, do not address the ongoing risk of recurrent stroke in the following years. Antiplatelet monotherapy with either aspirin or clopidogrel remains standard-of-care for long-term secondary stroke prevention in patients with non- cardioembolic stroke or TIA. On this regimen, the annual rate of major cardiovascular events (MACE), predominantly recurrent stroke, averages 4-8%, highlighting the need for better long-term stroke prevention. A large trial of stroke prevention in Japan suggested that long-term use of cilostazol cuts the risk of recurrent stroke and cardiovascular events (MACE) in half, likely through beneficial pleiotropic effects on platelet aggregation, blood pressure, plasma lipids, and vascular remodeling. Despite this robust effect, cilostazol is rarely prescribed in the United States for secondary stroke prevention (<1% of eligible patients) because prior trials had limitations including open-label design and a homogeneous population of predominantly Asian men. To address these limitations, we designed Cilostazol for Prevention of Recurrent Stroke (CLARITY), a double-blind placebo- controlled trial of cilostazol in a population that reflects the diversity of patients with stroke in the US. CLARITY will test the hypothesis that cilostazol, added to standard-of-care treatment with a single antiplatelet (aspirin or clopidogrel) within 180 days of stroke or high-risk TIA, will reduce ischemic stroke, myocardial infarction, and vascular death (MACE) during long-term follow-up (2+ years). The CLARITY trial will recruit 2,000 patients at 100 NINDS Stroke Net sites utilizing innovative strategies for broad, inclusive enrollment as well as trial conduct, specifically a novel coordinator-led and scalable approach to facilitate enrollment of a diverse cohort. Positive results of CLARITY would have a major public health impact because cilostazol is an inexpensive and safe medication that is already FDA-approved for claudication and will therefore be immediately available for secondary stroke prevention in millions of stroke and TIA survivors. Because cilostazol is a generic drug, and thus elicits little interest from large pharmaceutical companies to conduct clinical trials to test its efficacy, CLARITY is ideally suited for the NIH Stroke Net, where the trial will be conducted. The scientific premise of this trial is in direct support of NIH/NINDS’ primary mission to reduce the burden of neurological disease for all people. Project Number: 1UG3NS133209-01A1 | Fiscal Year: 2025 | NIH Institute/Center: National Institute of Neurological Disorders and Stroke (NINDS) | Principal Investigator: MAARTEN LANSBERG (+2 co-PIs) | Institution: STANFORD UNIVERSITY, STANFORD, CA | Award Amount: $5,747,701 | Activity Code: UG3 | Study Section: Special Emphasis Panel[ZNS1 SRB-W (26)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11141984