INCLUSION CRITERIA:

1. 18 years or older
2. Able to randomize within 72 hours of last normal (NOTE: In case of thrombectomy or tNK, randomization can only occur > 24 hours later and after imaging post procedure excludes hemorrhage).
3. Acute non-cardioembolic stroke with NIHSS ≤ 15 at randomization (defined as either persistent signs and symptoms for ≥ 24 hours OR acute infarction on MRI, CT or CTP) OR high-risk TIA with complete resolution of symptoms within < 24 hours and an ABCD2 score ≥ 6
4. All participants must have at least one of the following criteria a – c:
   • (A) Cerebrovascular atherosclerosis defined as vascular imaging (CTA, MRA, ultrasound, DSA) showing atherosclerotic plaque involving intracranial or extracranial cerebral arteries or the aortic arch (qualifying plaques are those that clearly protrude into the lumen) – plaque does NOT have to be in vascular territory of index stroke
   • (B) Medical history of atherosclerosis:
     • CAD or AMI with documented coronary atherosclerotic disease, prior CABG, or prior PCI; PAD requiring previous bypass surgery or stenting, limb or foot amputation for PAD (i.e., excludes trauma), OR history of intermittent claudication and one or more of the following: 1) an ankle/arm blood pressure (BP) ratio < 0.90, or 2) documented PAD
     • Documented aortic arch plaque
     • Carotid stenosis ≥ 50% or previous carotid revascularization
   • (C) Brain imaging demonstrating an acute non-lacunar infarct (CT, CT perfusion or DWI MRI) defined as cortical location and/or size >20 mm for DWI and >15 mm for CT.
     • NOTE: CTP  with deficits that resolve after EVT and/or thrombolysis are eligible and will be considered as imaging evidence of ischemic stroke. Also participants who undergo EVT and have all symptoms/signs resolve within 24 hours of onset and without imaging evidence of infarction are eligible and will be considered to have (aborted) brain infarction.
5. If no brain infarct is documented prior to randomization (i.e. clinical diagnosis of stroke or TIA with negative imaging) at least one of the following needs to be present that is not otherwise explainable and is related to the acute ischemic stroke/TIA event: motor deficits, speech deficits (aphasia/dysarthria), visual deficits (hemianopsia) and/or neglect. Thus, patients with isolated dizziness/vertigo or isolated numbness are not eligible.
6. Plan for secondary prevention of stroke/TIA with single or dual antiplatelet therapy including ASA, clopidogrel, ticagrelor, prasugrel, cilostazol and dipyridamole and in line with local guidelines.

EXCLUSION CRITERIA:

SEE PROHIBITED MEDICATION LIST BELOW

1. Recent ischemic stroke within 7 days before index stroke event
2. Strokes (index event) following procedures (e.g. TAVI, CABG) or strokes due to other rare causes (e.g. bacterial endocarditis, vertebral artery dissections)
3. Known premorbid (before index event) mRS ≥ 4
4. Dysphagia with inability to safely swallow study medication at time of randomization5.                  
5. History of atrial fibrillation / flutter, left ventricular thrombus, mechanical valve or other cardioembolic source of stroke requiring anticoagulation
6. Sustained uncontrolled hypertension after index stroke/TIA event
7. Known vascular malformation of the brain with high risk for bleeding (except isolated cavernoma, aneurysm treated and secured, or aneurysm with diameter <5 mm)
8. Active non-trivial bleeding (including PH1 or PH2 hemorrhagic transformation of the index stroke event, if known before randomization
9. Known chronic bleeding disorder (e.g. von Willebrand disease)
10. History of non-traumatic ICH (does not include cerebral microbleeds or asymptomatic hemorrhagic transformation of an ischemic stroke);
11. Other non-traumatic major bleeding or clinically significant gastrointestinal bleeding within last 6 months before randomization
12. Known significant liver disease (e.g. acute hepatitis, chronic active hepatitis, cirrhosis, or signs of coagulopathy) or known hepatic insufficiency classified as Child-Pugh B or C at randomization5
13. ESRD on dialysis or expected to be started on dialysis within the next 12 months

Contraindicated Prior/Concomitant Therapies:

• Oral anticoagulation
• Full dose and/or long-term anticoagulation therapy with heparin/LMWH during study conduct
• Chronic (more than 4 weeks continuous) therapy with NSAIDs during the study conduct
• Concomitant use of combined P-gp and strong/moderate CYP3A4 inducers, e.g. carbamazepine, phenobarbital, St John’s wort, as well as within 14 days (or at least five half-lives of the active substance, whichever is longer) before randomization.
• Concomitant use of combined P-gp and strong CYP3A4 inhibitors e.g. human immunodeficiency virus protease inhibitors, systemically used azole antimycotic agents (e.g. ketoconazole), clarithromycin, nefazodone, as well as within 14 days (or at least five half-lives of the active substance, whichever is longer) before randomization.
• Herbal or traditional medicine, and / or supplements with known anticoagulant and / or antiplatelet effect (a list of the most commonly used ones will be provided separately).

Bayer study 20604_OCEANIC-STROKE_List of most common medication that are prohibited
in line with BayerDrugGroupings, Certara Drug Interaction Solutions, and FDA

1. Prohibited combined P-gp and strong CYP3A4 inducer
   • apalutamide
   • avasimibe
   • carbamazepine
   • efavirenz
   • fosphenytoin
   • phenytoin
   • rifampicin
   • rifampin
   • rifapentin
   • St. John’s wort (Hypericum perforatum)
2. Prohibited combined P-gp and strong CYP3A4 inhibitor
   • adagrasib
   • clarithromycin
   • cobicistat
   • conivaptan
   • delavirdine
   • indinavir
   • itraconazole (systemic use only)
   • ketoconazole (systemic use only)
   • levoketoconazole
   • lonafarnib
   • mibefradil
   • miconazole (systemic use only)
   • mifepristone
   • nefazodone
   • nelfinavir
   • ombitasvir
   • paritaprevir
   • posaconazole (systemic use only)
   • ritonavir
   • saquinavir
   • telaprevir
   • telithromycin
   • tucatinib

Please note: This is not an exhaustive list.

In case of any questions regarding concomitant medication please contact the Study Medical Experts by sending your question to: 20604_sme@bayergroup.onmicrosoft.com