A Study of the Efficacy and Safety of Alteplase in Participants With Mild Stroke

Inclusion Criteria: * Mild ischemic stroke defined as the most recent pre-treatment NIHSS score of less than or equal to(\</=) 5 and determined as not clearly disabling by the investigator * Study treatment initiated within 3 hours of last time participant seen normal Exclusion Criteria: * Computed tomography (CT) or magnetic resonance imaging (MRI) findings of one of the following: 1. CT with clear large hypodensity that is greater than (\>) one-third middle cerebral artery (MCA) territory (or \>100 cubic centimeter \[cc\] if not in MCA territory) 2. MRI with clear large hyperintensity on concurrent diffusion-weighted (DW) and fluid-attenuated inversion recovery (FLAIR) that is greater than one-third MCA territory (or greater than 100 cc if not in MCA territory), 3. Imaging lesion consistent with acute hemorrhage, or 4. Evidence of intraparenchymal tumor * Disability prior to the presenting stroke * Standard contraindications to IV alteplase within 3 hours of symptom onset, including: 1. Head trauma, myocardial infarction, or previous stroke within the previous 3 months 2. Gastrointestinal or urinary tract hemorrhage within the previous 21 days 3. Major surgery within the previous 14 days 4. Arterial puncture at non-compressible site within the previous 7 days 5. Any history of ICH with the exception of those less than (\<) 5 chronic microbleeds on MRI 6. Elevated blood pressure defined by systolic blood pressure \>185 millimeters of mercury (mm Hg) or diastolic blood pressure \>110 mm Hg, or treatments requiring aggressive measures to achieve acceptable levels 7. Treatment with unfractioned heparin within past 48 hours and activated partial thromboplastin time outside normal range 8. Blood glucose \<50 milligrams per deciliter (mg/dL) 9. International normalized ratio \>1.7 10. Platelet count \<100,000 per cubic millimeter (/mm\^3) 11. Treatment with a direct thrombin inhibitor (dabigatran) or a factor Xa inhibitor (apixaban, rivaroxaban, edoxaban) within the last 48 hours * Allergic reaction to study drug, aspirin, or nonsteroidal anti-inflammatory drugs (NSAIDs) * Females of childbearing age who are known to be pregnant and/or lactating * Inability to swallow, which would prevent oral intake of aspirin or aspirin placebo tablet * Other serious, advanced, or terminal illness that would confound the clinical outcome at 90 days * Current or recent (within 3 months) participation in another investigational drug treatment protocol * Anticipated inability to obtain 3-month follow-up assessments * Previous enrollment in PRISMS * Any other condition deemed by the investigator that would pose hazard to the participant with alteplase treatment