The goal of this clinical trial is to learn if a combination of antiplatelet drugs works better than intravenous tissue plasminogen activator to treat small ischemic stroke (lacunar stroke). The main questions it aims to answer are:

Is a combination of antiplatelet drugs non-inferior to the current standard tissue plasminogen activator treatment? Does a combination of antiplatelet drugs reduce the bleeding complications than tissue plasminogen activator?

Researchers will compare a combination of antiplatelet drugs to tissue plasminogen activator to see if a combination of antiplatelet drugs works to treat small ischemic stroke (lacunar stroke).

Participants will:

Take a combination of antiplatelet drugs or be given intravenous tissue plasminogen activator Check the neurological status 3 months after stroke, in-person, by phone, or by mail.

Inclusion Criteria:

• Age ≥ 18 years.
• Acute ischemic stroke within 4.5 hours from onset. If onset time is unknown because of impaired consciousness or aphasia, use the "last known well" time.
• A single perforating-artery infarct on brain MRI:

located in the corona radiata, putamen, internal capsule, thalamus, or pons; solitary, mainly round or oval, with a maximum diameter ≤ 20 mm; lesions only in the centrum semiovale are not allowed, but extension from the above sites into the centrum semiovale is allowed.

• No disability in daily life before the stroke (modified Rankin Scale ≤ 1).
• National Institutes of Health Stroke Scale (NIHSS) score ≤ 5.
• Written informed consent obtained.

Exclusion Criteria:

• Antithrombotic therapy considered inappropriate because of active bleeding, low platelet count, or similar conditions.
• Any contraindication to intravenous rt-PA, without blood pressures.
• ≥ 50 % stenosis or occlusion of the artery responsible for the stroke * (see note below).
• Diseases that require anticoagulation (e.g., atrial fibrillation, deep-vein thrombosis) *
• Inability to take medicine orally.
• Any other reason judged by the principal investigator or co-investigators to make participation inappropriate.

Note: This study targets hyper-acute stroke within 4.5 hours. To avoid treatment delay, items marked with * must be judged using the similar examinations that each site normally performs before rt-PA administration.

On reasonable request.