Overview

Stroke is the second leading cause of death worldwide, and ischemic stroke is the most frequent type. Intravenous thrombolysis with recombinant tissue plasminogen activator within 4.5 hours of symptom onset is the most effective therapy for patients with acute ischemic stroke. However, ischemic stroke progression and early reocclusion are not an uncommon phenomenon in patients after intravenous thrombolysis, resulting in neurological deterioration, which is associated with unfavorable functional outcomes. The underlying mechanism mainly involves the augmented platelet activation, triggered by the activated coagulation cascade during thrombolysis, which peaks within 2 hours of initiating rt-PA administration. Therefore, early antiplatelet therapy following intravenous thrombolysis represents a promising therapeutic approach to prevent neurological deterioration and improve the functional outcome of patients treated with intravenous thrombolysis.

Currently, guidelines recommend initiating antiplatelet therapy 24 hours after intravenous thrombolysis due to the potential risk of increased bleeding. The safety and efficacy of early antiplatelet treatment following intravenous thrombolysis in patients with acute ischemic stroke remain clear.

The study aims to test the hypothesis that in patients with acute ischemic stroke treated with intravenous thrombolysis, early administration of oral aspirin will improve functional outcomes without increasing the risk of intracranial hemorrhage.

Eligibility

Inclusion Criteria:

1. Age ≥18 years old;
2. Acute ischemic stroke treated with intravenous thrombolysis with alteplase or tenecteplase within 4.5 hours of onset or time last known well and can receive the study drug treatment within 3 hours of initiating intravenous thrombolysis.
3. NIHSS score improvement ≤ 2 points or worsening ≤ 4 points one hour after initiating intravenous thrombolysis compared to pre-thrombolysis.
4. Residual NIHSS score > 5 points at randomization.
5. Informed consent obtained from patients or their acceptable surrogates.

Exclusion Criteria:

1. Stroke caused by definite large vessel occlusion (including A1 and A2 segments of the anterior cerebral artery, M1 and M2 segments of the middle cerebral artery, P1 and P2 segments of the posterior cerebral artery, intracranial and extracranial segments of the internal carotid artery, basilar artery, and bilateral vertebral artery occlusion) confirmed by imaging (including CTA or MRA).
2. Scheduled for endovascular treatment.
3. Intracranial hemorrhage confirmed by imaging post-thrombolysis.
4. Definite or suspected cardioembolic stroke.
5. Stroke caused by other determined causes, including moyamoya disease, artery dissection, arteritis, etc.
6. Pre-stroke mRS score > 1.
7. Severe consciousness disturbance with NIHSS item 1a (level of consciousness) ≥ 2 points.
8. Post-thrombolysis imaging indicates an infarct area larger than 1/2 responsible artery supply area.
9. Prior history of stroke events (manifesting as stroke symptoms, including hemorrhagic stroke and ischemic stroke).
10. Known contraindications for antiplatelet therapy, such as coagulation disorders, systemic bleeding, etc.
11. History of aspirin allergy.
12. Use of antiplatelet or anticoagulant therapy within one week pre-stroke.
13. There is definite anticipation of developing indications for anticoagulant therapy during the study period (e.g., atrial fibrillation, mechanical heart valve, deep vein thrombosis, pulmonary embolism, antiphospholipid syndrome, hypercoagulable state).
14. Presence of malignant tumors, chronic hemodialysis, severe renal insufficiency (GFR < 30 ml/min or serum Cr > 220 μmol/L (2.5 mg/dl)), severe hepatic insufficiency (serum ALT > 2 times the upper limit of normal, or serum AST > 2 times the upper limit of normal), severe heart failure (NYHA class III or IV).
15. Severe non-cardiovascular complications with an expected survival of less than 6 months.
16. Unavailability for follow-up.
17. Presence of dementia, psychiatric disorders, or other known neurological conditions that complicate follow-up.
18. Current participation in another therapeutic study with ongoing treatment and follow-up.
19. Other conditions that are not suitable for participation in this study as determined by the investigator.