Tirofiban Combined With Aspirin in Moderate Ischemic Stroke

Ischemic stroke accounts for the majority of stroke cases in China, and moderate ischemic stroke (NIHSS 4-10) carries a high risk of early neurologic deterioration (END) and long-term disability. Although intensified antiplatelet strategies reduce END, they have not consistently improved long-term functional outcome. Tirofiban, a selective glycoprotein IIb/IIIa receptor inhibitor, has shown a clinically meaningful trend toward better 90-day functional outcome (mRS 0-1) in prior tirofiban trials, but existing sample sizes were underpowered to detect this difference. TAMIS is a multicenter, randomized, double-blind, placebo-controlled superiority trial in patients with acute moderate ischemic stroke (NIHSS 4-10) within 24 hours of last known well. Eligible patients are randomized 1:1 to tirofiban plus aspirin versus placebo plus aspirin, both on a background of guideline-based standard medical care. The primary efficacy endpoint is the proportion of patients with an excellent functional outcome (mRS 0-1) at 90 days. The primary safety endpoint is symptomatic intracranial hemorrhage within 48 (±12) hours by the Heidelberg criteria.

Inclusion Criteria: 1. Age 18-80 years; 2. Acute ischemic stroke; time from last known well to randomization ≤ 24 hours; 3. Pre-randomization NIHSS score 4-10, with at least one of item 5 (upper limb) or item 6 (lower limb) ≥ 1; 4. Pre-stroke modified Rankin Scale (mRS) ≤ 1; 5. Written informed consent provided by the patient or a legally authorized representative. Exclusion Criteria: 1. Intracranial hemorrhage confirmed by CT or MRI; 2. Has received or is planned to receive reperfusion therapy (thrombolysis or endovascular treatment); 3. Any definite cardioembolic source: chronic/paroxysmal atrial fibrillation, sick sinus syndrome, mitral stenosis, mechanical heart valve, endocarditis, intracardiac thrombus or vegetation, myocardial infarction within 3 months, dilated cardiomyopathy, left atrial spontaneous echo contrast, ejection fraction \< 30%; 4. Definite indication for anticoagulation (atrial fibrillation, mechanical heart valve, deep vein thrombosis, pulmonary embolism); 5. Severe systemic disease (e.g., severe infection, severe hepatic or renal dysfunction); 6. Allergy to tirofiban and/or aspirin; 7. History of intracranial hemorrhage; 8. Planned use of NSAIDs affecting platelet function; 9. Gastrointestinal bleeding or major surgery within the past 3 months; 10. Planned or likely revascularization (any angioplasty or vascular surgery) within the next 3 months; 11. Planned surgery or intervention requiring discontinuation of antiplatelet therapy; 12. Stroke caused by angiography or surgery; 13. Prior non-atherosclerotic arterial disease, including moyamoya disease, arterial dissection, fibromuscular dysplasia; 14. Other structural brain disease (vascular malformation, tumor, abscess, multiple sclerosis, etc.) confirmed by CT/MRI; 15. Pregnancy or lactation; 16. Prior neurologic or psychiatric disease that would interfere with neurologic assessment; 17. Participation in another clinical trial; 18. Advanced disease with expected survival \< 6 months; 19. Expected inability to complete follow-up.