Ischemic Stroke, Acute
Conditions
Brief summary
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.
Interventions
DRUGTirofiban
Aspirin 100 mg once daily orally for 90 days, plus immediate intravenous tirofiban after randomization: 0.4 µg/kg/min for the first 30 minutes, then 0.1 µg/kg/min for a total of 24 hours. Plus guideline-based standard care.
DRUGTirofiban-matching placebo
Aspirin 100 mg once daily orally for 90 days, plus immediate intravenous tirofiban-matching placebo infusion (0.4 µg/kg/min × 30 min, then 0.1 µg/kg/min × 24 h). Plus guideline-based standard care.
Sponsors
Xinqiao Hospital of Chongqing
The First Affiliated Hospital of Nanchang University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients with mRS 0-1 at 90 days (%) | At 90 days after randomization | Proportion of patients achieving an excellent functional outcome, defined as a modified Rankin Scale (mRS) score of 0 or 1 at 90 days after randomization. |
| Symptomatic intracranial hemorrhage within 48 (±12) hours (Heidelberg criteria) (%) | 48 (±12) hours after randomization | Symptomatic intracranial hemorrhage within 48 (±12) hours (Heidelberg criteria) (%) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| mRS score at 90 days (ordinal shift analysis) | At 90 days after randomization | mRS score at 90 days (ordinal shift analysis) |
| Proportion with functional independence (mRS 0-2) at 90 days | At 90 days after randomization | Proportion with functional independence (mRS 0-2) at 90 days |
| Early neurologic deterioration (END) within 7 ± 1 days | Within 7 ± 1 days after randomization | Early neurologic deterioration (END) within 7 ± 1 days, defined as an increase in NIHSS ≥ 2 points within 7 days, with the hemiparesis item increasing ≥ 1 or the level-of-consciousness item increasing ≥ 1, after excluding intracranial hemorrhage or other non-stroke causes. |
| Change in NIHSS from pre-randomization to discharge or discharge-day 6 (±1) | Discharge or discharge-day 6 (±1) | Change in NIHSS from pre-randomization to discharge or discharge-day 6 (±1) |
| EQ-5D-5L at 90 days | At 90 days after randomization | EQ-5D-5L at 90 days |
| Any intracranial hemorrhage on imaging within 48 (±12) hours | Within 48 (±12) hours after randomization | Any intracranial hemorrhage on imaging within 48 (±12) hours |
| 90-day all-cause mortality | At 90 days after randomization | 90-day all-cause mortality |
| Major extracranial bleeding within 48 (±12) hours (GUSTO moderate and severe) | Within 48 (±12) hours after randomization | Major extracranial bleeding within 48 (±12) hours (GUSTO moderate and severe) |
| Non-hemorrhagic serious adverse event rate | Within 90 days after randomization | Non-hemorrhagic serious adverse event rate (including cerebral hernia, pneumonia, respiratory failure, circulatory failure, stress ulcer, secondary epilepsy, urinary tract infection, sepsis, renal failure, acute coronary syndrome, venous thrombosis, psychiatric symptoms, etc.) |
Countries
China
Contacts
CONTACTDaojun Hong, MD
CONTACTJing Lin, MD
PRINCIPAL_INVESTIGATORZhongming Qiu
Xinqiao Hospital of the Army Medical University
Outcome results
None listed