Tirofiban With Sequential Dual Antiplatelet Therapy in Mild Stroke

Official title

Tirofiban With Sequential Dual Antiplatelet Therapy Versus Dual Antiplatelet Therapy Alone in Mild Acute Ischemic Stroke (TiMIS): A Multicenter, Open-Label, Blinded-Endpoint, Parallel-Controlled, Randomized Clinical Trial

Overview

This study aims to evaluate whether initiating intravenous tirofiban within 48 hours of onset (with a 48-hour infusion), followed by sequential DAPT, can improve the likelihood of excellent functional outcomes (modified Rankin Scale score 0-1) in mild stroke patients, compared with standard DAPT therapy based on current guidelines.

Detailed description

Although dual antiplatelet therapy (DAPT) reduces stroke recurrence and disability risks, its efficacy is limited in patients with mild ischemic stroke (NIHSS ≤5), among whom early neurological deterioration (END) and poor functional outcomes are frequently observed. Notably, intravenous thrombolysis is not more effective than DAPT for mild stroke management. Tirofiban, a glycoprotein IIb/IIIa receptor inhibitor, has shown potential efficacy in mild-to-moderate ischemic stroke, but robust evidence specific to mild stroke remains lacking. This study aims to evaluate whether initiating intravenous tirofiban within 48 hours of onset (with a 48-hour infusion), followed by sequential DAPT, can improve the likelihood of excellent functional outcomes (modified Rankin Scale score 0-1) in mild stroke patients, compared with standard DAPT therapy based on current guidelines.

Interventions

• Drug Tirofiban+Oral Dual Antiplatelet Therapy
  Tirofiban will use a loading dose, 0.4 μg/kg/min × 30 minutes, then 0.1μg/kg/min infusion for 47.5 hours; sequential Oral Dual Antiplatelet Therapy (Aspirin 100mg qd; Clopidogrel 75mg qd)
• Drug Oral Dual Antiplatelet Therapy
  Aspirin 100mg qd; Clopidogrel 75mg qd (after first dose of 300mg)

Primary outcome measures

• Proportion of excellent functional outcomes (mRS 0-1) [Time frame: 90 days]

Secondary outcome measures (10)

• Incidence of early neurological deterioration [Time frame: 72 hours]
• Incidence of early neurological improvement [Time frame: 72 hours]
• Change in National Institutes of Health Stroke Scale score from baseline [Time frame: 7 days]
• Proportion of good functional outcomes (mRS 0-2) [Time frame: 90 days]
• Distribution of mRS scores [Time frame: 90 days]
• Incidence of schemic stroke [Time frame: 90 days]
• Incidence of major adverse cardiovascular events [Time frame: 90 days]
• Rate of symptomatic intracerebral hemorrhage [Time frame: 7 days]
• Rate of all-cause mortality [Time frame: 90 days]
• Rate of major bleeding events [Time frame: 90 days]

Eligibility criteria

Inclusion criteria

• Age: 18-80 years old.
• Acute mild non-cardioembolic stroke.
• NIHSS score ≤5.
• Time from onset to randomization of ≤48 hours; if the time of onset is unknown, time from the last known time of being well to randomization of ≤48 hours.
• The investigational drug can be administered within 48 hours of symptom onset.
• Signed informed consent by the patient or legally authorized representative.

Exclusion criteria

• Received or planned to receive intravenous thrombolysis or bridging therapy (with subsequent endovascular treatment)
• Intracranial hemorrhage confirmed by imaging.
• Pre-stroke modified Rankin Scale (mRS) score ≥2.
• Any confirmed cardioembolic source, including chronic or paroxysmal atrial fibrillation, sick sinus syndrome, mitral stenosis, mechanical heart valve, infective endocarditis, intracardiac thrombus or vegetation, myocardial infarction within 3 months, dilated cardiomyopathy, left atrial spontaneous echo contrast, ejection fraction <30%.
• History of primary intracerebral hemorrhage.
• History of other intracranial hemorrhage (intraventricular, subarachnoid, epidural, or subdural hemorrhage).
• Untreated or inadequately treated intracranial aneurysm or vascular malformation.
• Major systemic bleeding within 30 days.
• Active bleeding, including laboratory evidence of coagulopathy (platelet count <100 × 10⁹/L, activated partial thromboplastin time >50 seconds, or international normalized ratio >1.7), or treatment with direct oral anticoagulants within the preceding 48 hours.
• Major surgery within 14 days.
• Persistently elevated blood pressure (systolic >180 mmHg or diastolic >110 mmHg) despite treatment.
• Baseline platelet count <100 × 10⁹/L.
• Severe renal dysfunction (glomerular filtration rate <30 mL/min or serum creatinine >220 μmol/L \[2.5 mg/dL\]).
• Known allergy or contraindication to tirofiban or aspirin.
• Current pregnancy or lactation.
• Any intracranial tumor (except asymptomatic meningiomas ≤1.5 cm in diameter).
• Any terminal illness with life expectancy <6 months.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 18 centers

• Suzhou Municipal Hospital of Anhui Province — Suzhou
• Second Hospital of Hebei Medical University — Shijiazhuang
• Taikang Xian People's Hospital — Zhoukou
• WuYuan County People's Hospital — Bayan Nur
• Huai'an First People's Hospital — Huai'an
• Jiangsu Province (Suqian) Hospital — Suqian
• Second Affiliated Hospital of Soochow University — Suzhou
• Affiliated Jiangsu Shengze Hospital of Nanjing Medical University — Suzhou
• … and 10 more centers

Publications

• Xu J, Peng H, Zhu Y, Xu F, Zhu L, Yang J, Kang T, Wang S, Yu X, Liu J, Wang P, Zhang M, Liu CF, Cao Y, Shi J. Tirofiban with sequential dual antiplatelet therapy in mild acute ischemic stroke (TiMIS): protocol for a multicenter, randomized controlled trial. Ann Med. 2026 Dec;58(1):2644698. doi: 10.1080/07853890.2026.2644698. Epub 2026 Mar 15. PMID 41834238

Identifiers

NCT: NCT07095790 · LK2025063 · 2024yb48

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗