HR-MRI-Directed Tirofiban Therapy for Late-Window Acute Ischemic Stroke (TIAN)

Official title

Efficacy and Safety of Tirofiban Therapy in Acute Ischemic Stroke Patients Beyond the Time Window Guided by High-Resolution Magnetic Resonance Imaging

Overview

This study aims to address the existing clinical challenges by introducing high-resolution magnetic resonance vessel wall imaging (HR-MRI), an advanced imaging technology, to achieve precise etiological classification in patients with acute ischemic stroke (AIS) beyond the time window. HR-MRI allows clear visualization of intracranial arterial wall structures and direct identification of key pathological features of the culprit vessel, including atherosclerotic plaques, vascular wall remodeling, and intracranial hemorrhage, thereby enabling reliable differentiation between intracranial atherosclerotic large artery atherosclerosis (ICAS-LAA) stroke and other etiological subtypes such as cardiogenic embolism. Based on the latest clinical demands and advances in imaging technology, this study intends to evaluate the efficacy and safety of tirofiban in patients with ICAS-LAA stroke beyond the time window under the precise guidance of HR-MRI. It is expected to provide high-level evidence-based medical evidence for this specific patient population and further optimize clinical diagnosis and treatment strategies.

Interventions

• Drug Tirofiban
  Intravenous tirofiban was administered within 30 minutes of randomization, with an initial bolus infusion at a rate of 0.4 μg/(kg·min) for 30 minutes, followed by a continuous infusion at 0.1 μg/(kg·min) for 47.5 hours.
• Drug dual antiplatelet therapy
  Initiate dual antiplatelet therapy as early as possible (aspirin 100 mg/day plus clopidogrel 75 mg/day) for a total of 21 days, followed by long-term maintenance with aspirin 100 mg/day alone. For patients at high risk of stroke, such as those with severe stenosis of major blood vessels, dual antiplatelet therapy should be administered for 90 days.

Primary outcome measures

• Proportion of participants with functional independence outcome [modified Rankin Scale(mRS) score 0-1] [Time frame: 90 ± 7 days after randomization]

Secondary outcome measures (12)

• Proportion of participants with good prognosis (mRS score 0-2) [Time frame: 90 ± 7 days after randomization]
• Proportion of participants with mRS score 0-3 [Time frame: 90 ± 7 days after randomization]
• Distribution of mRS scores [Time frame: 90 ± 7 days after randomization]
• EuroQol Five-Dimension Questionnaire (EQ-5D) score [Time frame: 90 ± 7 days after randomization]
• Barthel Index (BI) score [Time frame: 90 ± 7 days after randomization]
• Proportion of participants with neurological improvement within 24 hours of randomization [≥2-point reduction in National Institutes of Health Stroke Scale (NIHSS) score from baseline] [Time frame: 24 ± 6 hours]
• National Institutes of Health Stroke Scale (NIHSS) scores [Time frame: Time Frame: 24h; before discharge; day7]
• Proportion of participants with symptomatic intracranial hemorrhage (sICH) within 24 hours of randomization [Time frame: 24 ± 6 hours]
• Early neurological deterioration(END) [Time frame: 24 ± 6 hours]
• Incidence of serious adverse events (SAEs) [Time frame: 24 ± 6 hours;]
• Incidence of any adverse events [Time frame: 24 ± 6 hours;]
• Recurrent stroke [Time frame: 90 ± 7 days after randomization]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years old;
• Acute ischemic stroke (AIS) in the anterior intracranial circulation (internal carotid artery system) confirmed by clinical symptoms and imaging examinations;
• Time from symptom onset or last known normal state to randomization: > 24 hours and ≤ 7 days;
• Stroke subtype confirmed as intracranial large artery atherosclerosis (ICAS) by high-resolution vessel wall imaging (HR-VWI) according to the TOAST classification, with cardiogenic embolism and other etiologies excluded;
• Baseline National Institutes of Health Stroke Scale (NIHSS) score of 4-20 at the time of randomization;
• Signed informed consent form obtained from the patient or their legal representative.

Exclusion criteria

• Planned to receive reperfusion therapy (endovascular therapy or intravenous thrombolysis)；
• Intracranial hemorrhage confirmed by computed tomography (CT)；
• Definite or suspected cardiogenic embolism；
• History of atrial fibrillation or current electrocardiogram indicating atrial fibrillation；
• Acute ischemic stroke caused by other etiologies, such as Moyamoya disease, arterial dissection, arteritis, etc；
• Imaging examinations indicating that the area of the current cerebral infarction exceeds 1/2 of the area of a single cerebral lobe;
• Known contraindications to antiplatelet therapy, including hematochezia, gastrointestinal bleeding, or any other hemorrhagic disorders;
• History of hypersensitivity to aspirin;
• Definite indication for anticoagulant therapy expected during the study period (e.g., atrial fibrillation, mechanical heart valve, deep vein thrombosis, pulmonary embolism, antiphospholipid antibody syndrome, hypercoagulable state, etc.);
• Complicated with malignant tumors, chronic hemodialysis, severe renal insufficiency (glomerular filtration rate \[GFR\] < 30 ml/min or serum creatinine \[Cr\] > 220 μmol/L (2.5 mg/dl)), or severe hepatic insufficiency (serum alanine aminotransferase \[ALT\] > 2 times the upper limit of normal \[ULN\], or serum aspartate aminotransferase \[AST\] > 2 times the ULN);
• Severe heart failure (New York Heart Association \[NYHA\] Functional Classification Class III or IV);
• Complicated with severe non-cardiovascular comorbidities, with an estimated survival time < 6 months;
• Concurrent new cerebral infarction in both anterior and posterior circulations;
• Inability to complete the follow-up procedures;
• Presence of other known neurological disorders that may complicate the follow-up;
• Concurrent participation in other therapeutic clinical trials with incomplete treatment and follow-up;
• Other conditions that the investigators consider inappropriate for enrollment in this study.

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 · 1 center

• Weifang People's Hospital — Weifang

Identifiers

NCT: NCT07379190 · TITAN

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗