Overview
This is a multicenter, double-blind, double-dummy, randomized clinical trial comparing the efficacy and safety of tirofiban versus placebo in preventing recurrence of stroke for patients with intracranial artery stenosis and high-risk acute non-disabling cerebrovascular events.
Description
This is a multicenter, double-blind, double-dummy, randomized clinical trial to assess the effects of tirofiban versus placebo in preventing recurrence of stroke at 3-month in patients with intracranial artery stenosis and high-risk acute non-disabling cerebrovascular events. The participants will receive study medication of tirofiban or placebo within 24 hours of symptom onset by a randomization ratio of 1:1. For tirofiban group - Initial infusion of tirofiban 0.4μg/kg body weight/minute for 30 minutes (a maximum dose of 1mg) within 24 hours of symptom onset, followed by a continuous infusion of tirofiban 0.1μg/kg body weight/minute for 48 hours. For placebo group - Initial infusion of saline placebo for 30 minutes within 24 hours of symptom onset, followed by a continuous infusion of placebo for 48 hours. The primary efficacy outcome is any new ischemic stroke at 3-month. The primary safety outcome is type 3 or 5 bleeding events according to the BARC criteria at 3-month.
Eligibility
Inclusion Criteria
- 40 years or older than 40 years;
- Acute cerebral ischemic event due to:
- Acute non-disabling ischemic stroke (NIHSS≤5 at the time of randomization) or,
- TIA with moderate-to-high risk of stroke (ABCD2 score ≥ 6 at the time of randomization);
- Accompanied with symptomatic intracranial artery stenosis, defined as ≥ 50% stenosis of the infarcted ipsilateral intracranial artery. Intracranial arteries include intracranial segments of internal carotid arteries, intracranial segments of vertebral arteries, M1-M2 segments of middle cerebral arteries, A1-A2 segments of anterior cerebral arteries, P1-P2 segments of posterior cerebral arteries, and basilar artery. The techniques for detecting intracranial artery stenosis are limited to: MRA, CTA, or DSA. The measurement for the degree of stenosis has been established by the WASID (Warfarin-Aspirin Symptomatic Intracranial Disease) study. (AJNR Am J Neuroradiol. 2000;21:643-646.);
- Can be treated with study drug within 24 hours of symptoms onset\(\Symptom onset is defined by the "last seen normal" principle);
- Informed consent signed.
Exclusion Criteria
- Malformation, tumor, abscess or other major non-ischemic brain disease (e.g., multiple sclerosis) on baseline head CT or MRI.
- Unable to complete the evaluation of intracranial artery stenosis before randomization.
- Isolated or pure sensory symptoms (e.g., numbness), isolated visual changes, or isolated dizziness/vertigo without evidence of acute infarction on baseline head CT or MRI.
- Iatrogenic causes (angioplasty or surgery) of minor stroke or TIA.
- A score of \> 2 on the modified Rankin scale before the symptom onset.
- Contraindication for tirofiban:
- Known allergy
- Severe renal (creatinine exceeding 1.5 times of the upper limit of normal range) or hepatic (ALT or AST \> twice the upper limit of normal range) insufficiency
- Severe cardiac failure (NYHA level: III to IV)
- History of hemostatic disorder or systemic bleeding
- History of thrombocytopenia or neutropenia
- History of drug-induced hematologic disorder or hepatic dysfunction
- Low white blood cell (\<2×109/L) or platelet count (\<100×109/L)
- Tirofiban has been used since this onset.
- Hematocrit (HCT) \<30%.
- Clear indication for anticoagulation (presumed cardiac source of embolus, e.g., atrial fibrillation, prosthetic cardiac valves known or suspected endocarditis).
- History of intracranial hemorrhage or amyloid angiopathy.
- History of aneurysm (including intracranial aneurysm and peripheral aneurysm).
- History of asthma or COPD (chronic obstructive pulmonary disease).
- High-risk for bradyarrhythmia (sinus node disease, first-degree or second-degree AV block, and brady-arrhythmic syncope without pacemaker).
- Planned or likely revascularization (any angioplasty or endovascular surgery) within the next 3 months.
- Scheduled for surgery or interventional treatment requiring study drug cessation.
- Severe non-cardiovascular comorbidity with life expectancy \< 3 months.
- Inability to understand and/or follow research procedures due to mental, cognitive, or emotional disorders.
- Current treatment (last dose given within 10 days before randomization) with heparin therapy or oral anti coagulation.
- Intravenous thrombolytic therapy (such as intravenous rtPA) or mechanical thrombectomy within 24 hours prior to randomization.
- Participants who have large areas (greater than half of middle cerebral artery territory) of obvious low density on the baseline CT scan.
- Gastrointestinal bleed within 3 months or major surgery within 30 days.
- Diagnosis or suspicious diagnosis of acute coronary syndrome.
- Participation in another clinical study with an experimental product during the last 30 days.
- Currently receiving an experimental drug or device.
- Pregnant, currently trying to become pregnant, or of child-bearing potential and not using birth control.
