Ischemic Stroke, Acute, Symptomatic Intracranial Artery Stenosis, TIA
Conditions
Brief summary
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.
Detailed 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.
Interventions
DRUGTirofiban
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.
DRUGPlacebo
Initial infusion of saline placebo for 30 minutes within 24 hours of symptom onset, followed by a continuous infusion of placebo for 48 hours.
Sponsors
Beijing Tiantan Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 40 years or older than 40 years; 2. 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); 3. 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.); 4. Can be treated with study drug within 24 hours of symptoms onset\*(\*Symptom onset is defined by the last seen normal principle); 5. Informed consent signed.
Exclusion criteria
1. Malformation, tumor, abscess or other major non-ischemic brain disease (e.g., multiple sclerosis) on baseline head CT or MRI. 2. Unable to complete the evaluation of intracranial artery stenosis before randomization. 3. 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. 4. Iatrogenic causes (angioplasty or surgery) of minor stroke or TIA. 5. A score of \> 2 on the modified Rankin scale before the symptom onset. 6. 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) 7. Tirofiban has been used since this onset. 8. Hematocrit (HCT) \<30%. 9. Clear indication for anticoagulation (presumed cardiac source of embolus, e.g., atrial fibrillation, prosthetic cardiac valves known or suspected endocarditis). 10. History of intracranial hemorrhage or amyloid angiopathy. 11. History of aneurysm (including intracranial aneurysm and peripheral aneurysm). 12. History of asthma or COPD (chronic obstructive pulmonary disease). 13. High-risk for bradyarrhythmia (sinus node disease, first-degree or second-degree AV block, and brady-arrhythmic syncope without pacemaker). 14. Planned or likely revascularization (any angioplasty or endovascular surgery) within the next 3 months. 15. Scheduled for surgery or interventional treatment requiring study drug cessation. 16. Severe non-cardiovascular comorbidity with life expectancy \< 3 months. 17. Inability to understand and/or follow research procedures due to mental, cognitive, or emotional disorders. 18. Current treatment (last dose given within 10 days before randomization) with heparin therapy or oral anti coagulation. 19. Intravenous thrombolytic therapy (such as intravenous rtPA) or mechanical thrombectomy within 24 hours prior to randomization. 20. Participants who have large areas (greater than half of middle cerebral artery territory) of obvious low density on the baseline CT scan. 21. Gastrointestinal bleed within 3 months or major surgery within 30 days. 22. Diagnosis or suspicious diagnosis of acute coronary syndrome. 23. Participation in another clinical study with an experimental product during the last 30 days. 24. Currently receiving an experimental drug or device. 25. Pregnant, currently trying to become pregnant, or of child-bearing potential and not using birth control.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Any new ischemic stroke at 3-month | at 3-month | Incidence of any new ischemic stroke at 3-month |
| Type 3 or 5 bleeding events according to the BARC criteria at 3-month | at 3-month | Incidence of type 3 or 5 bleeding events according to the BARC criteria at 3-month |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| New clinical vascular events (ischemic stroke/ hemorrhagic stroke/ TIA/ myocardial infarction/vascular death) within 3 months and 1 year; Each new vascular event will be independently evaluated. | Within 3 months after randomization and 1 year | Incidence of new clinical vascular events (ischemic stroke/ hemorrhagic stroke/ TIA/ myocardial infarction/vascular death) within 3 months and 1 year; Each new vascular event will be independently evaluated. |
| Any new ischemic stroke within 1 year | within 1 year | Incidence of any new ischemic stroke within 1 year |
| Disabling stroke (Modified Rankin Scale score, mRS>1) at 3 months and 1 year | at 3 months and 1 year | Proportion of patients with disabling stroke (Modified Rankin Scale score, mRS\>1) at 3 months and 1 year. Scores on the modified Rankin scale range from 0 (no neurologic deficit) to 6 (death). |
| Incidence and severity of recurrent stroke and TIA | Within 3 months after randomization and 1 year | Incidence and severity of recurrent stroke and TIA during follow-up to 3 months and 1-year (Severity is measured using a six-level ordered categorical scale that incorporates the mRS: fatal stroke/severe non-fatal stroke \[mRS 4 or 5\]/moderate stroke \[mRS 2 or 3\]/mild stroke \[mRS 0 or 1\]/TIA/no stroke-TIA) |
| Neurological impairment at 3 months (NIHSS increased≥4 from baseline ). | at 3 months | Proportion of patients with neurological impairment at 3 months ( National Institutes of Health Stroke Scale \[NIHSS\] score increased≥4 from baseline). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Type 2, 3 or 5 bleeding events according to the BARC criteria at 3-month and 1-year. | at 3-month and 1-year | Proportion of patients with type 2, 3 or 5 bleeding events according to the BARC criteria at 3-month and 1-year. |
| Total mortality at 3-month and 1-year | at 3-month and 1-year | Proportion of patients with total mortality at 3-month and 1-year |
| Adverse events/Severe adverse events reported by investigators at 3-month and 1-year | at 3-month and 1-year | — |
| All bleeding events (type 1-5 bleeding events according to the BARC criteria) | at 3-month and 1-year | All bleeding events (type 1-5 bleeding events according to the BARC criteria) at 3-month and 1-year; Each bleeding event will be independently evaluated |
| Type 3 or 5 bleeding events (BARC definition) at 1 year | at 1 year | Proportion of patients with type 3 or 5 bleeding events (BARC definition) at 1 year. |
Countries
China
Contacts
Primary ContactYongjun Wang
Backup ContactJing Jing
Outcome results
None listed