Tirofiban for Patients With intraCranial Artery Stenosis and High-risk Acute Non-disabling Cerebrovascular Events(CHANCE-4）

Official title

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(CHANCE-4）

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.

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

• Drug Tirofiban
  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.
• Drug Placebo
  Initial infusion of saline placebo for 30 minutes within 24 hours of symptom onset, followed by a continuous infusion of placebo for 48 hours.

Primary outcome measures

• Any new ischemic stroke at 3-month [Time frame: at 3-month]
• Type 3 or 5 bleeding events according to the BARC criteria at 3-month [Time frame: at 3-month]

Secondary outcome measures (5)

• Any new ischemic stroke within 1 year [Time frame: within 1 year]
• 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. [Time frame: Within 3 months after randomization and 1 year]
• Disabling stroke (Modified Rankin Scale score, mRS>1) at 3 months and 1 year [Time frame: at 3 months and 1 year]
• Incidence and severity of recurrent stroke and TIA [Time frame: Within 3 months after randomization and 1 year]
• Neurological impairment at 3 months (NIHSS increased≥4 from baseline ). [Time frame: at 3 months]

Eligibility criteria

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.

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

Quadruple blind

Primary purpose

Prevention

Study locations

China · 5 centers

• The 2nd Affiliated Hospital of Harbin Medical University — Harbin
• People's Hospital of Qihe County — Dezhou
• Liaocheng People's Hospital（Liaocheng Brain Hospital） — Liaocheng
• Third People's Hospital of Liaocheng — Liaocheng
• Yantai Penglai traditional Chinese medicine hospital — Yantai

Identifiers

NCT: NCT06319846 · ZLRK202312

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗