One Pass Tirofiban In Management of Ischemic Stroke Thrombectomy In China

Study Overview
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Brief Summary
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In recent years, the positive results of trials for mechanical thrombectomy (MT) have brought a new era for large artery occlusion patients, especially those beyond the time window of intravenous thrombolysis. However, interventional procedures can cause endothelial injuries leading to local activation of platelet aggregation and subsequent thromboembolic complications or early re-occlusion.Tirofiban is a specific antagonist of the platelet glycoprotein (GP) IIb/IIIa receptor, which is considered highly effective against the final common pathway of platelet aggregation and preventing vascular reocclusion. However, there is no consensus on if AIS patients treated with MT also benefit from intravenous tirofiban. This study aims to evaluate the effectiveness and safety of profiles of tirofiban during MT and provide reliable clinical evidence for the treatment of tirofiban in AIS patients.

Detailed Description
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This study is a multicenter, prospective, open-label, randomized controlled, blinded-endpoint trial with two parallel groups and a 3-month follow-up. A total of 200 eligible participants recruited from 4-6 stroke centers will be randomly allocated to either an experimental group (intravenous tirofiban + MT therapy) or a control group (MT alone) in a 1:1 ratio. The primary outcome is a composite endpoint, including the rate of recanalisation after the first embolectomy and the risk of symptomatic intracerebral haemorrhage. The secondary outcomes include clinical and neuroimaging outcomes, procedure-related complications, and adverse events to evaluate the effects of MT in combination with tirofiban treatment compared to MT alone in AIS patients. Intention-to-treat (ITT) analysis will be undertaken in this study, and the full analysis set (FAS) population serves as the primary population for the analysis of efficacy data.

Official Title
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Safety and Efficacy of Tirofiban in Acute Ischemic Stroke Patients Treated With Mechanical Thrombectomy-A Prospective, Randomized, Controlled, Open-Label, Assessor-Blind, Multicenter Clinical Study

Conditions
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Ischemic Stroke

Intervention / Treatment
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* Drug: Intravenous tirofiban combination therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female between the ages of 18 and 80; Acute ischemic stroke patients within 4.5-24 hours of stroke onset, with NIHSS scores > 5; Patients with large vessel occlusion including occlusion of the internal carotid artery (ICA) termination or middle cerebral artery (MCA, M1, or M2 segment), and who are scheduled to receive arterial thrombectomy; Complete an assessment with multimodal CT and meet the criteria as follow: penumbra volume > 10ml, infarct core volume < 70ml, mismatch ratio > 1.2; Patients planning to receive arterial thrombectomy treatment; All patients (or guardians of patients) provided written informed consent. Exclusion Criteria: Patients with a medical history of atrial fibrillation or atrial flutter, or a 12-lead electrocardiogram at admission, showing atrial flutter or atrial fibrillation; Patients who have received intravenous thrombolysis; Pre-existing functional impairment with an mRS score ≥ 2; With severe comorbidities (e.g. severe cardiopulmonary insufficiency, advanced malignancy with an expected survival of less than 90d); More than 1/3 areas of hypodense ischaemic changes supplied by the middle cerebral artery on baseline CT; Patients with known hypersensitivity or contraindications to the use of tirofiban; Patients with known hypersensitivity or contraindications to the use of contrast agents in multimodal CT/MRI examinations; Pregnant or lactating women; Patients who are currently participating in other clinical trial; Other conditions judged by the investigator to be inappropriate for inclusion in the clinical study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A prospective, randomized, controlled, open-Label, assessor-blind, multicenter clinical study
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br>The participants in the experimental group will receive intravenous tirofiban combined with a standard MT protocol recommended by the current guidelines for the management of AIS | Drug: Intravenous tirofiban combination therapy<br>* Patients will enter the tirofiban treatment protocol immediately within half an hour after randomization and prior to the femoral artery puncture. Tirofiban is administered as an intravenous bolus dose of 10 μg/kg injection within 3 min and then by an intravenous infusion at a rate of 0.1 μg/(kg·min) for 24 hours.<br>* Other names: Tirofiban;|
| No Intervention: Control group<br>Patients are treated with MT therapy with no antiplatelet drugs (intravenous or intra-arterial) are administered. Besides, they will receive a standard pharmacological treatment as per current clinical guidelines. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite rates of target vessel revascularization and no symptomatic intracerebral haemorrhage | Target vessel revascularization is defined as a modified thrombolysis in cerebral infarction (mTICI) grade after onepass thrombectomy procedure over grade 2b. Symptomatic intracerebral haemorrhage is defined according to per Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) criteria. | 24-72hours after thrombectomy; | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recanalisation rates of the target vessel | Neuroimaging outcomes | 24-72 hours after thrombectomy; | 
| Dichotomized mRS score/ ordinal mRS score | Functional prognosis of the patient，clinical outcomes | The 90-day after randomisation | 
| Symptomatic intracerebral haemorrhage | procedure-related complications and adverse events | By the end of the 90-day follow-up | 
| Death | procedure-related complications and adverse events | By the end of the 90-day follow-up | 
| The number of thrombectomy times | Treatment information | By the end of the 90-day follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tirofiban, Acute Ischemic Stroke, Mechanical thrombectomy, Revascularisation, Haemorrhage