Early Administration of Tirofiban in Patients Treated With Tenecteplase for Acute Ischemic Stroke

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and efficacy of early administration of tirofiban in patients treated with tenecteplase for acute ischemic stroke.

Detailed Description
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Intravenous thrombolysis with alteplase is recommended in treatment guidelines for patients with acute ischemic stroke. Previous studies showed that intravenous tenecteplase (0.25 mg/kg) is a reasonable alternative to alteplase for all patients presenting with acute ischemic stroke who meet standard criteria for thrombolysis. After thrombolysis-induced recanalisation, reocclusion occurs in 14-34% of patients, probably because of platelet activation. Early administration of antiplatelet therapy after intravenous thrombolysis could reduce the risk of reocclusion and improve outcome. The purpose of this study is to assess the safety and efficacy of early administration of tirofiban in patients treated with tenecteplase for acute ischemic stroke.

Official Title
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Safety and Efficacy of Early Administration of Tirofiban in Patients Treated With Tenecteplase for Acute Ischemic Stroke

Conditions
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Acute Ischemic Stroke

Intervention / Treatment
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* Drug: Tenecteplase plus Tirofiban
* Drug: Tenecteplase plus Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-80 years Ischemic stroke with measurable deficit on NIH Stroke Scale Treatment within 4.5 hours of stroke onset Be able to engage in daily life independently before the onset of this ischemic stroke (mRS score: 0-1) Patients awakening with symptoms are defined by the time last observed normal Written informed consent by patient or proxy Exclusion Criteria: Patients with premorbid modified Rankin Scale (mRS) score ≥3 Patients for whom a complete NIH Stroke Score cannot be obtained Hemiplegic migraine with no arterial occlusion on CTA Seizure at stroke onset and no visible occlusion on baseline CTA Intracranial haemorrhage on baseline CT Clinical presentation suggesting subarachnoid haemorrhage even if baseline CT is normal Large areas of hypodense ischaemic changes on baseline CT Patients with systolic blood pressure >185 mm Hg or diastolic blood pressure >110 mm Hg Female, pregnant or breast feeding Known bleeding diathesis Known allergic to tirofiban or other glycoprotein IIb/IIIa antagonist Use of oral anticoagulants and International Normalized Ratio (INR) ≥1,4 Use of new oral anticoagulants (NOAC) within the last 12 hours Heparin <48 hours and increased Activated partial thromboplastin tike (APTT) Low molecular weight heparin(oid) <24 hours Any other investigational drug <14 days Sepsis Patients with arterial puncture at a noncompressible site or lumbar puncture <7 days Major surgery or serious trauma <14 days Gastrointestinal or urinary tract hemorrhage <14 days Clinical stroke <2 months History of intracranial haemorrhage Brain neurosurgery <2 months Serious head trauma <2 months Pericarditis Any serious medical illness likely to interact with treatment Confounding pre-existent neurological or psychiatric disease Unlikely to complete follow-up Pregnancy

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tenecteplase plus Tirofiban<br>Patients will receive intravenous tenecteplase (0.25mg/kg, maximum 25mg, administered as a bolus over  10 seconds). Patients will receive a continuous intravenous infusion of tirofiban at a rate of 0.1 µg/kg per minute for 26.5 h after start of tenecteplase treatment within 90 min, if there was no parenchymal hemorrhage or extensive subarachnoid hemorrhage beyond the Sylvian fissure on the posttreatment computed tomography scan. Aspirin (100 mg/d) will be given orally at 4 hours before the end of infusion and continued for at least 3 months after intravenous thrombolysis . | Drug: Tenecteplase plus Tirofiban<br>* Patients will receive a continuous intravenous infusion of tirofiban at a rate of 0.1 µg/kg per minute for 26.5 h after start of tenecteplase treatment within 90 min<br>|
| Placebo Comparator: Tenecteplase plus Placebo<br>Patients will receive intravenous tenecteplase (0.25mg/kg, maximum 25mg, administered as a bolus over  10 seconds). Patients will receive a continuous intravenous infusion of placebo at a rate of 0.1 µg/kg per minute for 26.5 h after start of tenecteplase treatment within 90 min, if there was no parenchymal hemorrhage or extensive subarachnoid hemorrhage beyond the Sylvian fissure on the posttreatment computed tomography scan. Aspirin (100 mg/d) will be given orally at 4 hours before the end of infusion and continued for at least 3 months after intravenous thrombolysis . | Drug: Tenecteplase plus Placebo<br>* Patients will receive a continuous intravenous infusion of Placebo at a rate of 0.1 µg/kg per minute for 26.5 h after start of tenecteplase treatment within 90 min<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| functional independence | mRS score, 0-2 | 90 days | 
| mortality | mRS score, 6 | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| excellent functional outcome | mRS score, 0-1 | 90 days | 
| symptomatic intracranial hemorrhage |  | 48 hours | 
| any intracranial hemorrhage |  | 48 hours |