Feasibility Study of IV Recombinant Tissue Plasminogen Activator (rtPA) vs. Primary Endovascular Therapy for Acute Ischemic Stroke

Study Overview
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Brief Summary
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This pilot trial will be the first step toward direct comparison of delivery of endovascular reperfusion therapy to intravenous recombinant tissue plasminogen activator (rt-PA) in a time-to-treatment framework shown as most effective by the NINDS rt-PA Stroke Trial. A randomized trial is justified for the following reasons: 1) The high rate of death and disability associated with ischemic stroke despite treatment with intravenous rt-PA mandates critical analysis of alternate therapies with therapeutic potential, 2) endovascular treatment for acute ischemic stroke is expanding in North America without compelling evidence of safety and efficacy from well-designed clinical trials, 3) critical cost-effectiveness analysis cannot be done without acquiring pertinent outcomes data from controlled studies.

Official Title
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Endovascular Arterial Reperfusion vs. Intravenous ThromboLYsis for Acute Ischemic Stroke (EARLY): A Randomized Pilot Study of Ultra-early (<2 Hours) and Early (2-4.5 Hours) Reperfusion Therapy

Conditions
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Stroke, Ischemic Stroke

Intervention / Treatment
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* Drug: Intravenous Thrombolysis
* Device: Endovascular Arterial Reperfusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Definite or probable ischemic stroke CT angiographic (CTA) evidence of intracranial vascular occlusion (internal carotid, middle cerebral - M1 or M2 divisions, anterior cerebral, posterior cerebral, or basilar artery) within 3.5 hours of symptom onset Able to receive assigned treatment within 4.5 hours of symptom onset Written informed consent from patient or surrogate, if unable to provide consent Exclusion Criteria: CT evidence of early infarction in >1/3 of middle cerebral artery distribution Blood pressure > 185/110 mmHg refractory to anti-hypertensive therapy History of intracranial hemorrhage History of ischemic stroke within past 3 months History of major surgical procedure within past 14 days Gastrointestinal or genitourinary bleeding within past 14 days Glucose <50 or >400mg/dL Platelet count <100,000 International normalized ratio (INR) ≥ 1.7 Known history of bleeding diathesis

Ages Eligible for Study
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Minimum Age: 18 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intravenous Thrombolysis<br>0.9mg/kg intravenous rt-PA (max dose 90mg) - 10% administered as a bolus over 1 minute and the remainder infused over 60 minutes. | Drug: Intravenous Thrombolysis<br> <br> * Other names: Altelplase, rtPA;|
| Active Comparator: Endovascular Arterial Reperfusion<br>Therapeutic options will include mechanical thrombectomy/clot disruption (Penumbra aspiration system, Solitaire device, and/or Reflex catheter) and/or intracranial stent deployment. | Device: Endovascular Arterial Reperfusion<br> <br> * Other names: Penumbra, Solitaire;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recanalization Rate of Primary Intracranial Occlusion | The degree of recanalization (none, partial, complete) will be assessed in a blinded fashion on the 24-hour computed tomographic angiogram (CTA). | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Score on Modified Rankin Scale at 90 Days | Functional outcome at 90-days will be assessed with the modified Rankin Scale (mRS). The Modified Rankin Scale was completed by the physician; it is a 7 point scale rating any limitations in the study subject's social role. The scale ranges from 0 (no symptoms/disability) to 6 (death). | 90 days |