Safety of Intravenous Thrombolysis for Wake-up Stroke

Study Overview
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Brief Summary
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The purpose is to demonstrate the safety of intravenous tissue plasminogen activator (IV t-PA) in ischemic stroke patients who present to the emergency department (ED) after awakening with the symptoms of suspected ischemic stroke.

Detailed Description
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This is an open label, multi-center, safety study of acute treatment with IV alteplase in ischemic stroke patients who wake-up with their symptoms. The primary outcome of this study is the frequency of symptomatic hemorrhagic transformation evident within 24 hours of treatment with IV t-PA. Clinical improvement defined as a decrease in the National Institutes of Health Stroke Scale (NIHSS) score at 24 hours, 3 days and 90 days and modified Rankin Scale (mRS) score at 3 and 90 days. For patients that have computed tomographic angiogram (CTA) and computed tomographic perfusion (CTP), the incidence of large vessel occlusion will be quantified.

Official Title
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Safety of Intravenous Thrombolysis for Wake-up Stroke

Conditions
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Ischemic Stroke

Intervention / Treatment
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* Drug: Alteplase (iv t-PA)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Suspected acute ischemic stroke that occurred during sleep or patients who wake up with focal neurological symptoms. This includes all patients who were last known to be neurologically normal the night before,but then found upon awakening with stroke deficits. It will be considered that the last known onset time is the time when the patient was last known to be well. 18 to 80 years old NIHSS (National Institutes of Health Stroke Scale) ≤25 Blood Pressure ≤185 mmHg systolic & ≤110 mmHg diastolic at the time of enrollment. Treatment of higher systolic BP is permitted, prior to enrollment IV t-PA must be given within 3 hours of awakening from sleep Female patients of child-bearing potential must have a negative pregnancy test prior to enrollment Exclusion Criteria: CT Exclusion Criteria: Hypodensity >1/3 middle cerebral artery (MCA) territory on non-contrast cranial CT scan or evidence of intracranial or subarachnoid hemorrhage Prior ischemic stroke within 3 months of the presenting event History of intracranial hemorrhage Known secured or unsecured cerebral aneurysm or vascular malformation Inability to control systolic BP > 185 mmHg or diastolic BP > 110 mmHg with IV anti-hypertensive medications Known coagulopathy or evidence of active bleeding Surgical procedures, biopsy, subclavian venous or arterial puncture, trauma within 14 days of the event Gastrointestinal or genitourinary bleeding within 14 days of the event Treated with IV heparin within the previous 24 hours & an abnormal (partial thromboplastin time) PTT Oral anticoagulants & an (international normalized ratio) INR >1.7 Platelet count <100,000 Venous glucose either <50 or >450 Any patient who qualifies for this protocol should not be treated with (intra-arterial therapy) IAT If the treating physician believes a patient should undergo IAT, those patients should be identified a priori and not enrolled into this protocol

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: off label rt-PA used<br>off label rt-PA used on all subject enrolled within 3 hours of waking with stroke symptoms at the standard of care dose. | Drug: Alteplase (iv t-PA)<br>* 0.9 mg/kg (maximum of 90 mg) IV t-PA will be administered with 10% bolus given over 1 minute, the rest given as an infusion over the remaining hour.<br>* Other names: t-PA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Symptomatic Hemorrhagic Transformation Safety of iv Rt-PA in Wake up Stroke Patients | The primary outcome of this study is the frequency of symptomatic hemorrhagic transformation evident within 24 hours of treatment with IV t-PA. Symptomatic was defined as significant clinical deterioration with at least a 4 point or more increase in the NIH Stroke scale. | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 90-day Modified Rankin Scale (mRS) Score 0 or 1 | Number of patients with mRS of 0 or 1 at 90 days. The mRS is a clinician-reported measure of global disability that has been widely applied for evaluating recovery from stroke. It has a minimum of 0 and a maximum of 6. Zero represents a patient that has no disability or residual stroke symptoms. A score of 1 is defined as: no significant disability: despite symptoms, able to carry out all usual duties and activities. The maximum score, 6, indicates death. A score of 2 is defined as slight disability: unable to perform all previous activities but able to look after own affairs without assistance; a score of 3 is defined as moderate disability: requiring some help but able to walk without assistance; a score of 4 is moderately severe disability: unable to walk without assistance and unable to attend to own bodily needs without assistance; a score of 5 is severe disability: bedridden, incontinent and requiring constant nursing care and attention. | 90 days | 
| Mortality |  | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Wake-Up Stroke, Ischemic stroke, ischemic stroke patients who wake-up with their symptoms