Safety of Intravenous Thrombolysis for Wake-up Stroke

Phase 2

Completed

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
off label rt-PA used	Alteplase (iv t-PA)	off label rt-PA used on all subject enrolled within 3 hours of waking with stroke symptoms at the standard of care dose.

Primary Outcome Measures

Name	Time	Method
Frequency of Symptomatic Hemorrhagic Transformation Safety of iv Rt-PA in Wake up Stroke Patients	24 hours	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.

Secondary Outcome Measures

Name	Time	Method
90-day Modified Rankin Scale (mRS) Score 0 or 1	90 days	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.
Mortality	90 days

Locations (3): University of Alabama
🇺🇸
Birmingham, Alabama, United States
UT-Houston Health Science Center
🇺🇸
Houston, Texas, United States
Swedish Medical Center
🇺🇸
Englewood, Colorado, United States