Wake up Symptomatic Stroke - Benefit of Intravenous Clot Busters or Endovascular Intervention

Study Overview
=================
Brief Summary
-----------------
The purpose of the trial is to study the safety and the effectiveness of using CT Perfusion studies as an indicator to treat stroke patients with unknown time of onset.

Official Title
-----------------
Wake up Symptomatic Stroke in Acute Brain Ischemia (WASSABI) Trial

Conditions
-----------------
Stroke

Intervention / Treatment
-----------------
* Drug: Anti-platelets and statin
* Drug: alteplase
* Procedure: intra arterial intervention


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Inclusion Criteria: To be eligible for entry into this study, candidates must meet all of the following eligibility criteria at the time of Emergency Department presentation: Age: 18-80 years old Ischemic Wake Up Stroke (Unknown time of onset but less than 24 hours since last seen normal) National Institute of Health Stroke Scale (NIHSS) 8-22 Evidence of penumbra on Computed Tomography Perfusion(CTP) as mentioned above Alberta Stroke Program Early Computed Tomography (CT) Score (ASPECTS 7 or more) Signed informed consent Exclusion Criteria: Exclusion Criteria: Potential study patients will be excluded from study entry if any of the following exclusion criteria exist at the time of screening: Evidence of intracranial hemorrhage (Intracerebral hematoma, intraventricular hemorrhage, subarachnoid hemorrhage (SAH), epidural hemorrhage, acute or chronic subdural hematoma (SDH)) on the baseline CT Historical Modified Rankin Scale (mRS) of ≥2 National Institute of Health Stroke Scale (NIHSS)<8 at the time of treatment Positive pregnancy test in women at age of childbearing Intracranial or intraspinal surgery within 3 months Stroke or serious head injury within 3 months History of intracranial hemorrhage Uncontrolled hypertension at time of treatment (eg, >185 mm Hg systolic or >110 mm Hg diastolic) Seizure at the onset of stroke Active internal bleeding Intracranial neoplasm Arteriovenous malformation or aneurysm Clinical presentation suggesting post-MI pericarditis Known bleeding diathesis including but not limited to current use of oral anticoagulants producing an Internation normalized ratio (INR) >1.7 Internation normalized ratio (INR) >1.7 Administration of heparin within 48 hours preceding the onset of stroke with an elevated activated Partial Thromboplastin Time(aPTT) at presentation Platelet count <100,000/mm Major surgery within 2 weeks GastroIntestinal (GI) or urinary tract hemorrhage within 3 weeks Aggressive treatment required to lower blood pressure Glucose level <50 or >400 mg/dL Arterial puncture at a noncompressible site or lumbar puncture within 1 week

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Medical Therapy<br>Current standard of care per the latest stroke guidelines Permissive Hypertension up to 220 Antipletelets therapy: ASA 81 mg PO daily or Plavix 75 mg PO daily or Aggrenox 225mg PO twice daily Anti-inflammatory therapy: Lipitor 80 mg PO daily or Crestor 20 mg PO daily | Drug: Anti-platelets and statin<br> <br> |
| Experimental: Intravenous Thrombolysis<br>Full dose Intravenous thrombolysis 0.9 mg/kg Maximum dose is 90 mg 10% of the dose will be given over one minute 90% of the dose will be infused over 1 hour Admission to Neuro Intensive Care Unit(NICU) for 24 hours if no complications Neuro checks every 5 minutes during the infusion Neuro checks every hour after the infusion for 24 hours | Drug: alteplase<br>* Full dose Intravenous thrombolysis 0.9 mg/kg Maximum dose is 90 mg 10% of the dose will be given over one minute 90% of the dose will be infused over 1 hour Admission to Neuro Intensive Care Unit(NICU) for 24 hours if no complications Neuro checks every 5 minutes during the infusion Neuro checks every hour after the infusion for 24 hours<br>|
| Experimental: Intra-Arterial Therapy<br>-Choice of therapy per experienced Endovascular surgeon and includes: Intra arterial Activase (Maximum dose of 22 mg) MERCI device (Maximum of 3 tries per device, no standard time frame for how long the procedure takes) PENUMBRA device (no standard time frame for how long the procedure takes) | Procedure: intra arterial intervention<br>* Intra arterial Activase (Maximum dose of 22 mg) MERCI device (Maximum of 3 tries per device, no standard time frame for how long the procedure takes) PENUMBRA device (no standard time frame for how long the procedure takes)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Rankin Scale (mRS) | Modified Rankin Scale (mRS) 90 days post treatment | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| National Institute of Health Stroke Scale (NIHSS) | National Institute of Health Stroke Scale (NIHSS) 24 hours post treatment. | 24 hour | 
| National Institute of Health Stroke Scale (NIHSS) | National Institute of Health Stroke Scale (NIHSS) at discharge (3-29 days) | 3-29 day | 
| Modified Rankin Scale (mRS) | Modified Rankin Scale (mRS) at 30 days post treatment | 30 post treatment | 
| Thrombolysis In Myocardial Infarction (TIMI) Flow | Thrombolysis In Myocardial Infarction (TIMI) flow pre and post the intervention as an indicator of revascularization rate | Pre - up to1 hour prior to procedure and post will be up to1 hour after completion of procedure | 
| Thomboylsis in Cerebral Ischemia (TICI) flow | Thomboylsis in Cerebral Ischemia (TICI) flow pre and post intervention as an indicator of revascularization rate | Pre - will be no more than 1 hour prior to procedure and post will be no more then 1 hour after completion of procedure | 
| symptomatic intracranial Hemorrhage (ICH) | Incidence of symptomatic symptomatic intracranial Hemorrhage (ICH) within 72 hours of intervention defined by ECASSIII as 4 points worsening in NIHSS | 72 hours | 
| National Institute of Health Stroke Scale (NIHSS) | at 30 Day visit National Institute of Health Stroke Scale (NIHSS) will be assessed | 30 Days |