Safety of Intravenous Thrombolysis for Wake-up Stroke (Wake-Up Stroke)

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.

Study Overview

• Status: Completed
• Conditions: Ischemic Stroke
• Intervention / Treatment: Drug: Alteplase (iv t-PA)

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Swedish Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • UT-Houston Health Science Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: off label rt-PA used; 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); 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.; Other Names: Alteplase; t-PA; tissue plasminogen activator; Activase®

What is the study measuring?

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
Mortality		90 days
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

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Collaborators: Genentech, Inc.
• Investigators: Principal Investigator: Sean I Savitz, MD, UT-Houston Health Science Center; Principal Investigator: Andrew D Barreto, MD, Study Co-PI

Publications and helpful links

General Publications

• Barreto AD, Fanale CV, Alexandrov AV, Gaffney KC, Vahidy FS, Nguyen CB, Sarraj A, Rahbar M, Grotta JC, Savitz SI; Wake-Up Stroke Investigators. Prospective, open-label safety study of intravenous recombinant tissue plasminogen activator in wake-up stroke. Ann Neurol. 2016 Aug;80(2):211-8. doi: 10.1002/ana.24700. Epub 2016 Jul 12.

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: August 16, 2010
• First Submitted That Met QC Criteria: August 16, 2010
• First Posted (Estimate): August 17, 2010

Study Record Updates

• Last Update Posted (Estimate): November 25, 2014
• Last Update Submitted That Met QC Criteria: November 24, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: Ischemic stroke; Wake-Up Stroke; ischemic stroke patients who wake-up with their symptoms
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tissue Plasminogen Activator; Plasminogen
• Other Study ID Numbers: HSC-MS-10-0195