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

Primary Purpose

Ischemic Stroke

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Alteplase (iv t-PA)
Sponsored by
The University of Texas Health Science Center, Houston
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ischemic Stroke focused on measuring Wake-Up Stroke, Ischemic stroke, ischemic stroke patients who wake-up with their symptoms

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama
  • Swedish Medical Center
  • UT-Houston Health Science Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

off label rt-PA used

Arm Description

off label rt-PA used on all subject enrolled within 3 hours of waking with stroke symptoms at the standard of care dose.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Mortality

Full Information

First Posted
August 16, 2010
Last Updated
November 24, 2014
Sponsor
The University of Texas Health Science Center, Houston
Collaborators
Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01183533
Brief Title
Safety of Intravenous Thrombolysis for Wake-up Stroke
Acronym
Wake-Up Stroke
Official Title
Safety of Intravenous Thrombolysis for Wake-up Stroke
Study Type
Interventional

2. Study Status

Record Verification Date
November 2014
Overall Recruitment Status
Completed
Study Start Date
July 2010 (undefined)
Primary Completion Date
October 2013 (Actual)
Study Completion Date
January 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The University of Texas Health Science Center, Houston
Collaborators
Genentech, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ischemic Stroke
Keywords
Wake-Up Stroke, Ischemic stroke, ischemic stroke patients who wake-up with their symptoms

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
off label rt-PA used
Arm Type
Experimental
Arm Description
off label rt-PA used on all subject enrolled within 3 hours of waking with stroke symptoms at the standard of care dose.
Intervention Type
Drug
Intervention Name(s)
Alteplase (iv t-PA)
Other Intervention Name(s)
Activase®, Alteplase, tissue plasminogen activator, t-PA
Intervention Description
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.
Primary Outcome Measure Information:
Title
Frequency of Symptomatic Hemorrhagic Transformation Safety of iv Rt-PA in Wake up Stroke Patients
Description
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.
Time Frame
24 hours
Secondary Outcome Measure Information:
Title
90-day Modified Rankin Scale (mRS) Score 0 or 1
Description
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.
Time Frame
90 days
Title
Mortality
Time Frame
90 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sean I Savitz, MD
Organizational Affiliation
UT-Houston Health Science Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Andrew D Barreto, MD
Organizational Affiliation
Study Co-PI
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Swedish Medical Center
City
Englewood
State/Province
Colorado
ZIP/Postal Code
80113
Country
United States
Facility Name
UT-Houston Health Science Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
27273860
Citation
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.
Results Reference
derived

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Safety of Intravenous Thrombolysis for Wake-up Stroke

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