SAIL-ON: Safety of Intravenous Thrombolytics in Stroke on Awakening

• Sponsor: Johns Hopkins University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01643902
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 20
• Locations: 2
• Arm: 1
• Duration (Months): 35
• Patients Per Site: 10
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate the safety of intravenous tissue plasminogen activator (IV tPA) in patients waking up with symptoms of acute stroke and presenting to the Emergency Department (ED) within 4.5 hours from awakening, and meeting standard criteria for treatment with IV tPA for acute stroke.

The hypothesis is that patients that wake up with stroke symptoms may have developed the stroke at the time of awakening, and may be within the 4.5 hour window if they arrive to the ED within that time, therefore IV tPA should be safe and effective in this population.

Condition or Disease	Intervention/Treatment	Phase
Stroke	Drug: tPA	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety of Intravenous Thrombolytics in Stroke on Awakening
• Study Start Date: Jan 1, 2013
• Actual Primary Completion Date: Dec 1, 2015
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IV tPA Treatment will be initiated within 4.5 hours of awakening, for patients who meet inclusion criteria	Drug: tPA; IV tPA 0.9 mg/kg maximum of 90 mg. Administered by standard protocol. 10% of the dose by intravenous bolus injection, followed by infusion of the remainder over an hour. Treatment will be initiated within 4.5 hours of awakening with preferred target door to needle time of 60 minutes or less from ED arrival.; Other Names: Activase Alteplase

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Symptomatic Intracerebral Hemorrhage Within 36 Hours of Treatment [within 36 hours of treatment]

   Symptomatic intracerebral hemorrhage by using the European Cooperative Acute Stroke Study (ECASS) 3 criteria as well as the original National Institutes of Neurological Disorders and Stroke (NINDS) Intravenous tissue plasminogen activator (IV tPA) trial criteria for comparison. ECASS 3 criteria: hemorrhage in brain imaging, and an increase of 4 or more points on the National Institutes of Health Stroke Scale (NIHSS) from baseline. NINDS IV tPA trial criteria: a hemorrhage not seen in previous brain imaging, associated with a neurological decline attributable to the hemorrhage.

Secondary Outcome Measures

1. Functional Outcome by the Modified Rankin Scale at 90 Days [90 days]

   The modified Rankin scale (mRS) is a scale of disability after stroke, with a range of 0 to 6. 0, no symptoms at all. no significant disability despite symptoms; able to carry out all usual duties and activities. slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance. moderate disability; requiring some help, but able to walk without assistance. moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance. severe disability; bedridden, incontinent and requiring constant nursing care and attention. dead.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age greater or equal to 18 years, and lower or equal to 80 years.

• Signs and symptoms of acute ischemic stroke.

• Symptoms present upon awakening.

• Arriving to the Emergency Department within 4.5 hours of awakening. Treatment with IV tPA must be initiated prior to 4.5hours from waking up.

• NIHSS >3

• A non-contrast head CT without hemorrhage and without hypodensity more than 1/3 of the middle cerebral artery (MCA) territory; or MRI demonstrating no hemorrhage, and with a diffusion-weighted imaging (DWI) lesion no greater than 70 mL and FLAIR without a well defined hyperintense lesion that is more than 1/3 of the MCA territory.

• Pre-morbid modified Rankin score of 0 or 1.

Exclusion Criteria:

• Rapidly improving deficit to an NIHSS less than 3.

• Sustained systolic blood pressure greater than 185 mmHg or diastolic blood pressure greater than 110 mmHg despite treatment.

• Glucose less than 50 mg/dL.

• Stroke or head trauma within last 3 months.

• History of intracranial hemorrhage. Symptoms of subarachnoid hemorrhage.

• Major surgery within 14 days.

• Gastrointestinal (GI)/Genito-urinary (GU) hemorrhage within 21 days.

• International normalized ratio (INR) > 1.7.

• Heparin within 48 hours with an elevated activated partial thromboplastin time (aPTT).

• Platelet count less than 100,000.

• Presumed septic embolus or suspicion of bacterial endocarditis.

• Suspicion of aortic dissection.

• Use of anticoagulants such as dabigatran, rivaroxaban, apixaban, enoxaparin.

• Pregnant or lactating women.

• Known allergy or sensitivity to tPA.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Johns Hopkins Bayview Medical Center	Baltimore	Maryland	United States	21224
2	The Johns Hopkins Hospital	Baltimore	Maryland	United States	21287

Sponsors and Collaborators

• Johns Hopkins University
• Genentech, Inc.

Investigators

• Principal Investigator: Victor C Urrutia, MD, Johns Hopkins University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Victor C Urrutia, MD, Associate Professor, Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT01643902
• Other Study ID Numbers: ML28242
• First Posted: Jul 18, 2012
• Last Update Posted: Apr 17, 2017
• Last Verified: Mar 1, 2017

• Keywords provided by Victor C Urrutia, MD, Associate Professor, Johns Hopkins University: Stroke; Wake up; IV tPA; Thrombolytic
• Additional relevant MeSH terms: Stroke; Tissue Plasminogen Activator

Study Results

Participant Flow

Arm/Group Title	IV tPA
Arm/Group Description	Treatment will be initiated within 4.5 hours of awakening, for patients who meet inclusion criteria rt-PA: IV rt-PA 0.9 mg/kg minimum of 90 mg. Administered by standard protocol. 10% of the dose by intravenous bolus injection, followed by infusion of the remainder over an hour. Treatment will be initiated within 4.5 hours of awakening with preferred target foor to needle time of 60 minutes or less from ED arrival.
Period Title: Overall Study
STARTED	20
COMPLETED	20
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	IV tPA
Arm/Group Description	Treatment will be initiated within 4.5 hours of awakening, for patients who meet inclusion criteria IV tPA: IV tPA 0.9 mg/kg maximum of 90 mg. Administered by standard protocol. 10% of the dose by intravenous bolus injection, followed by infusion of the remainder over an hour. Treatment will be initiated within 4.5 hours of awakening with preferred target door to needle time of 60 minutes or less from ED arrival.
Overall Participants	20
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	9 45%
>=65 years	11 55%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	65
Sex: Female, Male (Count of Participants)
Female	8 40%
Male	12 60%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	20 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	10 50%
White	10 50%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	20 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Symptomatic Intracerebral Hemorrhage Within 36 Hours of Treatment
Description	Symptomatic intracerebral hemorrhage by using the European Cooperative Acute Stroke Study (ECASS) 3 criteria as well as the original National Institutes of Neurological Disorders and Stroke (NINDS) Intravenous tissue plasminogen activator (IV tPA) trial criteria for comparison. ECASS 3 criteria: hemorrhage in brain imaging, and an increase of 4 or more points on the National Institutes of Health Stroke Scale (NIHSS) from baseline. NINDS IV tPA trial criteria: a hemorrhage not seen in previous brain imaging, associated with a neurological decline attributable to the hemorrhage.
Time Frame	within 36 hours of treatment

Outcome Measure Data

Analysis Population Description

No symptomatic intracerebral hemorrhage was observed by either NINDS IV tPA trial or ECASS 3 criteria.

Arm/Group Title	IV Rt-PA
Arm/Group Description	Treatment will be initiated within 4.5 hours of awakening, for patients who meet inclusion criteria IV tPA: IV tPA 0.9 mg/kg maximum of 90 mg. Administered by standard protocol. 10% of the dose by intravenous bolus injection, followed by infusion of the remainder over an hour. Treatment will be initiated within 4.5 hours of awakening with preferred target door to needle time of 60 minutes or less from Emergency department (ED) arrival.
Measure Participants	20
Number [participants]	0 0%

2. Secondary Outcome

Title	Functional Outcome by the Modified Rankin Scale at 90 Days
Description	The modified Rankin scale (mRS) is a scale of disability after stroke, with a range of 0 to 6. 0, no symptoms at all. no significant disability despite symptoms; able to carry out all usual duties and activities. slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance. moderate disability; requiring some help, but able to walk without assistance. moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance. severe disability; bedridden, incontinent and requiring constant nursing care and attention. dead.
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV tPA
Arm/Group Description	Treatment will be initiated within 4.5 hours of awakening, for patients who meet inclusion criteria IV tPA: IV tPA 0.9 mg/kg maximum of 90 mg. Administered by standard protocol. 10% of the dose by intravenous bolus injection, followed by infusion of the remainder over an hour. Treatment will be initiated within 4.5 hours of awakening with preferred target door to needle time of 60 minutes or less from ED arrival.
Measure Participants	20
Mean (Full Range) [units on a scale]	1

Adverse Events

Arm/Group Title	IV tPA
Arm/Group Description	Treatment will be initiated within 4.5 hours of awakening, for patients who meet inclusion criteria IV tPA: IV tPA 0.9 mg/kg maximum of 90 mg. Administered by standard protocol. 10% of the dose by intravenous bolus injection, followed by infusion of the remainder over an hour. Treatment will be initiated within 4.5 hours of awakening with preferred target door to needle time of 60 minutes or less from ED arrival.
All Cause Mortality
	IV tPA
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	IV tPA
	Affected / at Risk (%)	# Events
Total	0/20 (0%)
Other (Not Including Serious) Adverse Events
	IV tPA
	Affected / at Risk (%)	# Events
Total	2/20 (10%)
Nervous system disorders
Asymptomatic intracerebral hemorrhage	2/20 (10%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.