Stroke
Conditions
Keywords
Stroke, Wake up, IV tPA, Thrombolytic
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.
Interventions
DRUGtPA
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.
Sponsors
Genentech, Inc.
Johns Hopkins University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. 1. no significant disability despite symptoms; able to carry out all usual duties and activities. 2. slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance. 3. moderate disability; requiring some help, but able to walk without assistance. 4. moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance. 5. severe disability; bedridden, incontinent and requiring constant nursing care and attention. 6. dead. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| IV tPA 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. | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | IV tPA |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 11 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Age, Continuous | 65 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
Number of Participants With Symptomatic Intracerebral Hemorrhage 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.
Time frame: within 36 hours of treatment
Population: No symptomatic intracerebral hemorrhage was observed by either NINDS IV tPA trial or ECASS 3 criteria.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IV Rt-PA | Number of Participants With Symptomatic Intracerebral Hemorrhage Within 36 Hours of Treatment | 0 participants |
Secondary
Functional Outcome by the Modified Rankin Scale at 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. 1. no significant disability despite symptoms; able to carry out all usual duties and activities. 2. slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance. 3. moderate disability; requiring some help, but able to walk without assistance. 4. moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance. 5. severe disability; bedridden, incontinent and requiring constant nursing care and attention. 6. dead.
Time frame: 90 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| IV Rt-PA | Functional Outcome by the Modified Rankin Scale at 90 Days | 1 units on a scale |