Stroke
Conditions
Keywords
wake-up stroke, thrombolysis, magnetic resonance imaging (MRI), diffusion weighted imaging (DWI), fluid attenuated inversion recovery (FLAIR)
Brief summary
WAKE-UP is an investigator initiated European multicenter randomized controlled clinical trial of MRI based thrombolysis in acute stroke patients with unknown time of symptom onset, e.g. due to recognition of stroke symptoms on awakening. Objective of WAKE-UP is to prove efficacy and safety of MRI-based intravenous thrombolysis with Alteplase in patients waking up with stroke symptoms or patients with otherwise unknown symptom onset.
Detailed description
WAKE-UP is a clinical trial of MRI based thrombolysis in acute stroke patients with unknown time of symptom onset, e.g. due to recognition of stroke symptoms on awakening. Intravenous thrombolysis with Alteplase is available as effective and safe treatment of acute stroke within 4.5 hours of symptom onset. However, in about 20% of acute stroke patients time of symptom onset is unknown. This large group of patients is currently excluded from treatment with Alteplase. The objective of the research proposed in the WAKE-UP project is to provide effective treatment options for this large group of acute stroke patients. WAKE-UP is designed to prove efficacy and safety of MRI-based intravenous thrombolysis with Alteplase in patients waking up with stroke symptoms or patients with otherwise unknown symptom onset. Patients will be enrolled based on MRI findings indicative of acute ischemic stroke less than 4.5 hours of age.
Interventions
DRUGAlteplase
Intravenous tissue plasminogen activator (Alteplase) 0.9 mg/kg body-weight up to a maximum of 90 mg, 10% as bolus, 90% over 1 hour as infusion
DRUGPlacebo
lyophilised powder to be reconstituted as solution indistinguishable from the active drug
Sponsors
Universitätsklinikum Hamburg-Eppendorf
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Clinical Inclusion Criteria * Clinical diagnosis of acute ischemic stroke with unknown symptom onset (e.g., stroke symptoms recognized on awakening) * Last known well (without neurological symptoms) \> 4.5 hours of treatment initiation * Measurable disabling neurological deficit (defined as an impairment of one or more of the following: language, motor function, cognition, gaze, vision, neglect) * Age 18-80 years * Treatment can be started within 4.5 hours of symptom recognition (e.g., awakening) * Written informed consent by patient or proxy Imaging Inclusion Criteria: * Acute stroke MRI including diffusion weighted imaging (DWI) and fluid attenuated inversion recovery (FLAIR) completed * MRI showing a pattern of DWI-FLAIR-mismatch, i.e. acute ischemic lesion visibly on DWI (positive DWI) but no marked parenchymal hyperintensity visible on FLAIR (negative FLAIR) indicative of an acute ischemic lesion ≤4.5 hours of age
Exclusion criteria
Clinical
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy | 90 day after stroke | Favourable outcome (Modified Rankin Scale 0-1) |
| Safety | 90 day after stroke | * Mortality * Death or dependency (Modified Rankin Scale 4-6) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy | 90 days after stroke | * Global outcome score * Responder analysis (Modified Rankin Scale 0, 0-1 or 0-2 depending on severity of symptoms assessed by the National Institutes of Health Stroke Scale on admission) * Outcome across all disability ranges (categorical shift in Modified Rankin Scale score) * Infarct volume (measured 22-36 hours after treatment) * Functional health status and quality of life * Use of health care system resources |
| Safety | 90 days after stroke | * Symptomatic intracranial haemorrhage (SICH) as defined in SITS-MOST * SICH as defined ECASS II * SICH as defined in NINDS * Parenchymal haemorrhage type 2 (PH-2) |
Countries
Belgium, Denmark, France, Germany, Spain, United Kingdom
Outcome results
None listed