WAKE-UP
MRI-guided thrombolysis for stroke with unknown time of onset
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Overview
MRI-selected alteplase improved functional outcome in stroke with unknown onset time.
Clinical takeaway
WAKE-UP extended thrombolysis thinking beyond the clock by using DWI-FLAIR mismatch to select patients likely within a treatable window.
Key result
Favorable functional outcome (mRS 0-1) at 90 days was 53.3% with alteplase vs 41.8% with placebo (adjusted OR 1.61; 95% CI 1.09-2.36; P=0.02).
Practice impact
Advanced imaging can identify selected unknown-onset stroke patients for thrombolysis.
Evidence
Study design
Randomized, double-blind, placebo-controlled trial.
Enrollment
503
Follow-up
90 days.
Geography
Europe
Clinical question
Does MRI-guided alteplase improve outcomes in ischemic stroke with unknown time of onset?
Population
- Patients with acute ischemic stroke of unknown onset time and MRI DWI-positive/FLAIR-negative mismatch.
Intervention
Intravenous alteplase.
Comparator
Placebo.
Primary outcome
Favorable functional outcome at 90 days, defined by modified Rankin Scale score 0 or 1.
MRI-guided alteplase improved favorable functional outcome in unknown-onset ischemic stroke.
Adjusted odds ratio / 1.61 / 95% CI 1.09-2.36 / p=0.02
Key results
- Favorable functional outcome (mRS 0-1) was more common with alteplase: 131 of 246 (53.3%) vs 102 of 244 (41.8%); adjusted OR 1.61 (95% CI 1.09-2.36; p=0.02).
- Symptomatic intracranial hemorrhage was numerically higher with alteplase (2.0% vs 0.4%; OR 4.95, 95% CI 0.57-42.87; p=0.15), as was death (4.1% vs 1.2%; OR 3.38, 95% CI 0.92-12.52; p=0.07).
- Trial was stopped early because funding ended, after 503 of an anticipated 800 patients.
Harms
- Symptomatic intracranial hemorrhage risk remains the major thrombolysis concern.
Clinical Use
Practice impact
- Supported imaging-selected thrombolysis for wake-up or unknown-onset ischemic stroke.
Applicability
- Patients with disabling ischemic stroke symptoms, unknown onset, no contraindications, and appropriate MRI mismatch.
Limitations
- Requires rapid MRI access and expertise.
- Stopped early; estimates are less precise.
Common misinterpretations
- Do not give alteplase to all wake-up strokes; imaging selection is the point.
Citation
Thomalla G, Simonsen CZ, Boutitie F, et al. MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset. N Engl J Med. 2018;379(7):611-622. doi:10.1056/NEJMoa1804355
A favorable outcome at 90 days was reported in 131 of 246 patients (53.3%) in the alteplase group and in 102 of 244 patients (41.8%) in the placebo group (adjusted odds ratio, 1.61; 95% confidence interval [CI], 1.09 to 2.36; P=0.02).
- PMID
- 29766770