- MRI-guided thrombolysis for ischemic stroke having an unknown time of onset improves neurologic outcome with trade-off of more deaths, intracranial bleeding.
Why this matters
- The trial was stopped early as funding ended.
- Rate of favorable outcome higher with alteplase (Activase) thrombolysis vs placebo (53.3% vs 41.8%; aOR, 1.61; P=.02).
- Median modified Rankin scale score was better with alteplase (1 vs 2; common aOR, 1.62; P=.003).
- Trends whereby alteplase group had more deaths (4.1% vs 1.2%; P=.07), symptomatic intracranial hemorrhages (2.0% vs 0.4%; P=.15).
- Editorialist: “Although the findings of the WAKE-UP trial provide reason for optimism, many questions remain. It is important that clinical equipoise be maintained so that confirmatory trials can be performed.”
- Multicenter randomized controlled trial among 503 patients having stroke with an unknown time of onset, but MRI ischemic lesion suggesting onset ~4.5 hours earlier (WAKE-UP trial).
- Randomization: intravenous alteplase, placebo.
- Main outcome: 90-day favorable outcome (score of 0 or 1 on modified Rankin scale).
- Funding: European Union Seventh Framework Program.
- Patients with planned thrombectomy excluded.
- Limited power.