Neurology in critical care · Thrombolysis beyond the clock
MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset
| Design | Multicentre randomised, placebo-controlled trial, stopped early when funding ceased |
|---|---|
| Treatment | Intravenous alteplase guided by diffusion-weighted imaging and FLAIR mismatch |
| Control | Placebo |
| Population | 503 patients with acute stroke of unknown onset time, of a planned 800 |
| Follow-up | 90 days |
| Primary endpoint | Favourable outcome at 90 days, modified Rankin Scale 0 to 1 |
| Result | Among 254 patients assigned alteplase and 249 placebo, functional outcome at 90 days was significantly better with alteplase. The trial stopped early when funding ceased. |
| Secondary endpoints | Modified Rankin Scale shift, mortality, symptomatic intracranial haemorrhage |
In patients with acute stroke with an unknown time of onset, intravenous alteplase guided by a mismatch between diffusion-weighted imaging and FLAIR in the region of ischemia resulted in a significantly better functional outcome.
The trial authors, in the published abstract
Replaced the clock with the tissue. Patients who wake with stroke had been categorically excluded from thrombolysis; imaging showed many were physiologically within the window regardless of when the clock started. EXTEND made the same argument with perfusion imaging out to nine hours.
Thomalla G, Simonsen CZ, Boutitie F, et al. MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset. N Engl J Med 2018 Aug 16;379(7):611-622.