First 10EM - By Justin Morgenstern - January 27, 2020
The paper: The WAKE UP Trial: Thomalla G, Simonsen CZ, Boutitie F, et al. MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset. The New England journal of medicine. 2018; 379(7):611-622. PMID: 29766770 [free full text] ClinicalTrials.gov: NCT01525290
"There have been a few new thrombolytic RCTs since I published my review of the stroke literature, and it is probably about time that I got around to writing about them. On the one hand, I think it is exciting that we are moving past the flawed time-based selection of patients, and exploring other options for deciding who might benefit from thrombolytics. On the other hand, the trials are flawed and don’t really provide any answers, so there isn’t much to be excited about. Tomorrow I will review a group of trials that uses perfusion based imaging to select patients with salvageable brain tissue. In my mind, that is the most promising approach. This review looks at the WAKE-UP trial, which uses an MRI technique that can identify strokes that are less than 4.5 hours old, regardless of the timing of the symptoms...
Bottom line
In this trial, which has significant risk of bias, using MRI to select patients with an unknown time of stroke onset and giving them alteplase resulted in an 11% improvement in 90 day neurologic outcomes, but also probably increased mortality. Using advanced imaging to select stroke patients for thrombolytic therapy is promising, but should be considered unproven at this point. (Thrombolytic therapy in general is unproven, as we still await the necessary NINDS replication study.)"