Serious adverse events and their impact on functional outcome in acute ischemic stroke in the WAKE-UP trial

Lettow, I. et al. (2021) Serious adverse events and their impact on functional outcome in acute ischemic stroke in the WAKE-UP trial. Stroke, 52(12), pp. 3768-3776. (doi: 10.1161/strokeaha.120.033425) (PMID:34433305)

Full text not currently available from Enlighten.


Background and Purpose: During the first days and weeks after an acute ischemic stroke, patients are prone to complications that can influence further treatment, recovery, and functional outcome. In clinical trials, severe complications are recorded as serious adverse events (SAE). We analyzed the effect of SAE on functional outcome and predictors of SAE in the randomized controlled WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke). Methods: We performed a post hoc analysis of WAKE-UP, a multicenter, randomized, placebo-controlled clinical trial of magnetic resonance imaging-guided intravenous thrombolysis with alteplase in patients with acute ischemic stroke and unknown time of onset. Functional outcome was assessed by the modified Rankin Scale 90 days after the stroke. SAE were reported to a central safety desk and recorded and categorized by organ system using Medical Dictionary for Regulatory Activities terminology. We used logistic regression analysis to determine the effect of SAE on functional outcome and linear multiple regression analysis to identify baseline predictors of SAE. Results: Among 503 patients randomized, 199 SAE were reported for n=110 (22%) patients. Of those patients who did suffer a SAE, 20 (10%) had a fatal outcome. Patients suffering from at least one SAE had a lower odds of reaching a favorable outcome (modified Rankin Scale score of 0–1) at 90 days (adjusted odds ratio, 0.36 [95% CI, 0.21–0.61], P <0.001). Higher age ( P =0.04) and male sex ( P =0.01) were predictors for the occurrence of SAE. Conclusions: SAEs were observed in about one in 5 patients, were more frequent in elderly and male patients and were associated with worse functional outcome. These results may help to assess the risk of SAE in future stroke trials and create awareness for severe complications after stroke in clinical practice. REGISTRATION: URL: ; Unique identifier: NCT01525290 and ; Unique identifier: 2011-005906-32.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Muir, Professor Keith
Authors: Lettow, I., Jensen, M., Schlemm, E., Boutitie, F., Quandt, F., Cheng, B., Ebinger, M., Endres, M., Fiebach, J. B., Thijs, V., Lemmens, R., Muir, K. W., Nighoghossian, N., Pedraza, S., Simonsen, C. Z., Gerloff, C., and Thomalla, G.
College/School:College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
Journal Name:Stroke
Publisher:American Heart Association
ISSN (Online):1524-4628
Published Online:26 August 2021

University Staff: Request a correction | Enlighten Editors: Update this record