A multicentre, randomized, double-blind, placebo-controlled trial to test efficacy and safety of MRI-based thrombolysis in wake-up stroke
Thomalla G, Cheng B, Ebinger M, Hao Q, Tourdias T, Wu O, et al. DWI-FLAIR mismatch for the identification of patients with acute ischaemic stroke within 4.5 h of symptom onset (PRE-FLAIR): a multicentre observational study. Lancet Neurol 2011; 10: 978-986.
Thomalla G, Fiebach JB, Ostergaard L, Pedraza S, Thijs V, Nighoghossian N, et al. A multicenter, randomized, double-blind, placebo-controlled trial to test efficacy and safety of magnetic resonance imaging-based thrombolysis in wake-up stroke (WAKE-UP). Int J Stroke 2014; 9: 829-36.
Thomalla G, Rossbach P, Rosenkranz M, Siemonsen S, Krutzelmann A, Fiehler J, et al. Negative fluid-attenuated inversion recovery imaging identifies acute ischemic stroke at 3 hours or less. Ann Neurol 2009; 65: 724-732.
Website and Flowchart of the WAKE-UP - Trial
In case of a mismatch between DWI and FLAIR (left side of the figure) there is a positive predictive value of 83% to being within 4.5 hours after symptom onset.
As published in Lancet Neurology, researchers from the Department of Neurology at the University Medical Center Hamburg-Eppendorf enrol the WAKE-UP trial.
In about 20% of acute ischemic stroke patients stroke occurs during sleep. These patients are generally excluded from intravenous thrombolysis. In preparatory studies we demonstrated that MRI can identify patients within the time-window for thrombolysis (<4.5 h from symptom onset) by a mismatch between the acute ischemic lesion visible on diffusion weighted imaging (DWI) but not visible on fluid-attenuated inversion recovery (FLAIR) imaging (Thomalla, 2011; Thomalla, 2009).
WAKE-UP is an investigator initiated, European, multicentre, randomized, double-blind, placebo-controlled clinical trial designed to test the efficacy and safety of MRI-guided thrombolysis with tissue plasminogen activator (rtPA) in ischemic stroke patients with unknown time of symptom onset, e.g., waking up with stroke symptoms (Thomalla, 2014).
The primary efficacy endpoint will be favourable outcome defined by modified Rankin Scale 0-1 at day 90. The primary safety outcome measures will be mortality and death or dependency defined by modified Rankin Scale 4-6 at 90 days.
If positive, WAKE-UP is expected to change clinical practice making effective and safe treatment available for a large group of acute stroke patients currently excluded from specific acute therapy.
WAKE-UP is registered with the EU Clinical Trials Register (EudraCT No. 2011-005906-32) and ClinicalTrials.gov (ClinicalTrials.gov Identifier NCT01525290).