title: 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).
abstract: BACKGROUND
  In about 20% of acute ischemic stroke patients stroke occurs during sleep. These patients are generally excluded from intravenous thrombolysis. 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.
  
  
  OBJECTIVE
  The study aims 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. We hypothesize that stroke patients with unknown time of symptom onset with a DWI-FLAIR-mismatch pattern on MRI will have improved outcome when treated with rtPA compared to placebo.
  
  
  METHODS
  WAKE-UP is an investigator initiated, European, multicentre, randomized, double-blind, placebo-controlled clinical trial. Patients with unknown time of symptom onset who fulfil clinical inclusion criteria (disabling neurological deficit, no contraindications against thrombolysis) will be studied by MRI. Patients with MRI findings of a DWI-FLAIR-mismatch will be randomised to either treatment with rtPA or placebo.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Götz
authors.initials: G
authors.lastname: Thomalla
authors.forename: Jochen B
authors.initials: JB
authors.lastname: Fiebach
authors.forename: Leif
authors.initials: L
authors.lastname: Østergaard
authors.forename: Salvador
authors.initials: S
authors.lastname: Pedraza
authors.forename: Vincent
authors.initials: V
authors.lastname: Thijs
authors.forename: Norbert
authors.initials: N
authors.lastname: Nighoghossian
authors.forename: Pascal
authors.initials: P
authors.lastname: Roy
authors.forename: Keith W
authors.initials: KW
authors.lastname: Muir
authors.forename: Martin
authors.initials: M
authors.lastname: Ebinger
authors.forename: Bastian
authors.initials: B
authors.lastname: Cheng
authors.forename: Ivana
authors.initials: I
authors.lastname: Galinovic
authors.forename: Tae-Hee
authors.initials: TH
authors.lastname: Cho
authors.forename: Josep
authors.initials: J
authors.lastname: Puig
authors.forename: Florent
authors.initials: F
authors.lastname: Boutitie
authors.forename: Claus Z
authors.initials: CZ
authors.lastname: Simonsen
authors.forename: Matthias
authors.initials: M
authors.lastname: Endres
authors.forename: Jens
authors.initials: J
authors.lastname: Fiehler
authors.forename: Christian
authors.initials: C
authors.lastname: Gerloff
mesh_terms: D002545:Brain Ischemia / Q000188:drug therapy*; D002985:Clinical Protocols; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D004311:Double-Blind Method; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D018579:Patient Selection; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D018401:Sample Size; D012890:Sleep; D020521:Stroke / Q000188:drug therapy* / Q000503:physiopathology; D015912:Thrombolytic Therapy / Q000009:adverse effects / Q000379:methods*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator
keywords: acute ischemic stroke; clinical trials; diffusion-weighted imaging; fluid-attenuated inversion recovery imaging; protocols; thrombolysis