title: A multicentre, randomized, double-blinded, placebo-controlled Phase III study to investigate EXtending the time for Thrombolysis in Emergency Neurological Deficits (EXTEND).
abstract: OBJECTIVE
  Thrombolytic therapy with tissue plasminogen activator is effective for acute ischaemic stroke within 4·5 h of onset. Patients who wake up with stroke are generally ineligible for stroke thrombolysis. We hypothesized that ischaemic stroke patients with significant penumbral mismatch on either magnetic resonance imaging or computer tomography at three- (or 4·5 depending on local guidelines) to nine-hours from stroke onset, or patients with wake-up stroke within nine-hours from midpoint of sleep duration, would have improved clinical outcomes when given tissue plasminogen activator compared to placebo.
  
  
  METHODS
  EXtending the time for Thrombolysis in Emergency Neurological Deficits is an investigator-driven, Phase III, randomized, multicentre, double-blind, placebo-controlled study. Ischaemic stroke patients presenting after the three- or 4·5-h treatment window for tissue plasminogen activator and within nine-hours of stroke onset or with wake-up stroke within nine-hours from the midpoint of sleep duration, who fulfil clinical (National Institutes of Health Stroke Score ≥4-26 and prestroke modified Rankin Scale <2) will undergo magnetic resonance imaging or computer tomography. Patients who also meet imaging criteria (infarct core volume <70 ml, perfusion lesion : infarct core mismatch ratio >1·2, and absolute mismatch >10 ml) will be randomized to either tissue plasminogen activator or placebo.
  
  
  RESULTS
  The primary outcome measure will be modified Rankin Scale 0-1 at day 90. Clinical secondary outcomes include categorical shift in modified Rankin Scale at 90 days, reduction in the National Institutes of Health Stroke Score by 8 or more points or reaching 0-1 at day 90, recurrent stroke, or death. Imaging secondary outcomes will include symptomatic intracranial haemorrhage, reperfusion and or recanalization at 24 h and infarct growth at day 90.
authors.affiliation: National Stroke Research Institute, Florey Neuroscience Institutes, Austin Health, University of Melbourne, Heidelberg Heights, Victoria, Australia.
authors.forename: Henry
authors.initials: H
authors.lastname: Ma
authors.forename: Mark W
authors.initials: MW
authors.lastname: Parsons
authors.forename: Soren
authors.initials: S
authors.lastname: Christensen
authors.forename: Bruce C V
authors.initials: BC
authors.lastname: Campbell
authors.forename: Leonid
authors.initials: L
authors.lastname: Churilov
authors.forename: Alan
authors.initials: A
authors.lastname: Connelly
authors.forename: Bernard
authors.initials: B
authors.lastname: Yan
authors.forename: Chris
authors.initials: C
authors.lastname: Bladin
authors.forename: Than
authors.initials: T
authors.lastname: Phan
authors.forename: Alan P
authors.initials: AP
authors.lastname: Barber
authors.forename: Stephen
authors.initials: S
authors.lastname: Read
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Hankey
authors.forename: Romesh
authors.initials: R
authors.lastname: Markus
authors.forename: Tissa
authors.initials: T
authors.lastname: Wijeratne
authors.forename: R
authors.initials: R
authors.lastname: Grimley
authors.forename: N
authors.initials: N
authors.lastname: Mahant
authors.forename: Tim
authors.initials: T
authors.lastname: Kleinig
authors.forename: John
authors.initials: J
authors.lastname: Sturm
authors.forename: A
authors.initials: A
authors.lastname: Lee
authors.forename: D
authors.initials: D
authors.lastname: Blacker
authors.forename: Richard
authors.initials: R
authors.lastname: Gerraty
authors.forename: M
authors.initials: M
authors.lastname: Krause
authors.forename: P M
authors.initials: PM
authors.lastname: Desmond
authors.forename: S J
authors.initials: SJ
authors.lastname: McBride
authors.forename: Leanne
authors.initials: L
authors.lastname: Carey
authors.forename: David W
authors.initials: DW
authors.lastname: Howells
authors.forename: C Y
authors.initials: CY
authors.lastname: Hsu
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Davis
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Donnan
mesh_terms: D004311:Double-Blind Method; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D012107:Research Design; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology; D015912:Thrombolytic Therapy / Q000379:methods*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*; D014057:Tomography, X-Ray Computed
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator