title: THrombolysis for Acute Wake-up and unclear-onset Strokes with alteplase at 0·6 mg/kg (THAWS) Trial.
abstract: BACKGROUND
  Because of lack of information regarding timing of stroke, patients who suffer stroke during sleep are generally ineligible for intravenous thrombolysis, although many of these patients could potentially recover with this treatment. Magnetic resonance image findings with positive diffusion-weighted imaging and no marked parenchymal hyperintensity on fluid-attenuated inversion recovery (negative pattern) can identify acute ischemic stroke patients within 4·5 h from symptom onset.
  
  
  OBJECTIVE
  The THrombolysis for Acute Wake-up and unclear-onset Strokes with alteplase at 0·6 mg/kg trial aims to determine the efficacy and safety of intravenous thrombolysis with alteplase at 0·6 mg/kg body weight, the approved dose for Japanese stroke patients, using magnetic resonance image-based selection in ischemic stroke patients with unclear time of symptom onset, and compare findings with standard treatment.
  
  
  METHODS
  This is an investigator-initiated, multicenter, prospective, randomized, open-treatment, blinded-end-point clinical trial. The design is similar to the Efficacy and Safety of MRI-based Thrombolysis in Wake-up Stroke trial. Patients with unclear-onset time of stroke symptoms beyond 4·5 h and within 12 h after the time of the last-known-well period and within 4·5 h after symptom recognition, who showed a negative fluid-attenuated inversion recovery pattern, are randomized to either intravenous thrombolysis or standard treatment.
  
  
  RESULTS
  The primary efficacy end-point is modified Rankin Scale 0-1 at 90 days. The safety outcome measures are symptomatic intracranial hemorrhage at 22-36 h, and major bleeding and mortality at 90 days.
  
  
  CONCLUSIONS
  This trial may help determine if low-dose alteplase at 0·6 mg/kg should be recommended as a routine clinical strategy for ischemic stroke patients with unclear-onset time.
authors.affiliation: Division of Stroke Care Unit, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Koga
authors.forename: Kazunori
authors.initials: K
authors.lastname: Toyoda
authors.forename: Kazumi
authors.initials: K
authors.lastname: Kimura
authors.forename: Haruko
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Makoto
authors.initials: M
authors.lastname: Sasaki
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Hamasaki
authors.forename: Takanari
authors.initials: T
authors.lastname: Kitazono
authors.forename: Junya
authors.initials: J
authors.lastname: Aoki
authors.forename: Kenta
authors.initials: K
authors.lastname: Seki
authors.forename: Kazunari
authors.initials: K
authors.lastname: Homma
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Sato
authors.forename: Kazuo
authors.initials: K
authors.lastname: Minematsu
mesh_terms: D000328:Adult; D000368:Aged; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D007564:Japan; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020521:Stroke / Q000188:drug therapy*; D015912:Thrombolytic Therapy / Q000379:methods*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator
keywords: acute ischemic stroke; clinical trials; diffusion-weighted imaging; fluid-attenuated inversion recovery imaging; thrombolysis; unclear-onset time
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