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. 2018 Aug 21;2018(8):CD010995. doi: 10.1002/14651858.CD010995.pub2

NCT02002325.

Trial name or title THrombolysis for Acute Wake‐up and unclear‐onset Strokes with alteplase at 0.6 mg/kg Trial (THAWS)
Methods Randomised, single‐blinded, controlled trial
Participants 300 participants
Inclusion criteria
  • Clinical diagnosis of acute ischaemic stroke with unknown symptom onset (e.g. acute wake‐up ischaemic stroke, acute ischaemic stroke with unknown time of symptom onset)

  • Last known well without neurological symptoms > 4.5 hours and < 12 hours of treatment initiation

  • Treatment can be started within 4.5 hours of symptom recognition (e.g. awaking)

  • Acute stroke MRI including DWI and FLAIR completed

  • ASPECTS on initial DWI is 5 or more

  • No marked parenchymal hyperintensity visible on FLAIR

  • Initial NIHSS ≥ 5 and ≤ 25

  • Written informed consent by patient or next of kin


Exclusion criteria
  • Pre‐stroke mRS > 1 (patients who have inability to carry out all daily activities and require some help or supervision)

  • Contraindications in the Japanese guideline for the intravenous application of recombinant tissue‐type plasminogen activator (alteplase)

  • History of non‐traumatic intracranial haemorrhage

  • History of stroke within the last 1 month (excluding transient ischaemic attack)

  • History of significant head/spinal injury or surgery within the last 3 months

  • History of gastrointestinal or urinary tract bleeding within the last 21 days

  • History of major surgery or significant trauma other than head injury within the last 14 days

  • Hypersensitivity to alteplase

  • Suspected subarachnoid haemorrhage

  • Concurrent acute aortic dissection

  • Concurrent haemorrhage (e.g. intracranial, gastrointestinal, urinary tract, or retroperitoneal, haemoptysis)

  • Systolic blood pressure ≥ 185 mmHg despite antihypertensive therapy

  • Diastolic blood pressure ≥ 110 mmHg despite antihypertensive therapy

  • Significant hepatic disorder

  • Acute pancreatitis

  • Blood glucose < 50 mg/dL or > 400 mg/dL

  • Platelet count ≤ 100,000/mm3

  • International normalised ratio of prothrombin time > 1.7 or prolonged aPTT > 1.5 times the baseline value (> approximately 40 seconds only as a guide) for patients on anticoagulation therapy or those with abnormal coagulation

  • Any contraindication to MRI (e.g. cardiac pacemaker)

  • Extensive early ischaemic change in brainstem or cerebellum (e.g. more than half of brainstem or more than 1 hemisphere of cerebellum)

  • Planned or anticipated treatment with surgery or endovascular reperfusion strategies (e.g. intra‐arterial thrombolysis, mechanical recanalisation techniques)

  • Pregnant, lactating, or potentially pregnant

  • Life expectancy 6 months or less by judgement of the investigator

  • Inappropriate for study enrolment by judgement of the investigator

Interventions
  • Intravenous tissue plasminogen activator (alteplase) 0.6 mg/kg body weight up to a maximum of 60 mg, 10% as bolus, 90% over 1 hour as infusion

  • Best medical care

Outcomes Favourable outcome (mRS score 0 to 1) at 90 days' follow‐up
Starting date April 2014
Contact information Principal Investigator: Kazunori Toyoda, National Cerebral and Cardiovascular Center, Japan
Contact person: Masatoshi Koga, koga@ncvc.go.jp
Notes ClinicalTrials.gov identifier: NCT02002325