THrombolysis for Acute Wake-up and Unclear-onset Strokes With Alteplase at 0.6 mg/kg Trial (THAWS) "THAWS"

Recruiting

Phase 3 Results N/A

Eligibility Criteria

Inclusion Criteria

- Clinical diagnosis of acute ischemic stroke with unknown symptom onset (e.g. acute wake-up ischemic stroke, acute ischemic stroke with unknown time of symptom onset)
- Last known well without neurological symptoms >4.5 hours of treatment initiation
- Treatment can be started within 4.5 hours of symptom recognition (e.g. awaking)
- Acute stroke MRI including diffusion weighted imaging (DWI) and fluid attenuated inversion recovery (FLAIR) completed
- Alberta Stroke Program Early CT score (ASPECTS) on initial DWI is 5 or more
- No marked parenchymal hyperintensity visible on FLAIR
- Initial NIHSS ≥2
- Written informed consent by patient or next of kin

Exclusion Criteria

- Pre-stroke Modified Rankin Scale (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 nontraumatic intracranial hemorrhage
- History of stroke within the last 1 month (excluding transient ischemic 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 hemorrhage
- Concurrent acute aortic dissection
- Concurrent hemorrhage (e.g., intracranial, gastrointestinal, urinary tract, or retroperitoneal, hemoptysis)
- Systolic blood pressure ≥185 mmHg despite antihypertensive therapy
- Diastolic blood pressure ≥110 mmhg despite antihypertensive therapy
- Significant hepatic disorder
- Acute pancreatitis
- Blood glucose <50mg/dL or >400 mg/dL
- Platelet count ≤100,000/mm3
- International normalized ratio of prothrombin time (PT-INR) >1.7 or Prolonged activated partial thromboplastin time (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 ischemic change in brain stem or cerebellum (e.g., more than half of brain stem or more than one hemisphere of cerebellum)
- Planned or anticipated treatment with surgery or endovascular reperfusion strategies (e.g., intra-arterial thrombolysis, mechanical recanalization techniques)
- Pregnant, lactating, or potentially pregnant
- Life expectancy 6 months or less by judgment of the investigator
- Inappropriate for study enrollment by judgment of the investigator