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

• Status: Unknown status
• Trial end date: 2020-03-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to clarify efficacy and safety of MRI-based intravenous thrombolysis with alteplase for patients with acute wake-up ischemic stroke and those having acute ischemic stroke with unknown time of symptom onset.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cerebral and Cardiovascular Center
• Collaborators: Charitable Trust Mihara Cerebrovascular Disorder Research Promotion Fund; Japan Agency for Medical Research and Development
• Treatments: Plasminogen; Tissue Plasminogen Activator

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