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

National Cerebral and Cardiovascular Center, Japan

Status and phase

Unknown

Phase 3

Conditions

Stroke

Treatments

Drug: Tissue-type plasminogen activator (alteplase)

Other: Standard care

Study type

Interventional

Funder types

Other

Identifiers

NCT02002325

NCVC-STROKE-001

UMIN000011630 (Registry Identifier)

Details and patient eligibility

About

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.

Full description

THAWS is an investigator initiated Japanese multicenter randomized controlled clinical trial of MRI based thrombolysis in patients with acute wake-up ischemic stroke and those having acute ischemic stroke with unknown time of symptom onset. Intravenous thrombolysis with alteplase of 0.6mg/kg, different from 0.9mg/kg used in other countries, is available as effective and safe treatment of acute stroke within 4.5 hours of symptom onset in Japan. However, time of symptom onset is unknown in about 25% of acute stroke patients. These patients are currently excluded from intravenous thrombolysis with alteplase. The objective of the THAWS project is to provide effective treatment options for acute stroke patients with unknown time of symptom onset. The purpose of this study is to clarify efficacy and safety of MRI-based intravenous thrombolysis with alteplase of 0.6mg/kg for patients with acute wake-up ischemic stroke and those having acute ischemic stroke with unknown time of symptom onset. Eligible patients will be selected based on MRI findings indicative of acute ischemic stroke less than 4.5 hours of age.

Enrollment

300 estimated patients

Sex

All

Ages

20+ years old

Volunteers

No Healthy Volunteers

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