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

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ClinicalTrials.gov Identifier: NCT02002325
Recruitment Status : Recruiting
First Posted : December 5, 2013
Last Update Posted : April 25, 2018
Sponsor:
Collaborators:
Charitable Trust Mihara Cerebrovascular Disorder Research Promotion Fund
Japan Agency for Medical Research and Development
Information provided by (Responsible Party):
Kazunori Toyoda, National Cerebral and Cardiovascular Center

Study Description
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Brief 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.

Condition or disease Intervention/treatment Phase
Stroke Drug: Tissue-type plasminogen activator (alteplase) Other: Standard care Phase 3

Detailed 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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: THrombolysis for Acute Wake-up and Unclear-onset Strokes With Alteplase at 0.6 mg/kg Trial (THAWS)
Actual Study Start Date : May 2014
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : March 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Alteplase

Arms and Interventions
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Arm Intervention/treatment
Experimental: Alteplase
Intravenous tissue-type plasminogen activator (alteplase)
 Drug: Tissue-type plasminogen activator (alteplase)
Intravenous tissue-type plasminogen activator (alteplase) 0.6mg/kg body-weight up to a maximum of 60 mg, 10% as bolus, 90% over 1 hour as infusion (plus other standard treatment if needed)
Other Names:
  • rt-PA
  • Activacin
  • Grtpa
  • Actilyse
  • Activase
Standard Care
Standard treatment for acute stroke
 Other: Standard care
Standard treatment for acute stroke without intravenous alteplase.


Outcome Measures
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Primary Outcome Measures :
  1. Modified Rankin Scale 0-1 [ Time Frame: 90 days after stroke ]

Secondary Outcome Measures :
  1. Categorical shift in National Institutes of Health (NIHSS) score from baseline [ Time Frame: 24 hours after stroke ]
  2. Categorical shift in NIHSS score from baseline [ Time Frame: 7 days after stroke ]
  3. Modified Rankin Scale 0-2 [ Time Frame: 90 days after stroke ]
  4. Categorical shift in modified Rankin Scale score from baseline [ Time Frame: 90 days after stroke ]
  5. Symptomatic intracranial hemorrhage (sICH) in SITS-MOST [ Time Frame: 24 hours after treatment ]
    MRI proven SICH

  6. sICH as defined in European Cooperative Acute Stroke Study (ECASS) II [ Time Frame: 24 hours after stroke ]
    MRI proven SICH

  7. sICH as defined in National Institute of Neurological Disorders and Stroke (NINDS) [ Time Frame: 24 hours after stroke ]
    MRI proven SICH

  8. Parenchymal hemorrhage type-2 (PH-2) [ Time Frame: 24 hours after stroke ]
    MRI proven SICH

  9. Major bleeding [ Time Frame: Up to 90 days after stroke ]
    Fatal bleeding, symptomatic bleeding in a critical area or organ, such as intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome, or bleeding causing a fall in hemoglobin level of ≥2g/dL, or leading to transfusion of ≥4.5 units of whole blood or red cells according to the definition of the International Society on Thrombosis and Haemostasis

  10. Modified Rankin Scale 6 [ Time Frame: 90 days after stroke ]
    Death due to any cause

  11. Infarct volume [ Time Frame: 24 hours after stroke ]
    Infarct volume on DWI at 24 hours

  12. Infarct volume growth on DWI [ Time Frame: 24 hours after stroke ]
    Infarct volume on DWI at 24 hours minus infarct volume on DWI at baseline


Eligibility Criteria
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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02002325


Contacts
Contact: Masatoshi Koga, MD +81-6-6833-5012 ext 8701 koga@ncvc.go.jp

Locations
Japan
National Cerebral and Cardiovascular Center Recruiting
Suita, Osaka, Japan, 565-8565
Contact: Masatoshi Koga, MD    +81-6-6833-5012 ext 8701    koga@ncvc.go.jp   
Principal Investigator: Kazunori Toyoda, MD         
Sponsors and Collaborators
National Cerebral and Cardiovascular Center
Charitable Trust Mihara Cerebrovascular Disorder Research Promotion Fund
Japan Agency for Medical Research and Development
Investigators
Principal Investigator: Kazunori Toyoda, MD National Cerebral and Cardiovascular Center
More Information
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Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:
THrombolysis for Acute Wake-up and unclear-onset Strokes with alteplase at 0&#183;6 mg/kg (THAWS) Trial  This link exits the ClinicalTrials.gov site

Publications:

Responsible Party: Kazunori Toyoda, Director and Chair, Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center
ClinicalTrials.gov Identifier: NCT02002325     History of Changes
Other Study ID Numbers: NCVC-STROKE-001
UMIN000011630 ( Registry Identifier: UMIN )
First Posted: December 5, 2013    Key Record Dates
Last Update Posted: April 25, 2018
Last Verified: April 2018

Additional relevant MeSH terms:
Stroke
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
 Cardiovascular Diseases
Plasminogen
Tissue Plasminogen Activator
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action