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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by National Cerebral and Cardiovascular Center
Sponsor:
Collaborator:
Mihara Cerebrovascular Disorder Research Promotion Fund
Information provided by (Responsible Party):
Kazunori Toyoda, National Cerebral and Cardiovascular Center
ClinicalTrials.gov Identifier:
NCT02002325
First received: November 28, 2013
Last updated: July 7, 2014
Last verified: July 2014
  Purpose

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 Intervention Phase
Stroke
Drug: Tissue type plasminogen activator (alteplase)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (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)

Resource links provided by NLM:


Further study details as provided by National Cerebral and Cardiovascular Center:

Primary Outcome Measures:
  • Modified Rankin Scale 0-1 [ Time Frame: 90 days after stroke ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Categorical shift in National Institutes of Health (NIHSS) score from baseline [ Time Frame: 24 hours after stroke ] [ Designated as safety issue: No ]
  • Categorical shift in NIHSS score from baseline [ Time Frame: 7 days after stroke ] [ Designated as safety issue: No ]
  • Modified Rankin Scale 0-2 [ Time Frame: 90 days after stroke ] [ Designated as safety issue: No ]
  • Categorical shift in modified Rankin Scale score from baseline [ Time Frame: 90 days after stroke ] [ Designated as safety issue: No ]
  • Symptomatic intracranial hemorrhage (sICH) in SITS-MOST [ Time Frame: 24 hours after treatment ] [ Designated as safety issue: Yes ]
    MRI proven SICH

  • sICH as defined in European Cooperative Acute Stroke Study (ECASS) II [ Time Frame: 24 hours after stroke ] [ Designated as safety issue: Yes ]
    MRI proven SICH

  • sICH as defined in National Institute of Neurological Disorders and Stroke (NINDS) [ Time Frame: 24 hours after stroke ] [ Designated as safety issue: Yes ]
    MRI proven SICH

  • Parenchymal hemorrhage type-2 (PH-2) [ Time Frame: 24 hours after stroke ] [ Designated as safety issue: Yes ]
    MRI proven SICH

  • Major bleeding [ Time Frame: Up to 90 days after stroke ] [ Designated as safety issue: Yes ]
    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

  • Modified Rankin Scale 6 [ Time Frame: 90 days after stroke ] [ Designated as safety issue: Yes ]
    Death due to any cause


Estimated Enrollment: 300
Study Start Date: May 2014
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Alteplase
Intravenous tissue plasminogen activator (alteplase) 0.6mg/kg body-weight up to a maximum of 60 mg, 10% as bolus, 90% over 1 hour as infusion
Drug: Tissue type plasminogen activator (alteplase)
Comparison between intravenous rt-PA (plus other standard treatment if needed) and standard treatment other than rt-PA
Other Names:
  • rt-PA
  • Activacin
  • Grtpa
  • Actilyse
  • Activase
No Intervention: Standard
Standard care for acute stroke without intravenous alteplase

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.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
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 and <12 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 ≥5 and ≤25
  • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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
Mihara Cerebrovascular Disorder Research Promotion Fund
Investigators
Principal Investigator: Kazunori Toyoda, MD National Cerebral and Cardiovascular Center
  More Information

No publications provided

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
Study First Received: November 28, 2013
Last Updated: July 7, 2014
Health Authority: Japan: Pharmaceutical and Food Safety Bureau

Additional relevant MeSH terms:
Stroke
Cerebral Infarction
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Brain Infarction
Brain Ischemia
Plasminogen
Tissue Plasminogen Activator
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Hematologic Agents

ClinicalTrials.gov processed this record on July 22, 2014