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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

November 28, 2013
July 7, 2014
May 2014
December 2016   (final data collection date for primary outcome measure)
Modified Rankin Scale 0-1 [ Time Frame: 90 days after stroke ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT02002325 on ClinicalTrials.gov Archive Site
  • 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
  • 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 ECASS II [ Time Frame: 24 hours after stroke ] [ Designated as safety issue: Yes ]
    MRI proven SICH
  • SICH as defined in 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
Not Provided
Not Provided
 
THrombolysis for Acute Wake-up and Unclear-onset Strokes With Alteplase at 0.6 mg/kg Trial (THAWS)
THrombolysis for Acute Wake-up and Unclear-onset Strokes With Alteplase at 0.6 mg/kg Trial (THAWS)

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Stroke
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
  • 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
    Intervention: Drug: Tissue type plasminogen activator (alteplase)
  • No Intervention: Standard
    Standard care for acute stroke without intravenous alteplase
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
300
March 2017
December 2016   (final data collection date for primary outcome measure)

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
Both
20 Years and older
No
Contact: Masatoshi Koga, MD +81-6-6833-5012 ext 8701 koga@ncvc.go.jp
Japan
 
NCT02002325
NCVC-STROKE-001, UMIN000011630
Yes
Kazunori Toyoda, National Cerebral and Cardiovascular Center
National Cerebral and Cardiovascular Center
Mihara Cerebrovascular Disorder Research Promotion Fund
Principal Investigator: Kazunori Toyoda, MD National Cerebral and Cardiovascular Center
National Cerebral and Cardiovascular Center
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP