THrombolysis for Acute Wake-up and Unclear-onset Strokes With Alteplase at 0.6 mg/kg Trial (THAWS) (THAWS)
This study is currently recruiting participants.
(see Contacts and Locations)
Verified September 2016 by National Cerebral and Cardiovascular Center
Sponsor:
National Cerebral and Cardiovascular Center
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
ClinicalTrials.gov Identifier:
NCT02002325
First received: November 28, 2013
Last updated: September 22, 2016
Last verified: September 2016
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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) Other: Standard care |
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 2018 |
| Estimated Primary Completion Date: | December 2017 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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:
|
|
Standard Care
Standard treatment for acute stroke
|
Other: Standard care
Standard treatment 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 (Adult, Senior) |
| 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 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
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
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
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
Additional Information:
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 |
| Study First Received: | November 28, 2013 |
| Last Updated: | September 22, 2016 |
| Health Authority: | Japan: Pharmaceutical and Food Safety Bureau |
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 |
ClinicalTrials.gov processed this record on September 30, 2016