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

Stroke Clinical Trial

— THAWS  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02002325
• Other study ID #: NCVC-STROKE-001
• Secondary ID: UMIN000011630
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: May 2014
• Est. completion date: March 2020

Study information

• Verified date: August 2018
• Source: National Cerebral and Cardiovascular Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 300
• Est. completion date: March 2020
• Est. primary completion date: December 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Stroke

Intervention

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:
• Standard care
Standard treatment for acute stroke without intravenous alteplase.

Locations

Country	Name	City	State
Japan	National Cerebral and Cardiovascular Center	Suita	Osaka

Sponsors (3)

Lead Sponsor	Collaborator
National Cerebral and Cardiovascular Center	Charitable Trust Mihara Cerebrovascular Disorder Research Promotion Fund, Japan Agency for Medical Research and Development

Country where clinical trial is conducted

Japan, 

References & Publications (2)

Koga M, Toyoda K, Kimura K, Yamamoto H, Sasaki M, Hamasaki T, Kitazono T, Aoki J, Seki K, Homma K, Sato S, Minematsu K; THAWS investigators. THrombolysis for Acute Wake-up and unclear-onset Strokes with alteplase at 0·6 mg/kg (THAWS) Trial. Int J Stroke. 2014 Dec;9(8):1117-24. doi: 10.1111/ijs.12360. Epub 2014 Aug 4. — View Citation

Toyoda K, Koga M, Hayakawa M, Yamagami H. Acute reperfusion therapy and stroke care in Asia after successful endovascular trials. Stroke. 2015 Jun;46(6):1474-81. doi: 10.1161/STROKEAHA.115.008781. Epub 2015 May 5. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Modified Rankin Scale 0-1		90 days after stroke onset
Secondary	Categorical shift in National Institutes of Health (NIHSS) score at 24 h		24 hours after the initiation of treatment
Secondary	Categorical shift in NIHSS score at 7 days		7 days after the initiation of treatment
Secondary	Modified Rankin Scale 0-2		90 days after stroke onset
Secondary	Categorical shift in modified Rankin Scale score		90 days after stroke onset
Secondary	Parenchymal hemorrhage type-2 (PH-2)	MRI proven SICH	24 hours after the initiation of treatment
Secondary	Symptomatic intracranial hemorrhage (sICH) in SITS-MOST	MRI proven SICH	24 hours after the initiation of treatment
Secondary	sICH as defined in European Cooperative Acute Stroke Study (ECASS) II	MRI proven SICH	24 hours after the initiation of treatment
Secondary	sICH as defined in National Institute of Neurological Disorders and Stroke (NINDS)	MRI proven SICH	24 hours after the initiation of treatment
Secondary	Major bleeding	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	Up to 90 days after stroke onset
Secondary	Modified Rankin Scale 6	Death due to any cause	90 days after stroke onset
Secondary	Infarct volume	Infarct volume on FLAIR	7 days after stroke onset
Secondary	Infarct volume growth	Infarct volume on FLAIR at 7 days minus infarct volume on DWI at baseline	7 days after stroke onset

External Links

•   THrombolysis for Acute Wake-up and unclear-onset Strokes with alteplase at 0·6 mg/kg (THAWS) Trial