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

NCT ID: NCT02002325

Last Updated: 2018-12-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

300 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-05-31

Study Completion Date

2020-03-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Stroke

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Alteplase

Intravenous tissue-type plasminogen activator (alteplase)

Group Type EXPERIMENTAL

Tissue-type plasminogen activator (alteplase)

Intervention Type DRUG

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)

Standard Care

Standard treatment for acute stroke

Group Type OTHER

Standard care

Intervention Type OTHER

Standard treatment for acute stroke without intravenous alteplase.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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)

Intervention Type DRUG

Standard care

Standard treatment for acute stroke without intravenous alteplase.

Intervention Type OTHER

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

rt-PA Activacin Grtpa Actilyse Activase

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

20 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Charitable Trust Mihara Cerebrovascular Disorder Research Promotion Fund

UNKNOWN

Sponsor Role collaborator

Japan Agency for Medical Research and Development

OTHER_GOV

Sponsor Role collaborator

National Cerebral and Cardiovascular Center, Japan

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Kazunori Toyoda

Director and Chair, Department of Cerebrovascular Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Kazunori Toyoda, MD

Role: PRINCIPAL_INVESTIGATOR

National Cerebral and Cardiovascular Center, Japan

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

National Cerebral and Cardiovascular Center

Suita, Osaka, Japan

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Japan

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 25088843 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25944322 (View on PubMed)

Toyoda K, Inoue M, Yoshimura S, Yamagami H, Sasaki M, Fukuda-Doi M, Kimura K, Asakura K, Miwa K, Kanzawa T, Ihara M, Kondo R, Shiozawa M, Ohtaki M, Kamiyama K, Itabashi R, Iwama T, Aoki J, Minematsu K, Yamamoto H, Koga M; THAWS trial investigators*. Magnetic Resonance Imaging-Guided Thrombolysis (0.6 mg/kg) Was Beneficial for Unknown Onset Stroke Above a Certain Core Size: THAWS RCT Substudy. Stroke. 2021 Jan;52(1):12-19. doi: 10.1161/STROKEAHA.120.030848. Epub 2020 Dec 10.

Reference Type DERIVED
PMID: 33297866 (View on PubMed)

Koga M, Yamamoto H, Inoue M, Asakura K, Aoki J, Hamasaki T, Kanzawa T, Kondo R, Ohtaki M, Itabashi R, Kamiyama K, Iwama T, Nakase T, Yakushiji Y, Igarashi S, Nagakane Y, Takizawa S, Okada Y, Doijiri R, Tsujino A, Ito Y, Ohnishi H, Inoue T, Takagi Y, Hasegawa Y, Shiokawa Y, Sakai N, Osaki M, Uesaka Y, Yoshimura S, Urabe T, Ueda T, Ihara M, Kitazono T, Sasaki M, Oita A, Yoshimura S, Fukuda-Doi M, Miwa K, Kimura K, Minematsu K, Toyoda K; THAWS Trial Investigators. Thrombolysis With Alteplase at 0.6 mg/kg for Stroke With Unknown Time of Onset: A Randomized Controlled Trial. Stroke. 2020 May;51(5):1530-1538. doi: 10.1161/STROKEAHA.119.028127. Epub 2020 Apr 6.

Reference Type DERIVED
PMID: 32248771 (View on PubMed)

Related Links

Access external resources that provide additional context or updates about the study.

http://onlinelibrary.wiley.com/doi/10.1111/ijs.12360/abstract;jsessionid=763C32F84872E896DA9F27975D7843B6.f01t04

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

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

NCVC-STROKE-001

Identifier Type: -

Identifier Source: org_study_id

UMIN000011630

Identifier Type: REGISTRY

Identifier Source: secondary_id