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StrokePhase 3THAWSNCT02002325

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

A Phase 3 study testing Tissue-type plasminogen activator (alteplase) in people with Stroke, run by National Cerebral and Cardiovascular Center, Japan at 1 site in Japan.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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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. Read more about this study

Who is it for?
Ages 20 years and older
Conditions the study is for
Stroke
What is being tested?
Tissue-type plasminogen activator (alteplase)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
300 participants
Where
1 siteJapan
Study dates
May 2014to Mar 2020
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 24Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Japan1 site

  • National Cerebral and Cardiovascular Center

    Suita, Osaka, 565-8565

Other trials in Japan

About this study

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.

Read the 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.

Conditions
Stroke
Being tested
Tissue-type plasminogen activator (alteplase), Standard care
Medical subject headings
Stroke

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tissue-type plasminogen activator (alteplase)Drug

    Also called rt-PA, Activacin, Grtpa, Actilyse

    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 careOther

    Standard treatment for acute stroke without intravenous alteplase.

Study groups in NCT02002325
Study groupRoleWhat they receive
AlteplaseExperimentalIntravenous tissue-type plasminogen activator (alteplase)
Receives: Drug: Tissue-type plasminogen activator (alteplase)
Standard CareOtherStandard treatment for acute stroke
Receives: Other: Standard care

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Modified Rankin Scale 0-1

    Measured: 90 days after stroke onset

Secondary outcomes (12)

  1. Categorical shift in National Institutes of Health (NIHSS) score at 24 h

    Measured: 24 hours after the initiation of treatment

  2. Categorical shift in NIHSS score at 7 days

    Measured: 7 days after the initiation of treatment

  3. Modified Rankin Scale 0-2

    Measured: 90 days after stroke onset

  4. Categorical shift in modified Rankin Scale score

    Measured: 90 days after stroke onset

  5. Parenchymal hemorrhage type-2 (PH-2)

    MRI proven SICH

    Measured: 24 hours after the initiation of treatment

  6. Symptomatic intracranial hemorrhage (sICH) in SITS-MOST

    MRI proven SICH

    Measured: 24 hours after the initiation of treatment

  7. sICH as defined in European Cooperative Acute Stroke Study (ECASS) II

    MRI proven SICH

    Measured: 24 hours after the initiation of treatment

  8. sICH as defined in National Institute of Neurological Disorders and Stroke (NINDS)

    MRI proven SICH

    Measured: 24 hours after the initiation of treatment

  9. 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

    Measured: Up to 90 days after stroke onset

  10. Modified Rankin Scale 6

    Death due to any cause

    Measured: 90 days after stroke onset

  11. Infarct volume

    Infarct volume on FLAIR

    Measured: 7 days after stroke onset

  12. Infarct volume growth

    Infarct volume on FLAIR at 7 days minus infarct volume on DWI at baseline

    Measured: 7 days after stroke onset

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Dec 2013 (estimated)
  2. Study startMay 2014
  3. Primary completionDec 2019 (estimated)
  4. Study completionMar 2020 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
300 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02002325
Sponsor's protocol ID
NCVC-STROKE-001
Other IDs
UMIN000011630
Acronym
THAWS
Status last verified
Aug 2018
First submitted
28 Nov 2013
Last updated
20 Dec 2018
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 25088843

  • 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.

    PubMed 25944322

  • Inoue M, Kamogawa N, Koga M, Yoshimura S, Fukuda-Doi M, Miwa K, Sasaki M, Aoki J, Kimura K, Ihara M, Toyoda K. Associations between fluid-attenuated inversion recovery vessel hyperintensities and Alberta stroke program early CT score and clinical outcomes in stroke patients with unknown time of onset: A sub-analysis from a randomized controlled trial. Int J Stroke. 2026 Mar;21(3):409-418. doi: 10.1177/17474930251377522. Epub 2025 Aug 30.

    PubMed 40884089

  • 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.

    PubMed 33297866

  • 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.

    PubMed 32248771

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tissue-type plasminogen activator (alteplase) in people with Stroke, run by National Cerebral and Cardiovascular Center, Japan at 1 site in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 20 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Modified Rankin Scale 0-1 (time frame: 90 days after stroke onset). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02002325, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Dec 2018.

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