NCT02002325

Brief 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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
300

participants targeted

Target at P25-P50 for phase_3 stroke

Timeline
Completed

Started May 2014

Longer than P75 for phase_3 stroke

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 28, 2013

Completed
7 days until next milestone

First Posted

Study publicly available on registry

December 5, 2013

Completed
5 months until next milestone

Study Start

First participant enrolled

May 1, 2014

Completed
5.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2019

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2020

Completed
Last Updated

December 20, 2018

Status Verified

August 1, 2018

Enrollment Period

5.6 years

First QC Date

November 28, 2013

Last Update Submit

December 18, 2018

Conditions

Stroke

Outcome Measures

Primary Outcomes (1)

  • Modified Rankin Scale 0-1

    90 days after stroke onset

Secondary Outcomes (12)

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

    24 hours after the initiation of treatment

  • Categorical shift in NIHSS score at 7 days

    7 days after the initiation of treatment

  • Modified Rankin Scale 0-2

    90 days after stroke onset

  • Categorical shift in modified Rankin Scale score

    90 days after stroke onset

  • Parenchymal hemorrhage type-2 (PH-2)

    24 hours after the initiation of treatment

  • +7 more secondary outcomes

Study Arms (2)

Alteplase

EXPERIMENTAL

Intravenous tissue-type plasminogen activator (alteplase)

Drug: Tissue-type plasminogen activator (alteplase)

Standard Care

OTHER

Standard treatment for acute stroke

Other: Standard care

Interventions

Standard careOTHER

Standard treatment for acute stroke without intravenous alteplase.

Standard Care
Tissue-type plasminogen activator (alteplase)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)

Also known as: rt-PA, Activacin, Grtpa, Actilyse, Activase
Alteplase

Eligibility Criteria

Age20 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • +9 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

National Cerebral and Cardiovascular Center

Suita, Osaka, 565-8565, Japan

Location

Related Publications (4)

  • 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.

    PMID: 25088843BACKGROUND

  • 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.

    PMID: 25944322BACKGROUND

  • 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.

    PMID: 33297866DERIVED

  • 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.

    PMID: 32248771DERIVED

Related Links

MeSH Terms

Conditions

Stroke

Interventions

Tissue Plasminogen ActivatorStandard of Care

Condition Hierarchy (Ancestors)

Cerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

Serine EndopeptidasesEndopeptidasesPeptide HydrolasesHydrolasesEnzymesEnzymes and CoenzymesSerine ProteasesPlasminogen ActivatorsBlood Coagulation FactorsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsBiological FactorsQuality Indicators, Health CareQuality of Health CareHealth Services AdministrationHealth Care Quality, Access, and Evaluation

Study Officials

  • Kazunori Toyoda, MD

    National Cerebral and Cardiovascular Center, Japan

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Director and Chair, Department of Cerebrovascular Medicine

Study Record Dates

First Submitted

November 28, 2013

First Posted

December 5, 2013

Study Start

May 1, 2014

Primary Completion

December 1, 2019

Study Completion

March 1, 2020

Last Updated

December 20, 2018

Record last verified: 2018-08

Locations

JP(1)