Japan Alteplase Clinical Trial (J-ACT): Efficacy and Safety Study of Tissue Plasminogen Activator (Alteplase) for Ischemic Stroke

February 29, 2012 updated by: Mitsubishi Tanabe Pharma Corporation

Japan Alteplase Clinical Trial (J-ACT): Phase 3 Efficacy and Safety Study of Tissue Plasminogen Activator (Alteplase) for Acute Ischemic Stroke Within 3 Hours of Onset

Based on previous studies comparing Duteplase[a recombinant tissue plasminogen activator (rt-PA) very similar to alteplase] doses, we performed a clinical trial with 0.6mg/kg, which is lower than the internationally approved dosage of 0.9mg/kg, aiming to assess the efficacy and safety of alteplase for the Japanese.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Based on previous studies comparing Duteplase ( an rt-PA very similar to alteplase) doses, we performed a clinical trial with 0.6mg/kg, which is lower than the internationally approved dosage of 0.9mg/kg, aiming to assess the efficacy and safety of alteplase for the Japanese.

The primary endpoints were the rate of patients with mRS score of 0-1 at 3 months and the incidence of sICH within 36 hours. Thresholds for these endpoints were determined by calculating 90% confidence intervals of weighted averages derived from published reports. The protocol was defined according to the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA stroke study with slight modifications.

Study Type

Interventional

Enrollment (Actual)

103

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
    • Osaka
      • Suita, Osaka, Japan, 565-8565
        • National Cardiovascular Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Patients with acute ischemic stroke within 3 hours of onset, with a clearly defined time of onset

Exclusion Criteria:

  1. patients with rapidly improving neurological symptoms or with minor neurological deficit (National Institutes of Health Stroke Scale (NIHSS) score of ≤4) prior to the start of treatment
  2. Computed Tomography (CT) evidence of non-minor early ischemic signs (minor early ischemic sign was defined as the involvement of one-third or less of the middle cerebral artery area)
  3. CT evidence of cerebral hemorrhage or subarachnoid hemorrhage
  4. symptoms suggestive of subarachnoid hemorrhage
  5. lactation, pregnancy or suggestive pregnancy; menstruation
  6. platelet count below 100,000/mm3
  7. heparin administration within 48 hours preceding stroke onset with an elevated activated partial thromboplastin time (APTT); current use of oral anticoagulants with an International Normalized Ratio (INR) of ≥1.7; use of drugs not allowed to be administered concomitantly with alteplase (other thrombolytic agents, ozagrel sodium, argatroban and edaravone) prior to the study treatment
  8. major surgery or serious trauma within the preceding 14 days; serious head or spinal cord trauma within the preceding 3 months
  9. a history of gastrointestinal or urinary tract hemorrhage within the previous 21 days
  10. arterial puncture at a noncompressible site within the preceding 7 days
  11. a history of stroke within the preceding 3 months; a history of intracranial hemorrhage or increased risk of intracranial hemorrhage because of cerebral aneurysm, arteriovenous malformation, neoplasm, etc.
  12. concurrent severe hepatic or renal dysfunction
  13. malignant tumor under treatment
  14. a systolic blood pressure of >185 mmHg or diastolic blood pressure of >110 mmHg
  15. a need for aggressive treatment to reduce blood pressure to below these limits(14))
  16. blood glucose levels of <50 mg/dL or >400 mg/dL
  17. acute myocardial infarction(AMI) or endocarditis after AMI
  18. concurrent infectious endocarditis, moya-moya disease (Willis circle occlusion syndrome), aortic dissection, neck trauma, etc.; strong suspicion of ischemic cerebrovascular disorder caused by non-thrombotic occlusion or any other hemodynamic condition
  19. seizure at the onset of stroke
  20. coma (a Japan Coma Scale score of ≥100)
  21. an mRS score of ≥2 before stroke onset
  22. a history of hypersensitivity to protein preparations
  23. difficulty in monitoring for 3 months
  24. less than 3 months since any other clinical trial

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Alteplase
0.6mg/kg intravenous alteplase with 10% being administered as a bolus followed by continuous infusion of the remainder over 1 hour
Drug: Alteplase
0.6mg/kg intravenous alteplase with 10% being administered as a bolus followed by continuous infusion of the remainder over 1 hour

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients With a Modified Rankin Scale (mRS) Score of 0-1 at 3 Months
Time Frame: at 3 months
The number of patients with a mRS score of 0-1. The mRS has 6 items, where 0 = No symptoms at all, 1 = No significant disability despite symptoms, 2 = Slight disability, 3 = Moderate disability, 4 = Moderately severe disability, 5 = Severe disability. The higher scores reflect increased disability.
at 3 months
Number of Patients With Symptomatic Intracranial Hemorrhage (sICH) Within 36 Hours
Time Frame: within 36 hours
The number of patients with sICH
within 36 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mitsubishi Tanabe Pharma Corporation

Collaborators

Kyowa Hakko Kogyo Co., Ltd.

Investigators

  • Study Chair: Takenori Yamaguchi, MD, National Cerebral and Cardiovascular Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2002

Study Completion

September 1, 2003

Study Registration Dates

First Submitted

September 5, 2005

First Submitted That Met QC Criteria

September 5, 2005

First Posted (ESTIMATE)

September 7, 2005

Study Record Updates

Last Update Posted (ESTIMATE)

March 1, 2012

Last Update Submitted That Met QC Criteria

February 29, 2012

Last Verified

February 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 527-0110

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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