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

This study has been completed.
Sponsor:
Collaborator:
Kyowa Hakko Kogyo Co., Ltd.
Information provided by:
Mitsubishi Tanabe Pharma Corporation
ClinicalTrials.gov Identifier:
NCT00147316
First received: September 5, 2005
Last updated: February 29, 2012
Last verified: February 2012
  Purpose

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.


Condition Intervention Phase
Cerebral Infarction
Brain Ischemia
Drug: Alteplase
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Mitsubishi Tanabe Pharma Corporation:

Primary Outcome Measures:
  • Number of Patients With a Modified Rankin Scale (mRS) Score of 0-1 at 3 Months [ Time Frame: at 3 months ] [ Designated as safety issue: No ]
    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.

  • Number of Patients With Symptomatic Intracranial Hemorrhage (sICH) Within 36 Hours [ Time Frame: within 36 hours ] [ Designated as safety issue: No ]
    The number of patients with sICH


Enrollment: 103
Study Start Date: April 2002
Estimated Study Completion Date: September 2003
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00147316

Locations
Japan
National Cardiovascular Center
Suita, Osaka, Japan, 565-8565
Sponsors and Collaborators
Mitsubishi Tanabe Pharma Corporation
Kyowa Hakko Kogyo Co., Ltd.
Investigators
Study Chair: Takenori Yamaguchi, MD National Cerebral and Cardiovascular Center
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00147316     History of Changes
Other Study ID Numbers: 527-0110
Study First Received: September 5, 2005
Results First Received: January 19, 2012
Last Updated: February 29, 2012
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Mitsubishi Tanabe Pharma Corporation:
acute stroke
thrombolytic therapy
tissue plasminogen activator

Additional relevant MeSH terms:
Cerebral Infarction
Stroke
Brain Ischemia
Infarction
Ischemia
Brain Infarction
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Necrosis
Plasminogen
Tissue Plasminogen Activator
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Hematologic Agents

ClinicalTrials.gov processed this record on April 14, 2014