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
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Tanabe Pharma Corporation
- Enrollment
- 103
- Locations
- 1
- Primary Endpoint
- Number of Patients With a Modified Rankin Scale (mRS) Score of 0-1 at 3 Months
Study Overview
Brief Summary
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.
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 Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 20 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients with acute ischemic stroke within 3 hours of onset, with a clearly defined time of onset
Exclusion Criteria
- •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
- •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)
- •CT evidence of cerebral hemorrhage or subarachnoid hemorrhage
- •symptoms suggestive of subarachnoid hemorrhage
- •lactation, pregnancy or suggestive pregnancy; menstruation
- •platelet count below 100,000/mm3
- •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
- •major surgery or serious trauma within the preceding 14 days; serious head or spinal cord trauma within the preceding 3 months
- •a history of gastrointestinal or urinary tract hemorrhage within the previous 21 days
- •arterial puncture at a noncompressible site within the preceding 7 days
- •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.
- •concurrent severe hepatic or renal dysfunction
- •malignant tumor under treatment
- •a systolic blood pressure of >185 mmHg or diastolic blood pressure of >110 mmHg
- •a need for aggressive treatment to reduce blood pressure to below these limits(14))
- •blood glucose levels of <50 mg/dL or >400 mg/dL
- •acute myocardial infarction(AMI) or endocarditis after AMI
- •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
- •seizure at the onset of stroke
- •coma (a Japan Coma Scale score of ≥100)
- •an mRS score of ≥2 before stroke onset
- •a history of hypersensitivity to protein preparations
- •difficulty in monitoring for 3 months
- •less than 3 months since any other clinical trial
Arms & Interventions
Alteplase
0.6mg/kg intravenous alteplase with 10% being administered as a bolus followed by continuous infusion of the remainder over 1 hour
Intervention: Alteplase (Drug)
Outcomes
Primary Outcomes
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.
Number of Patients With Symptomatic Intracranial Hemorrhage (sICH) Within 36 Hours
Time Frame: within 36 hours
The number of patients with sICH
Secondary Outcomes
No secondary outcomes reported