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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Cerebral Infarction, Brain Ischemia

Intervention / Treatment
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* Drug: Alteplase


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 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 | The number of patients with sICH | within 36 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute stroke, thrombolytic therapy, tissue plasminogen activator