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

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.

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