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

 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