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

Condition(s) targeted: Cerebral Infarction; Brain Ischemia

Intervention: alteplase (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Mitsubishi Tanabe Pharma Corporation

Official(s) and/or principal investigator(s):
Takenori Yamaguchi, MD, Study Chair, Affiliation: National Cardiovascular Center

Based on previous studies comparing different rt-PA 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.

Official title: Japan Alteplase Clinical Trial(J-ACT): Phase 3 Efficacy and Safety Study of Tissue Plasminogen Activator for Acute Ischemic Stroke Within 3 Hours of Onset

Study design: Treatment, Non-Randomized, Open Label, Historical Control, Single Group Assignment, Safety/Efficacy Study

Primary outcome:

The rate of patients with a modified Rankin Scale score of 0-1 at 3 months

The incidence of symptomatic intracranial hemorrhage within 36 hours

Detailed description: Based on previous studies comparing different rt-PA 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 a modified Rankin Scale (mRS) score of 0-1 at 3 months and the incidence of symptomatic intracranial hemorrhage (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.

Minimum age: 20 Years. Maximum age: N/A. Gender(s): Both.

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 (an NIHSS score of ≤4) prior to the start of treatment

2. 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

National Cardiovascular Center, Suita, Osaka 565-8565, Japan

Starting date: April 2002
Ending date: September 2003
Last updated: September 5, 2005