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

Cerebral Infarction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00147316
• Other study ID #: 527-0110
• Status: Completed
• Phase: Phase 3
• First received: September 5, 2005
• Last updated: February 29, 2012
• Start date: April 2002
• Est. completion date: September 2003

Study information

• Verified date: February 2012
• Source: Mitsubishi Tanabe Pharma Corporation
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 103
• Est. completion date: September 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Ischemia
• Cerebral Infarction

Intervention

Drug:
• Alteplase
0.6mg/kg intravenous alteplase with 10% being administered as a bolus followed by continuous infusion of the remainder over 1 hour

Locations

Country	Name	City	State
Japan	National Cardiovascular Center	Suita	Osaka

Sponsors (2)

Lead Sponsor	Collaborator
Mitsubishi Tanabe Pharma Corporation	Kyowa Hakko Kogyo Co., Ltd.

Country where clinical trial is conducted

Japan, 

References & Publications (1)

Yamaguchi T, Mori E, Minematsu K, Nakagawara J, Hashi K, Saito I, Shinohara Y; Japan Alteplase Clinical Trial (J-ACT) Group. Alteplase at 0.6 mg/kg for acute ischemic stroke within 3 hours of onset: Japan Alteplase Clinical Trial (J-ACT). Stroke. 2006 Jul — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	Number of Patients With Symptomatic Intracranial Hemorrhage (sICH) Within 36 Hours	The number of patients with sICH	within 36 hours	No