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

Mitsubishi Tanabe Pharma

Status and phase: Completed; Phase 3

Conditions: Brain Ischemia; Cerebral Infarction

Treatments: Drug: Alteplase

Study type: Interventional

Funder types: Industry

Identifiers

NCT00147316

527-0110

Details and patient eligibility

About

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.

Full 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.

Enrollment: 103 patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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103 participants in 1 patient group

Alteplase

Experimental group

Description:

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

Treatment:

Drug: Alteplase