Clinical trial NCT00147316: Japan Alteplase Clinical Trial (J-ACT): Efficacy and Safety Study of Tissue Plasminogen Activator (Alteplase) for Ischemic Stroke
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cerebral Infarction
Brain Ischemia
Keywords: acute stroke
thrombolytic therapy
tissue plasminogen activator
Lead sponsor: Mitsubishi Tanabe Pharma Corporation
Sponsor class: INDUSTRY
Collaborators: name: Kyowa Hakko Kogyo Co., Ltd.
First posted: 2005-09-07
Enrollment: 103
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility 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 (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

Primary outcomes:
measure: Number of Patients With a Modified Rankin Scale (mRS) Score of 0-1 at 3 Months
timeFrame: at 3 months
measure: Number of Patients With Symptomatic Intracranial Hemorrhage (sICH) Within 36 Hours
timeFrame: within 36 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Suita
country: Japan
facility: National Cardiovascular Center
state: Osaka
Study officials:
affiliation: National Cerebral and Cardiovascular Center, Japan
name: Takenori Yamaguchi, MD
role: STUDY_CHAIR
References:
citation: 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;37(7):1810-5. doi: 10.1161/01.STR.0000227191.01792.e3. Epub 2006 Jun 8.
citation: Hirano T, Sasaki M, Tomura N, Ito Y, Kobayashi S; Japan Alteplase Clinical Trial Group. Low Alberta stroke program early computed tomography score within 3 hours of onset predicts subsequent symptomatic intracranial hemorrhage in patients treated with 0.6 mg/kg Alteplase. J Stroke Cerebrovasc Dis. 2012 Nov;21(8):898-902. doi: 10.1016/j.jstrokecerebrovasdis.2011.05.018. Epub 2011 Jul 7.