Post-marketing Clinical Study of Alteplase for Acute Ischemic Stroke （Japan Alteplase Clinical Trial Ⅱ：J-ACT Ⅱ）

Study Overview
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Brief Summary
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The purpose of this study is to confirm the efficacy and safety of intravenously administered alteplase in patients with acute ischemic stroke based on the rate of recanalization assessed by magnetic resonance angiography (MRA), the rate of patients with a modified Rankin Scale (mRS) score of 0-1, and the incidence of symptomatic intracranial hemorrhage (sICH), in comparison with the data reported in the current literature.

Official Title
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Post-marketing Clinical Study of Alteplase for Acute Ischemic Stroke (Phase 4)

Conditions
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Stroke

Intervention / Treatment
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* Drug: Alteplase


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with acute ischemic stroke within 3 hours of onset, with a clearly defined time of onset. Patients who have been revealed to have occlusion on one side of the middle cerebral artery (M1 or M2 portion) on MRA before the start of treatment. Patients for whom consent has been obtained from either themselves or from their legally acceptable representatives in written form. Exclusion Criteria: Patients with very light neurological symptoms (an NIHSS score of <= 4) or with rapidly improving symptoms before the start of treatment. Patients with serious neurological disorders (an NIHSS score of >= 23), or serious consciousness disorders (a Japan Coma Scale score of >= 100) before the start of treatment. Patients with functional disorders (a mRS score of >= 2) before stroke onset. Patients who have been administered drugs that are not allowed to be administered concomitantly with alteplase (other thrombolytic agents) after the stroke onset. Patients who have been revealed to have extensive early ischemic change (an Alberta Stroke Program Early CT score of <= 6) on computed tomography (CT) before treatment. Patients who have been revealed to have obvious occlusion in the blood vessel except for the middle cerebral artery on MRA before treatment. Patients who are forbidden to undergo magnetic resonance imaging (MRI). Patients who are defined as having cerebral hemorrhage or subarachnoid hemorrhage (SAH) on CT before treatment. Patients whose symptoms suggest SAH. Patients with hemorrhage (gastrointestinal hemorrhage, urinary hemorrhage, retroperitoneal hemorrhage, or hemoptysis). Patients with a platelet count below 100,000/mm3. Patients with fasting blood glucose levels of < 50 mg/dL or > 400 mg/dL. Patients whose activated partial thromboplastin time (APTT) is prolonged due to heparin administration within 48 hours before stroke onset. Patients who have been administered oral anticoagulants with values of the international normalized ratio of prothrombin time (PT-INR) of > 1.7. Patients who have a systolic blood pressure of > 185 mmHg or a diastolic blood pressure of > 110 mmHg. Patients who need antihypertensive therapy (e.g. continuous infusion of antihypertensive drug etc.) to lower blood pressure below those limits under the preceding article. Patients who have a history of intracranial hemorrhage, or who have a disease considered to increase the risk of intracranial hemorrhage such as an intracranial tumor, cerebral aneurysm, or intracranial arteriovenous malformation, etc. Patients who have a history of stroke within 3 months before onset. Patients who were operated on or injured their head or spinal cord within 3 months before onset. Patients who have a history of gastrointestinal or urinary tract hemorrhage within 21 days before onset. Patients who had a major surgery or serious trauma (except for head or spinal cord trauma) within 14 days before onset. Patients who have a history of organ biopsy, arterial puncture, or lumbar puncture within 10 days before onset. Patients with severe hepatic dysfunction or severe renal dysfunction. Patients with acute pancreatitis. Patients who had a seizure at the onset of stroke. Patients who have a history of hypersensitivity to protein preparations. Patients who are lactating, pregnant, probably pregnant, or menstruating. Patients with malignant tumors. Patients with acute myocardial infarction (AMI) or pericarditis after AMI. Patients with concurrent infectious endocarditis, moyamoya disease (Willis circle occlusion syndrome), aortic dissection, or neck trauma, etc. Patients with strong suspicion of ischemic cerebrovascular disorder caused by non-thrombotic occlusion or any other hemodynamic condition. Patients judged to be difficult in monitoring for 3 months by their physician. Patients who have participated in other clinical trials during the last 3 months. In addition to the above exclusion criteria, patients judged to be inadequate to participate in this study by their physician.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alteplase<br>0.6mg/kg intravenous alteplase with 10% being administered as a bolus followed by continuous infusion of the remainder over 1 hour | Drug: Alteplase<br>* 0.6 mg/kg of Alteplase is intravenously administered<br>* Other names: ACTIVACIN;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Valid Recanalization Assessed by Magnetic Resonance Angiography (MRA) | Recanalization was evaluated according to the modified Mori grade: Grade 0, no reperfusion; Grade 1, movement of thrombus not associated with any flow improvement; Grade 2, partial (branch) recanalization in <50% of the branches in the occluded-arterial territory; Grade 3, nearly complete recanalization with reperfusion in ≥50% of the branches in the occluded-arterial territory. The recanalization rate was estimated by regarding Grades 2 and 3 as valid recanalization. | within 6 hours, from 24 to 36 hours after onset | 
| Number of Patients With a Modified Rankin Scale (mRS) Score of 0-1 a 3 Months | The number of patients with an 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. | 3 months after onset | 
| Number of Patients With Symptomatic Intracranial Hemorrhage (sICH) Within 36 Hours | The number of patients with sICH | within 36 hours after starting treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| National Institutes of Health Stroke Scale (NIHSS) Score | from 0 (normal) to 40 (most severe) | within 6 hours, from 24 to 36 hours, 3 months after onset. | 
| Barthel Index (BI) | from 100 (Independent) to 0 (full assistance) | the day of discharge within 3 months after onset, and 3 months after onset | 
| Percentage of Participants With Adverse Events and Adverse Drug Reactions |  | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cerebral Infarction, acute ischemic stroke, Brain ischemia