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

Primary Purpose

Stroke

Status
Completed
Phase
Phase 4
Locations
Japan
Study Type
Interventional
Intervention
Alteplase
Sponsored by
Mitsubishi Tanabe Pharma Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stroke focused on measuring Cerebral Infarction, acute ischemic stroke, Brain ischemia

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Investigational site 01

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Alteplase

Arm Description

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

Outcomes

Primary Outcome Measures

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.
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.
Number of Patients With Symptomatic Intracranial Hemorrhage (sICH) Within 36 Hours
The number of patients with sICH

Secondary Outcome Measures

National Institutes of Health Stroke Scale (NIHSS) Score
from 0 (normal) to 40 (most severe)
Barthel Index (BI)
from 100 (Independent) to 0 (full assistance)
Percentage of Participants With Adverse Events and Adverse Drug Reactions

Full Information

First Posted
December 17, 2006
Last Updated
December 20, 2017
Sponsor
Mitsubishi Tanabe Pharma Corporation
Collaborators
Kyowa Kirin Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT00412867
Brief Title
Post-marketing Clinical Study of Alteplase for Acute Ischemic Stroke （Japan Alteplase Clinical Trial Ⅱ：J-ACT Ⅱ）
Official Title
Post-marketing Clinical Study of Alteplase for Acute Ischemic Stroke (Phase 4)
Study Type
Interventional

2. Study Status

Record Verification Date
December 2017
Overall Recruitment Status
Completed
Study Start Date
December 2006 (undefined)
Primary Completion Date
June 2008 (Actual)
Study Completion Date
June 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mitsubishi Tanabe Pharma Corporation
Collaborators
Kyowa Kirin Co., Ltd.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stroke
Keywords
Cerebral Infarction, acute ischemic stroke, Brain ischemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
58 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Alteplase
Arm Type
Experimental
Arm Description
0.6mg/kg intravenous alteplase with 10% being administered as a bolus followed by continuous infusion of the remainder over 1 hour
Intervention Type
Drug
Intervention Name(s)
Alteplase
Other Intervention Name(s)
Tissue Plasminogen Activator, GRTPA, ACTIVACIN
Intervention Description
0.6 mg/kg of Alteplase is intravenously administered
Primary Outcome Measure Information:
Title
Number of Patients With Valid Recanalization Assessed by Magnetic Resonance Angiography (MRA)
Description
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.
Time Frame
within 6 hours, from 24 to 36 hours after onset
Title
Number of Patients With a Modified Rankin Scale (mRS) Score of 0-1 a 3 Months
Description
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.
Time Frame
3 months after onset
Title
Number of Patients With Symptomatic Intracranial Hemorrhage (sICH) Within 36 Hours
Description
The number of patients with sICH
Time Frame
within 36 hours after starting treatment
Secondary Outcome Measure Information:
Title
National Institutes of Health Stroke Scale (NIHSS) Score
Description
from 0 (normal) to 40 (most severe)
Time Frame
within 6 hours, from 24 to 36 hours, 3 months after onset.
Title
Barthel Index (BI)
Description
from 100 (Independent) to 0 (full assistance)
Time Frame
the day of discharge within 3 months after onset, and 3 months after onset
Title
Percentage of Participants With Adverse Events and Adverse Drug Reactions
Time Frame
3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Takenori Yamaguchi, M.D.
Organizational Affiliation
National Cerebral and Cardiovascular Center, Japan
Official's Role
Study Chair
Facility Information:
Facility Name
Investigational site 01
City
Hokkaido
Country
Japan

12. IPD Sharing Statement

Citations:
PubMed Identifier
20075341
Citation
Mori E, Minematsu K, Nakagawara J, Yamaguchi T, Sasaki M, Hirano T; Japan Alteplase Clinical Trial II Group. Effects of 0.6 mg/kg intravenous alteplase on vascular and clinical outcomes in middle cerebral artery occlusion: Japan Alteplase Clinical Trial II (J-ACT II). Stroke. 2010 Mar;41(3):461-5. doi: 10.1161/STROKEAHA.109.573477. Epub 2010 Jan 14.
Results Reference
result
PubMed Identifier
21030700
Citation
Hirano T, Sasaki M, Mori E, Minematsu K, Nakagawara J, Yamaguchi T; Japan Alteplase Clinical Trial II Group. Residual vessel length on magnetic resonance angiography identifies poor responders to alteplase in acute middle cerebral artery occlusion patients: exploratory analysis of the Japan Alteplase Clinical Trial II. Stroke. 2010 Dec;41(12):2828-33. doi: 10.1161/STROKEAHA.110.594333. Epub 2010 Oct 28.
Results Reference
derived

Learn more about this trial

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

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