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

Sponsor:	Mitsubishi Tanabe Pharma Corporation
Collaborator:	Kyowa Hakko Kirin Company, Limited
Information provided by (Responsible Party):	Mitsubishi Tanabe Pharma Corporation
ClinicalTrials.gov Identifier:	NCT00412867

Purpose

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.

Condition	Intervention	Phase
Stroke	Drug: Alteplase	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Post-marketing Clinical Study of Alteplase for Acute Ischemic Stroke (Phase 4)

Further study details as provided by Mitsubishi Tanabe Pharma Corporation:

Primary Outcome Measures:

Number of Patients With Valid Recanalization Assessed by Magnetic Resonance Angiography (MRA) [ Time Frame: within 6 hours, from 24 to 36 hours after onset ] [ Designated as safety issue: No ]
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 [ Time Frame: 3 months after onset ] [ Designated as safety issue: No ]
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 [ Time Frame: within 36 hours after starting treatment ] [ Designated as safety issue: No ]
The number of patients with sICH

Secondary Outcome Measures:

National Institutes of Health Stroke Scale (NIHSS) Score [ Time Frame: within 6 hours, from 24 to 36 hours, 3 months after onset, etc. ] [ Designated as safety issue: No ]
Barthel Index (BI) [ Time Frame: the day of discharge within 3 months after onset, and 3 months after onset ] [ Designated as safety issue: No ]
Safety [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Enrollment:	58
Study Start Date:	December 2006
Study Completion Date:	June 2008
Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Alteplase 0.6mg/kg intravenous alteplase with 10% being administered as a bolus followed by continuous infusion of the remainder over 1 hour	Drug: Alteplase 0.6 mg/kg of Alteplase is intravenously administered Other Names: Tissue Plasminogen Activator GRTPA ACTIVACIN

Eligibility

Ages Eligible for Study:	20 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00412867

Sponsors and Collaborators

Mitsubishi Tanabe Pharma Corporation

Kyowa Hakko Kirin Company, Limited

Investigators

Study Chair:

Takenori Yamaguchi, M.D.

National Cerebral and Cardiovascular Center

More Information

Publications:

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. Epub 2010 Jan 14.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. Epub 2010 Oct 28.

Responsible Party:	Mitsubishi Tanabe Pharma Corporation
ClinicalTrials.gov Identifier:	NCT00412867 History of Changes
Obsolete Identifiers:	NCT00412945
Other Study ID Numbers:	527-0611
Study First Received:	December 17, 2006
Results First Received:	January 19, 2012
Last Updated:	February 29, 2012
Health Authority:	Japan: Ministry of Health, Labor and Welfare

Keywords provided by Mitsubishi Tanabe Pharma Corporation:

Cerebral Infarction
acute ischemic stroke
Brain ischemia

Additional relevant MeSH terms:

Stroke
Cerebral Infarction
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Brain Infarction

Brain Ischemia
Tissue Plasminogen Activator
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Hematologic Agents

ClinicalTrials.gov processed this record on May 24, 2012