Clinical trial NCT00412867: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Stroke
Keywords: Cerebral Infarction
acute ischemic stroke
Brain ischemia
Lead sponsor: Mitsubishi Tanabe Pharma Corporation
Sponsor class: INDUSTRY
Collaborators: name: Kyowa Kirin Co., Ltd.
First posted: 2006-12-19
Enrollment: 58
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: 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.


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.

Primary outcomes:
measure: Number of Patients With Valid Recanalization Assessed by Magnetic Resonance Angiography (MRA)
timeFrame: within 6 hours, from 24 to 36 hours after onset
measure: Number of Patients With a Modified Rankin Scale (mRS) Score of 0-1 a 3 Months
timeFrame: 3 months after onset
measure: Number of Patients With Symptomatic Intracranial Hemorrhage (sICH) Within 36 Hours
timeFrame: within 36 hours after starting treatment
Secondary outcomes:
measure: National Institutes of Health Stroke Scale (NIHSS) Score
timeFrame: within 6 hours, from 24 to 36 hours, 3 months after onset.
measure: Barthel Index (BI)
timeFrame: the day of discharge within 3 months after onset, and 3 months after onset
measure: Percentage of Participants With Adverse Events and Adverse Drug Reactions
timeFrame: 3 months
Other outcomes:
Locations:
city: Hokkaido
country: Japan
facility: Investigational site 01
Study officials:
affiliation: National Cerebral and Cardiovascular Center, Japan
name: Takenori Yamaguchi, M.D.
role: STUDY_CHAIR
References:
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.
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.