Edaravone and Argatroban Stroke Therapy Study for Acute Ischemic Stroke - Full Text View

Purpose

Edaravone, a free radical scavenger, is a novel neuroprotective agent, and argatroban is a selective thrombin inhibitor. Both the drugs were approved by the Japanese Government, and have frequently been used for the treatment of acute brain infarction in Japan. The effect of combination therapy of these drugs, however, has not yet been elucidated. This study will test the safety and efficacy of the combination therapy with these agents in patients with acute non-cardioembolic and non-lacunar ischemic stroke.

Condition	Intervention	Phase
Stroke	Drug: Edaravone	Phase IV

Drug Information available for:

Argatroban

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Official Title:	Multicenter Randomized Open-Label Comparison Study on the Efficacy and Safety of Argatroban Monotherapy With Argatroban-Edaravone Combination Therapy

Further study details as provided by Combination Therapy for Acute Ischemic Stroke Study Group:

Primary Outcome Measures:

Modified Rankin Scale (MRS) score [ Time Frame: at 3 months ] [ Designated as safety issue: Yes ]
Symptomatic intracranial hemorrhage [ Time Frame: for the initial 3 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

NIHSS score, JSS score, Barthel Index, modified Rankin Scale score [ Time Frame: at various time-points ] [ Designated as safety issue: Yes ]
Various adverse effects [ Time Frame: for the 3 months ] [ Designated as safety issue: Yes ]

Enrollment:	814
Study Start Date:	August 2004
Study Completion Date:	May 2008
Primary Completion Date:	March 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Active Comparator The patients who are allocated to Argatroban monotherapy	Drug: Edaravone 30mg/20mL vial, twice per day, not longer than two weeks
B: Active Comparator The patients who are allocated to Edaravone-Argatroban combination therapy	Drug: Edaravone 30mg/20mL vial, twice per day, not longer than two weeks

Eligibility

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

Criteria

Inclusion Criteria:

Acute ischemic stroke < 24 hours of onset
Measurable neurological deficits caused by the present attack, ranging from 1 to 22 of NIHSS score on admission

Exclusion Criteria:

Definite or possible cardiogenic brain infarction
Definite lacunar infarction
Prior ischemic stroke within 6 months
Evidence of hemorrhagic brain infarction, epidural hematoma, intracerebral hematoma, or intraventricular hemorrhage
Severe consciousness disturbances (semicoma to deep coma)
Neurological signs clearing spontaneously
Disability of 2 or more on mRS score before the index stroke aPTT being out of the normal range or 1.5 times longer than the pretreatment value
If taking an oral anticoagulant, INR being 1.6 or more, or no INR data
Treatment with urokinase, t-PA, heparin, ozagrel sodium, warfarin, or antiplatelet except for aspirin before enrollment
Intravascular surgery, surgical operation, hyperbaric oxygen therapy, or hypothermia therapy before enrollment
Serum creatinine >1.5 mg/dL
Severe hepatic or cardiac disorders, infectious disorders, dehydration, etc.
Neoplasm
Pregnancy
Hypersensitivity to test drugs

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00153946

Locations


Japan, Osaka
	EAST Study Office c/o National Cardiovascular Center
	Suita, Osaka, Japan, 565-8565

Sponsors and Collaborators

Combination Therapy for Acute Ischemic Stroke Study Group

Japan Cardiovascular Research Foundation

Investigators


Study Chair:	Takenori Yamaguchi, MD, PhD	National Cardiovascular Center

Principal Investigator:	Takenori Yamaguchi, MD, PhD	National Cardiovascular Center

More Information

Publications:

Yong-Jian Jin, Tatsuo Mima, Valerica Raicu, et al: Combined argatroban and edaravone caused additive neuroprotection against 15 min of forebrain ischemia in gerbils. Neuroscience Research 2002;43:75-79 The Edaravone Acute Brain Infarction Study Group: Effect of a novel free radical scavenger, Edaravone (MCI-186), on acute brain infarction. Randomized, placebo-controlled, double-blind study at multicenters. Cerebrovasc Dis 2003;15: 222-229

Responsible Party:	National Cardiovascular Center ( Takenori Yamaguchi, M.D., President Emeritus )
Study ID Numbers:	EAST
First Received:	September 8, 2005
Last Updated:	May 12, 2008
ClinicalTrials.gov Identifier:	NCT00153946
Health Authority:	Japan: Ministry of Health, Labor and Welfare

Keywords provided by Combination Therapy for Acute Ischemic Stroke Study Group:

Free Radical Scavenger

Selective Thrombin Inhibitor

Acute ischemic stroke (nonlacunar and noncardioembolic)

Study placed in the following topic categories:

Thrombin

Cerebral Infarction

Stroke

Vascular Diseases

Central Nervous System Diseases

Ischemia

Brain Diseases

Cerebrovascular Disorders

Argatroban

Brain Ischemia

Brain Infarction

Infarction

Phenylmethylpyrazolone

Additional relevant MeSH terms:

Antioxidants

Anticoagulants

Molecular Mechanisms of Pharmacological Action

Therapeutic Uses

Physiological Effects of Drugs

Free Radical Scavengers

Hematologic Agents

Nervous System Diseases

Platelet Aggregation Inhibitors

Cardiovascular Diseases

Protective Agents

Pharmacologic Actions

ClinicalTrials.gov processed this record on November 20, 2008

Sponsors and Collaborators:	Combination Therapy for Acute Ischemic Stroke Study Group Japan Cardiovascular Research Foundation
Information provided by:	Combination Therapy for Acute Ischemic Stroke Study Group
ClinicalTrials.gov Identifier:	NCT00153946