Edaravone and Argatroban Stroke Therapy Study for Acute Ischemic Stroke (EAST)

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

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.

Study Overview

• Status: Completed
• Conditions: Stroke
• Intervention / Treatment: Drug: Edaravone

• Study Type: Interventional
• Enrollment (Actual): 814
• Phase: Phase 4

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A; The patients who are allocated to Argatroban monotherapy	Drug: Edaravone; 30mg/20mL vial, twice per day, not longer than two weeks
Active Comparator: B; The patients who are allocated to Edaravone-Argatroban combination therapy	Drug: Edaravone; 30mg/20mL vial, twice per day, not longer than two weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Modified Rankin Scale (MRS) score	at 3 months
Symptomatic intracranial hemorrhage	for the initial 3 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
NIHSS score, JSS score, Barthel Index, modified Rankin Scale score	at various time-points
Various adverse effects	for the 3 months

Collaborators and Investigators

• Sponsor: Combination Therapy for Acute Ischemic Stroke Study Group
• Collaborators: Japan Cardiovascular Research Foundation
• Investigators: Study Chair: Takenori Yamaguchi, MD, PhD, National Cerebral and Cardiovascular Center; Principal Investigator: Takenori Yamaguchi, MD, PhD, National Cerebral and Cardiovascular Center

Publications and helpful links

General Publications

• Jin YJ, Mima T, Raicu V, Park KC, Shimizu K. Combined argatroban and edaravone caused additive neuroprotection against 15 min of forebrain ischemia in gerbils. Neurosci Res. 2002 May;43(1):75-9. doi: 10.1016/s0168-0102(02)00019-6.
• Kumagai N, Origasa H, Nagao T, Takekawa H, Okuhara Y, Yamaguchi T. Prognostic significance of smoking in patients with acute ischemic stroke within 3 months of onset. J Stroke Cerebrovasc Dis. 2013 Aug;22(6):792-8. doi: 10.1016/j.jstrokecerebrovasdis.2012.04.010. Epub 2012 May 24.

Study record dates

Study Major Dates

• Study Start: August 1, 2004
• Primary Completion (Actual): March 1, 2008
• Study Completion (Actual): May 1, 2008

Study Registration Dates

• First Submitted: September 8, 2005
• First Submitted That Met QC Criteria: September 8, 2005
• First Posted (Estimate): September 12, 2005

Study Record Updates

• Last Update Posted (Estimate): May 14, 2008
• Last Update Submitted That Met QC Criteria: May 12, 2008
• Last Verified: May 1, 2008

More Information

Terms related to this study

• Keywords: Free Radical Scavenger; Selective Thrombin Inhibitor; Acute ischemic stroke (nonlacunar and noncardioembolic)
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neuroprotective Agents; Protective Agents; Antioxidants; Free Radical Scavengers; Edaravone
• Other Study ID Numbers: EAST