Clinical trial NCT00153946: Edaravone and Argatroban Stroke Therapy Study for Acute Ischemic Stroke
Official title: Multicenter Randomized Open-Label Comparison Study on the Efficacy and Safety of Argatroban Monotherapy With Argatroban-Edaravone Combination Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Stroke
Keywords: Free Radical Scavenger
Selective Thrombin Inhibitor
Acute ischemic stroke (nonlacunar and noncardioembolic)
Lead sponsor: Combination Therapy for Acute Ischemic Stroke Study Group
Sponsor class: OTHER
Collaborators: name: Japan Cardiovascular Research Foundation
First posted: 2005-09-12
Enrollment: 814
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: Modified Rankin Scale (MRS) score
timeFrame: at 3 months
measure: Symptomatic intracranial hemorrhage
timeFrame: for the initial 3 weeks
Secondary outcomes:
measure: NIHSS score, JSS score, Barthel Index, modified Rankin Scale score
timeFrame: at various time-points
measure: Various adverse effects
timeFrame: for the 3 months
Other outcomes:
Locations:
city: Suita
country: Japan
facility: EAST Study Office c/o National Cardiovascular Center
state: Osaka
Study officials:
affiliation: National Cerebral and Cardiovascular Center, Japan
name: Takenori Yamaguchi, MD, PhD
role: STUDY_CHAIR
affiliation: National Cerebral and Cardiovascular Center, Japan
name: Takenori Yamaguchi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.