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Eicosapentaenoic Acid Cerebral Vasospasm Therapy Study (EVAS)

This study has been completed.
Sponsor:
Collaborators:
Nakamura Memorial Hospital
Iwate Medical University
Tohoku University
Ootemachi Hospital
Information provided by:
Yamaguchi University Hospital
ClinicalTrials.gov Identifier:
NCT00839449
First received: February 4, 2009
Last updated: September 1, 2009
Last verified: September 2009
  Purpose

Cerebral vasospasm following subarachnoid hemorrhage (SAH) is the most common cause of morbidity and mortality. Recent studies indicate that Rho-kinase play an important role in the occurrence of such cerebral vasospasm. Eicosapentaenoic acid (EPA) inhibits sphingosylphosphorylcholine (SPC)-induced Rho-kinase activation in vitro. So this study examines whether EPA prevents cerebral vasospasm occurrence after SAH in patients.


Condition Intervention Phase
Subarachnoid Hemorrhage
Cerebral Vasospasm
Drug: Eicosapentaenoic acid ethyl ester
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Eicosapentaenoic Acid Cerebral Vasospasm Therapy Study (EVAS): Effect of Eicosapentaenoic Acid on Cerebral Vasospasm Following Subarachnoid Hemorrhage

Resource links provided by NLM:


Further study details as provided by Yamaguchi University Hospital:

Primary Outcome Measures:
  • Cerebral vasospasms: Symptomatic vasospasm defined as documented arterial vasospasm consistent with new neurological deterioration. New low-density areas on CT scans associated with vasospasm. [ Time Frame: Between 4 and 30 days after the onset of SAH ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Patient's Glasgow Outcome Scale (GOS). [ Time Frame: At 1 month after onset of SAH. ] [ Designated as safety issue: Yes ]

Enrollment: 200
Study Start Date: December 2004
Study Completion Date: December 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
Patients in the group A are orally administered eicosapentaenoic acid ethyl ester.
Drug: Eicosapentaenoic acid ethyl ester
Orally administered 900 mg eicosapentaenoic acid ethyl ester three times a day (2700 mg ⁄ day) from the surgery next day to 30 days after the onset of SAH.
Other Name: EPADEL S900 TM (EPA ethyl ester, purity >98%)
No Intervention: B
Patients in the group B (control) are not administered eicosapentaenoic acid ethyl ester.

Detailed Description:

Cerebral vasospasm occasionally seen after subarachnoid hemorrhage (SAH) due to a ruptured intracranial aneurysm is the most common cause of morbidity and mortality in these cases. Recent studies indicate that Rho-kinase plays an important role in such cerebral vasospasm and that numerous agents, such as thromboxane A2 (TXA2), sphingosylphosphorylcholine (SPC) and arachidonic acid (AA), can activate Rho-kinase directly or through receptors in the cell membrane; among these agents, SPC has been described as a novel messenger for Rho-kinase-mediated Ca2+ sensitization of vascular smooth muscle contraction. Eicosapentaenoic acid (EPA) has recently been reported to inhibit SPC-induced Rho-kinase activation in vitro, and thereby vascular smooth muscle contraction, through the inhibition of Src family protein tyrosine kinases translocation. Moreover, the concentration of AA increases in the cerebrospinal fluid of patients with SAH, suggesting that this substance has a potential role in the occurrence of cerebral vasospasm following SAH, while EPA is known to change the constitution ratios of AA and EPA in cell membrane phospholipid, resulting in the inhibition of TXA2 synthesis. These observations lead us to hypothesize that EPA may inhibit cerebral vasospasm following SAH through the inhibition of Rho-kinase activation.

  Eligibility

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

Inclusion Criteria:

  • Subarachnoid hemorrhage (SAH)
  • The ruptured cerebral aneurysms conformed by cerebral angiography
  • The patients with treated by craniotomy and clip application within 72h after the onset of SAH

Exclusion Criteria:

  • Traumatic or mycotic aneurysms
  • A history or complication of serious stroke
  • Moya Moya disease
  • A history of SAH
  • Complication of serious heart or hepatic disease or infection or renal failure
  • Malignant tumor
  • Patients judged to be inappropriate by physician in charge
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00839449

Locations
Japan
Ootemachi Hospital
Kitakyushu, Fukuoka, Japan, 803-8543
Nakamura Memorial Hospital
Sapporo, Hokkaido, Japan, 060-8570
Iwate Medical University
Morioka, Iwate, Japan, 020-8505
Tohoku University
Sendai, Miyagi, Japan, 980-8574
Yamaguchi University Hospital
Ube, Yamaguchi, Japan, 755-8505
Sponsors and Collaborators
Yamaguchi University Hospital
Nakamura Memorial Hospital
Iwate Medical University
Tohoku University
Ootemachi Hospital
Investigators
Principal Investigator: Michiyasu Suzuki, MD, PhD Yamaguchi University Hospital
  More Information

No publications provided by Yamaguchi University Hospital

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Eicosapentaenoic acid Cerebral Vasospasm Therapy Study (EVAS) Group, Yamaguchi University Hospital
ClinicalTrials.gov Identifier: NCT00839449     History of Changes
Other Study ID Numbers: Y-2004
Study First Received: February 4, 2009
Last Updated: September 1, 2009
Health Authority: Japan: Institutional Review Board

Keywords provided by Yamaguchi University Hospital:
subarachnoid hemorrhage
cerebral vasospasm
eicosapentaenoic acid

Additional relevant MeSH terms:
Hemorrhage
Subarachnoid Hemorrhage
Vasospasm, Intracranial
Brain Diseases
Cardiovascular Diseases
Central Nervous System Diseases
Cerebrovascular Disorders
Intracranial Hemorrhages
Nervous System Diseases
Pathologic Processes
Vascular Diseases
Eicosapentaenoic acid ethyl ester
Hematologic Agents
Pharmacologic Actions
Platelet Aggregation Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014