EVAS: Eicosapentaenoic Acid Cerebral Vasospasm Therapy Study

• Sponsor: Yamaguchi University Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00839449
• Collaborator: Nakamura Memorial Hospital (Other), Iwate Medical University (Other), Tohoku University (Other), Ootemachi Hospital (Other)
• Enrollment: 200
• Locations: 5
• Arms: 2
• Duration (Months): 48
• Patients Per Site: 40
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Subarachnoid Hemorrhage; Cerebral Vasospasm	Drug: Eicosapentaenoic acid ethyl ester	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Eicosapentaenoic Acid Cerebral Vasospasm Therapy Study (EVAS): Effect of Eicosapentaenoic Acid on Cerebral Vasospasm Following Subarachnoid Hemorrhage
• Study Start Date: Dec 1, 2004
• Actual Primary Completion Date: Jun 1, 2008
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
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 Names: EPADEL S900 TM (EPA ethyl ester, purity >98%)
No Intervention: B Patients in the group B (control) are not administered eicosapentaenoic acid ethyl ester.

Outcome Measures

Primary Outcome Measures

1. Cerebral vasospasms: Symptomatic vasospasm defined as documented arterial vasospasm consistent with new neurological deterioration. New low-density areas on CT scans associated with vasospasm. [Between 4 and 30 days after the onset of SAH]

Secondary Outcome Measures

1. Patient's Glasgow Outcome Scale (GOS). [At 1 month after onset of SAH.]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Ootemachi Hospital	Kitakyushu	Fukuoka	Japan	803-8543
2	Nakamura Memorial Hospital	Sapporo	Hokkaido	Japan	060-8570
3	Iwate Medical University	Morioka	Iwate	Japan	020-8505
4	Tohoku University	Sendai	Miyagi	Japan	980-8574
5	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00839449
• Other Study ID Numbers: Y-2004
• First Posted: Feb 9, 2009
• Last Update Posted: Sep 3, 2009
• Last Verified: Sep 1, 2009

• Keywords provided by , ,: subarachnoid hemorrhage; cerebral vasospasm; eicosapentaenoic acid
• Additional relevant MeSH terms: Subarachnoid Hemorrhage; Vasospasm, Intracranial; Hemorrhage; Eicosapentaenoic acid ethyl ester

Study Results

No Results Posted as of Sep 3, 2009