Eicosapentaenoic Acid Cerebral Vasospasm Therapy Study

Subarachnoid Hemorrhage Clinical Trial

— EVAS  

Official title:

Eicosapentaenoic Acid Cerebral Vasospasm Therapy Study (EVAS): Effect of Eicosapentaenoic Acid on Cerebral Vasospasm Following Subarachnoid Hemorrhage

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00839449
• Other study ID #: Y-2004
• Status: Completed
• Phase: Phase 4
• First received: February 4, 2009
• Last updated: September 1, 2009
• Start date: December 2004
• Est. completion date: December 2008

Study information

• Verified date: September 2009
• Source: Yamaguchi University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: December 2008
• Est. primary completion date: June 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cerebral Vasospasm
• Hemorrhage
• Subarachnoid Hemorrhage
• Vasospasm, Intracranial

Intervention

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.

Locations

Country	Name	City	State
Japan	Ootemachi Hospital	Kitakyushu	Fukuoka
Japan	Iwate Medical University	Morioka	Iwate
Japan	Nakamura Memorial Hospital	Sapporo	Hokkaido
Japan	Tohoku University	Sendai	Miyagi
Japan	Yamaguchi University Hospital	Ube	Yamaguchi

Sponsors (5)

Lead Sponsor	Collaborator
Yamaguchi University Hospital	Iwate Medical University, Nakamura Memorial Hospital, Ootemachi Hospital, Tohoku University

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Patient's Glasgow Outcome Scale (GOS).		At 1 month after onset of SAH.	Yes