Eicosapentaenoic Acid Cerebral Vasospasm Therapy Study (EVAS)

Yamaguchi University Hospital

Status and phase: Completed; Phase 4

Conditions: Subarachnoid Hemorrhage; Cerebral Vasospasm

Treatments: Drug: Eicosapentaenoic acid ethyl ester

Study type: Interventional

Funder types: Other

Identifiers

NCT00839449

Y-2004

Details and patient eligibility

About

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.

Full 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.

Enrollment: 200 patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

200 participants in 2 patient groups

A

Experimental group

Description:

Patients in the group A are orally administered eicosapentaenoic acid ethyl ester.

Treatment:

Drug: Eicosapentaenoic acid ethyl ester

B

No Intervention group

Description:

Patients in the group B (control) are not administered eicosapentaenoic acid ethyl ester.