Subarachnoid HemorrhagePhase 4EVASNCT00839449
Eicosapentaenoic Acid Cerebral Vasospasm Therapy Study
A Phase 4 study testing Eicosapentaenoic acid ethyl ester in people with Subarachnoid Hemorrhage and Cerebral Vasospasm, run by Yamaguchi University Hospital at 5 sites in Japan.
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. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Subarachnoid Hemorrhage, Cerebral Vasospasm
- What is being tested?
- Eicosapentaenoic acid ethyl ester
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 5 sitesJapan
- Study dates
- Dec 2004to Dec 2008
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
5 sites in 1 country.
5 sites in 1 country
Japan5 sites
Ootemachi Hospital
Kitakyushu, Fukuoka, 803-8543
Iwate Medical University
Morioka, Iwate, 020-8505
Nakamura Memorial Hospital
Sapporo, Hokkaido, 060-8570
Tohoku University
Sendai, Miyagi, 980-8574
Yamaguchi University Hospital
Ube, Yamaguchi, 755-8505
About this study
Official title: Eicosapentaenoic Acid Cerebral Vasospasm Therapy Study (EVAS): Effect of Eicosapentaenoic Acid on Cerebral Vasospasm Following Subarachnoid Hemorrhage
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.
Read the 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.
- Conditions
- Subarachnoid Hemorrhage, Cerebral Vasospasm
- Being tested
- Eicosapentaenoic acid ethyl ester
- Keywords
- subarachnoid hemorrhage, cerebral vasospasm, eicosapentaenoic acid
- Medical subject headings
- Subarachnoid Hemorrhage, Vasospasm, Intracranial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Eicosapentaenoic acid ethyl esterDrug
Also called EPADEL S900 TM (EPA ethyl ester, purity >98%)
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.
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | Patients in the group A are orally administered eicosapentaenoic acid ethyl ester. Receives: Drug: Eicosapentaenoic acid ethyl ester |
| B | No intervention | Patients in the group B (control) are not administered eicosapentaenoic acid ethyl ester. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cerebral vasospasms: Symptomatic vasospasm defined as documented arterial vasospasm consistent with new neurological deterioration. New low-density areas on CT scans associated with vasospasm.
Measured: Between 4 and 30 days after the onset of SAH
Secondary outcomes (1)
Patient's Glasgow Outcome Scale (GOS).
Measured: At 1 month after onset of SAH.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2009 (estimated)
- Study startDec 2004
- Primary completionJun 2008
- Study completionDec 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Subarachnoid HemorrhageStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yamaguchi University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Nakamura Memorial Hospital, Iwate Medical University, Tohoku University, Ootemachi Hospital
- Investigators
- Michiyasu Suzuki, MD, PhD, Principal investigator, Yamaguchi University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00839449
- Sponsor's protocol ID
- Y-2004
- Acronym
- EVAS
- Status last verified
- Sep 2009
- First submitted
- 4 Feb 2009
- Last updated
- 3 Sep 2009
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Yoneda H, Shirao S, Nakagawara J, Ogasawara K, Tominaga T, Suzuki M. A prospective, multicenter, randomized study of the efficacy of eicosapentaenoic acid for cerebral vasospasm: the EVAS study. World Neurosurg. 2014 Feb;81(2):309-15. doi: 10.1016/j.wneu.2012.09.020. Epub 2012 Sep 29.
PubMed 23032083
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Eicosapentaenoic Acid Cerebral Vasospasm Therapy Study (EVAS): Effect of Eicosapentaenoic Acid on Cerebral Vasospasm Following Subarachnoid Hemorrhage
- ClinicalTrials.gov ID
- NCT00839449
- Acronym / sponsor ID
- EVAS / Y-2004
- Conditions
- Subarachnoid Hemorrhage, Cerebral Vasospasm
- Keywords
- subarachnoid hemorrhage, cerebral vasospasm, eicosapentaenoic acid
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 200 participants (actual)
- Lead sponsor
- Yamaguchi University HospitalUniversity, hospital or other
- Collaborators
- Nakamura Memorial Hospital, Iwate Medical University, Tohoku University, Ootemachi Hospital
- Study start
- Dec 2004
- Primary completion
- Jun 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 9 Feb 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: Eicosapentaenoic acid ethyl esterPatients in the group A are orally administered eicosapentaenoic acid ethyl ester. |
| B | No intervention | –Patients in the group B (control) are not administered eicosapentaenoic acid ethyl ester. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Eicosapentaenoic acid ethyl esterAlso: EPADEL S900 TM (EPA ethyl ester, purity >98%)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. | Drug | A |
Primary outcome
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
1 secondary outcome
Patient's Glasgow Outcome Scale (GOS).
Time frame: At 1 month after onset of SAH.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2009.
- Derived from this study: PubMed 23032083Yoneda H, Shirao S, Nakagawara J, Ogasawara K, Tominaga T, Suzuki M. A prospective, multicenter, randomized study of the efficacy of eicosapentaenoic acid for cerebral vasospasm: the EVAS study. World Neurosurg. 2014 Feb;81(2):309-15. doi: 10.1016/j.wneu.2012.09.020. Epub 2012 Sep 29.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michiyasu Suzuki, MD, PhD principal investigator
Yamaguchi University Hospital
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Eicosapentaenoic acid ethyl ester in people with Subarachnoid Hemorrhage and Cerebral Vasospasm, run by Yamaguchi University Hospital at 5 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Sep 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00839449, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Sep 2009.