Phase 2 N=20 Randomized Quadruple-blind Treatment

Subarachnoid Hemorrhage and Soluble Epoxide Hydrolase Inhibition Trial

Subarachnoid Hemorrhage, Aneurysmal · Delayed Cerebral Ischemia · Vasospasm, Cerebral · Endothelial Dysfunction

Bottom Line

View on ClinicalTrials.gov: NCT03318783 ↗

Enrolled (actual)

Serious AEs

47.4%

Results posted

Jan 2021

Primary outcome: Primary: Participants With Adverse Events — 2; 0; 0; 0 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: GSK2256294 (Drug); Placebo (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Oregon Health and Science University
Primary completion: Apr 2019

Outcome Measures

Outcome	Result	p-value
PRIMARY Participants With Adverse Events	2; 0; 0; 0; 1; 1	—
SECONDARY Study Day 7 and Study Day 10 Serum and CSF EET/ Dihyroxyeicosatrienoic (DHET) Ratio, by Mass Spectroscopic Analysis (ng/mL)	.17; .19; .45; .52; .30; .12	—
SECONDARY Study Day 7 and Study Day 10 Serum Epoxyoctadecenoic Acid (EPOME) to Dihydroxyoctadec-12-enoic Acid (DPOME) Ratio, by Mass Spectroscopic Analysis (ng/mL)	6.0; 1.8; 8.7; 1.7	—
SECONDARY Serum Biomarkers of Endothelial Injury From Blood Samples Obtained on Study Day 7 and Study Day 10	8.4; 8.3; 17.8; 6.7; 8.3; 7.9	—
SECONDARY CSF Biomarkers of Neuroinflammation, From Blood Samples Obtained on Study Day 7 and Study Day 10	1.9; 4.6; 1.5; 5.8; 1.6; 5.0	—

Summary

Soluble epoxide hydrolase (sEH) is the metabolizing enzyme of epoxyeicosatrienoic acids (EETs), which may play a role in reducing neuroinflammation and regulating cerebral blood flow after subarachnoid hemorrhage (SAH). Hypotheses: Pharmacologic inhibition of the sEH enzyme is safe and will result in increased EETs availability in the blood and cerebrospinal fluid. This study is a double-blind, placebo-controlled, phase 1b randomized trial to evaluate the safety and efficacy of GSK2256294, a novel soluble epoxide hydrolase inhibitor in patients with aneurysmal SAH.

Eligibility Criteria

Inclusion Criteria

Age > 18
Head CT evidence of subarachnoid hemorrhage
Digital subtraction cerebral angiography or CT angiogram documenting the presence of a cerebral aneurysm.

Exclusion Criteria

Symptom onset compatible with SAH of > 3 days prior to admission to OHSU
Absence of an indwelling external ventricular drain
Administration of any of the following inducers/inhibitors of CYP3A4: ritonavir, indinavir, nelfinavir, saquinavir, clarithromycin, telithromycin, chloramphenicol, ketoconazole, itraconazole, nefazodone, cobicistat or enzalutamide.
Suspected or confirmed pregnancy
Preexisting severe neurologic deficit or condition
Chronic renal failure requiring dialysis
Severe terminal disease with life expectancy <6 months
Unable to read or understand written or spoken English or Spanish
Refusal of informed consent

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03318783). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.