Phase 2
Completed N=20
Subarachnoid Hemorrhage and Soluble Epoxide Hydrolase Inhibition Trial
Subarachnoid Hemorrhage, Aneurysmal · Delayed Cerebral Ischemia · Vasospasm, Cerebral · Endothelial Dysfunction
Source: ClinicalTrials.gov NCT03318783 ↗
Enrolled (actual)
20
Serious AEs
47.4%
Results posted
Jan 2021
Primary outcomePrimary: Participants With Adverse Events — 2; 0; 0; 0 Participants
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.
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 | — |
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
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. Informational only — not medical advice.