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NCT03318783: SUSHI

Subarachnoid Hemorrhage and Soluble Epoxide Hydrolase Inhibition Trial

Completed Phase 1, PHASE2 Results posted Last updated 22 January 2021
What this trial tests

Phase 1, PHASE2 trial testing GSK2256294 in Subarachnoid Hemorrhage, Aneurysmal in 20 participants. Completed in 9 January 2020.

Timeline
2 May 2018
Primary endpoint
3 April 2019
9 January 2020

Quick facts

Lead sponsorOregon Health and Science University
PhasePhase 1, PHASE2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment20
Start date2 May 2018
Primary completion3 April 2019
Estimated completion9 January 2020
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Oregon Health and Science University

Who can join

18 and older, any sex, with Subarachnoid Hemorrhage, Aneurysmal or Delayed Cerebral Ischemia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Participants With Adverse Events Primary · 90 days

Summary tables and listings will be provided for all reported adverse events, defined as adverse events that start on or after the first administration of study drug. The reported adverse event term will be assigned a standardized preferred term. Adverse events will be summarized based on the number and percentage of patients experiencing the event. In the event a patient experiences repeat episodes of the same adverse event, then the event with the highest severity grade and strongest causal relationship to study treatment will be used for purposes of incidence tabulations. All deaths will

Venous Thromboembolism
GroupValue95% CI
GSK22562942
Placebo0
Myocardial Infarction
GroupValue95% CI
GSK22562940
Placebo0
Seizure
GroupValue95% CI
GSK22562941
Placebo1
Any Documented Infection
GroupValue95% CI
GSK22562944
Placebo6
Cerebral Salt Wasting
GroupValue95% CI
GSK22562943
Placebo2
Leukopenia
GroupValue95% CI
GSK22562940
Placebo1
Aneurysm Rebleed
GroupValue95% CI
GSK22562940
Placebo1
Acute Respiratory Distress Syndrome
GroupValue95% CI
GSK22562940
Placebo1
Study Day 7 and Study Day 10 Serum and CSF EET/ Dihyroxyeicosatrienoic (DHET) Ratio, by Mass Spectroscopic Analysis (ng/mL) Secondary · 10 days

Day 7 and day 10 serum EET/DHET ratios will be measured by liquid chromatography and mass spectroscopy of collected blood samples. Day 7 and day 10 CSF EET/DHET ratios will be measured by liquid chromatography and mass spectroscopy of collected CSF samples.

Study day 7 CSF 14,15-EET/DHET ratio
GroupValue95% CI
GSK2256294.17± .07
Placebo.19± .16
Study day 10 CSF 14,15-EET/DHET ratio
GroupValue95% CI
GSK2256294.45± .78
Placebo.52± 1.04
Study day 7 serum 14,15-EET/DHET ratio
GroupValue95% CI
GSK2256294.30± .11
Placebo.12± .03
Study day 10 serum 14,15-EET/DHET ratio
GroupValue95% CI
GSK2256294.27± .07
Placebo.12± .02
Study Day 7 and Study Day 10 Serum Epoxyoctadecenoic Acid (EPOME) to Dihydroxyoctadec-12-enoic Acid (DPOME) Ratio, by Mass Spectroscopic Analysis (ng/mL) Secondary · 10 days

Study day 7 and study day 10 serum epoxyoctadecenoic acid (EPOME) to dihydroxyoctadec-12-enoic acid (DPOME) ratio, will be measure by mass spectroscopic analysis of collected blood samples.

Day 7 serum 12,13 EpOME/DiHOME ratio
GroupValue95% CI
GSK22562946.0± 4.3
Placebo1.8± .92
Day 10 serum 12,13 EpOME/DiHOME ratio
GroupValue95% CI
GSK22562948.7± 7.1
Placebo1.7± .90
Serum Biomarkers of Endothelial Injury From Blood Samples Obtained on Study Day 7 and Study Day 10 Secondary · 10 days

The following serum biomarkers will be obtained from collected blood samples by Luminex assay: e-selectin, p-selectin, Vascular cell adhesion marker (VCAM-1), Platelet endothelial cell adhesion marker (PECAM-1, CD31), intercellular adhesion molecule (ICAM-1).

Serum Day 7 ICAM
GroupValue95% CI
GSK22562948.4± 7.5
Placebo8.3± 6.8
Serum Day 10 ICAM
GroupValue95% CI
GSK225629417.8± 27
Placebo6.7± 6.6
Serum Day 7 VCAM
GroupValue95% CI
GSK22562948.3± 3.0
Placebo7.9± 2.0
Serum Day 10 VCAM
GroupValue95% CI
GSK22562948.9± 2.9
Placebo7.9± 2.1
Serum Day 7 PECAM-1
GroupValue95% CI
GSK22562941.4± .56
Placebo1.7± .90
Serum Day 10 PECAM-1
GroupValue95% CI
GSK22562941.7± .90
Placebo1.6± .65
Serum Day 7 E-Selectin
GroupValue95% CI
GSK225629446.6± 25.3
Placebo48.0± 33.0
Serum Day 10 E-Selectin
GroupValue95% CI
GSK225629453.0± 23.8
Placebo44.7± 30.3
CSF Biomarkers of Neuroinflammation, From Blood Samples Obtained on Study Day 7 and Study Day 10 Secondary · 10 days

The following CSF biomarker will be obtained from collected CSF samples by Luminex assay: Tumor necrosis factor alpha (TNF-α) (pg/mL), Interleukin 1β (IL-1β) (pg/mL), Interferon gamma (IFN-γ) (pg/mL), Interleukin 6 (IL-6) (pg/mL), Interleukin 8 (IL-8) (pg/mL), Monocyte chemoattractant protein 1 (MCP-1) (pg/mL)

CSF Day 7 IFN-gamma
GroupValue95% CI
GSK22562941.9± 1.0
Placebo4.6± 6.8
CSF Day 10 IFN-gamma
GroupValue95% CI
GSK22562941.5± .84
Placebo5.8± 12.9
CSF Day 7 IL-1b
GroupValue95% CI
GSK22562941.6± .82
Placebo5.0± 9.6
CSF Day 10 IL-1b
GroupValue95% CI
GSK22562941.0± .50
Placebo4.4± 9.2
CSF Day 7 IL-6
GroupValue95% CI
GSK22562942991.2± 3420.0
Placebo3417.9± 4110.2
CSF Day 10 IL-6
GroupValue95% CI
GSK22562942089.4± 3248.4
Placebo2051.6± 3570.7
CSF Day 7 IL-8
GroupValue95% CI
GSK22562941652.4± 1374.4
Placebo3971.0± 3298.9
CSF Day 10 IL-8
GroupValue95% CI
GSK22562941093.6± 775.3
Placebo1485.8± 1002.2
Hospital Length of Stay in Days Secondary · 90 days

The hospital length of stay will be recorded in days, at the time of hospital discharge.

GroupValue95% CI
GSK225629416.9± 3.3
Placebo28.8± 19.8
Discharge Disposition Secondary · 90 days

The disposition from the hospital in one of the following categories: home, home with services, rehab, long term acute care facility, skilled nursing facility, hospice, death

GroupValue95% CI
GSK22562947
Placebo2
GSK22562943
Placebo7
Number of Participants With New Stroke on Hospital Discharge Imaging Secondary · 90 days

The last head CT or other brain imaging to detect the presence of a new area of cerebral infarction will be reviewed at the time of hospital discharge. A cerebral infarction will be defined as a one identified on hospital discharge that was not present on imaging between 24-48 hours after aneurysm occlusion, and not attributable to other causes such as surgical clipping or endovascular treatment. Hypodensities resulting from extraventricular drains or residual intraparencyhmal hematomas will not be considered new strokes.

GroupValue95% CI
GSK22562941
Placebo1
Modified Rankin Scale (mRS) at Hospital Discharge and 90 Day Follow up Secondary · 90 days

The mRS score will be determined by patient or surrogate interview, at both hospital discharge and 90 day follow up. Scores will be assigned based on the following: 0 - no symptoms, 1 - no significant disability, able to carry out all usual activities despite some symptoms, 2 - slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities, 3 - moderate disability, requires some help, but able to walk unassisted, 4 - moderately severe disability, unable to attend to own bodily needs without assistance, and unable to walk unassisted, 5 - se

Hospital Discharge mRS
GroupValue95% CI
GSK22562943.4± 1.5
Placebo4.1± 1.4
90 day follow-up mRS
GroupValue95% CI
GSK22562942.2± 1.6
Placebo3.3± 1.7
Extended Glasgow Outcome Scale (GOSE) Score at 90 Day Follow up Secondary · 90 days

At 90 day follow up, the GOSE will be determined by patient or surrogate telephone interview, based on a structured interview of 19 questions. The GOSE is a scale of 1-8 where 1 - deceased, 2 - vegetative state, 3 - low severe disability, 4 - upper severe disability, 5 - low moderate disability, 6 -upper moderate disability, 7 - low good recovery, 8 - upper good recovery.

GroupValue95% CI
GSK22562945.4± 2.4
Placebo4.1± 2.4

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse event data was collected up to 90 days after hospital discharge at the time of followup phone visit. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

GSK2256294
Serious: 4/10 (40%)
Deaths: 0/10
Placebo
Serious: 5/9 (56%)
Deaths: 1/9

Serious adverse events (9 terms)

ReactionSystemGSK2256294Placebo
Delayed Cerebral IschemiaNervous system disorders
Deep Vein ThrombosisBlood and lymphatic system disorders
Urinary Tract InfectionInfections and infestations
Rebleed of Unsecured AneurysmNervous system disorders
Aspiration PneumoniaInfections and infestations
LeukopeniaBlood and lymphatic system disorders
Central Line Associated Bloodstream InfectionInfections and infestations
Acute Respiratory Distress SyndromeRespiratory, thoracic and mediastinal disorders
Pseudomonas Ventriculitis, Bacteremia, Urinary Tract InfectionInfections and infestations

Most-reported serious reactions: Delayed Cerebral Ischemia, Deep Vein Thrombosis, Urinary Tract Infection, Rebleed of Unsecured Aneurysm, Aspiration Pneumonia, Leukopenia, Central Line Associated Bloodstream Infection, Acute Respiratory Distress Syndrome.

Data from ClinicalTrials.gov NCT03318783 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Metabolism pathways of arachidonic acids: mechanisms and potential therapeutic targets.
    Wang B, Wu L, Chen J, Dong L, et al · · 2021 · cited 900× · PMID 33637672 · DOI 10.1038/s41392-020-00443-w
  2. Omega-3 polyunsaturated fatty acids protect against inflammation through production of LOX and CYP450 lipid mediators: relevance for major depression and for human hippocampal neurogenesis.
    Borsini A, Nicolaou A, Camacho-Muñoz D, Kendall AC, et al · · 2021 · cited 162× · PMID 34131267 · DOI 10.1038/s41380-021-01160-8
  3. Small-molecule discovery through DNA-encoded libraries.
    Peterson AA, Liu DR. · · 2023 · cited 145× · PMID 37328653 · DOI 10.1038/s41573-023-00713-6
  4. The Multifaceted Role of Epoxide Hydrolases in Human Health and Disease.
    Gautheron J, Jéru I. · · 2020 · cited 77× · PMID 33374956 · DOI 10.3390/ijms22010013
  5. A Double-Blind, Randomized, Placebo-Controlled Trial of Soluble Epoxide Hydrolase Inhibition in Patients with Aneurysmal Subarachnoid Hemorrhage.
    Martini RP, Siler D, Cetas J, Alkayed NJ, et al · · 2022 · cited 35× · PMID 34873674 · DOI 10.1007/s12028-021-01398-8
  6. The role of soluble epoxide hydrolase and its inhibitors in depression.
    Borsini A. · · 2021 · cited 14× · PMID 34514442 · DOI 10.1016/j.bbih.2021.100325
  7. Lipid metabolism in homeostasis and disease.
    Li Z, Deng W, Yang L, Tang C, et al · · 2026 · cited 2× · PMID 41692800 · DOI 10.1038/s41392-025-02357-x
  8. Upregulated Nuclear Expression of Soluble Epoxide Hydrolase Predicts Poor Outcome in Breast Cancer Patients: Importance of the Digital Pathology Approach.
    Montecillo-Aguado M, Soca-Chafre G, Antonio-Andres G, Morales-Martinez M, et al · · 2024 · cited 2× · PMID 39125591 · DOI 10.3390/ijms25158024

Verify or expand the search:

Other trials of GSK2256294

Trials testing the same drug.

Other recruiting trials for Subarachnoid Hemorrhage, Aneurysmal

Currently open trials in the same condition.

Other Oregon Health and Science University trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03318783.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing