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Subarachnoid Hemorrhage and Soluble Epoxide Hydrolase Inhibition Trial (SUSHI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03318783
Recruitment Status : Active, not recruiting
First Posted : October 24, 2017
Last Update Posted : April 10, 2019
Sponsor:
Information provided by (Responsible Party):
Ross Martini, MD, Oregon Health and Science University

Brief 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.

Condition or disease Intervention/treatment Phase
Subarachnoid Hemorrhage, Aneurysmal Delayed Cerebral Ischemia Vasospasm, Cerebral Endothelial Dysfunction Drug: GSK2256294 Drug: Placebo Phase 1 Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Subjects will be randomized to one of the two treatment arms based on an unrestricted or "fair-coin" randomization procedure.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Investigational pharmacy staff will maintain the randomization list and study/drug placebo assignment. Participants, care providers, the investigators and outcomes assessors will be blinded to the grouping.
Primary Purpose: Treatment
Official Title: Subarachnoid Hemorrhage and Soluble Epoxide Hydrolase Inhibition Trial
Actual Study Start Date : May 2, 2018
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bleeding

Arm Intervention/treatment
Active Comparator: GSK2256294
10mg capsules of GSK2256294 will be administered in a single dose once daily enterally for a duration of 10 days.
Drug: GSK2256294
GSK2256294 will be administered in a single dose once daily enteral for a duration of 10 days.

Placebo Comparator: Placebo
10mg matched placebo capsules will be administered in a single dose once daily enterally for a duration of 10 days.
Drug: Placebo
Placebo will be administered in a single dose once daily enteral for a duration of 10 days.




Primary Outcome Measures :
  1. Number of participants with treatment-related adverse events [ Time Frame: 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. Tabular summaries will be provided for all adverse events, the relationship to study drug treatment the maximum severity grade, action taken, and whether the event qualified serious adverse event or not.

    All deaths will be reported in a patient listing, which will include the primary cause of death and the number of days between the date of the last dose of study drug and death.



Secondary Outcome Measures :
  1. Study day 7 and study day 10 serum and CSF EET/ dihyroxyeicosatrienoic (DHET) ratio, by mass spectroscopic analysis (ng/mL) [ Time Frame: 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.


  2. Study day 7 and study day 10 serum epoxyoctadecenoic acid (EPOME) to dihydroxyoctadec-12-enoic acid (DPOME) ratio, by mass spectroscopic analysis (ng/mL) [ Time Frame: 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.

  3. Serum biomarkers of endothelial injury from blood samples obtained on study day 7 and study day 10 [ Time Frame: 10 days ]
    The following serum biomarkers will be obtained from collected blood samples by Luminex assay: e-selectin (pg/mL), p-selectin (pg/mL), Vascular cell adhesion marker (VCAM-1) (pg/mL), Platelet endothelial cell adhesion marker (PECAM-1, CD31) (pg/mL), intercellular adhesion molecule (ICAM-1) (pg/mL)

  4. CSF biomarkers of neuroinflammation, from blood samples obtained on study day 7 and study day 10 [ Time Frame: 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)


Other Outcome Measures:
  1. Hospital length of stay in days [ Time Frame: 90 days ]
    The hospital length of stay will be recorded in days, at the time of hospital discharge.

  2. Discharge disposition [ Time Frame: 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

  3. Incidence of new stroke on hospital discharge imaging [ Time Frame: 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.

  4. Modified Rankin scale (mRS) at hospital discharge and 90 day follow up [ Time Frame: 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 - severe disability, requires constant nursing care and attention, bedridden, incontinent, 6 - deceased.

  5. Extended Glasgow Outcome Scale (GOSE) Score at 90 day follow up [ Time Frame: 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 will be recorded on an 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03318783


Locations
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United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
Sponsors and Collaborators
Oregon Health and Science University
Investigators
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Principal Investigator: Ross Martini, MD Oregon Health and Science University

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Responsible Party: Ross Martini, MD, Principal Investigator, Oregon Health and Science University
ClinicalTrials.gov Identifier: NCT03318783     History of Changes
Other Study ID Numbers: 17614
First Posted: October 24, 2017    Key Record Dates
Last Update Posted: April 10, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ross Martini, MD, Oregon Health and Science University:
Eicosanoids
Epoxyeicosatrienoic Acids
Additional relevant MeSH terms:
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Subarachnoid Hemorrhage
Brain Ischemia
Cerebral Infarction
Vasospasm, Intracranial
Hemorrhage
Ischemia
Pathologic Processes
Intracranial Hemorrhages
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Brain Infarction
Stroke