SUSHI: Subarachnoid Hemorrhage and Soluble Epoxide Hydrolase Inhibition Trial
Study Details
Study Description
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 |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
Study 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).
Hypothesis: Pharmacologic inhibition of the sEH enzyme is safe and will result in increased EETs availability at the neurovascular unit, and a measured increase in the EET/DHET ratio in the serum and cerebrospinal fluid. This study is a double-blind, placebo-controlled, phase 1b randomized trial to evaluate the safety and of GSK2256294, an inhibitor of soluble epoxide hydrolase, in patients with aneurysmal SAH.
Objectives:
Primary Objective:
Determine the safety of administration of GSK2256294 in patients with aneurysmal SAH.
Secondary Objective:
Determine the pharmacodynamic effect of administration of GSK2256294 in patients with aneurysmal SAH on reducing EETs metabolism and biomarkers of cerebrovascular inflammation and endothelial injury.
Tertiary Objective:
Provide preliminary estimates of clinical endpoints to inform the design of a larger trial
Endpoints:
Primary Endpoints:
Determination of safety
Secondary endpoints:
-
Study days 7 and 10 serum EET/DHET ratios
-
Study days 7 and 10 cerebrospinal fluid (CSF) EET/DHET ratios
-
Study days 7 and 10 serum EPOME/DPOME ratio
-
Neuroinflammatory and endothelial injury biomarker levels from the blood and CSF at day 7 and day 10.
Tertiary, exploratory endpoints:
Clinical outcomes associated with SAH including neurologic status, disposition, vital status and incidence of delayed cerebral ischemia.
20 subjects will be randomized. Patients age 18 or above with confirmed ruptured aneurysms will be approached to provide written informed consent
Phase: Phase 1B
Description of Sites/Facilities Enrolling Participants: The study will take place at Oregon Health & Science University Hospital, with enrollment of patients admitted to the OHSU NSICU, a part of a comprehensive stroke center certified by the American Heart Association and Joint Commission for Accreditation of Healthcare Organizations, with a catchment area including the state of Oregon, Southwest Washington and Northern California. Approximately 80-100 patients with aneurysmal SAH are admitted each year.
Description of Study Intervention: Twenty patients will be equally randomized to receive once daily either 10 mg dose of GSK2256294 or placebo enterally for a duration of 10 days.
Study Duration: 24 months
Participant Duration: 90 days
Study Design
Arms and Interventions
| 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.
|
Outcome Measures
Primary Outcome Measures
- Participants With Adverse Events [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 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
- Study Day 7 and Study Day 10 Serum and CSF EET/ Dihyroxyeicosatrienoic (DHET) Ratio, by Mass Spectroscopic Analysis (ng/mL) [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 and Study Day 10 Serum Epoxyoctadecenoic Acid (EPOME) to Dihydroxyoctadec-12-enoic Acid (DPOME) Ratio, by Mass Spectroscopic Analysis (ng/mL) [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.
- Serum Biomarkers of Endothelial Injury From Blood Samples Obtained on Study Day 7 and Study Day 10 [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).
- CSF Biomarkers of Neuroinflammation, From Blood Samples Obtained on Study Day 7 and Study Day 10 [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
- Hospital Length of Stay in Days [90 days]
The hospital length of stay will be recorded in days, at the time of hospital discharge.
- Discharge Disposition [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
- Number of Participants With New Stroke on Hospital Discharge Imaging [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.
- Modified Rankin Scale (mRS) at Hospital Discharge and 90 Day Follow up [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.
- Extended Glasgow Outcome Scale (GOSE) Score at 90 Day Follow up [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.
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Oregon Health & Science University | Portland | Oregon | United States | 97239 |
Sponsors and Collaborators
- Oregon Health and Science University
- Foundation for Anesthesia Education and Research
- GlaxoSmithKline
Investigators
- Principal Investigator: Ross Martini, MD, Oregon Health and Science University
Study Documents (Full-Text)
More Information
Publications
None provided.- 17614
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | GSK2256294 | Placebo |
|---|---|---|
| Arm/Group Description | 10mg capsules of GSK2256294 will be administered in a single dose once daily enterally for a duration of 10 days. GSK2256294: GSK2256294 will be administered in a single dose once daily enteral for a duration of 10 days. | 10mg matched placebo capsules will be administered in a single dose once daily enterally for a duration of 10 days. Placebo: Placebo will be administered in a single dose once daily enteral for a duration of 10 days. |
| Period Title: Overall Study | ||
| STARTED | 10 | 10 |
| COMPLETED | 10 | 8 |
| NOT COMPLETED | 0 | 2 |
Baseline Characteristics
| Arm/Group Title | GSK2256294 | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | 10mg capsules of GSK2256294 will be administered in a single dose once daily enterally for a duration of 10 days. GSK2256294: GSK2256294 will be administered in a single dose once daily enteral for a duration of 10 days. | 10mg matched placebo capsules will be administered in a single dose once daily enterally for a duration of 10 days. Placebo: Placebo will be administered in a single dose once daily enteral for a duration of 10 days. | Total of all reporting groups |
| Overall Participants | 10 | 9 | 19 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
61.2
(11.2)
|
60.4
(11.4)
|
60.8
(11.1)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
6
60%
|
6
66.7%
|
12
63.2%
|
| Male |
4
40%
|
3
33.3%
|
7
36.8%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
0
0%
|
2
22.2%
|
2
10.5%
|
| Not Hispanic or Latino |
10
100%
|
7
77.8%
|
17
89.5%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
2
20%
|
0
0%
|
2
10.5%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
| White |
8
80%
|
8
88.9%
|
16
84.2%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
1
11.1%
|
1
5.3%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
10
100%
|
9
100%
|
19
100%
|
| Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [kg/m^2] |
28.8
(6.6)
|
27.7
(4.7)
|
28.2
(5.6)
|
| Smoking (Count of Participants) | |||
| Never/Passive Smoker |
2
20%
|
5
55.6%
|
7
36.8%
|
| Active Smoker |
5
50%
|
3
33.3%
|
8
42.1%
|
| Former Smoker |
3
30%
|
1
11.1%
|
4
21.1%
|
| History of Hypertension (Count of Participants) | |||
| Count of Participants [Participants] |
6
60%
|
9
100%
|
15
78.9%
|
| History of Seizure (Count of Participants) | |||
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
| History of Prior Brain Aneurysm (Count of Participants) | |||
| Count of Participants [Participants] |
1
10%
|
0
0%
|
1
5.3%
|
| Pre-Admission Antihypertensives (Count of Participants) | |||
| Count of Participants [Participants] |
3
30%
|
8
88.9%
|
11
57.9%
|
| Pre-Admission Anticoagulants (Count of Participants) | |||
| Count of Participants [Participants] |
0
0%
|
2
22.2%
|
2
10.5%
|
| Pre-Admission Antiplatelet Agents (Count of Participants) | |||
| Count of Participants [Participants] |
2
20%
|
2
22.2%
|
4
21.1%
|
| Pre-Admission Statins (Count of Participants) | |||
| Count of Participants [Participants] |
1
10%
|
1
11.1%
|
2
10.5%
|
| Pre-Admission Antidiabetic Agents (Count of Participants) | |||
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
| Hunt and Hess Scale (units on a scale) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [units on a scale] |
3.0
(.94)
|
3.0
(1.0)
|
3.0
(.94)
|
| Modified Fisher Grade (units on a scale) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [units on a scale] |
3.9
(.32)
|
3.7
(.71)
|
3.8
(.54)
|
| Glasgow Coma Scale at Randomization (units on a scale) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [units on a scale] |
13.3
(2.7)
|
10.7
(3.6)
|
12.1
(3.3)
|
| Location of Aneurysm (Count of Participants) | |||
| Anterior Cerebral Artery/Branches |
4
40%
|
2
22.2%
|
6
31.6%
|
| Middle Cerebral/Internal Carotid Artery/Branches |
3
30%
|
4
44.4%
|
7
36.8%
|
| Posterior Cerebral Artery/Branches |
1
10%
|
0
0%
|
1
5.3%
|
| Vertebrobasilar System |
2
20%
|
3
33.3%
|
5
26.3%
|
| Treatment of Aneursym (Count of Participants) | |||
| Craniotomy |
4
40%
|
2
22.2%
|
6
31.6%
|
| Endovascular |
6
60%
|
6
66.7%
|
12
63.2%
|
| Unsecured |
0
0%
|
1
11.1%
|
1
5.3%
|
| Baseline Aspartate Aminotransferase (units/liter) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [units/liter] |
22.7
(5.7)
|
25.5
(11.8)
|
24.1
(9.0)
|
| Baseline Aanine Transaminase (units/liter) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [units/liter] |
27.5
(13.4)
|
24.4
(15.7)
|
26.1
(14.2)
|
| Baseline QTc Interval (milliseconds) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [milliseconds] |
451.5
(24.3)
|
456.4
(31.5)
|
453.2
(27.0)
|
| Admitted Intubated (Count of Participants) | |||
| Count of Participants [Participants] |
2
20%
|
4
44.4%
|
6
31.6%
|
Outcome Measures
| Title | Participants With Adverse Events |
|---|---|
| Description | 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 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. |
| Time Frame | 90 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | GSK2256294 | Placebo |
|---|---|---|
| Arm/Group Description | 10mg capsules of GSK2256294 will be administered in a single dose once daily enterally for a duration of 10 days. GSK2256294: GSK2256294 will be administered in a single dose once daily enteral for a duration of 10 days. | 10mg matched placebo capsules will be administered in a single dose once daily enterally for a duration of 10 days. Placebo: Placebo will be administered in a single dose once daily enteral for a duration of 10 days. |
| Measure Participants | 10 | 9 |
| Venous Thromboembolism |
2
20%
|
0
0%
|
| Myocardial Infarction |
0
0%
|
0
0%
|
| Seizure |
1
10%
|
1
11.1%
|
| Any Documented Infection |
4
40%
|
6
66.7%
|
| Cerebral Salt Wasting |
3
30%
|
2
22.2%
|
| Leukopenia |
0
0%
|
1
11.1%
|
| Aneurysm Rebleed |
0
0%
|
1
11.1%
|
| Acute Respiratory Distress Syndrome |
0
0%
|
1
11.1%
|
| Death |
0
0%
|
1
11.1%
|
| Title | Study Day 7 and Study Day 10 Serum and CSF EET/ Dihyroxyeicosatrienoic (DHET) Ratio, by Mass Spectroscopic Analysis (ng/mL) |
|---|---|
| Description | 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. |
| Time Frame | 10 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Missing data occurred due to no sample collection from the CSF in patients who had external ventricular drains removed as part of their standard ICU care, prior to the study visit for sample collection. Missing serum samples are the result of one patient in the placebo group who died prior to sample collection visit, and multiple unsuccessful attempts at blood collection from another patient. |
| Arm/Group Title | GSK2256294 | Placebo |
|---|---|---|
| Arm/Group Description | 10mg capsules of GSK2256294 will be administered in a single dose once daily enterally for a duration of 10 days. GSK2256294: GSK2256294 will be administered in a single dose once daily enteral for a duration of 10 days. | 10mg matched placebo capsules will be administered in a single dose once daily enterally for a duration of 10 days. Placebo: Placebo will be administered in a single dose once daily enteral for a duration of 10 days. |
| Measure Participants | 10 | 9 |
| Study day 7 CSF 14,15-EET/DHET ratio |
.17
(.07)
|
.19
(.16)
|
| Study day 10 CSF 14,15-EET/DHET ratio |
.45
(.78)
|
.52
(1.04)
|
| Study day 7 serum 14,15-EET/DHET ratio |
.30
(.11)
|
.12
(.03)
|
| Study day 10 serum 14,15-EET/DHET ratio |
.27
(.07)
|
.12
(.02)
|
| Title | Study Day 7 and Study Day 10 Serum Epoxyoctadecenoic Acid (EPOME) to Dihydroxyoctadec-12-enoic Acid (DPOME) Ratio, by Mass Spectroscopic Analysis (ng/mL) |
|---|---|
| Description | 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. |
| Time Frame | 10 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Missing data occurred due to no sample collection from the CSF in patients who had external ventricular drains removed as part of their standard ICU care, prior to the study visit for sample collection. Missing serum samples are the result of one patient in the placebo group who died prior to sample collection visit, and multiple unsuccessful attempts at blood collection from another patient. |
| Arm/Group Title | GSK2256294 | Placebo |
|---|---|---|
| Arm/Group Description | 10mg capsules of GSK2256294 will be administered in a single dose once daily enterally for a duration of 10 days. GSK2256294: GSK2256294 will be administered in a single dose once daily enteral for a duration of 10 days. | 10mg matched placebo capsules will be administered in a single dose once daily enterally for a duration of 10 days. Placebo: Placebo will be administered in a single dose once daily enteral for a duration of 10 days. |
| Measure Participants | 10 | 9 |
| Day 7 serum 12,13 EpOME/DiHOME ratio |
6.0
(4.3)
|
1.8
(.92)
|
| Day 10 serum 12,13 EpOME/DiHOME ratio |
8.7
(7.1)
|
1.7
(.90)
|
| Title | Serum Biomarkers of Endothelial Injury From Blood Samples Obtained on Study Day 7 and Study Day 10 |
|---|---|
| Description | 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). |
| Time Frame | 10 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Missing data occurred due to no sample collection from the CSF in patients who had external ventricular drains removed as part of their standard ICU care, prior to the study visit for sample collection. Missing serum samples are the result of one patient in the placebo group who died prior to sample collection visit, and multiple unsuccessful attempts at blood collection from another patient. |
| Arm/Group Title | GSK2256294 | Placebo |
|---|---|---|
| Arm/Group Description | 10mg capsules of GSK2256294 will be administered in a single dose once daily enterally for a duration of 10 days. GSK2256294: GSK2256294 will be administered in a single dose once daily enteral for a duration of 10 days. | 10mg matched placebo capsules will be administered in a single dose once daily enterally for a duration of 10 days. Placebo: Placebo will be administered in a single dose once daily enteral for a duration of 10 days. |
| Measure Participants | 10 | 9 |
| Serum Day 7 ICAM |
8.4
(7.5)
|
8.3
(6.8)
|
| Serum Day 10 ICAM |
17.8
(27)
|
6.7
(6.6)
|
| Serum Day 7 VCAM |
8.3
(3.0)
|
7.9
(2.0)
|
| Serum Day 10 VCAM |
8.9
(2.9)
|
7.9
(2.1)
|
| Serum Day 7 PECAM-1 |
1.4
(.56)
|
1.7
(.90)
|
| Serum Day 10 PECAM-1 |
1.7
(.90)
|
1.6
(.65)
|
| Serum Day 7 E-Selectin |
46.6
(25.3)
|
48.0
(33.0)
|
| Serum Day 10 E-Selectin |
53.0
(23.8)
|
44.7
(30.3)
|
| Serum Day 7 P-Selectin |
1.4
(.83)
|
1.1
(.28)
|
| Serum Day 10 P-Selectin |
1.7
(.90)
|
2.0
(2.2)
|
| Title | CSF Biomarkers of Neuroinflammation, From Blood Samples Obtained on Study Day 7 and Study Day 10 |
|---|---|
| Description | 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) |
| Time Frame | 10 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Missing data occurred due to no sample collection from the CSF in patients who had external ventricular drains removed as part of their standard ICU care, prior to the study visit for sample collection. Missing serum samples are the result of one patient in the placebo group who died prior to sample collection visit, and multiple unsuccessful attempts at blood collection from another patient. |
| Arm/Group Title | GSK2256294 | Placebo |
|---|---|---|
| Arm/Group Description | 10mg capsules of GSK2256294 will be administered in a single dose once daily enterally for a duration of 10 days. GSK2256294: GSK2256294 will be administered in a single dose once daily enteral for a duration of 10 days. | 10mg matched placebo capsules will be administered in a single dose once daily enterally for a duration of 10 days. Placebo: Placebo will be administered in a single dose once daily enteral for a duration of 10 days. |
| Measure Participants | 10 | 9 |
| CSF Day 7 IFN-gamma |
1.9
(1.0)
|
4.6
(6.8)
|
| CSF Day 10 IFN-gamma |
1.5
(.84)
|
5.8
(12.9)
|
| CSF Day 7 IL-1b |
1.6
(.82)
|
5.0
(9.6)
|
| CSF Day 10 IL-1b |
1.0
(.50)
|
4.4
(9.2)
|
| CSF Day 7 IL-6 |
2991.2
(3420.0)
|
3417.9
(4110.2)
|
| CSF Day 10 IL-6 |
2089.4
(3248.4)
|
2051.6
(3570.7)
|
| CSF Day 7 IL-8 |
1652.4
(1374.4)
|
3971.0
(3298.9)
|
| CSF Day 10 IL-8 |
1093.6
(775.3)
|
1485.8
(1002.2)
|
| CSF Day 7 TNF-alpha |
7.8
(2.6)
|
13.1
(15.6)
|
| CSF Day 10 TNF-alpha |
5.9
(2.8)
|
8.1
(9.9)
|
| Title | Hospital Length of Stay in Days |
|---|---|
| Description | The hospital length of stay will be recorded in days, at the time of hospital discharge. |
| Time Frame | 90 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | GSK2256294 | Placebo |
|---|---|---|
| Arm/Group Description | 10mg capsules of GSK2256294 will be administered in a single dose once daily enterally for a duration of 10 days. GSK2256294: GSK2256294 will be administered in a single dose once daily enteral for a duration of 10 days. | 10mg matched placebo capsules will be administered in a single dose once daily enterally for a duration of 10 days. Placebo: Placebo will be administered in a single dose once daily enteral for a duration of 10 days. |
| Measure Participants | 10 | 9 |
| Mean (Standard Deviation) [days] |
16.9
(3.3)
|
28.8
(19.8)
|
| Title | Discharge Disposition |
|---|---|
| Description | 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 |
| Time Frame | 90 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | GSK2256294 | Placebo |
|---|---|---|
| Arm/Group Description | 10mg capsules of GSK2256294 will be administered in a single dose once daily enterally for a duration of 10 days. GSK2256294: GSK2256294 will be administered in a single dose once daily enteral for a duration of 10 days. | 10mg matched placebo capsules will be administered in a single dose once daily enterally for a duration of 10 days. Placebo: Placebo will be administered in a single dose once daily enteral for a duration of 10 days. |
| Measure Participants | 10 | 9 |
| Discharged to home |
7
70%
|
2
22.2%
|
| Discharged to rehab, long term acute care facility, skilled nursing facility, hospice, death |
3
30%
|
7
77.8%
|
| Title | Number of Participants With New Stroke on Hospital Discharge Imaging |
|---|---|
| Description | 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. |
| Time Frame | 90 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | GSK2256294 | Placebo |
|---|---|---|
| Arm/Group Description | 10mg capsules of GSK2256294 will be administered in a single dose once daily enterally for a duration of 10 days. GSK2256294: GSK2256294 will be administered in a single dose once daily enteral for a duration of 10 days. | 10mg matched placebo capsules will be administered in a single dose once daily enterally for a duration of 10 days. Placebo: Placebo will be administered in a single dose once daily enteral for a duration of 10 days. |
| Measure Participants | 10 | 9 |
| Count of Participants [Participants] |
1
10%
|
1
11.1%
|
| Title | Modified Rankin Scale (mRS) at Hospital Discharge and 90 Day Follow up |
|---|---|
| Description | 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. |
| Time Frame | 90 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| One subject in GSK2256294 group lost to followup |
| Arm/Group Title | GSK2256294 | Placebo |
|---|---|---|
| Arm/Group Description | 10mg capsules of GSK2256294 will be administered in a single dose once daily enterally for a duration of 10 days. GSK2256294: GSK2256294 will be administered in a single dose once daily enteral for a duration of 10 days. | 10mg matched placebo capsules will be administered in a single dose once daily enterally for a duration of 10 days. Placebo: Placebo will be administered in a single dose once daily enteral for a duration of 10 days. |
| Measure Participants | 10 | 9 |
| Hospital Discharge mRS |
3.4
(1.5)
|
4.1
(1.4)
|
| 90 day follow-up mRS |
2.2
(1.6)
|
3.3
(1.7)
|
| Title | Extended Glasgow Outcome Scale (GOSE) Score at 90 Day Follow up |
|---|---|
| Description | 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. |
| Time Frame | 90 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Missing data due to one subject in the GSK2256294 lost to followup |
| Arm/Group Title | GSK2256294 | Placebo |
|---|---|---|
| Arm/Group Description | 10mg capsules of GSK2256294 will be administered in a single dose once daily enterally for a duration of 10 days. GSK2256294: GSK2256294 will be administered in a single dose once daily enteral for a duration of 10 days. | 10mg matched placebo capsules will be administered in a single dose once daily enterally for a duration of 10 days. Placebo: Placebo will be administered in a single dose once daily enteral for a duration of 10 days. |
| Measure Participants | 9 | 9 |
| Mean (Standard Deviation) [score on a scale] |
5.4
(2.4)
|
4.1
(2.4)
|
Adverse Events
| Time Frame | Adverse event data was collected up to 90 days after hospital discharge at the time of followup phone visit | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | GSK2256294 | Placebo | ||
| Arm/Group Description | 10mg capsules of GSK2256294 will be administered in a single dose once daily enterally for a duration of 10 days. GSK2256294: GSK2256294 will be administered in a single dose once daily enteral for a duration of 10 days. | 10mg matched placebo capsules will be administered in a single dose once daily enterally for a duration of 10 days. Placebo: Placebo will be administered in a single dose once daily enteral for a duration of 10 days. | ||
All Cause Mortality |
||||
| GSK2256294 | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/10 (0%) | 1/9 (11.1%) | ||
Serious Adverse Events |
||||
| GSK2256294 | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/10 (40%) | 5/9 (55.6%) | ||
| Blood and lymphatic system disorders | ||||
| Leukopenia | 0/10 (0%) | 0 | 1/9 (11.1%) | 1 |
| Deep Vein Thrombosis | 2/10 (20%) | 2 | 0/9 (0%) | 0 |
| Infections and infestations | ||||
| Aspiration Pneumonia | 1/10 (10%) | 1 | 1/9 (11.1%) | 1 |
| Central Line Associated Bloodstream Infection | 1/10 (10%) | 1 | 0/9 (0%) | 0 |
| Pseudomonas Ventriculitis, Bacteremia, Urinary Tract Infection | 0/10 (0%) | 0 | 1/9 (11.1%) | 1 |
| Urinary Tract Infection | 1/10 (10%) | 1 | 2/9 (22.2%) | 2 |
| Nervous system disorders | ||||
| Delayed Cerebral Ischemia | 2/10 (20%) | 2 | 1/9 (11.1%) | 1 |
| Rebleed of Unsecured Aneurysm | 0/10 (0%) | 0 | 1/9 (11.1%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute Respiratory Distress Syndrome | 0/10 (0%) | 0 | 1/9 (11.1%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| GSK2256294 | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/10 (0%) | 0/10 (0%) | ||
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Ross Martini |
|---|---|
| Organization | Oregon Health and Science University |
| Phone | 4013386803 |
| martinir@ohsu.edu |
- 17614