Subarachnoid Hemorrhage
Conditions
Brief summary
The purpose of this study is to examine the effects of the study drug--Galantamine-on patients with subarachnoid hemorrhage (SAH). The study will examine how patients with SAH will tolerate the study drug and how it may improve brain functioning in patients after SAH.
Interventions
DRUGPlacebo
Placebo will match drug capsules.
DRUG8mg galantamine twice daily
Drug will be administered within 36 hours of hospitalization and continued for 90 days.
DRUG12mg galantamine twice daily
Drug will be administered within 36 hours of hospitalization and continued for 90 days.
Sponsors
The University of Texas Health Science Center, Houston
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Spontaneous subarachnoid hemorrhage * Presentation to hospital within 72 hours of symptoms * Fisher grade 3 hemorrhage (thick subarachnoid clot) on initial computed tomography (CT) scan * Hunt and Hess grade 1-5 at time of randomization * Presence of a cerebral aneurysm on computed tomographic angiography (CTA) or Angiogram for which clipping or coiling is possible * Ability to obtain medication within 36 hours of presentation
Exclusion criteria
* subarachnoid hemorrhage (SAH) due to causes other than aneurysm rupture (trauma, arteriovenous malformation (AVM), mycotic aneurysms, Moyamoya) * Pre-existing disability with modified Rankin Scale (mRS) score ≥2, * Renal disease as defined by creatinine clearance less than 9 milliliters/min * History of severe hepatic impairment (Child-Pugh score of 10-15) * History of chronic obstructive pulmonary disease (COPD) or asthma * History of dementia * Co-morbid conditions likely to complicate therapy, including clinically significant arrhythmia, acquired immune deficiency syndrome (AIDS), autoimmune disease, malignancy, and expected mortality within 72 hours * Expected mortality within 72 hours as determined by PI, treating neurointensivist and neurosurgeon. (Clinically manifested by no attempt at securing aneurysm) * Females who are pregnant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tolerability as Assessed by the Number of Participants Who Stop Study Medication Due to Adverse Event Possibly Associated With Study Drug | 90 days | — |
| Mortality | 90 days | — |
| Modified Rankin Score | 90 days | The Modified Rankin Score (mRS) is scored as follows: 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. \- Dead. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Montreal Cognitive Assessment (MoCA) | baseline (in hospital) | MoCA scores range between 0 and 30. Higher scores indicate a better outcome, and a score of 26 or over is considered to be normal. |
| EuroQOL Score as Assessed by a Visual Analogue Scale (VAS) | 90 days | In the EuroQOL VAS assessment, health status is marked on a 20 cm vertical scale with end points of 0 and 100. 0 corresponds to the worst health you can imagine, and 100 corresponds to the best health you can imagine. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Galantamine 8mg or 12mg galantamine twice daily: Drug will be administered within 36 hours of hospitalization and continued for 90 days. | 30 |
| Placebo Placebo: Placebo will match drug capsules. | 30 |
| Total | 60 |
Baseline characteristics
| Characteristic | Galantamine | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 48.3 years STANDARD_DEVIATION 12.6 | 54.2 years STANDARD_DEVIATION 10.4 | 51.25 years STANDARD_DEVIATION 11.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 17 Participants | 16 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 14 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 30 participants | 30 participants | 60 participants |
| Sex: Female, Male Female | 19 Participants | 23 Participants | 42 Participants |
| Sex: Female, Male Male | 11 Participants | 7 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 30 | 4 / 30 |
| other Total, other adverse events | 26 / 30 | 29 / 30 |
| serious Total, serious adverse events | 17 / 30 | 17 / 30 |
Outcome results
Primary
Modified Rankin Score
The Modified Rankin Score (mRS) is scored as follows: 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. \- Dead.
Time frame: 90 days
Population: Data was not collected for 3 in the galantamine arm and 2 in the placebo arm. Because of the small sample size of this study, which is underpowered to detect differences between the 8mg and 12mg galantamine arms, the pre-specified analysis approach was to combine data for the two galantamine arms when comparing to the placebo arm.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Galantamine | Modified Rankin Score | 2 | 4 Participants |
| Galantamine | Modified Rankin Score | 4 | 4 Participants |
| Galantamine | Modified Rankin Score | 1 | 8 Participants |
| Galantamine | Modified Rankin Score | 5 | 4 Participants |
| Galantamine | Modified Rankin Score | 3 | 3 Participants |
| Galantamine | Modified Rankin Score | 6 | 1 Participants |
| Galantamine | Modified Rankin Score | 0 | 3 Participants |
| Placebo | Modified Rankin Score | 6 | 4 Participants |
| Placebo | Modified Rankin Score | 0 | 2 Participants |
| Placebo | Modified Rankin Score | 1 | 2 Participants |
| Placebo | Modified Rankin Score | 2 | 12 Participants |
| Placebo | Modified Rankin Score | 3 | 3 Participants |
| Placebo | Modified Rankin Score | 4 | 2 Participants |
| Placebo | Modified Rankin Score | 5 | 3 Participants |
Primary
Mortality
Time frame: 90 days
Population: Because of the small sample size of this study, which is underpowered to detect differences between the 8mg and 12mg galantamine arms, the pre-specified analysis approach was to combine data for the two galantamine arms when comparing to the placebo arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Galantamine | Mortality | 1 Participants |
| Placebo | Mortality | 4 Participants |
Primary
Tolerability as Assessed by the Number of Participants Who Stop Study Medication Due to Adverse Event Possibly Associated With Study Drug
Time frame: 90 days
Population: Because of the small sample size of this study, which is underpowered to detect differences between the 8mg and 12mg galantamine arms, the pre-specified analysis approach was to combine data for the two galantamine arms when comparing to the placebo arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Galantamine | Tolerability as Assessed by the Number of Participants Who Stop Study Medication Due to Adverse Event Possibly Associated With Study Drug | 1 Participants |
| Placebo | Tolerability as Assessed by the Number of Participants Who Stop Study Medication Due to Adverse Event Possibly Associated With Study Drug | 1 Participants |
Secondary
EuroQOL Score as Assessed by a Visual Analogue Scale (VAS)
In the EuroQOL VAS assessment, health status is marked on a 20 cm vertical scale with end points of 0 and 100. 0 corresponds to the worst health you can imagine, and 100 corresponds to the best health you can imagine.
Time frame: 90 days
Population: Data was not collected for 5 in the galantamine arm and 6 in the placebo arm. Because of the small sample size of this study, which is underpowered to detect differences between the 8mg and 12mg galantamine arms, the pre-specified analysis approach was to combine data for the two galantamine arms when comparing to the placebo arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Galantamine | EuroQOL Score as Assessed by a Visual Analogue Scale (VAS) | 76.2 units on a scale | Standard Deviation 19.4 |
| Placebo | EuroQOL Score as Assessed by a Visual Analogue Scale (VAS) | 74.0 units on a scale | Standard Deviation 22.6 |
Secondary
Montreal Cognitive Assessment (MoCA)
MoCA scores range between 0 and 30. Higher scores indicate a better outcome, and a score of 26 or over is considered to be normal.
Time frame: baseline (in hospital)
Population: Data was not collected for 1 in the galantamine arm and 6 in the placebo arm. Because of the small sample size of this study, which is underpowered to detect differences between the 8mg and 12mg galantamine arms, the pre-specified analysis approach was to combine data for the two galantamine arms when comparing to the placebo arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Galantamine | Montreal Cognitive Assessment (MoCA) | 7.5 score on a scale | Standard Deviation 9.2 |
| Placebo | Montreal Cognitive Assessment (MoCA) | 8.2 score on a scale | Standard Deviation 8.9 |
Secondary
Montreal Cognitive Assessment (MoCA)
MoCA scores range between 0 and 30. Higher scores indicate a better outcome, and a score of 26 or over is considered to be normal.
Time frame: 90 days
Population: Data was not collected for 6 in the galantamine arm and 6 in the placebo arm. Because of the small sample size of this study, which is underpowered to detect differences between the 8mg and 12mg galantamine arms, the pre-specified analysis approach was to combine data for the two galantamine arms when comparing to the placebo arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Galantamine | Montreal Cognitive Assessment (MoCA) | 14.0 score on a scale | Standard Deviation 11.5 |
| Placebo | Montreal Cognitive Assessment (MoCA) | 15.8 score on a scale | Standard Deviation 10.1 |