Subarachnoid Hemorrhage
Conditions
Keywords
subarachnoid hemorrhage, vasospasm, cerebral blood flow, cerebral metabolism, autoregulation, statin, Vasospasm associated with Subarachnoid hemorrhage
Brief summary
The primary objective of this project is to investigate the effect of statin therapy on cerebral blood flow in patients with aneurysmal SAH who are randomized to receive or not receive statins in a blinded design.
Detailed description
We will determine if statin therapy improves CBF in patients with aneurysmal subarachnoid hemorrhage. This improvement, if present, may be due to improved basal CBF, improved autoregulatory function, or a mitigation of large arterial narrowing. The information gain from this study will help us to better understand the mechanism of action of statins. This knowledge may be useful in the design of future studies with statins and in the development of other therapies aimed at similar mechanisms.
Interventions
DRUGSimvastatin, 80 mg/day for 21 days
Active treatment group
DRUGplacebo
Control group
Sponsors
Washington University School of Medicine
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Age \> 18 * SAH from ruptured cerebral aneurysm within 48 hours of admission. * Modified Fisher grade 2,3,or 4 * Planned surgical or endovascular aneurysm repair
Exclusion criteria
* Pregnancy * SAH secondary to traumatic or mycotic aneurysms * Pre-ictal statin therapy * Contraindication to stain therapy * WFNS grade 5 * Contraindications to MAP elevation on day 7-10
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Resting Cerebral Blood Flow During Peak Period of Vasospasm Risk | 7-10 days after hemorrhage | Resting cerebral blood flow during peak period of vasospasm risk measured by PET |
| Cerebral Autoregulation During Peak Period of Vasospasm Risk | 7-10 days after hemorrhage | Fraction of patients with impaired static autoregulation (% change in MAP/% change in CVR) \* 100 A value of \<60 is considered abnormal. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Impact of Statin on Oxygen Extraction Fraction and Cerebral Metabolism During Peak Period of Vasospasm Risk | 7-10 days after hemorrhage | Oxygen extraction fraction (OEF) is the ratio of Oxygen delivery (ml/100 g/min) and oxygen utilization (ml/100 g/min). It describes the fraction of the oxygen that reaches the brain that it actually uses for energy production. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Simvastatin Simvastatin, 80 mg/day
Simvastatin, 80 mg/day for 21 days: Active treatment group | 21 |
| Control placebo: Control group | 21 |
| Total | 42 |
Baseline characteristics
| Characteristic | Control | Total | Simvastatin |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants | 42 Participants | 21 Participants |
| Age, Continuous | 60 years STANDARD_DEVIATION 10 | 60 years STANDARD_DEVIATION 11 | 59 years STANDARD_DEVIATION 12 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 18 Participants | 37 Participants | 19 Participants |
| Region of Enrollment United States | 21 participants | 42 participants | 21 participants |
| Sex: Female, Male Female | 14 Participants | 26 Participants | 12 Participants |
| Sex: Female, Male Male | 7 Participants | 16 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 21 | 0 / 21 |
| serious Total, serious adverse events | 0 / 21 | 0 / 21 |
Outcome results
Primary
Cerebral Autoregulation During Peak Period of Vasospasm Risk
Fraction of patients with impaired static autoregulation (% change in MAP/% change in CVR) \* 100 A value of \<60 is considered abnormal.
Time frame: 7-10 days after hemorrhage
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Simvastatin | Cerebral Autoregulation During Peak Period of Vasospasm Risk | 2 participants |
| Control | Cerebral Autoregulation During Peak Period of Vasospasm Risk | 2 participants |
Primary
Resting Cerebral Blood Flow During Peak Period of Vasospasm Risk
Resting cerebral blood flow during peak period of vasospasm risk measured by PET
Time frame: 7-10 days after hemorrhage
Population: Of the total population enrolled complete data sets were available on 25. This was due to patient refusal to perform the PET study, logistical difficulties and technical problems.~be completed in seven due to logistical difficulties (n = 4) or patient refusal (n = 3). Two of the completed studies could not be analyzed for technical reasons
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Simvastatin | Resting Cerebral Blood Flow During Peak Period of Vasospasm Risk | .34 mL/100 g/min | Standard Deviation 0.1 |
| Control | Resting Cerebral Blood Flow During Peak Period of Vasospasm Risk | .30 mL/100 g/min | Standard Deviation 0.18 |
Secondary
Impact of Statin on Oxygen Extraction Fraction and Cerebral Metabolism During Peak Period of Vasospasm Risk
Oxygen extraction fraction (OEF) is the ratio of Oxygen delivery (ml/100 g/min) and oxygen utilization (ml/100 g/min). It describes the fraction of the oxygen that reaches the brain that it actually uses for energy production.
Time frame: 7-10 days after hemorrhage
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Simvastatin | Impact of Statin on Oxygen Extraction Fraction and Cerebral Metabolism During Peak Period of Vasospasm Risk | .34 ratio | Standard Deviation 0.1 |
| Control | Impact of Statin on Oxygen Extraction Fraction and Cerebral Metabolism During Peak Period of Vasospasm Risk | .3 ratio | Standard Deviation 0.18 |