Cerebral Vasospasm, Subarachnoid Hemorrhage
Conditions
Brief summary
Each year, approximately 30,000 people in the United States suffer an intra-cranial hemorrhage due to aneurysmal rupture. Of those surviving the initial event, up to 40% will go on to have further neurological injury secondary to stroke (delayed cerebral ischemia) caused by constriction of blood vessels (i.e. vasospasm). Previous studies have shown that the medication sildenafil, given intravenously, improves vasospasm, but has an associated degree of hypotension. The degree of hypotension was well within safety thresholds for these patients. Sildenafil is a medication that strongly inhibits the protein phosphodiesterase-V (PDE-V). The hypothesis for this study is that oral sildenafil will also improve vasospasm, but does not result in as much hypotension. Specifically, the investigators look to show that comparable doses of oral sildenafil produces the same degree of PDE-V inhibition as an intravenous dose while the degree of hypotension is reduced. Additionally, using measurements of cerebral blood flow regulation acquired using transcranial Doppler ultrasound, the investigators look to show that oral sildenafil produces the same degree of improvement in vasospasm and blood flow regulation.
Interventions
DRUGLow dose sildenafil citrate
DRUGHigh dose sildenafil citrate
Sponsors
University of Mississippi Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients will be randomly assigned to either low dose sildenafil (20mg oral and 10mg intravenous) or high dose sildenafil (60mg oral and 30 mg intravenous)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age \>= 21 2. Onset of symptoms within 72 hours from presentation 3. Subarachnoid hemorrhage from ruptured cerebral aneurysm 4. Cerebral vasospasm diagnosed on transcranial doppler, CT angiography, or digital subtraction angiography
Exclusion criteria
1. Pregnancy 2. Subarachnoid hemorrhage secondary to traumatic or mycotic aneurysm 3. Pre-ictal sildenafil therapy (last dose within 1 week of presentation) 4. Contraindications to sildenafil therapy (i.e. use of nitrates, left ventricular outflow obstruction, impaired autonomic blood pressure control)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline in mean arterial blood pressure | baseline and 2 hours post-dose |
| Area under the plasma concentration versus time curve (AUC) of sildenafil | 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 20, and 24 hours post-dose |
Secondary
| Measure | Time frame |
|---|---|
| Area under the cerebral spinal fluid concentration versus time curve (AUC) of sildenafil | 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 20, and 24 hours post-dose |
| Change from baseline in cerebral autoregulation | baseline and 2 hours post-dose |
Countries
United States
Outcome results
None listed