Sildenafil for the Treatment of Delayed Cerebral Ischemia Following Subarachnoid Hemorrhage
试验速览
- 阶段
- 1 期
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Area under the plasma concentration versus time curve (AUC) of sildenafil
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Onset of symptoms within 72 hours from presentation
- •Subarachnoid hemorrhage from ruptured cerebral aneurysm
- •Cerebral vasospasm diagnosed on transcranial doppler, CT angiography, or digital subtraction angiography
排除标准
- •Subarachnoid hemorrhage secondary to traumatic or mycotic aneurysm
- •Pre-ictal sildenafil therapy (last dose within 1 week of presentation)
- •Contraindications to sildenafil therapy (i.e. use of nitrates, left ventricular outflow obstruction, impaired autonomic blood pressure control)
研究组 & 干预措施
Low dose sildenafil
Twelve patients with cerebral vasospasm following aneurysmal subarachnoid hemorrhage will be assigned to low dose sildenafil citrate and will receive a 20mg oral dose and a subsequent 10mg intravenous dose of sildenafil citrate.
干预措施: Low dose sildenafil citrate (Drug)
High dose sildenafil
Twelve patients with cerebral vasospasm following aneurysmal subarachnoid hemorrhage will be assigned to high dose sildenafil citrate and will receive a 60mg oral dose and a subsequent 30mg intravenous dose of sildenafil citrate.
干预措施: High dose sildenafil citrate (Drug)
结局指标
主要结局
Area under the plasma concentration versus time curve (AUC) of sildenafil
时间窗: 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 mean arterial blood pressure
时间窗: baseline and 2 hours post-dose
次要结局
- 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)