Sildenafil for DCI

Phase 1

• Conditions: Subarachnoid Hemorrhage; Cerebral Vasospasm
• Interventions: Drug: High dose sildenafil citrate; Drug: Low dose sildenafil citrate

• Registration Number: NCT03028298
• Lead Sponsor: University of Mississippi Medical Center

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-12
• Study First Submitted: 2017-01-13
• Study First Submitted QC: 2017-01-19
• Study First Posted: 2017-01-23
• Status Verified: 2021-06
• Last Update Submitted: 2021-06-05
• Last Update Posted: 2021-06-08
• Primary Completion: 2022-12
• Study Completion: 2023-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 24

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
High dose sildenafil	High dose sildenafil citrate	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.
Low dose sildenafil	Low dose sildenafil citrate	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.

Primary Outcome Measures

Name	Time	Method
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
Change from baseline in mean arterial blood pressure	baseline and 2 hours post-dose

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

University of Mississippi Medical Center; 🇺🇸 Jackson, Mississippi, United States