Sildenafil for DCI

Subarachnoid Hemorrhage Clinical Trial

Official title:

Sildenafil for the Treatment of Delayed Cerebral Ischemia Following Subarachnoid Hemorrhage

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03028298
• Other study ID #: 2016-0134
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: December 2016
• Est. completion date: July 2023

Study information

• Verified date: June 2021
• Source: University of Mississippi Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 24
• Est. completion date: July 2023
• Est. primary completion date: December 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Cerebral Vasospasm
• Hemorrhage
• Subarachnoid Hemorrhage
• Vasospasm, Intracranial

Intervention

Drug:
• Low dose sildenafil citrate

• High dose sildenafil citrate

Locations

Country	Name	City	State
United States	University of Mississippi Medical Center	Jackson	Mississippi

Sponsors (1)

Lead Sponsor	Collaborator
University of Mississippi Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (2)

Dhar R, Washington C, Diringer M, Zazulia A, Jafri H, Derdeyn C, Zipfel G. Acute Effect of Intravenous Sildenafil on Cerebral Blood Flow in Patients with Vasospasm After Subarachnoid Hemorrhage. Neurocrit Care. 2016 Oct;25(2):201-4. doi: 10.1007/s12028-016-0243-0. — View Citation

Washington CW, Derdeyn CP, Dhar R, Arias EJ, Chicoine MR, Cross DT, Dacey RG Jr, Han BH, Moran CJ, Rich KM, Vellimana AK, Zipfel GJ. A Phase I proof-of-concept and safety trial of sildenafil to treat cerebral vasospasm following subarachnoid hemorrhage. J Neurosurg. 2016 Feb;124(2):318-27. doi: 10.3171/2015.2.JNS142752. Epub 2015 Aug 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in mean arterial blood pressure		baseline and 2 hours post-dose
Primary	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	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
Secondary	Change from baseline in cerebral autoregulation		baseline and 2 hours post-dose