Sildenafil for DCI

NCT ID: NCT03028298

Last Updated: 2021-06-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-31
• Study Completion Date: 2023-07-31

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.

Conditions

Subarachnoid Hemorrhage; Cerebral Vasospasm

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Low dose sildenafil citrate

Intervention Type: 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.

Group Type: EXPERIMENTAL

High dose sildenafil citrate

Intervention Type: DRUG

Interventions

Low dose sildenafil citrate

Intervention Type: DRUG

High dose sildenafil citrate

Intervention Type: DRUG

Eligibility Criteria

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)

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Mississippi Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chad W Washington, MS, MD, MPHS

Role: PRINCIPAL_INVESTIGATOR

University of Mississippi Medical Center

Locations

University of Mississippi Medical Center

Jackson, Mississippi, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 26314998 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26940913 (View on PubMed)

Other Identifiers

2016-0134

Identifier Type: -

Identifier Source: org_study_id