Sildenafil for DCI

University of Mississippi

Status and phase: Unknown; Phase 1

Conditions: Subarachnoid Hemorrhage; Cerebral Vasospasm

Treatments: Drug: Low dose sildenafil citrate; Drug: High dose sildenafil citrate

Study type: Interventional

Funder types: Other

Identifiers

NCT03028298

2016-0134

Details and patient eligibility

About

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.

Enrollment: 24 estimated patients

Sex: All

Ages: 21+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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24 participants in 2 patient groups

Low dose sildenafil

Experimental group

Description:

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.

Treatment:

Drug: Low dose sildenafil citrate

High dose sildenafil

Experimental group

Description:

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.

Treatment:

Drug: High dose sildenafil citrate