Sildenafil for DCI

NCT03028298 | Unknown Phase 1 DMC

• 1 other identifier: 2016-0134
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (2)

• Change from baseline in mean arterial blood pressure

  baseline and 2 hours post-dose

• 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 Outcomes (2)

• 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

Study Arms (2)

Low dose sildenafil

EXPERIMENTAL

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.

Drug: Low dose sildenafil citrate

High dose sildenafil

EXPERIMENTAL

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.

Drug: High dose sildenafil citrate

Interventions

Low dose sildenafil citrate DRUG

Low dose sildenafil

High dose sildenafil citrate DRUG

High dose sildenafil

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>= 21
• 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

You may not qualify if:

• Pregnancy
• 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)

Sponsors & Collaborators

• University of Mississippi Medical Center: lead

Study Sites (1)

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Related Publications (2)

• 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.

  PMID: 26314998 BACKGROUND

• 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.

  PMID: 26940913 BACKGROUND

MeSH Terms

Conditions

Subarachnoid Hemorrhage; Vasospasm, Intracranial

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Chad W Washington, MS, MD, MPHS

  University of Mississippi Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients will be randomly assigned to either low dose sildenafil (20mg oral and 10mg intravenous) or high dose sildenafil (60mg oral and 30 mg intravenous)

Study Record Dates

• First Submitted: January 13, 2017
• First Posted: January 23, 2017
• Study Start: December 1, 2016
• Primary Completion: December 1, 2022
• Study Completion: July 1, 2023
• Last Updated: June 8, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)