Acute Hemodynamic Effects of Sildenafil in Patients With Severe Aortic Stenosis

NCT01060020 | Completed Phase 4 Results DMC

• 1 other identifier: 09-1780
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Pulmonary hypertension is common in patients with aortic stenosis and is associated with worse operative and long-term outcomes. Sildenafil has been shown to reduce pulmonary artery pressure and improve exercise performance in patients with left-sided heart failure, but this has not been tested in patients with aortic stenosis. We hypothesize that Sildenafil will produce a clinically significant decrease in pulmonary artery pressure in patients with severe aortic stenosis. The dose of Sildenafil that produces a significant decrease in pulmonary artery pressure will be safe and well tolerated in patients with and without a depressed ejection fraction.

Conditions

Aortic Stenosis

Keywords

Aortic valve stenosis; Sildenafil; Phosphodiesterase inhibitors; Hypertension, Pulmonary

Outcome Measures

Primary Outcomes (1)

• Percent Change in Mean Pulmonary Artery Pressure in the Whole Cohort.

  Baseline and 60 minutes after drug administered

Secondary Outcomes (4)

• Percent Change in Pulmonary Vascular Resistance in the Whole Cohort.

  Baseline and 60 minutes after drug administered

• Percent Change in Cardiac Index.

  Baseline and 60 minutes after drug administered

• Load Independent Index of Diastolic Filling.

  Baseline and 60 minutes after drug administered

• Global Longitudinal Strain

  Baseline and 60 minutes after drug administered

Study Arms (1)

Sildenafil 40mg or 80mg

EXPERIMENTAL

A single oral dose of Sildenafil (either 40mg or 80mg) will be administered to a participant after baseline hemodynamics are measured in the catheterization lab. Each dose will be equally distributed among those with preserved (≥50%) and reduced (\<50%) EF.

Drug: Sildenafil

Interventions

Sildenafil DRUG

Single oral dose of 40mg or 80mg of Sildenafil

Also known as: Revatio, Viagra

Sildenafil 40mg or 80mg

Eligibility Criteria

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

You may qualify if:

• Severe aortic stenosis (AVA \< 1.0 cm2)
• Referred for a clinically ordered right and left heart catheterization
• years of age and older
• Able and willing to comply with all requirements of the study

You may not qualify if:

• Nitrate use within 24 hours
• SBP \< 110 mmHg or MAP \< 75 mmHg
• Severe mitral regurgitation
• Severe aortic regurgitation
• Increased risk of priapism
• Retinal or optic nerve problems or unexplained visual disturbance
• Alpha antagonists or cytochrome P450 3A4 inhibitors use within 24 hours
• Current or recent (≤ 30 days) acute coronary syndrome
• O2 sat \< 90% on room air
• Females that are pregnant or believe they may be pregnant
• Any condition which the PI determines will place the subject at increased risk or is likely to yield unreliable hemodynamic data
• Unwilling to provide informed consent

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Barnes-Jewish Hospital: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• Lindman BR, Zajarias A, Madrazo JA, Shah J, Gage BF, Novak E, Johnson SN, Chakinala MM, Hohn TA, Saghir M, Mann DL. Effects of phosphodiesterase type 5 inhibition on systemic and pulmonary hemodynamics and ventricular function in patients with severe symptomatic aortic stenosis. Circulation. 2012 May 15;125(19):2353-62. doi: 10.1161/CIRCULATIONAHA.111.081125. Epub 2012 Mar 25.

  PMID: 22447809 RESULT

MeSH Terms

Conditions

Aortic Valve Stenosis; Hypertension, Pulmonary

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction; Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases

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

Results Point of Contact

• Title: Brian R. Lindman, MD, Assistant Professor of Medicine
• Organization: Washington University School of Medicine

brlindman@wustl.edu

314-747-3617

Study Officials

• Brian R. Lindman, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: January 28, 2010
• First Posted: February 1, 2010
• Study Start: January 1, 2010
• Primary Completion: September 1, 2011
• Study Completion: October 1, 2011
• Last Updated: April 25, 2018
• Results First Posted: April 25, 2018

Record last verified: 2018-04

Locations

US (1)