Acute Hemodynamic Effects of Sildenafil in Patients With Severe Aortic Stenosis

The Washington University

Status and phase: Completed; Phase 4

Conditions: Aortic Stenosis

Treatments: Drug: Sildenafil

Study type: Interventional

Funder types: Other

Identifiers

NCT01060020

09-1780

Details and patient eligibility

About

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.

Full description

Patients with severe aortic stenosis referred for a clinically ordered right and left heart catheterization will be eligible. Twenty subjects will be enrolled: 10 patients will receive 40mg and 10 patients will receive 80mg; each dose will be equally distributed among those with preserved (≥50%) and reduced (<50%) EF. Subjects will get a baseline echo prior to the heart catheterization. Baseline invasive hemodynamic measurements will be performed using a Swan Ganz catheter. A single oral dose of sildenafil will then be administered (40mg or 80mg), followed by invasive hemodynamic measurements at 30 and 60 minutes. Also at 60 minutes, limited echocardiographic images will be obtained.

Enrollment: 20 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 1 patient group

Sildenafil 40mg or 80mg

Experimental group

Description:

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.

Treatment:

Drug: Sildenafil