Clinical trial NCT01060020: Acute Hemodynamic Effects of Sildenafil in Patients With Severe Aortic Stenosis
Official title: Acute Hemodynamic Effects of Sildenafil in Patients With Severe Aortic Stenosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Aortic Stenosis
Keywords: Aortic valve stenosis
Sildenafil
Phosphodiesterase inhibitors
Hypertension, Pulmonary
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Barnes-Jewish Hospital
First posted: 2010-02-01
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Percent Change in Mean Pulmonary Artery Pressure in the Whole Cohort.
timeFrame: Baseline and 60 minutes after drug administered
Secondary outcomes:
measure: Percent Change in Pulmonary Vascular Resistance in the Whole Cohort.
timeFrame: Baseline and 60 minutes after drug administered
measure: Percent Change in Cardiac Index.
timeFrame: Baseline and 60 minutes after drug administered
measure: Load Independent Index of Diastolic Filling.
timeFrame: Baseline and 60 minutes after drug administered
measure: Global Longitudinal Strain
timeFrame: Baseline and 60 minutes after drug administered
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Brian R. Lindman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.