Acute Hemodynamic Effects of Sildenafil in Patients With Severe Aortic Stenosis

NCT ID: NCT01060020

Last Updated: 2018-04-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-31
• Study Completion Date: 2011-10-31

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.

Conditions

Aortic Stenosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sildenafil 40mg or 80mg

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.

Group Type: EXPERIMENTAL

Sildenafil

Intervention Type: DRUG

Single oral dose of 40mg or 80mg of Sildenafil

Interventions

Sildenafil

Single oral dose of 40mg or 80mg of Sildenafil

Intervention Type: DRUG

Other Intervention Names

Revatio; Viagra

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Barnes-Jewish Hospital

OTHER

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Brian Lindman, MD

Assistant Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Brian R. Lindman, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 22447809 (View on PubMed)

Other Identifiers

09-1780

Identifier Type: -

Identifier Source: org_study_id