Acute Hemodynamic Effects of Sildenafil in Patients With Severe Aortic Stenosis

Aortic Stenosis Clinical Trial

Official title:

Acute Hemodynamic Effects of Sildenafil in Patients With Severe Aortic Stenosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01060020
• Other study ID #: 09-1780
• Status: Completed
• Phase: Phase 4
• First received: January 28, 2010
• Last updated: April 16, 2018
• Start date: January 2010
• Est. completion date: October 2011

Study information

• Verified date: April 2018
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: October 2011
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Aortic Stenosis
• Aortic Valve Stenosis
• Constriction, Pathologic

Intervention

Drug:
• Sildenafil
Single oral dose of 40mg or 80mg of Sildenafil

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Washington University School of Medicine	Barnes-Jewish Hospital

Country where clinical trial is conducted

United States, 

References & 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 symp — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change in Mean Pulmonary Artery Pressure in the Whole Cohort.		Baseline and 60 minutes after drug administered
Secondary	Percent Change in Pulmonary Vascular Resistance in the Whole Cohort.		Baseline and 60 minutes after drug administered
Secondary	Percent Change in Cardiac Index.	Cardiac index is cardiac output divided by body surface area.	Baseline and 60 minutes after drug administered
Secondary	Load Independent Index of Diastolic Filling.	Measurements of the load independent index of diastolic filling were made with the parameterized diastolic filling formalism as previously described and validated with the use of transmitral Doppler E waves recorded during different respiratory states (regular breathing and held expiration and inspiration).	Baseline and 60 minutes after drug administered
Secondary	Global Longitudinal Strain	Global longitudinal strain was measured at baseline and 60 minutes after drug administration.	Baseline and 60 minutes after drug administered