Acute Hemodynamic Effects of Sildenafil in Patients With Severe Aortic Stenosis
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Aortic Stenosis |
Drug: Sildenafil |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Acute Hemodynamic Effects of Sildenafil in Patients With Severe Aortic Stenosis |
- Change in mean pulmonary artery pressure in the whole cohort and in those with pulmonary hypertension on baseline hemodynamics. [ Time Frame: 60 minutes after drug administered ] [ Designated as safety issue: No ]
- Change in pulmonary vascular resistance in the whole cohort and in those with an elevated pulmonary vascular resistance on baseline hemodynamics. [ Time Frame: 60 minutes after drug administered ] [ Designated as safety issue: No ]
- Change in cardiac output/index. [ Time Frame: 60 minutes after drug administered ] [ Designated as safety issue: No ]
- Change in echocardiographic measures of diastolic function. [ Time Frame: 60 minutes after drug administered ] [ Designated as safety issue: No ]
- Change in echocardiographic measures of systolic function and mechanics. [ Time Frame: 60 minutes after drug administered ] [ Designated as safety issue: No ]
- Safety and tolerability at both doses (40mg and 80mg). [ Time Frame: 3 hours after drug administration ] [ Designated as safety issue: Yes ]
| Enrollment: | 20 |
| Study Start Date: | January 2010 |
| Study Completion Date: | October 2011 |
| Primary Completion Date: | September 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 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.
|
Drug: Sildenafil
Single oral dose of 40mg or 80mg of Sildenafil
Other Names:
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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| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| United States, Missouri | |
| Washington University School of Medicine | |
| St. Louis, Missouri, United States, 63110 | |
| Principal Investigator: | Brian R. Lindman, MD | Washington University School of Medicine |
More Information
Publications:
| Responsible Party: | Brian Lindman, MD, Assistant Professor of Medicine, Washington University School of Medicine |
| ClinicalTrials.gov Identifier: | NCT01060020 History of Changes |
| Other Study ID Numbers: | 09-1780 |
| Study First Received: | January 28, 2010 |
| Last Updated: | December 18, 2012 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by Washington University School of Medicine:
|
Aortic valve stenosis Sildenafil Phosphodiesterase inhibitors Hypertension, Pulmonary |
Additional relevant MeSH terms:
|
Aortic Valve Stenosis Constriction, Pathologic Heart Valve Diseases Heart Diseases Cardiovascular Diseases Ventricular Outflow Obstruction Pathological Conditions, Anatomical Phosphodiesterase Inhibitors |
Sildenafil Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Vasodilator Agents Cardiovascular Agents Therapeutic Uses Phosphodiesterase 5 Inhibitors |
ClinicalTrials.gov processed this record on May 16, 2013