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| Name | Class |
|---|---|
| Barnes-Jewish Hospital | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sildenafil 40mg or 80mg | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sildenafil | Drug | Single oral dose of 40mg or 80mg of Sildenafil |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change in Mean Pulmonary Artery Pressure in the Whole Cohort. | Baseline and 60 minutes after drug administered |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change in Pulmonary Vascular Resistance in the Whole Cohort. | Baseline and 60 minutes after drug administered | |
| Percent Change in Cardiac Index. | Cardiac index is cardiac output divided by body surface area. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Brian R. Lindman, MD | Washington University School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22447809 | Result | 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. |
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Participants stratified according to ejection fraction and randomized to either Sildenafil 40mg and 80mg Groups were combined into a single Arm/Group for analysis as pre-specified in the study protocol.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. Sildenafil: Single oral dose of 40mg or 80mg of Sildenafil |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. Sildenafil: Single oral dose of 40mg or 80mg of Sildenafil |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percent Change in Mean Pulmonary Artery Pressure in the Whole Cohort. | Posted | Median | Inter-Quartile Range | percent change | Baseline and 60 minutes after drug administered |
|
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. Sildenafil: Single oral dose of 40mg or 80mg of Sildenafil |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypotension | Cardiac disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| hypertensive emergency | Cardiac disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Brian R. Lindman, MD, Assistant Professor of Medicine | Washington University School of Medicine | 314-747-3617 | brlindman@wustl.edu |
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| ID | Term |
|---|---|
| D001024 | Aortic Valve Stenosis |
| D006976 | Hypertension, Pulmonary |
| ID | Term |
|---|---|
| D000082862 | Aortic Valve Disease |
| D006349 | Heart Valve Diseases |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D000068677 | Sildenafil Citrate |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D013450 | Sulfones |
| D013457 |
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| Baseline and 60 minutes after drug administered |
| 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 |
| Global Longitudinal Strain | Global longitudinal strain was measured at baseline and 60 minutes after drug administration. | Baseline and 60 minutes after drug administered |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
|
| Secondary | Percent Change in Pulmonary Vascular Resistance in the Whole Cohort. | Posted | Median | Inter-Quartile Range | percent change | Baseline and 60 minutes after drug administered |
|
|
|
| Secondary | Percent Change in Cardiac Index. | Cardiac index is cardiac output divided by body surface area. | Posted | Median | Inter-Quartile Range | percent change | 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). | Posted | Mean | Standard Deviation | unitless | Baseline and 60 minutes after drug administered |
|
|
|
| Secondary | Global Longitudinal Strain | Global longitudinal strain was measured at baseline and 60 minutes after drug administration. | Posted | Mean | Standard Deviation | percent | Baseline and 60 minutes after drug administered |
|
|
|
| 3 |
| 20 |
| 1 |
| 20 |
| SVT | Cardiac disorders | Systematic Assessment |
|
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| D014694 |
| Ventricular Outflow Obstruction |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D006973 | Hypertension |
| D014652 | Vascular Diseases |
| Sulfur Compounds |
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |