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Acute Hemodynamic Effects of Sildenafil in Patients With Severe Aortic Stenosis

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ClinicalTrials.gov Identifier: NCT01060020
Recruitment Status : Completed
First Posted : February 1, 2010
Results First Posted : April 25, 2018
Last Update Posted : April 25, 2018
Sponsor:
Collaborator:
Barnes-Jewish Hospital
Information provided by (Responsible Party):
Brian Lindman, MD, Washington University School of Medicine

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.

Condition or disease Intervention/treatment Phase
Aortic Stenosis Drug: Sildenafil Phase 4

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Acute Hemodynamic Effects of Sildenafil in Patients With Severe Aortic Stenosis
Study Start Date : January 2010
Actual Primary Completion Date : September 2011
Actual Study Completion Date : October 2011


Arm Intervention/treatment
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:
  • Revatio
  • Viagra




Primary Outcome Measures :
  1. Percent Change in Mean Pulmonary Artery Pressure in the Whole Cohort. [ Time Frame: Baseline and 60 minutes after drug administered ]

Secondary Outcome Measures :
  1. Percent Change in Pulmonary Vascular Resistance in the Whole Cohort. [ Time Frame: Baseline and 60 minutes after drug administered ]
  2. Percent Change in Cardiac Index. [ Time Frame: Baseline and 60 minutes after drug administered ]
    Cardiac index is cardiac output divided by body surface area.

  3. Load Independent Index of Diastolic Filling. [ Time Frame: Baseline and 60 minutes after drug administered ]
    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).

  4. Global Longitudinal Strain [ Time Frame: Baseline and 60 minutes after drug administered ]
    Global longitudinal strain was measured at baseline and 60 minutes after drug administration.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01060020


Locations
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Barnes-Jewish Hospital
Investigators
Principal Investigator: Brian R. Lindman, MD Washington University School of Medicine

Publications of Results:
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
First Posted: February 1, 2010    Key Record Dates
Results First Posted: April 25, 2018
Last Update Posted: April 25, 2018
Last Verified: April 2018

Keywords provided by Brian Lindman, MD, Washington University School of Medicine:
Aortic valve stenosis
Sildenafil
Phosphodiesterase inhibitors
Hypertension, Pulmonary

Additional relevant MeSH terms:
Constriction, Pathologic
Aortic Valve Stenosis
Pathological Conditions, Anatomical
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases
Ventricular Outflow Obstruction
Sildenafil Citrate
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents