Acute Hemodynamic Effects of Sildenafil in Patients With Severe Aortic Stenosis

This study has been completed.
Sponsor:
Collaborator:
Barnes-Jewish Hospital
Information provided by (Responsible Party):
Brian Lindman, MD, Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01060020
First received: January 28, 2010
Last updated: December 18, 2012
Last verified: December 2012
  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

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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:
  • Revatio
  • Viagra

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
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01060020

Locations
United States, Missouri
Washington University School of Medicine
St. 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
  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
Pathological Conditions, Anatomical
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases
Ventricular Outflow Obstruction
Sildenafil
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents

ClinicalTrials.gov processed this record on September 16, 2014