Acute Hemodynamic Effects of Sildenafil in Patients With Severe Aortic Stenosis

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01060020

Enrollment

Registered

2010-02-01

Start date

2010-01-31

Completion date

2011-10-31

Last updated

2018-04-25

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Aortic Stenosis

Keywords

Aortic valve stenosis, Sildenafil, Phosphodiesterase inhibitors, Hypertension, Pulmonary

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.

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.

Interventions

DRUGSildenafil

Single oral dose of 40mg or 80mg of Sildenafil

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame
Percent Change in Mean Pulmonary Artery Pressure in the Whole Cohort.	Baseline and 60 minutes after drug administered

Secondary

Measure	Time frame	Description
Percent Change in Pulmonary Vascular Resistance in the Whole Cohort.	Baseline and 60 minutes after drug administered	—
Percent Change in Cardiac Index.	Baseline and 60 minutes after drug administered	Cardiac index is cardiac output divided by body surface area.
Load Independent Index of Diastolic Filling.	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).
Global Longitudinal Strain	Baseline and 60 minutes after drug administered	Global longitudinal strain was measured at baseline and 60 minutes after drug administration.

Countries

United States

Participant flow

Pre-assignment details

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.

Participants by arm

Arm	Count
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	20
Total	20

Baseline characteristics

Characteristic	Sildenafil 40mg or 80mg
Age, Continuous	86 years STANDARD_DEVIATION 10
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	1 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	19 Participants
Sex: Female, Male Female	10 Participants
Sex: Female, Male Male	10 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	1 / 20
serious Total, serious adverse events	3 / 20