Acute Effects of Inorganic Nitrite on Cardiovascular Hemodynamics in Heart Failure With Preserved Ejection Fraction

Pulmonary Hypertension Clinical Trial

Official title:

Acute Effects of Inorganic Nitrite on Cardiovascular Hemodynamics in Heart Failure With Preserved Ejection Fraction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01932606
• Other study ID #: 13-004077
• Status: Completed
• Phase: Phase 2
• First received: August 27, 2013
• Last updated: February 15, 2016
• Start date: August 2013
• Est. completion date: October 2014

Study information

• Verified date: February 2016
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Heart failure with preserved ejection fraction (HFpEF) is a major public health problem that has no proven effective treatment. This study assessed the effects of acute nitrite administration on resting and exercise hemodynamics in patients with HFpEF.

Description:

Subjects were studied on their long-term medications in the post-absorptive state and supine position. Right heart catheterization was performed with simultaneous expired gas analysis at rest and during supine exercise at a 20 Watts workload for 5 minutes. After the first exercise phase (before any drug administration) and after return to steady-state baseline hemodynamic values, subjects were randomized. Study drug or placebo was infused for 5 minutes. After a 10 minute observation period, hemodynamic measurements were repeated at rest, followed by repeat supine exercise at a 20 Watts workload for 5 minutes, identical to the study's first phase. Arterial and venous blood samples and hemodynamic and expired gas data were acquired during each stage of the protocol.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Scheduled to undergo a cardiac catheterization procedure.

• Clinical symptoms of shortness of breath and fatigue

• Normal left ventricular ejection fraction (=50%)

• Elevated left ventricular filling pressures at cardiac catheterization (defined as resting pulmonary capillary wedge pressure (PCWP)>15 mmHg and/or PCWP=25 mmHg during exercise)

Exclusion Criteria:

• Systolic BP <120 mmHg

• Prior nitrate therapy (within previous 2 weeks)

• Glucose 6-phosphate dehydrogenase (G6PD) deficiency

• Other "non-HFpEF" specific causes of heart failure such as significant valvular disease (>moderate left-sided regurgitation, >mild stenosis), severe pulmonary disease, unstable coronary disease or coronary spasm, primary renal or hepatic disease, constrictive pericarditis, or infiltrative, restrictive, or hypertrophic cardiomyopathies

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Exercise Intolerance
• Heart Disease
• Heart Failure
• Heart Failure With Preserved Ejection Fraction
• Hypertension, Pulmonary
• Pulmonary Hypertension

Intervention

Drug:
• Nitrite
Study drug (NaNO_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.
• Saline Placebo for Nitrite
Normal saline placebo will be infused for 5 minutes during the cardiac catheterization procedure. Hemodynamics will then be measured at baseline after study drug infusion and again during low level exercise (20 Watts).

Locations

Country	Name	City	State
United States	Mayo Clinic in Rochester	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Barry Borlaug

Country where clinical trial is conducted

United States, 

References & Publications (1)

Borlaug BA, Koepp KE, Melenovsky V. Sodium Nitrite Improves Exercise Hemodynamics and Ventricular Performance in Heart Failure With Preserved Ejection Fraction. J Am Coll Cardiol. 2015 Oct 13;66(15):1672-82. doi: 10.1016/j.jacc.2015.07.067. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Exercise Pulmonary Capillary Wedge Pressure (PCWP)	Pulmonary capillary wedge pressure (PCWP) provides an indirect estimate of left atrial pressure (LAP). PCWP is the pressure measured by wedging a pulmonary catheter with an inflated balloon into a small pulmonary arterial branch.	during repeat exercise run, approximately 30 minutes after study drug administration	No
Secondary	Change in Central Pressures After Study Drug (Resting)	Values are resting values after receiving study drug minus resting values before study drug (on the same day.)	baseline, approximately 30 minutes after study drug administration	No
Secondary	Change in Heart Rate After Study Drug (Resting)	Values are resting values after receiving study drug minus resting values before study drug (on the same day.)	baseline, approximately 30 minutes after study drug administration	No
Secondary	Change in Blood Pressure After Study Drug (Resting)	Values are resting values after receiving study drug minus resting values before study drug (on the same day.)	baseline, approximately 30 minutes after study drug administration	No
Secondary	Change in Pulmonary Vascular Resistance (PVR) After Study Drug (Resting)	Values are resting values after receiving study drug minus resting values before study drug (on the same day.) Pulmonary Vascular Resistance (PVR) is the resistance to flow that must be overcome to push blood through the pulmonary vasculature. Acute and chronic lung disease can both cause an increase in PVR. Chronic PVR can lead to right sided heart failure.	baseline, approximately 30 minutes after study drug administration	No
Secondary	Change in Pulmonary Artery (PA) Compliance After Study Drug (Resting)	Values are resting values after receiving study drug minus resting values before study drug (on the same day.) Pulmonary artery compliance is an index of the elasticity of the blood vessel, an indication of arterial stiffness.	baseline, approximately 30 minutes after study drug administration	No
Secondary	Change in Systemic Vascular Resistance (SVR) After Study Drug (Resting)	Values are resting values after receiving study drug minus resting values before study drug (on the same day.) Systemic vascular resistance (SVR) refers to the resistance to blood flow offered by all of the systemic vasculature, excluding the pulmonary vasculature.	baseline, approximately 30 minutes after study drug administration	No
Secondary	Change in Left Ventricular Stroke Work (LVSW) After Study Drug (Resting)	Values are resting values after receiving study drug minus resting values before study drug (on the same day.) Stroke work refers to the work done by the ventricle to eject a volume of blood (i.e., stroke volume) into the aorta. Ventricular stroke work can be estimated as the product of stroke volume and mean aortic pressure during ejection.	baseline, approximately 30 minutes after study drug administration	No
Secondary	Change in Oxygen Consumption (VO_2) After Study Drug (Resting)	Values are resting values after receiving study drug minus resting values before study drug (on the same day.)	baseline, approximately 30 minutes after study drug administration	No
Secondary	Change in Arteriovenous Oxygen Content Difference After Study Drug (Resting)	Values are resting values after receiving study drug minus resting values before study drug (on the same day.) Arteriovenous oxygen difference is the difference in the oxygen content of the blood between the arterial blood and the venous blood. It is an indication of how much oxygen is removed from the blood in capillaries as the blood circulates in the body.	baseline, approximately 30 minutes after study drug administration	No
Secondary	Change in Cardiac Output After Study Drug (Resting)	Values are resting values after receiving study drug minus resting values before study drug (on the same day.) The volume of blood pumped per minute by each ventricle of the heart. Cardiac output is equal to the stroke volume (the amount of blood pumped from a ventricle in a single heartbeat) times the heart rate.	baseline, approximately 30 minutes after study drug administration	No
Secondary	Change in Stroke Volume After Study Drug (Resting)	Values are resting values after receiving study drug minus resting values before study drug (on the same day.) Stroke volume is the amount of blood pumped out of the heart (left ventricle - to the body) during each contraction.	baseline, approximately 30 minutes after study drug administration	No
Secondary	Change in Central Pressures After Study Drug (Exercise)	Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.)	baseline, approximately 30 minutes after study drug administration	No
Secondary	Change in Heart Rate After Study Drug (Exercise)	Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.)	baseline, approximately 30 minutes after study drug administration	No
Secondary	Change in Blood Pressure After Study Drug (Exercise)	Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.)	baseline, approximately 30 minutes after study drug administration	No
Secondary	Change in PVR After Study Drug (Exercise)	Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.) Pulmonary Vascular Resistance (PVR) is the resistance to flow that must be overcome to push blood through the pulmonary vasculature. Acute and chronic lung disease can both cause an increase in PVR. Chronic PVR can lead to right sided heart failure.	baseline, approximately 30 minutes after study drug administration	No
Secondary	Change in PA Compliance After Study Drug (Exercise)	Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.) Pulmonary artery compliance is an index of the elasticity of the blood vessel, an indication of arterial stiffness.	baseline, approximately 30 minutes after study drug administration	No
Secondary	Change in SVR After Study Drug (Exercise)	Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.) Systemic vascular resistance (SVR) refers to the resistance to blood flow offered by all of the systemic vasculature, excluding the pulmonary vasculature.	baseline, approximately 30 minutes after study drug administration	No
Secondary	Change in LVSW After Study Drug (Exercise)	Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.) Stroke work refers to the work done by the ventricle to eject a volume of blood (i.e., stroke volume) into the aorta. Ventricular stroke work can be estimated as the product of stroke volume and mean aortic pressure during ejection.	baseline, approximately 30 minutes after study drug administration	No
Secondary	Change in Oxygen Consumption (VO_2) After Study Drug (Exercise)	Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.)	baseline, approximately 30 minutes after study drug administration	No
Secondary	Change in Arteriovenous Oxygen Difference After Study Drug (Exercise)	Arteriovenous oxygen difference is the difference in the oxygen content of the blood between the arterial blood and the venous blood. It is an indication of how much oxygen is removed from the blood in capillaries as the blood circulates in the body.	baseline, approximately 30 minutes after study drug administration	No
Secondary	Change in Cardiac Output After Study Drug (Exercise)	Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.) Cardiac output is equal to the stroke volume (the amount of blood pumped from a ventricle in a single heartbeat) times the heart rate.	baseline, approximately 30 minutes after study drug administration	No
Secondary	Change in Stroke Volume After Study Drug (Exercise)	Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.) Stroke volume is the amount of blood pumped out of the heart (left ventricle - to the body) during each contraction.	baseline, approximately 30 minutes after study drug administration	No