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

February 15, 2016 updated by: Barry Borlaug
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

28

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic in Rochester

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Nitrite
Study drug (NaNO_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.
Drug: Nitrite
Study drug (NaNO_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.
Placebo Comparator: Saline
Saline Placebo for Nitrite will be infused for 5 minutes during the cardiac catheterization procedure.
Drug: 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Exercise Pulmonary Capillary Wedge Pressure (PCWP)
Time Frame: during repeat exercise run, approximately 30 minutes after study drug administration
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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Central Pressures After Study Drug (Resting)
Time Frame: baseline, approximately 30 minutes after study drug administration
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
Change in Heart Rate After Study Drug (Resting)
Time Frame: baseline, approximately 30 minutes after study drug administration
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
Change in Blood Pressure After Study Drug (Resting)
Time Frame: baseline, approximately 30 minutes after study drug administration
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
Change in Pulmonary Vascular Resistance (PVR) After Study Drug (Resting)
Time Frame: baseline, approximately 30 minutes after study drug administration
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
Change in Pulmonary Artery (PA) Compliance After Study Drug (Resting)
Time Frame: baseline, approximately 30 minutes after study drug administration
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
Change in Systemic Vascular Resistance (SVR) After Study Drug (Resting)
Time Frame: baseline, approximately 30 minutes after study drug administration
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
Change in Left Ventricular Stroke Work (LVSW) After Study Drug (Resting)
Time Frame: baseline, approximately 30 minutes after study drug administration
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
Change in Oxygen Consumption (VO_2) After Study Drug (Resting)
Time Frame: baseline, approximately 30 minutes after study drug administration
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
Change in Arteriovenous Oxygen Content Difference After Study Drug (Resting)
Time Frame: baseline, approximately 30 minutes after study drug administration
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
Change in Cardiac Output After Study Drug (Resting)
Time Frame: baseline, approximately 30 minutes after study drug administration
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
Change in Stroke Volume After Study Drug (Resting)
Time Frame: baseline, approximately 30 minutes after study drug administration
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
Change in Central Pressures After Study Drug (Exercise)
Time Frame: baseline, approximately 30 minutes after study drug administration
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
Change in Heart Rate After Study Drug (Exercise)
Time Frame: baseline, approximately 30 minutes after study drug administration
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
Change in Blood Pressure After Study Drug (Exercise)
Time Frame: baseline, approximately 30 minutes after study drug administration
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
Change in PVR After Study Drug (Exercise)
Time Frame: baseline, approximately 30 minutes after study drug administration
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
Change in PA Compliance After Study Drug (Exercise)
Time Frame: baseline, approximately 30 minutes after study drug administration
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
Change in SVR After Study Drug (Exercise)
Time Frame: baseline, approximately 30 minutes after study drug administration
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
Change in LVSW After Study Drug (Exercise)
Time Frame: baseline, approximately 30 minutes after study drug administration
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
Change in Oxygen Consumption (VO_2) After Study Drug (Exercise)
Time Frame: baseline, approximately 30 minutes after study drug administration
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
Change in Arteriovenous Oxygen Difference After Study Drug (Exercise)
Time Frame: baseline, approximately 30 minutes after study drug administration
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
Change in Cardiac Output After Study Drug (Exercise)
Time Frame: baseline, approximately 30 minutes after study drug administration
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
Change in Stroke Volume After Study Drug (Exercise)
Time Frame: baseline, approximately 30 minutes after study drug administration
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Barry Borlaug

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2013

Primary Completion (Actual)

October 1, 2014

Study Completion (Actual)

October 1, 2014

Study Registration Dates

First Submitted

August 27, 2013

First Submitted That Met QC Criteria

August 29, 2013

First Posted (Estimate)

August 30, 2013

Study Record Updates

Last Update Posted (Estimate)

March 14, 2016

Last Update Submitted That Met QC Criteria

February 15, 2016

Last Verified

February 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 13-004077

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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