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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Barry Borlaug, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01932606
First received: August 27, 2013
Last updated: February 15, 2016
Last verified: February 2016
  Purpose
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.

Condition Intervention Phase
Heart Disease
Heart Failure With Preserved Ejection Fraction
Exercise Intolerance
Pulmonary Hypertension
Drug: Nitrite
Drug: Saline Placebo for Nitrite
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Acute Effects of Inorganic Nitrite on Cardiovascular Hemodynamics in Heart Failure With Preserved Ejection Fraction

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Exercise Pulmonary Capillary Wedge Pressure (PCWP) [ Time Frame: during repeat exercise run, approximately 30 minutes after study drug administration ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change in Central Pressures After Study Drug (Resting) [ Time Frame: baseline, approximately 30 minutes after study drug administration ] [ Designated as safety issue: No ]
    Values are resting values after receiving study drug minus resting values before study drug (on the same day.)

  • Change in Heart Rate After Study Drug (Resting) [ Time Frame: baseline, approximately 30 minutes after study drug administration ] [ Designated as safety issue: No ]
    Values are resting values after receiving study drug minus resting values before study drug (on the same day.)

  • Change in Blood Pressure After Study Drug (Resting) [ Time Frame: baseline, approximately 30 minutes after study drug administration ] [ Designated as safety issue: No ]
    Values are resting values after receiving study drug minus resting values before study drug (on the same day.)

  • Change in Pulmonary Vascular Resistance (PVR) After Study Drug (Resting) [ Time Frame: baseline, approximately 30 minutes after study drug administration ] [ Designated as safety issue: No ]
    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.

  • Change in Pulmonary Artery (PA) Compliance After Study Drug (Resting) [ Time Frame: baseline, approximately 30 minutes after study drug administration ] [ Designated as safety issue: No ]
    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.

  • Change in Systemic Vascular Resistance (SVR) After Study Drug (Resting) [ Time Frame: baseline, approximately 30 minutes after study drug administration ] [ Designated as safety issue: No ]
    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.

  • Change in Left Ventricular Stroke Work (LVSW) After Study Drug (Resting) [ Time Frame: baseline, approximately 30 minutes after study drug administration ] [ Designated as safety issue: No ]
    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.

  • Change in Oxygen Consumption (VO_2) After Study Drug (Resting) [ Time Frame: baseline, approximately 30 minutes after study drug administration ] [ Designated as safety issue: No ]
    Values are resting values after receiving study drug minus resting values before study drug (on the same day.)

  • Change in Arteriovenous Oxygen Content Difference After Study Drug (Resting) [ Time Frame: baseline, approximately 30 minutes after study drug administration ] [ Designated as safety issue: No ]
    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.

  • Change in Cardiac Output After Study Drug (Resting) [ Time Frame: baseline, approximately 30 minutes after study drug administration ] [ Designated as safety issue: No ]
    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.

  • Change in Stroke Volume After Study Drug (Resting) [ Time Frame: baseline, approximately 30 minutes after study drug administration ] [ Designated as safety issue: No ]
    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.

  • Change in Central Pressures After Study Drug (Exercise) [ Time Frame: baseline, approximately 30 minutes after study drug administration ] [ Designated as safety issue: No ]
    Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.)

  • Change in Heart Rate After Study Drug (Exercise) [ Time Frame: baseline, approximately 30 minutes after study drug administration ] [ Designated as safety issue: No ]
    Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.)

  • Change in Blood Pressure After Study Drug (Exercise) [ Time Frame: baseline, approximately 30 minutes after study drug administration ] [ Designated as safety issue: No ]
    Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.)

  • Change in PVR After Study Drug (Exercise) [ Time Frame: baseline, approximately 30 minutes after study drug administration ] [ Designated as safety issue: No ]
    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.

  • Change in PA Compliance After Study Drug (Exercise) [ Time Frame: baseline, approximately 30 minutes after study drug administration ] [ Designated as safety issue: No ]
    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.

  • Change in SVR After Study Drug (Exercise) [ Time Frame: baseline, approximately 30 minutes after study drug administration ] [ Designated as safety issue: No ]
    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.

  • Change in LVSW After Study Drug (Exercise) [ Time Frame: baseline, approximately 30 minutes after study drug administration ] [ Designated as safety issue: No ]
    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.

  • Change in Oxygen Consumption (VO_2) After Study Drug (Exercise) [ Time Frame: baseline, approximately 30 minutes after study drug administration ] [ Designated as safety issue: No ]
    Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.)

  • Change in Arteriovenous Oxygen Difference After Study Drug (Exercise) [ Time Frame: baseline, approximately 30 minutes after study drug administration ] [ Designated as safety issue: No ]
    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.

  • Change in Cardiac Output After Study Drug (Exercise) [ Time Frame: baseline, approximately 30 minutes after study drug administration ] [ Designated as safety issue: No ]
    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.

  • Change in Stroke Volume After Study Drug (Exercise) [ Time Frame: baseline, approximately 30 minutes after study drug administration ] [ Designated as safety issue: No ]
    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.


Enrollment: 28
Study Start Date: August 2013
Study Completion Date: October 2014
Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).

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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01932606

Locations
United States, Minnesota
Mayo Clinic in Rochester
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Barry Borlaug
Investigators
Principal Investigator: Barry Borlaug, MD Mayo Clinic
  More Information

Publications:
Responsible Party: Barry Borlaug, M.D., Associate Professor of Medicine, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01932606     History of Changes
Other Study ID Numbers: 13-004077 
Study First Received: August 27, 2013
Results First Received: January 15, 2016
Last Updated: February 15, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Hypertension, Pulmonary
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on December 06, 2016