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Inhaled Sodium Nitrite on Heart Failure With Preserved Ejection Fraction

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02262078
Recruitment Status : Completed
First Posted : October 10, 2014
Results First Posted : January 19, 2017
Last Update Posted : August 29, 2017
Aires Pharmaceuticals, Inc.
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Barry Borlaug, Mayo Clinic

Brief Summary:
Heart failure with preserved ejection fraction (HFpEF) is a major public health problem that has no proven effective treatment. This study will assess the effects of nebulized inhaled nitrite administration on resting and exercise hemodynamics in patients with HFpEF referred to the catheterization lab.

Condition or disease Intervention/treatment Phase
Heart Failure Drug: Sodium Nitrite Inhalation Solution Other: Placebo Phase 2

Detailed Description:

Patients referred to the cardiac catheterization laboratory for invasive exercise stress testing will be prospectively recruited. Standard right heart catheterization using high fidelity micromanometers (Millar Instruments) will be performed at rest and during supine exercise with simultaneous expired gas analysis (Medgraphics) as is the investigator's current practice. The protocol is rest-passive leg elevation--20 Watts exercise x 5 minutes, and then graded workload increases in 10Watt increments (3 minute stages) to exhaustion. Hemodynamic, arterial and mixed venous blood gas and expired gas data are acquired at rest, during each exercise stage and at peak exercise. Venous blood samples will be obtained at rest and at peak exercise. Perceived symptoms of dyspnea and fatigue will be quantified using the Borg dyspnea and effort scores at each stage of exercise.

After the initial exercise study and hemodynamics have returned to baseline, previously prepared study drug (normal saline placebo or Sodium Nitrite Inhalation Solution (AIR001) 90mg placed into the medication chamber) will be nebulized utilizing the Aerogen Solo-Idehaler over 10-15 minutes. After a 15 minute observation period post completion of nebulization, resting hemodynamic and expired gas data will be acquired exactly as in the initial run. Subjects will then repeat the leg elevation-20 Watt x 5 minutes exercise phase. Blood samples will be again obtained at rest and with exercise. Subjects will repeat exercise only at the 20 Watt stage, rather repeating the entire study. This is done to increase the feasibility and shorten the time of the case. The investigators have previously observed that the vast majority (>85%) of the elevation in cardiac filling pressures and reduction in venous oxygen content in people with HFpEF occurs at the low 20 Watt workload, so repeating exercise hemodynamic assessment at this load should be sufficient to detect any clinically meaningful treatment effect.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Diagnostic
Official Title: Acute Effects of Inhaled Sodium Nitrite on Cardiovascular Hemodynamics in Heart Failure With Preserved Ejection Fraction
Study Start Date : October 2014
Actual Primary Completion Date : December 2015
Actual Study Completion Date : December 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arm Intervention/treatment
Placebo Comparator: Placebo (Saline)
Participants receive normal saline, administered by inhalation over 10-15 minutes, using a nebulizer
Other: Placebo
Normal saline will be administered (by inhalation) to participants prior to exercise.
Other Name: Saline

Experimental: Sodium Nitrite
Participants receive Sodium Nitrite inhalation solution, administered by inhalation over 10-15 minutes, using a nebulizer
Drug: Sodium Nitrite Inhalation Solution
90mg of (nebulized) inhaled sodium nitrite will be administered (by inhalation) to participants prior to exercise.
Other Name: AIR001, NaNO2, Sodium Nitrite

Primary Outcome Measures :
  1. Change in Pulmonary Capillary Wedge Pressure During Exercise [ Time Frame: Baseline, after study drug dosing, approximately 4 minutes after starting exercise ]
    Pulmonary capillary wedge pressure is a measure of cardiac filling pressure, measured in millimeters of mercury (mmHg)

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Heart Failure with preserved Ejection Fraction (HFpEF) is defined by clinical symptoms of dyspnea and fatigue
  • Normal left ventricular ejection fraction (>/=50%)
  • And elevated Left Ventricular (LV) filling pressure at cardiac catheterization (defined as resting Pulmonary Capillary Wedge Pressure (PCWP)>15 mmHg and/or PCWP >/=25 mmHg during exercise).

Exclusion Criteria:

  • Systolic Blood Pressure <120 mmHg (during catheterization)
  • 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 (end stage renal failure/on dialysis or clinical diagnosis of hepatitis or hepatic cirrhosis)
  • Constrictive pericarditis, or infiltrative, restrictive, or hypertrophic cardiomyopathies
  • Pregnant

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02262078

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United States, Minnesota
Mayo Clinic in Rochester
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Aires Pharmaceuticals, Inc.
National Heart, Lung, and Blood Institute (NHLBI)
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Principal Investigator: Barry Borlaug, MD Mayo Clinic
Publications of Results:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Barry Borlaug, Principal Investigator, Mayo Clinic Identifier: NCT02262078    
Other Study ID Numbers: 14-005091
R01HL128526 ( U.S. NIH Grant/Contract )
U10HL110262 ( U.S. NIH Grant/Contract )
First Posted: October 10, 2014    Key Record Dates
Results First Posted: January 19, 2017
Last Update Posted: August 29, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Barry Borlaug, Mayo Clinic:
Preserved Ejection Fraction
Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardiovascular Diseases