Inhaled Sodium Nitrite on Heart Failure With Preserved Ejection Fraction

NCT ID: NCT02262078

Last Updated: 2017-08-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-31
• Study Completion Date: 2015-12-31

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.

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.

Conditions

Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo (Saline)

Participants receive normal saline, administered by inhalation over 10-15 minutes, using a nebulizer

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Normal saline will be administered (by inhalation) to participants prior to exercise.

Sodium Nitrite

Participants receive Sodium Nitrite inhalation solution, administered by inhalation over 10-15 minutes, using a nebulizer

Group Type: EXPERIMENTAL

Sodium Nitrite Inhalation Solution

Intervention Type: DRUG

90mg of (nebulized) inhaled sodium nitrite will be administered (by inhalation) to participants prior to exercise.

Interventions

Sodium Nitrite Inhalation Solution

90mg of (nebulized) inhaled sodium nitrite will be administered (by inhalation) to participants prior to exercise.

Intervention Type: DRUG

Placebo

Normal saline will be administered (by inhalation) to participants prior to exercise.

Intervention Type: OTHER

Other Intervention Names

AIR001, NaNO2, Sodium Nitrite; Saline

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Aires Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Barry Borlaug

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Barry Borlaug, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Countries

United States

References

Borlaug BA, Melenovsky V, Koepp KE. Inhaled Sodium Nitrite Improves Rest and Exercise Hemodynamics in Heart Failure With Preserved Ejection Fraction. Circ Res. 2016 Sep 16;119(7):880-6. doi: 10.1161/CIRCRESAHA.116.309184. Epub 2016 Jul 25.

Reference Type: RESULT

PMID: 27458234 (View on PubMed)

Reddy YNV, Stewart GM, Obokata M, Koepp KE, Borlaug BA. Peripheral and pulmonary effects of inorganic nitrite during exercise in heart failure with preserved ejection fraction. Eur J Heart Fail. 2021 May;23(5):814-823. doi: 10.1002/ejhf.2093. Epub 2021 Feb 1.

Reference Type: DERIVED

PMID: 33421267 (View on PubMed)

Other Identifiers

R01HL128526

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HL110262

Identifier Type: NIH

Identifier Source: secondary_id

View Link

14-005091

Identifier Type: -

Identifier Source: org_study_id