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

NCT ID: NCT01932606

Last Updated: 2016-03-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-31
• Study Completion Date: 2014-10-31

Brief 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.

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.

Conditions

Heart Disease; Heart Failure With Preserved Ejection Fraction; Exercise Intolerance; Pulmonary Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Nitrite

Study drug (NaNO\_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.

Group Type: EXPERIMENTAL

Nitrite

Intervention Type: DRUG

Study drug (NaNO\_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.

Saline

Saline Placebo for Nitrite will be infused for 5 minutes during the cardiac catheterization procedure.

Group Type: PLACEBO_COMPARATOR

Saline Placebo for Nitrite

Intervention Type: DRUG

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).

Interventions

Nitrite

Study drug (NaNO\_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.

Intervention Type: 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).

Intervention Type: DRUG

Eligibility 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

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

Sponsors

Barry Borlaug

OTHER

Sponsor Role: lead

Responsible Party

Barry Borlaug

M.D., Associate Professor of Medicine

Responsibility Role: SPONSOR_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, 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.

Reference Type: RESULT

PMID: 26449137 (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

13-004077

Identifier Type: -

Identifier Source: org_study_id