Clinical trial NCT01932606: Acute Effects of Inorganic Nitrite on Cardiovascular Hemodynamics in Heart Failure With Preserved Ejection Fraction
Official title: Acute Effects of Inorganic Nitrite on Cardiovascular Hemodynamics in Heart Failure With Preserved Ejection Fraction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Disease
Heart Failure With Preserved Ejection Fraction
Exercise Intolerance
Pulmonary Hypertension
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2013-08-30
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Exercise Pulmonary Capillary Wedge Pressure (PCWP)
timeFrame: during repeat exercise run, approximately 30 minutes after study drug administration
Secondary outcomes:
measure: Change in Central Pressures After Study Drug (Resting)
timeFrame: baseline, approximately 30 minutes after study drug administration
measure: Change in Heart Rate After Study Drug (Resting)
timeFrame: baseline, approximately 30 minutes after study drug administration
measure: Change in Blood Pressure After Study Drug (Resting)
timeFrame: baseline, approximately 30 minutes after study drug administration
measure: Change in Pulmonary Vascular Resistance (PVR) After Study Drug (Resting)
timeFrame: baseline, approximately 30 minutes after study drug administration
measure: Change in Pulmonary Artery (PA) Compliance After Study Drug (Resting)
timeFrame: baseline, approximately 30 minutes after study drug administration
measure: Change in Systemic Vascular Resistance (SVR) After Study Drug (Resting)
timeFrame: baseline, approximately 30 minutes after study drug administration
measure: Change in Left Ventricular Stroke Work (LVSW) After Study Drug (Resting)
timeFrame: baseline, approximately 30 minutes after study drug administration
measure: Change in Oxygen Consumption (VO_2) After Study Drug (Resting)
timeFrame: baseline, approximately 30 minutes after study drug administration
measure: Change in Arteriovenous Oxygen Content Difference After Study Drug (Resting)
timeFrame: baseline, approximately 30 minutes after study drug administration
measure: Change in Cardiac Output After Study Drug (Resting)
timeFrame: baseline, approximately 30 minutes after study drug administration
measure: Change in Stroke Volume After Study Drug (Resting)
timeFrame: baseline, approximately 30 minutes after study drug administration
measure: Change in Central Pressures After Study Drug (Exercise)
timeFrame: baseline, approximately 30 minutes after study drug administration
measure: Change in Heart Rate After Study Drug (Exercise)
timeFrame: baseline, approximately 30 minutes after study drug administration
measure: Change in Blood Pressure After Study Drug (Exercise)
timeFrame: baseline, approximately 30 minutes after study drug administration
measure: Change in PVR After Study Drug (Exercise)
timeFrame: baseline, approximately 30 minutes after study drug administration
measure: Change in PA Compliance After Study Drug (Exercise)
timeFrame: baseline, approximately 30 minutes after study drug administration
measure: Change in SVR After Study Drug (Exercise)
timeFrame: baseline, approximately 30 minutes after study drug administration
measure: Change in LVSW After Study Drug (Exercise)
timeFrame: baseline, approximately 30 minutes after study drug administration
measure: Change in Oxygen Consumption (VO_2) After Study Drug (Exercise)
timeFrame: baseline, approximately 30 minutes after study drug administration
measure: Change in Arteriovenous Oxygen Difference After Study Drug (Exercise)
timeFrame: baseline, approximately 30 minutes after study drug administration
measure: Change in Cardiac Output After Study Drug (Exercise)
timeFrame: baseline, approximately 30 minutes after study drug administration
measure: Change in Stroke Volume After Study Drug (Exercise)
timeFrame: baseline, approximately 30 minutes after study drug administration
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Barry Borlaug, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.