Inhaled Sodium Nitrite on Heart Failure With Preserved Ejection Fraction

July 31, 2017 updated by: Barry Borlaug, Mayo Clinic

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

26

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic in Rochester

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • AIR001, NaNO2, Sodium Nitrite

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
Baseline, after study drug dosing, approximately 4 minutes after starting exercise

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mayo Clinic

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)
Aires Pharmaceuticals, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2014

Primary Completion (Actual)

December 1, 2015

Study Completion (Actual)

December 1, 2015

Study Registration Dates

First Submitted

September 30, 2014

First Submitted That Met QC Criteria

October 7, 2014

First Posted (Estimate)

October 10, 2014

Study Record Updates

Last Update Posted (Actual)

August 29, 2017

Last Update Submitted That Met QC Criteria

July 31, 2017

Last Verified

July 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 14-005091
  • R01HL128526 (U.S. NIH Grant/Contract)
  • U10HL110262 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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