Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Inhaled Beta-adrenergic Agonists to Treat Pulmonary Vascular Disease in Heart Failure With Preserved EF (BEAT HFpEF): A Randomized Controlled Trial (BEAT HFpEF)

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.
ClinicalTrials.gov Identifier: NCT02885636
Recruitment Status : Completed
First Posted : August 31, 2016
Results First Posted : February 5, 2019
Last Update Posted : February 22, 2019
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Barry Borlaug, Mayo Clinic

Brief Summary:

The enormous and rapidly growing burden of Heart Failure with Preserved Ejection Fraction (HFpEF) has led to a need to understand the pathogenesis and treatment options for this morbid disease. Recent research from the investigator's group and others have shown that pulmonary hypertension (PH) is highly prevalent in HFpEF, and right ventricular (RV) dysfunction is present in both early and advanced stages of HFpEF.

These abnormalities in the RV and pulmonary vasculature are coupled with limitations in pulmonary vasodilation during exercise. There are no therapies directly targeted at the pulmonary vasculature that have been clearly shown to be effective in HFpEF. A recent study by Mayo Clinic Investigators has demonstrated pulmonary vasodilation with dobutamine (a beta 2 agonist) in HFpEF. As an intravenous therapy, this is not feasible for outpatient use.

In the proposed randomized, placebo-controlled double blinded trial, the investigators seek to evaluate whether the commonly used inhaled bronchodilator albuterol (a beta 2 agonist), administered through a high-efficiency nebulizer device that achieves true alveolar drug delivery, improves pulmonary vascular resistance (PVR) at rest and during exercise in patients with HFpEF as compared to placebo. This has the potential to lead to a simple cost effective intervention to improve symptoms in HFpEF, and potentially be tested in other World Health Organization (WHO) Pulmonary Hypertension groups. PVR is an excellent surrogate marker for pulmonary vasodilation and has been used in previous early trials of PH therapy.


Condition or disease Intervention/treatment Phase
Congestive Heart Failure Heart Failure, Left-Sided Left-Sided Heart Failure Drug: Albuterol Other: Saline placebo Phase 3

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Inhaled Beta-adrenergic Agonists to Treat Pulmonary Vascular Disease in Heart Failure With Preserved EF (BEAT HFpEF): A Randomized Controlled Trial
Study Start Date : September 2016
Actual Primary Completion Date : September 2017
Actual Study Completion Date : September 2017


Arm Intervention/treatment
Experimental: Inhaled albuterol
2.5 mg inhaled albuterol through a high efficiency nebulizer -single dose
Drug: Albuterol

: Experimental: Inhaled albuterol

2.5 mg inhaled albuterol through a high efficiency nebulizer as a single dose

Other Name: Proventil, AccuNeb, Proair, Ventolin, and Vospire

Placebo Comparator: Inhaled saline placebo
Inhaled saline through a high efficiency nebulizer -single dose
Other: Saline placebo
Saline inhaled through a nebulizer as a single dose




Primary Outcome Measures :
  1. Change in 20 Watt Exercise Pulmonary Vascular Resistance (PVR) [ Time Frame: Baseline, 10 minutes after intervention during exercise ]
    The exercise PVR at 20 Watts after study drug relative to the exercise PVR at 20 Watts in the initial assessment prior to study drug. This measurement is made by subtracting pulmonary capillary wedge pressure from the mean pulmonary arterial pressure and dividing by cardiac output in liters per minute and reported as wood units. A decrease in PVR measured by wood units would be considered a favorable response.


Secondary Outcome Measures :
  1. Change in Resting Pulmonary Vascular Resistance [ Time Frame: Baseline, 10 minutes after intervention ]
    The resting PVR after study drug relative to the resting PVR in the initial assessment prior to study drug. This measurement is made by subtracting pulmonary capillary wedge pressure from the mean pulmonary arterial pressure and dividing by cardiac output in liters per minute and reported as wood units.

  2. Change in Exercise Pulmonary Capillary Wedge Pressure (PCWP) [ Time Frame: Baseline, 10 minutes after intervention during exercise ]
    Pulmonary capillary wedge pressure was measured using a high-fidelity micromanometer advanced through the lumen of a fluid-filled catheter. PCWP position was confirmed by appearance on fluoroscopy, characteristic pressure waveforms, and oximetry.

  3. Change in Resting Pulmonary Capillary Wedge Pressure (PCWP) [ Time Frame: Baseline, 10 minutes after intervention ]
    Pulmonary capillary wedge pressure was measured using a high-fidelity micromanometer advanced through the lumen of a fluid-filled catheter. PCWP position was confirmed by appearance on fluoroscopy, characteristic pressure waveforms, and oximetry.

  4. Change in Exercise Pulmonary Artery Compliance [ Time Frame: Baseline, 10 minutes after intervention during exercise ]
    Pulmonary artery compliance was calculated as the ratio of stroke volume/pulmonary artery pulse pressure.

  5. Change in Resting Pulmonary Artery Compliance [ Time Frame: Baseline, 10 minutes after intervention ]
    Pulmonary artery compliance was calculated as the ratio of stroke volume/pulmonary artery pulse pressure.

  6. Change in Exercise Pulmonary Artery Pressure [ Time Frame: Baseline, 10 minutes after intervention during exercise ]
    Pulmonary artery pressure was measured using a high-fidelity micromanometer advanced through the lumen of a fluid-filled catheter.

  7. Change in Resting Pulmonary Artery Pressure [ Time Frame: Baseline, 10 minutes after intervention ]
    Pulmonary artery pressure was measured using a high-fidelity micromanometer advanced through the lumen of a fluid-filled catheter.

  8. Change in Exercise Right Atrial Pressure (RA) [ Time Frame: Baseline, 10 minutes after intervention during exercise ]
    RA was measured using a high-fidelity micromanometer advanced through the lumen of a fluid-filled catheter.

  9. Change in Resting Right Atrial Pressure (RA) [ Time Frame: Baseline, 10 minutes after intervention ]
    RA was measured using a high-fidelity micromanometer advanced through the lumen of a fluid-filled catheter.

  10. Change in Exercise Cardiac Output [ Time Frame: Baseline, 10 minutes after intervention during exercise ]
    Cardiac output was calculated using the direct Fick method of breath-by-breath oxygen consumption (V02)/arterial-venous oxygen content difference (AVO2 diff).

  11. Change in Resting Cardiac Output [ Time Frame: Baseline, 10 minutes after intervention ]
    Cardiac output was calculated using the direct Fick method of breath-by-breath oxygen consumption (V02)/arterial-venous oxygen content difference (AVO2 diff).

  12. Change in Exercise Pulmonary Elastance [ Time Frame: Baseline, 10 minutes after intervention during exercise ]
    Pulmonary elastance was calculated by the ratio of pulmonary artery systolic pressure/stroke volume.

  13. Change in Resting Pulmonary Elastance [ Time Frame: Baseline, 10 minutes after intervention ]
    Pulmonary elastance was calculated by the ratio of pulmonary artery systolic pressure/stroke volume.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  • Heart Failure with Preserved Ejection Fraction (HFpEF)
  • Normal left ventricular ejection fraction (≥50%)
  • Elevated Left Ventricular filling pressures at cardiac catheterization (defined as resting Pulmonary Capillary Wedge Pressure>15 mmHg and/or ≥25 mmHg during exercise).

Exclusion Criteria:

  • Prior albuterol therapy (within previous 48 hours)
  • Current long acting inhaled beta agonist use
  • Significant hypokalemia (<3meq/L)
  • Significant valvular disease (>moderate left-sided regurgitation, >mild stenosis)
  • High output heart failure
  • Severe pulmonary disease
  • Unstable coronary disease
  • Constrictive pericarditis
  • Restrictive cardiomyopathy
  • Hypertrophic cardiomyopathy

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 ClinicalTrials.gov identifier (NCT number): NCT02885636


Locations
Layout table for location information
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Layout table for investigator information
Principal Investigator: Barry A Borlaug, MD Mayo Clinic
  Study Documents (Full-Text)

Documents provided by Barry Borlaug, Mayo Clinic:

Publications:
Layout table for additonal information
Responsible Party: Barry Borlaug, Associate Professor of Medicine, Mayo Clinic
ClinicalTrials.gov Identifier: NCT02885636     History of Changes
Other Study ID Numbers: 16-005140A
R01HL128526 ( U.S. NIH Grant/Contract )
R01HL126638 ( U.S. NIH Grant/Contract )
U01HL125205 ( U.S. NIH Grant/Contract )
U10HL110262 ( U.S. NIH Grant/Contract )
First Posted: August 31, 2016    Key Record Dates
Results First Posted: February 5, 2019
Last Update Posted: February 22, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Barry Borlaug, Mayo Clinic:
Heart Failure with Preserved Ejection Fraction
Pulmonary Hypertension

Additional relevant MeSH terms:
Layout table for MeSH terms
Albuterol
Heart Failure
Vascular Diseases
Heart Diseases
Cardiovascular Diseases
Adrenergic Agents
Adrenergic Agonists
Adrenergic beta-Agonists
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Tocolytic Agents
Reproductive Control Agents
Adrenergic beta-2 Receptor Agonists
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action