Trial Outcomes & Findings for Inhaled Beta-adrenergic Agonists to Treat Pulmonary Vascular Disease in Heart Failure With Preserved EF (BEAT HFpEF): A Randomized Controlled Trial (NCT NCT02885636)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

30 participants

Primary outcome timeframe

Baseline, 10 minutes after intervention during exercise

Results posted on

2019-02-22

Participant Flow

Participant milestones

Participant milestones
Measure	Inhaled Albuterol 2.5 mg inhaled albuterol through a high efficiency nebulizer -single dose Albuterol: : Experimental: Inhaled albuterol 2.5 mg inhaled albuterol through a high efficiency nebulizer as a single dose	Inhaled Saline Placebo Inhaled saline through a high efficiency nebulizer -single dose Saline placebo: Saline inhaled through a nebulizer as a single dose
Overall Study STARTED	15	15
Overall Study COMPLETED	15	15
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Total n=30 Participants Total of all reporting groups	Inhaled Albuterol n=15 Participants 2.5 mg inhaled albuterol through a high efficiency nebulizer -single dose Albuterol: : Experimental: Inhaled albuterol 2.5 mg inhaled albuterol through a high efficiency nebulizer as a single dose	Inhaled Saline Placebo n=15 Participants Inhaled saline through a high efficiency nebulizer -single dose Saline placebo: Saline inhaled through a nebulizer as a single dose
Age, Continuous	66 years STANDARD_DEVIATION 12 • n=30 Participants	68 years STANDARD_DEVIATION 8 • n=15 Participants	64 years STANDARD_DEVIATION 17 • n=15 Participants
Sex: Female, Male Female	14 Participants n=30 Participants	6 Participants n=15 Participants	8 Participants n=15 Participants
Sex: Female, Male Male	16 Participants n=30 Participants	9 Participants n=15 Participants	7 Participants n=15 Participants
Race and Ethnicity Not Collected	0 Participants Race and Ethnicity were not collected from any participant.	—	—
Region of Enrollment United States	30 participants n=30 Participants	15 participants n=15 Participants	15 participants n=15 Participants
Body mass index	34.6 kg/m^2 STANDARD_DEVIATION 8.1 • n=30 Participants	33.7 kg/m^2 STANDARD_DEVIATION 7 • n=15 Participants	35.6 kg/m^2 STANDARD_DEVIATION 9.2 • n=15 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Inhaled Albuterol n=15 Participants 2.5 mg inhaled albuterol through a high efficiency nebulizer -single dose Albuterol: : Experimental: Inhaled albuterol 2.5 mg inhaled albuterol through a high efficiency nebulizer as a single dose	Inhaled Saline Placebo n=15 Participants Inhaled saline through a high efficiency nebulizer -single dose Saline placebo: Saline inhaled through a nebulizer as a single dose
Change in 20 Watt Exercise Pulmonary Vascular Resistance (PVR)	-0.6 wood units Standard Deviation 0.5	0.1 wood units Standard Deviation 0.7

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Inhaled Albuterol n=15 Participants 2.5 mg inhaled albuterol through a high efficiency nebulizer -single dose Albuterol: : Experimental: Inhaled albuterol 2.5 mg inhaled albuterol through a high efficiency nebulizer as a single dose	Inhaled Saline Placebo n=15 Participants Inhaled saline through a high efficiency nebulizer -single dose Saline placebo: Saline inhaled through a nebulizer as a single dose
Change in Resting Pulmonary Vascular Resistance	-0.6 wood units Standard Deviation 0.5	-0.3 wood units Standard Deviation 0.8

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Inhaled Albuterol n=15 Participants 2.5 mg inhaled albuterol through a high efficiency nebulizer -single dose Albuterol: : Experimental: Inhaled albuterol 2.5 mg inhaled albuterol through a high efficiency nebulizer as a single dose	Inhaled Saline Placebo n=15 Participants Inhaled saline through a high efficiency nebulizer -single dose Saline placebo: Saline inhaled through a nebulizer as a single dose
Change in Exercise Pulmonary Capillary Wedge Pressure (PCWP)	-2 mm Hg Standard Deviation 6	-3 mm Hg Standard Deviation 3

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Inhaled Albuterol n=15 Participants 2.5 mg inhaled albuterol through a high efficiency nebulizer -single dose Albuterol: : Experimental: Inhaled albuterol 2.5 mg inhaled albuterol through a high efficiency nebulizer as a single dose	Inhaled Saline Placebo n=15 Participants Inhaled saline through a high efficiency nebulizer -single dose Saline placebo: Saline inhaled through a nebulizer as a single dose
Change in Resting Pulmonary Capillary Wedge Pressure (PCWP)	-2 mm Hg Standard Deviation 2	-2 mm Hg Standard Deviation 3

SECONDARY outcome

Timeframe: Baseline, 10 minutes after intervention during exercise

Pulmonary artery compliance was calculated as the ratio of stroke volume/pulmonary artery pulse pressure.

Outcome measures

Outcome measures
Measure	Inhaled Albuterol n=15 Participants 2.5 mg inhaled albuterol through a high efficiency nebulizer -single dose Albuterol: : Experimental: Inhaled albuterol 2.5 mg inhaled albuterol through a high efficiency nebulizer as a single dose	Inhaled Saline Placebo n=15 Participants Inhaled saline through a high efficiency nebulizer -single dose Saline placebo: Saline inhaled through a nebulizer as a single dose
Change in Exercise Pulmonary Artery Compliance	1.6 mL/mm Hg Standard Deviation 1.6	0.0 mL/mm Hg Standard Deviation 0.7

SECONDARY outcome

Timeframe: Baseline, 10 minutes after intervention

Pulmonary artery compliance was calculated as the ratio of stroke volume/pulmonary artery pulse pressure.

Outcome measures

Outcome measures
Measure	Inhaled Albuterol n=15 Participants 2.5 mg inhaled albuterol through a high efficiency nebulizer -single dose Albuterol: : Experimental: Inhaled albuterol 2.5 mg inhaled albuterol through a high efficiency nebulizer as a single dose	Inhaled Saline Placebo n=15 Participants Inhaled saline through a high efficiency nebulizer -single dose Saline placebo: Saline inhaled through a nebulizer as a single dose
Change in Resting Pulmonary Artery Compliance	1.2 mL/mm Hg Standard Deviation 1.0	0.7 mL/mm Hg Standard Deviation 1.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Inhaled Albuterol n=15 Participants 2.5 mg inhaled albuterol through a high efficiency nebulizer -single dose Albuterol: : Experimental: Inhaled albuterol 2.5 mg inhaled albuterol through a high efficiency nebulizer as a single dose	Inhaled Saline Placebo n=15 Participants Inhaled saline through a high efficiency nebulizer -single dose Saline placebo: Saline inhaled through a nebulizer as a single dose
Change in Exercise Pulmonary Artery Pressure	-8 mm Hg Standard Deviation 4	-2 mm Hg Standard Deviation 4

SECONDARY outcome

Timeframe: Baseline, 10 minutes after intervention

Pulmonary artery pressure was measured using a high-fidelity micromanometer advanced through the lumen of a fluid-filled catheter.

Outcome measures

Outcome measures
Measure	Inhaled Albuterol n=15 Participants 2.5 mg inhaled albuterol through a high efficiency nebulizer -single dose Albuterol: : Experimental: Inhaled albuterol 2.5 mg inhaled albuterol through a high efficiency nebulizer as a single dose	Inhaled Saline Placebo n=15 Participants Inhaled saline through a high efficiency nebulizer -single dose Saline placebo: Saline inhaled through a nebulizer as a single dose
Change in Resting Pulmonary Artery Pressure	-5 mm Hg Standard Deviation 3	-3 mm Hg Standard Deviation 3

SECONDARY outcome

Timeframe: Baseline, 10 minutes after intervention during exercise

RA was measured using a high-fidelity micromanometer advanced through the lumen of a fluid-filled catheter.

Outcome measures

Outcome measures
Measure	Inhaled Albuterol n=15 Participants 2.5 mg inhaled albuterol through a high efficiency nebulizer -single dose Albuterol: : Experimental: Inhaled albuterol 2.5 mg inhaled albuterol through a high efficiency nebulizer as a single dose	Inhaled Saline Placebo n=15 Participants Inhaled saline through a high efficiency nebulizer -single dose Saline placebo: Saline inhaled through a nebulizer as a single dose
Change in Exercise Right Atrial Pressure (RA)	-5 mm Hg Standard Deviation 3	-1 mm Hg Standard Deviation 2

SECONDARY outcome

Timeframe: Baseline, 10 minutes after intervention

RA was measured using a high-fidelity micromanometer advanced through the lumen of a fluid-filled catheter.

Outcome measures

Outcome measures
Measure	Inhaled Albuterol n=15 Participants 2.5 mg inhaled albuterol through a high efficiency nebulizer -single dose Albuterol: : Experimental: Inhaled albuterol 2.5 mg inhaled albuterol through a high efficiency nebulizer as a single dose	Inhaled Saline Placebo n=15 Participants Inhaled saline through a high efficiency nebulizer -single dose Saline placebo: Saline inhaled through a nebulizer as a single dose
Change in Resting Right Atrial Pressure (RA)	-3 mm Hg Standard Deviation 2	-1 mm Hg Standard Deviation 2

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Inhaled Albuterol n=15 Participants 2.5 mg inhaled albuterol through a high efficiency nebulizer -single dose Albuterol: : Experimental: Inhaled albuterol 2.5 mg inhaled albuterol through a high efficiency nebulizer as a single dose	Inhaled Saline Placebo n=15 Participants Inhaled saline through a high efficiency nebulizer -single dose Saline placebo: Saline inhaled through a nebulizer as a single dose
Change in Exercise Cardiac Output	2.0 L/min Standard Deviation 2.1	0.1 L/min Standard Deviation 1.0

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Inhaled Albuterol n=15 Participants 2.5 mg inhaled albuterol through a high efficiency nebulizer -single dose Albuterol: : Experimental: Inhaled albuterol 2.5 mg inhaled albuterol through a high efficiency nebulizer as a single dose	Inhaled Saline Placebo n=15 Participants Inhaled saline through a high efficiency nebulizer -single dose Saline placebo: Saline inhaled through a nebulizer as a single dose
Change in Resting Cardiac Output	0.6 L/min Standard Deviation 1.2	0.4 L/min Standard Deviation 1.2

SECONDARY outcome

Timeframe: Baseline, 10 minutes after intervention during exercise

Pulmonary elastance was calculated by the ratio of pulmonary artery systolic pressure/stroke volume.

Outcome measures

Outcome measures
Measure	Inhaled Albuterol n=15 Participants 2.5 mg inhaled albuterol through a high efficiency nebulizer -single dose Albuterol: : Experimental: Inhaled albuterol 2.5 mg inhaled albuterol through a high efficiency nebulizer as a single dose	Inhaled Saline Placebo n=15 Participants Inhaled saline through a high efficiency nebulizer -single dose Saline placebo: Saline inhaled through a nebulizer as a single dose
Change in Exercise Pulmonary Elastance	-0.17 mm Hg/mL Standard Deviation 0.11	-0.05 mm Hg/mL Standard Deviation 0.11

SECONDARY outcome

Timeframe: Baseline, 10 minutes after intervention

Pulmonary elastance was calculated by the ratio of pulmonary artery systolic pressure/stroke volume.

Outcome measures

Outcome measures
Measure	Inhaled Albuterol n=15 Participants 2.5 mg inhaled albuterol through a high efficiency nebulizer -single dose Albuterol: : Experimental: Inhaled albuterol 2.5 mg inhaled albuterol through a high efficiency nebulizer as a single dose	Inhaled Saline Placebo n=15 Participants Inhaled saline through a high efficiency nebulizer -single dose Saline placebo: Saline inhaled through a nebulizer as a single dose
Change in Resting Pulmonary Elastance	-0.11 mm Hg/mL Standard Deviation 0.13	-0.03 mm Hg/mL Standard Deviation 0.13

Adverse Events

Inhaled Albuterol

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Inhaled Saline Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Barry Borlaug

Mayo Clinic

Phone: 507-284-8846

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place