Trial Outcomes & Findings for Acute Effects of Inorganic Nitrite on Cardiovascular Hemodynamics in Heart Failure With Preserved Ejection Fraction (NCT NCT01932606)

NCT ID: NCT01932606

Last Updated: 2016-03-14

Results Overview

Pulmonary capillary wedge pressure (PCWP) provides an indirect estimate of left atrial pressure (LAP). PCWP is the pressure measured by wedging a pulmonary catheter with an inflated balloon into a small pulmonary arterial branch.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 28 participants
• Primary outcome timeframe: during repeat exercise run, approximately 30 minutes after study drug administration
• Results posted on: 2016-03-14

Participant Flow

Subjects were enrolled in the trial between January and September 2014.

Participant milestones

Measure	Nitrite Study drug (NaNO\_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.	Placebo Saline Placebo for Nitrite will be infused for 5 minutes during the cardiac catheterization procedure.
Overall Study STARTED	14	14
Overall Study COMPLETED	14	14
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Nitrite n=14 Participants Study drug (NaNO\_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.	Placebo n=14 Participants Saline Placebo for Nitrite will be infused for 5 minutes during the cardiac catheterization procedure.	Total n=28 Participants Total of all reporting groups
Age, Continuous	69 years STANDARD_DEVIATION 6 • n=5 Participants	70 years STANDARD_DEVIATION 8 • n=7 Participants	69 years STANDARD_DEVIATION 8 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Region of Enrollment United States	14 participants n=5 Participants	14 participants n=7 Participants	28 participants n=5 Participants

PRIMARY outcome

Timeframe: during repeat exercise run, approximately 30 minutes after study drug administration

Pulmonary capillary wedge pressure (PCWP) provides an indirect estimate of left atrial pressure (LAP). PCWP is the pressure measured by wedging a pulmonary catheter with an inflated balloon into a small pulmonary arterial branch.

Outcome measures

Measure	Nitrite n=14 Participants Study drug (NaNO\_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.	Placebo n=14 Participants Saline Placebo for Nitrite will be infused for 5 minutes during the cardiac catheterization procedure.
Exercise Pulmonary Capillary Wedge Pressure (PCWP)	19.0 mm Hg Standard Deviation 5.0	28.0 mm Hg Standard Deviation 6.0

SECONDARY outcome

Timeframe: baseline, approximately 30 minutes after study drug administration

Values are resting values after receiving study drug minus resting values before study drug (on the same day.)

Outcome measures

Measure	Nitrite n=14 Participants Study drug (NaNO\_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.	Placebo n=14 Participants Saline Placebo for Nitrite will be infused for 5 minutes during the cardiac catheterization procedure.
Change in Central Pressures After Study Drug (Resting) Right atrial pressure	-2 mm Hg Standard Deviation 2	0 mm Hg Standard Deviation 1
Change in Central Pressures After Study Drug (Resting) Pulmonary artery systolic pressure	-8 mm Hg Standard Deviation 5	-3 mm Hg Standard Deviation 4
Change in Central Pressures After Study Drug (Resting) Mean pulmonary artery pressure	-6 mm Hg Standard Deviation 3	-1 mm Hg Standard Deviation 3
Change in Central Pressures After Study Drug (Resting) PCWP	-3 mm Hg Standard Deviation 3	0 mm Hg Standard Deviation 1

SECONDARY outcome

Timeframe: baseline, approximately 30 minutes after study drug administration

Values are resting values after receiving study drug minus resting values before study drug (on the same day.)

Outcome measures

Measure	Nitrite n=14 Participants Study drug (NaNO\_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.	Placebo n=14 Participants Saline Placebo for Nitrite will be infused for 5 minutes during the cardiac catheterization procedure.
Change in Heart Rate After Study Drug (Resting)	0 beats/minute Standard Deviation 5	-3 beats/minute Standard Deviation 5

SECONDARY outcome

Timeframe: baseline, approximately 30 minutes after study drug administration

Values are resting values after receiving study drug minus resting values before study drug (on the same day.)

Outcome measures

Measure	Nitrite n=14 Participants Study drug (NaNO\_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.	Placebo n=14 Participants Saline Placebo for Nitrite will be infused for 5 minutes during the cardiac catheterization procedure.
Change in Blood Pressure After Study Drug (Resting) Systolic Blood Pressure	-7 mm Hg Standard Deviation 8	-2 mm Hg Standard Deviation 10
Change in Blood Pressure After Study Drug (Resting) Mean Blood Pressure	-3 mm Hg Standard Deviation 4	-1 mm Hg Standard Deviation 6

SECONDARY outcome

Timeframe: baseline, approximately 30 minutes after study drug administration

Values are resting values after receiving study drug minus resting values before study drug (on the same day.) Pulmonary Vascular Resistance (PVR) is the resistance to flow that must be overcome to push blood through the pulmonary vasculature. Acute and chronic lung disease can both cause an increase in PVR. Chronic PVR can lead to right sided heart failure.

Outcome measures

Measure	Nitrite n=14 Participants Study drug (NaNO\_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.	Placebo n=14 Participants Saline Placebo for Nitrite will be infused for 5 minutes during the cardiac catheterization procedure.
Change in Pulmonary Vascular Resistance (PVR) After Study Drug (Resting)	-0.3 mm Hg/L/min Standard Deviation 0.4	-0.4 mm Hg/L/min Standard Deviation 0.6

SECONDARY outcome

Timeframe: baseline, approximately 30 minutes after study drug administration

Values are resting values after receiving study drug minus resting values before study drug (on the same day.) Pulmonary artery compliance is an index of the elasticity of the blood vessel, an indication of arterial stiffness.

Outcome measures

Measure	Nitrite n=14 Participants Study drug (NaNO\_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.	Placebo n=14 Participants Saline Placebo for Nitrite will be infused for 5 minutes during the cardiac catheterization procedure.
Change in Pulmonary Artery (PA) Compliance After Study Drug (Resting)	0.8 ml/mm Hg Standard Deviation 1.3	0.2 ml/mm Hg Standard Deviation 0.6

SECONDARY outcome

Timeframe: baseline, approximately 30 minutes after study drug administration

Values are resting values after receiving study drug minus resting values before study drug (on the same day.) Systemic vascular resistance (SVR) refers to the resistance to blood flow offered by all of the systemic vasculature, excluding the pulmonary vasculature.

Outcome measures

Measure	Nitrite n=14 Participants Study drug (NaNO\_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.	Placebo n=14 Participants Saline Placebo for Nitrite will be infused for 5 minutes during the cardiac catheterization procedure.
Change in Systemic Vascular Resistance (SVR) After Study Drug (Resting)	140 dyne/s * cm^5 Standard Deviation 350	20 dyne/s * cm^5 Standard Deviation 160

SECONDARY outcome

Timeframe: baseline, approximately 30 minutes after study drug administration

Values are resting values after receiving study drug minus resting values before study drug (on the same day.) Stroke work refers to the work done by the ventricle to eject a volume of blood (i.e., stroke volume) into the aorta. Ventricular stroke work can be estimated as the product of stroke volume and mean aortic pressure during ejection.

Outcome measures

Measure	Nitrite n=14 Participants Study drug (NaNO\_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.	Placebo n=14 Participants Saline Placebo for Nitrite will be infused for 5 minutes during the cardiac catheterization procedure.
Change in Left Ventricular Stroke Work (LVSW) After Study Drug (Resting)	-6 g/beat Standard Deviation 18	0 g/beat Standard Deviation 9

SECONDARY outcome

Timeframe: baseline, approximately 30 minutes after study drug administration

Values are resting values after receiving study drug minus resting values before study drug (on the same day.)

Outcome measures

Measure	Nitrite n=14 Participants Study drug (NaNO\_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.	Placebo n=14 Participants Saline Placebo for Nitrite will be infused for 5 minutes during the cardiac catheterization procedure.
Change in Oxygen Consumption (VO_2) After Study Drug (Resting)	-2 ml/min Standard Deviation 38	-6 ml/min Standard Deviation 15

SECONDARY outcome

Timeframe: baseline, approximately 30 minutes after study drug administration

Values are resting values after receiving study drug minus resting values before study drug (on the same day.) Arteriovenous oxygen difference is the difference in the oxygen content of the blood between the arterial blood and the venous blood. It is an indication of how much oxygen is removed from the blood in capillaries as the blood circulates in the body.

Outcome measures

Measure	Nitrite n=14 Participants Study drug (NaNO\_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.	Placebo n=14 Participants Saline Placebo for Nitrite will be infused for 5 minutes during the cardiac catheterization procedure.
Change in Arteriovenous Oxygen Content Difference After Study Drug (Resting)	0.4 ml/dl Standard Deviation 0.5	0 ml/dl Standard Deviation 0.4

SECONDARY outcome

Timeframe: baseline, approximately 30 minutes after study drug administration

Values are resting values after receiving study drug minus resting values before study drug (on the same day.) The volume of blood pumped per minute by each ventricle of the heart. Cardiac output is equal to the stroke volume (the amount of blood pumped from a ventricle in a single heartbeat) times the heart rate.

Outcome measures

Measure	Nitrite n=14 Participants Study drug (NaNO\_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.	Placebo n=14 Participants Saline Placebo for Nitrite will be infused for 5 minutes during the cardiac catheterization procedure.
Change in Cardiac Output After Study Drug (Resting)	-0.4 L/min Standard Deviation 0.8	-0.2 L/min Standard Deviation 0.5

SECONDARY outcome

Timeframe: baseline, approximately 30 minutes after study drug administration

Values are resting values after receiving study drug minus resting values before study drug (on the same day.) Stroke volume is the amount of blood pumped out of the heart (left ventricle - to the body) during each contraction.

Outcome measures

Measure	Nitrite n=14 Participants Study drug (NaNO\_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.	Placebo n=14 Participants Saline Placebo for Nitrite will be infused for 5 minutes during the cardiac catheterization procedure.
Change in Stroke Volume After Study Drug (Resting)	-5 ml Standard Deviation 16	-1 ml Standard Deviation 9

SECONDARY outcome

Timeframe: baseline, approximately 30 minutes after study drug administration

Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.)

Outcome measures

Measure	Nitrite n=14 Participants Study drug (NaNO\_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.	Placebo n=14 Participants Saline Placebo for Nitrite will be infused for 5 minutes during the cardiac catheterization procedure.
Change in Central Pressures After Study Drug (Exercise) Right atrial pressure	-5 mm Hg Standard Deviation 2	-1 mm Hg Standard Deviation 2
Change in Central Pressures After Study Drug (Exercise) Pulmonary artery systolic pressure	-11 mm Hg Standard Deviation 6	-4 mm Hg Standard Deviation 8
Change in Central Pressures After Study Drug (Exercise) Mean pulmonary artery pressure	10 mm Hg Standard Deviation 4	-2 mm Hg Standard Deviation 5
Change in Central Pressures After Study Drug (Exercise) PCWP	-11 mm Hg Standard Deviation 5	-2 mm Hg Standard Deviation 5

SECONDARY outcome

Timeframe: baseline, approximately 30 minutes after study drug administration

Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.)

Outcome measures

Measure	Nitrite n=14 Participants Study drug (NaNO\_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.	Placebo n=14 Participants Saline Placebo for Nitrite will be infused for 5 minutes during the cardiac catheterization procedure.
Change in Heart Rate After Study Drug (Exercise)	-1 beats/minute Standard Deviation 6	0 beats/minute Standard Deviation 3

SECONDARY outcome

Timeframe: baseline, approximately 30 minutes after study drug administration

Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.)

Outcome measures

Measure	Nitrite n=14 Participants Study drug (NaNO\_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.	Placebo n=14 Participants Saline Placebo for Nitrite will be infused for 5 minutes during the cardiac catheterization procedure.
Change in Blood Pressure After Study Drug (Exercise) Systolic Blood Pressure	-5 mm Hg Standard Deviation 13	2 mm Hg Standard Deviation 10
Change in Blood Pressure After Study Drug (Exercise) Diastolic Blood Pressure	-5 mm Hg Standard Deviation 8	0 mm Hg Standard Deviation 2

SECONDARY outcome

Timeframe: baseline, approximately 30 minutes after study drug administration

Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.) Pulmonary Vascular Resistance (PVR) is the resistance to flow that must be overcome to push blood through the pulmonary vasculature. Acute and chronic lung disease can both cause an increase in PVR. Chronic PVR can lead to right sided heart failure.

Outcome measures

Measure	Nitrite n=14 Participants Study drug (NaNO\_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.	Placebo n=14 Participants Saline Placebo for Nitrite will be infused for 5 minutes during the cardiac catheterization procedure.
Change in PVR After Study Drug (Exercise)	0 mm Hg/L/min Standard Deviation 0.4	0.2 mm Hg/L/min Standard Deviation 0.4

SECONDARY outcome

Timeframe: baseline, approximately 30 minutes after study drug administration

Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.) Pulmonary artery compliance is an index of the elasticity of the blood vessel, an indication of arterial stiffness.

Outcome measures

Measure	Nitrite n=14 Participants Study drug (NaNO\_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.	Placebo n=14 Participants Saline Placebo for Nitrite will be infused for 5 minutes during the cardiac catheterization procedure.
Change in PA Compliance After Study Drug (Exercise)	0.8 ml/mm Hg Standard Deviation 0.9	0.5 ml/mm Hg Standard Deviation 0.9

SECONDARY outcome

Timeframe: baseline, approximately 30 minutes after study drug administration

Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.) Systemic vascular resistance (SVR) refers to the resistance to blood flow offered by all of the systemic vasculature, excluding the pulmonary vasculature.

Outcome measures

Measure	Nitrite n=14 Participants Study drug (NaNO\_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.	Placebo n=14 Participants Saline Placebo for Nitrite will be infused for 5 minutes during the cardiac catheterization procedure.
Change in SVR After Study Drug (Exercise)	-70 dyne/s * cm^5 Standard Deviation 140	70 dyne/s * cm^5 Standard Deviation 100

SECONDARY outcome

Timeframe: baseline, approximately 30 minutes after study drug administration

Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.) Stroke work refers to the work done by the ventricle to eject a volume of blood (i.e., stroke volume) into the aorta. Ventricular stroke work can be estimated as the product of stroke volume and mean aortic pressure during ejection.

Outcome measures

Measure	Nitrite n=14 Participants Study drug (NaNO\_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.	Placebo n=14 Participants Saline Placebo for Nitrite will be infused for 5 minutes during the cardiac catheterization procedure.
Change in LVSW After Study Drug (Exercise)	15 g/beat Standard Deviation 12	-2 g/beat Standard Deviation 8

SECONDARY outcome

Timeframe: baseline, approximately 30 minutes after study drug administration

Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.)

Outcome measures

Measure	Nitrite n=14 Participants Study drug (NaNO\_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.	Placebo n=14 Participants Saline Placebo for Nitrite will be infused for 5 minutes during the cardiac catheterization procedure.
Change in Oxygen Consumption (VO_2) After Study Drug (Exercise)	70 ml/min Standard Deviation 138	-30 ml/min Standard Deviation 67

SECONDARY outcome

Timeframe: baseline, approximately 30 minutes after study drug administration

Arteriovenous oxygen difference is the difference in the oxygen content of the blood between the arterial blood and the venous blood. It is an indication of how much oxygen is removed from the blood in capillaries as the blood circulates in the body.

Outcome measures

Measure	Nitrite n=14 Participants Study drug (NaNO\_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.	Placebo n=14 Participants Saline Placebo for Nitrite will be infused for 5 minutes during the cardiac catheterization procedure.
Change in Arteriovenous Oxygen Difference After Study Drug (Exercise)	0.2 ml/dl Standard Deviation 0.4	0 ml/dl Standard Deviation 0.6

SECONDARY outcome

Timeframe: baseline, approximately 30 minutes after study drug administration

Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.) Cardiac output is equal to the stroke volume (the amount of blood pumped from a ventricle in a single heartbeat) times the heart rate.

Outcome measures

Measure	Nitrite n=14 Participants Study drug (NaNO\_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.	Placebo n=14 Participants Saline Placebo for Nitrite will be infused for 5 minutes during the cardiac catheterization procedure.
Change in Cardiac Output After Study Drug (Exercise)	0.5 L/min Standard Deviation 0.7	-0.4 L/min Standard Deviation 0.7

SECONDARY outcome

Timeframe: baseline, approximately 30 minutes after study drug administration

Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.) Stroke volume is the amount of blood pumped out of the heart (left ventricle - to the body) during each contraction.

Outcome measures

Measure	Nitrite n=14 Participants Study drug (NaNO\_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.	Placebo n=14 Participants Saline Placebo for Nitrite will be infused for 5 minutes during the cardiac catheterization procedure.
Change in Stroke Volume After Study Drug (Exercise)	7 ml Standard Deviation 8	-5 ml Standard Deviation 6

Adverse Events

Nitrite

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

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 A. Borlaug

Mayo Clinic

Phone: 507-284-6704

Email: Borlaug.Barry@mayo.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place