A Phase 2 interventional study of Nitrite and Saline Placebo for Nitrite in Heart Disease, Heart Failure With Preserved Ejection Fraction and Exercise Intolerance, sponsored by Barry Borlaug. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2016-03-14.
Sponsored by Barry Borlaug · Phase 2, Interventional, and Treatment
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.
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.
1,105 studies on the registry are indexed under Hypertension, Pulmonary; 234 are open to participants now.
This study's enrollment of 28 is below the median of 35 across 649 interventional studies indexed under Hypertension, Pulmonary.
Browse Hypertension, Pulmonary studies →Barry Borlaug is the lead sponsor of 2 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Study drug (NaNO_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.
Drug: Nitrite
Saline Placebo for Nitrite will be infused for 5 minutes during the cardiac catheterization procedure.
Drug: Saline Placebo for Nitrite
Study drug (NaNO_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.
Normal saline placebo will be infused for 5 minutes during the cardiac catheterization procedure. Hemodynamics will then be measured at baseline after study drug infusion and again during low level exercise (20 Watts).
Exercise Pulmonary Capillary Wedge Pressure (PCWP)
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.
Time frame: during repeat exercise run, approximately 30 minutes after study drug administration
Change in Central Pressures After Study Drug (Resting)
Values are resting values after receiving study drug minus resting values before study drug (on the same day.)
Time frame: baseline, approximately 30 minutes after study drug administration
Change in Heart Rate After Study Drug (Resting)
Values are resting values after receiving study drug minus resting values before study drug (on the same day.)
Time frame: baseline, approximately 30 minutes after study drug administration
Change in Blood Pressure After Study Drug (Resting)
Values are resting values after receiving study drug minus resting values before study drug (on the same day.)
Time frame: baseline, approximately 30 minutes after study drug administration
Change in Pulmonary Vascular Resistance (PVR) After Study Drug (Resting)
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.
Time frame: baseline, approximately 30 minutes after study drug administration
Change in Pulmonary Artery (PA) Compliance After Study Drug (Resting)
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.
Time frame: baseline, approximately 30 minutes after study drug administration
Change in Systemic Vascular Resistance (SVR) After Study Drug (Resting)
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.
Time frame: baseline, approximately 30 minutes after study drug administration
Change in Left Ventricular Stroke Work (LVSW) After Study Drug (Resting)
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.
Time frame: baseline, approximately 30 minutes after study drug administration
Change in Oxygen Consumption (VO_2) After Study Drug (Resting)
Values are resting values after receiving study drug minus resting values before study drug (on the same day.)
Time frame: baseline, approximately 30 minutes after study drug administration
Change in Arteriovenous Oxygen Content Difference After Study Drug (Resting)
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.
Time frame: baseline, approximately 30 minutes after study drug administration
Change in Cardiac Output After Study Drug (Resting)
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.
Time frame: baseline, approximately 30 minutes after study drug administration
Change in Stroke Volume After Study Drug (Resting)
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.
Time frame: baseline, approximately 30 minutes after study drug administration
Change in Central Pressures After Study Drug (Exercise)
Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.)
Time frame: baseline, approximately 30 minutes after study drug administration
Change in Heart Rate After Study Drug (Exercise)
Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.)
Time frame: baseline, approximately 30 minutes after study drug administration
Change in Blood Pressure After Study Drug (Exercise)
Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.)
Time frame: baseline, approximately 30 minutes after study drug administration
Change in PVR After Study Drug (Exercise)
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.
Time frame: baseline, approximately 30 minutes after study drug administration
Change in PA Compliance After Study Drug (Exercise)
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.
Time frame: baseline, approximately 30 minutes after study drug administration
Change in SVR After Study Drug (Exercise)
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.
Time frame: baseline, approximately 30 minutes after study drug administration
Change in LVSW After Study Drug (Exercise)
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.
Time frame: baseline, approximately 30 minutes after study drug administration
Change in Oxygen Consumption (VO_2) After Study Drug (Exercise)
Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.)
Time frame: baseline, approximately 30 minutes after study drug administration
Change in Arteriovenous Oxygen Difference After Study Drug (Exercise)
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.
Time frame: baseline, approximately 30 minutes after study drug administration
Change in Cardiac Output After Study Drug (Exercise)
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.
Time frame: baseline, approximately 30 minutes after study drug administration
Change in Stroke Volume After Study Drug (Exercise)
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.
Time frame: baseline, approximately 30 minutes after study drug administration
Subjects were enrolled in the trial between January and September 2014.
| Milestone | Nitrite | Placebo |
|---|---|---|
| Started | 14 | 14 |
| Completed | 14 | 14 |
| Not completed | 0 | 0 |
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.
| mm Hg | Nitrite | Placebo |
|---|---|---|
| Exercise Pulmonary Capillary Wedge Pressure (PCWP) | 19.0 ± 5.0 | 28.0 ± 6.0 |
Values are resting values after receiving study drug minus resting values before study drug (on the same day.)
| mm Hg | Nitrite | Placebo |
|---|---|---|
| Right atrial pressure | -2 ± 2 | 0 ± 1 |
| Pulmonary artery systolic pressure | -8 ± 5 | -3 ± 4 |
| Mean pulmonary artery pressure | -6 ± 3 | -1 ± 3 |
| PCWP | -3 ± 3 | 0 ± 1 |
Values are resting values after receiving study drug minus resting values before study drug (on the same day.)
| beats/minute | Nitrite | Placebo |
|---|---|---|
| Change in Heart Rate After Study Drug (Resting) | 0 ± 5 | -3 ± 5 |
Values are resting values after receiving study drug minus resting values before study drug (on the same day.)
| mm Hg | Nitrite | Placebo |
|---|---|---|
| Systolic Blood Pressure | -7 ± 8 | -2 ± 10 |
| Mean Blood Pressure | -3 ± 4 | -1 ± 6 |
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.
| mm Hg/L/min | Nitrite | Placebo |
|---|---|---|
| Change in Pulmonary Vascular Resistance (PVR) After Study Drug (Resting) | -0.3 ± 0.4 | -0.4 ± 0.6 |
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.
| ml/mm Hg | Nitrite | Placebo |
|---|---|---|
| Change in Pulmonary Artery (PA) Compliance After Study Drug (Resting) | 0.8 ± 1.3 | 0.2 ± 0.6 |
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.
| dyne/s * cm^5 | Nitrite | Placebo |
|---|---|---|
| Change in Systemic Vascular Resistance (SVR) After Study Drug (Resting) | 140 ± 350 | 20 ± 160 |
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.
| g/beat | Nitrite | Placebo |
|---|---|---|
| Change in Left Ventricular Stroke Work (LVSW) After Study Drug (Resting) | -6 ± 18 | 0 ± 9 |
Values are resting values after receiving study drug minus resting values before study drug (on the same day.)
| ml/min | Nitrite | Placebo |
|---|---|---|
| Change in Oxygen Consumption (VO_2) After Study Drug (Resting) | -2 ± 38 | -6 ± 15 |
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.
| ml/dl | Nitrite | Placebo |
|---|---|---|
| Change in Arteriovenous Oxygen Content Difference After Study Drug (Resting) | 0.4 ± 0.5 | 0 ± 0.4 |
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.
| L/min | Nitrite | Placebo |
|---|---|---|
| Change in Cardiac Output After Study Drug (Resting) | -0.4 ± 0.8 | -0.2 ± 0.5 |
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.
| ml | Nitrite | Placebo |
|---|---|---|
| Change in Stroke Volume After Study Drug (Resting) | -5 ± 16 | -1 ± 9 |
Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.)
| mm Hg | Nitrite | Placebo |
|---|---|---|
| Right atrial pressure | -5 ± 2 | -1 ± 2 |
| Pulmonary artery systolic pressure | -11 ± 6 | -4 ± 8 |
| Mean pulmonary artery pressure | 10 ± 4 | -2 ± 5 |
| PCWP | -11 ± 5 | -2 ± 5 |
Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.)
| beats/minute | Nitrite | Placebo |
|---|---|---|
| Change in Heart Rate After Study Drug (Exercise) | -1 ± 6 | 0 ± 3 |
Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.)
| mm Hg | Nitrite | Placebo |
|---|---|---|
| Systolic Blood Pressure | -5 ± 13 | 2 ± 10 |
| Diastolic Blood Pressure | -5 ± 8 | 0 ± 2 |
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.
| mm Hg/L/min | Nitrite | Placebo |
|---|---|---|
| Change in PVR After Study Drug (Exercise) | 0 ± 0.4 | 0.2 ± 0.4 |
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.
| ml/mm Hg | Nitrite | Placebo |
|---|---|---|
| Change in PA Compliance After Study Drug (Exercise) | 0.8 ± 0.9 | 0.5 ± 0.9 |
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.
| dyne/s * cm^5 | Nitrite | Placebo |
|---|---|---|
| Change in SVR After Study Drug (Exercise) | -70 ± 140 | 70 ± 100 |
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.
| g/beat | Nitrite | Placebo |
|---|---|---|
| Change in LVSW After Study Drug (Exercise) | 15 ± 12 | -2 ± 8 |
Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.)
| ml/min | Nitrite | Placebo |
|---|---|---|
| Change in Oxygen Consumption (VO_2) After Study Drug (Exercise) | 70 ± 138 | -30 ± 67 |
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.
| ml/dl | Nitrite | Placebo |
|---|---|---|
| Change in Arteriovenous Oxygen Difference After Study Drug (Exercise) | 0.2 ± 0.4 | 0 ± 0.6 |
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.
| L/min | Nitrite | Placebo |
|---|---|---|
| Change in Cardiac Output After Study Drug (Exercise) | 0.5 ± 0.7 | -0.4 ± 0.7 |
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.
| ml | Nitrite | Placebo |
|---|---|---|
| Change in Stroke Volume After Study Drug (Exercise) | 7 ± 8 | -5 ± 6 |
Collected over Subjects will be followed for adverse event reporting during the procedure and the recovery period, approximately 3 hours after the procedure on Day 1.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Nitrite | — | 0/14 (0%) | 0/14 (0%) |
| Placebo | — | 0/14 (0%) | 0/14 (0%) |
| Age, Continuous(years) | Nitrite | Placebo | Total |
|---|---|---|---|
| Mean | 69 ± 6 | 70 ± 8 | 69 ± 8 |
| Sex: Female, Male(Participants) | Nitrite | Placebo | Total |
|---|---|---|---|
| Female | 9 | 8 | 17 |
| Male | 5 | 6 | 11 |
| Region of Enrollment(participants) | Nitrite | Placebo | Total |
|---|---|---|---|
| United States | 14 | 14 | 28 |
This study is completed, as verified in Feb 2016. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.