Heart DiseasePhase 2NCT01932606
Acute Effects of Inorganic Nitrite on Cardiovascular Hemodynamics in Heart Failure With Preserved Ejection Fraction
A Phase 2 study testing Nitrite in people with Heart Disease and Heart Failure With Preserved Ejection Fraction, run by Barry Borlaug at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Disease, Heart Failure With Preserved Ejection Fraction, Exercise Intolerance
- What is being tested?
- Nitrite
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2013to Oct 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Scheduled to undergo a cardiac catheterization procedure.
- Clinical symptoms of shortness of breath and fatigue
- Normal left ventricular ejection fraction (≥50%)
- Elevated left ventricular filling pressures at cardiac catheterization (defined as resting pulmonary capillary wedge pressure (PCWP)>15 mmHg and/or PCWP≥25 mmHg during exercise)
Who cannot join
- Systolic BP <120 mmHg
- 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, constrictive pericarditis, or infiltrative, restrictive, or hypertrophic cardiomyopathies
Trial locations and contacts
1 site in 1 country.
United States1 site
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
About this study
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.
Read the detailed description
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.
- Conditions
- Heart Disease, Heart Failure With Preserved Ejection Fraction, Exercise Intolerance, Pulmonary Hypertension
- Being tested
- Nitrite, Saline Placebo for Nitrite
- Medical subject headings
- Heart Diseases, Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NitriteDrug
Study drug (NaNO_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.
Saline Placebo for NitriteDrug
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).
| Study group | Role | What they receive |
|---|---|---|
| Nitrite | Experimental | Study drug (NaNO_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure. Receives: Drug: Nitrite |
| Saline | Placebo comparator | Saline Placebo for Nitrite will be infused for 5 minutes during the cardiac catheterization procedure. Receives: Drug: Saline Placebo for Nitrite |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: during repeat exercise run, approximately 30 minutes after study drug administration
Secondary outcomes (22)
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.)
Measured: 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.)
Measured: 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.)
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.)
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.)
Measured: 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.)
Measured: 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.)
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.)
Measured: 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.
Measured: 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.
Measured: 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.
Measured: baseline, approximately 30 minutes after study drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2013 (estimated)
- Study startAug 2013
- Primary completionOct 2014
- Study completionOct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Heart DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Barry Borlaug
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Barry Borlaug, Mayo Clinic
- Investigators
- Barry Borlaug, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01932606
- Sponsor's protocol ID
- 13-004077
- Status last verified
- Feb 2016
- First submitted
- 27 Aug 2013
- Last updated
- 14 Mar 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Borlaug BA, Koepp KE, Melenovsky V. Sodium Nitrite Improves Exercise Hemodynamics and Ventricular Performance in Heart Failure With Preserved Ejection Fraction. J Am Coll Cardiol. 2015 Oct 13;66(15):1672-82. doi: 10.1016/j.jacc.2015.07.067.
PubMed 26449137Reddy YNV, Stewart GM, Obokata M, Koepp KE, Borlaug BA. Peripheral and pulmonary effects of inorganic nitrite during exercise in heart failure with preserved ejection fraction. Eur J Heart Fail. 2021 May;23(5):814-823. doi: 10.1002/ejhf.2093. Epub 2021 Feb 1.
PubMed 33421267
Study at a glance
From the registry record, last updated by the sponsor on 14 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acute Effects of Inorganic Nitrite on Cardiovascular Hemodynamics in Heart Failure With Preserved Ejection Fraction
- ClinicalTrials.gov ID
- NCT01932606
- Acronym / sponsor ID
- 13-004077
- Conditions
- Heart Disease, Heart Failure With Preserved Ejection Fraction, Exercise Intolerance, Pulmonary Hypertension
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Barry BorlaugUniversity, hospital or other
- Study start
- Aug 2013
- Primary completion
- Oct 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 30 Aug 2013 (estimated)
- Results
- Posted 15 Feb 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nitrite | Experimental | Drug: NitriteStudy drug (NaNO_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure. |
| Saline | Placebo comparator | Drug: Saline Placebo for NitriteSaline Placebo for Nitrite will be infused for 5 minutes during the cardiac catheterization procedure. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Scheduled to undergo a cardiac catheterization procedure.
- Clinical symptoms of shortness of breath and fatigue
- Normal left ventricular ejection fraction (≥50%)
- Elevated left ventricular filling pressures at cardiac catheterization (defined as resting pulmonary capillary wedge pressure (PCWP)>15 mmHg and/or PCWP≥25 mmHg during exercise)
Key exclusion criteria (4 listed)
- Systolic BP <120 mmHg
- 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, constrictive pericarditis, or infiltrative, restrictive, or hypertrophic cardiomyopathies
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NitriteStudy drug (NaNO_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure. | Drug | Nitrite |
| Saline Placebo for NitriteNormal 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). | Drug | Saline |
Primary outcome
Exercise Pulmonary Capillary Wedge Pressure (PCWP)
Time frame: 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.
22 secondary outcomes
Change in Central Pressures After Study Drug (Resting)
Time frame: baseline, approximately 30 minutes after study drug administration
Change in Heart Rate After Study Drug (Resting)
Time frame: baseline, approximately 30 minutes after study drug administration
Change in Blood Pressure After Study Drug (Resting)
Time frame: baseline, approximately 30 minutes after study drug administration
Change in Pulmonary Vascular Resistance (PVR) After Study Drug (Resting)
Time frame: baseline, approximately 30 minutes after study drug administration
Change in Pulmonary Artery (PA) Compliance After Study Drug (Resting)
Time frame: baseline, approximately 30 minutes after study drug administration
Change in Systemic Vascular Resistance (SVR) After Study Drug (Resting)
Time frame: baseline, approximately 30 minutes after study drug administration
Change in Left Ventricular Stroke Work (LVSW) After Study Drug (Resting)
Time frame: baseline, approximately 30 minutes after study drug administration
Change in Oxygen Consumption (VO_2) After Study Drug (Resting)
Time frame: baseline, approximately 30 minutes after study drug administration
Change in Arteriovenous Oxygen Content Difference After Study Drug (Resting)
Time frame: baseline, approximately 30 minutes after study drug administration
Change in Cardiac Output After Study Drug (Resting)
Time frame: baseline, approximately 30 minutes after study drug administration
Change in Stroke Volume After Study Drug (Resting)
Time frame: baseline, approximately 30 minutes after study drug administration
Change in Central Pressures After Study Drug (Exercise)
Time frame: baseline, approximately 30 minutes after study drug administration
Change in Heart Rate After Study Drug (Exercise)
Time frame: baseline, approximately 30 minutes after study drug administration
Change in Blood Pressure After Study Drug (Exercise)
Time frame: baseline, approximately 30 minutes after study drug administration
Change in PVR After Study Drug (Exercise)
Time frame: baseline, approximately 30 minutes after study drug administration
Change in PA Compliance After Study Drug (Exercise)
Time frame: baseline, approximately 30 minutes after study drug administration
Change in SVR After Study Drug (Exercise)
Time frame: baseline, approximately 30 minutes after study drug administration
Change in LVSW After Study Drug (Exercise)
Time frame: baseline, approximately 30 minutes after study drug administration
Change in Oxygen Consumption (VO_2) After Study Drug (Exercise)
Time frame: baseline, approximately 30 minutes after study drug administration
Change in Arteriovenous Oxygen Difference After Study Drug (Exercise)
Time frame: baseline, approximately 30 minutes after study drug administration
Change in Cardiac Output After Study Drug (Exercise)
Time frame: baseline, approximately 30 minutes after study drug administration
Change in Stroke Volume After Study Drug (Exercise)
Time frame: baseline, approximately 30 minutes after study drug administration
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Mar 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 26449137Borlaug BA, Koepp KE, Melenovsky V. Sodium Nitrite Improves Exercise Hemodynamics and Ventricular Performance in Heart Failure With Preserved Ejection Fraction. J Am Coll Cardiol. 2015 Oct 13;66(15):1672-82. doi: 10.1016/j.jacc.2015.07.067.
- Derived from this study: PubMed 33421267Reddy YNV, Stewart GM, Obokata M, Koepp KE, Borlaug BA. Peripheral and pulmonary effects of inorganic nitrite during exercise in heart failure with preserved ejection fraction. Eur J Heart Fail. 2021 May;23(5):814-823. doi: 10.1002/ejhf.2093. Epub 2021 Feb 1.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Barry Borlaug, MD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nitrite in people with Heart Disease and Heart Failure With Preserved Ejection Fraction, run by Barry Borlaug at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Exercise Pulmonary Capillary Wedge Pressure (PCWP) (time frame: during repeat exercise run, approximately 30 minutes after study drug administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01932606, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Mar 2016.