Heart FailurePhase 2NCT02262078
Inhaled Sodium Nitrite on Heart Failure With Preserved Ejection Fraction
A Phase 2 study testing Sodium Nitrite Inhalation Solution in people with Heart Failure, run by Mayo Clinic 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 will assess the effects of nebulized inhaled nitrite administration on resting and exercise hemodynamics in patients with HFpEF referred to the catheterization lab. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure
- What is being tested?
- Sodium Nitrite Inhalation Solution
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2014to Dec 2015
- 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
- Heart Failure with preserved Ejection Fraction (HFpEF) is defined by clinical symptoms of dyspnea and fatigue
- Normal left ventricular ejection fraction (>/=50%)
- And elevated Left Ventricular (LV) filling pressure at cardiac catheterization (defined as resting Pulmonary Capillary Wedge Pressure (PCWP)>15 mmHg and/or PCWP >/=25 mmHg during exercise).
Who cannot join
- Systolic Blood Pressure <120 mmHg (during catheterization)
- 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
Show all 9Show fewer
- Primary renal or hepatic disease (end stage renal failure/on dialysis or clinical diagnosis of hepatitis or hepatic cirrhosis)
- Constrictive pericarditis, or infiltrative, restrictive, or hypertrophic cardiomyopathies
- Pregnant
Trial locations and contacts
1 site in 1 country.
United States1 site
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
About this study
Official title: Acute Effects of Inhaled Sodium Nitrite on Cardiovascular Hemodynamics in Heart Failure With Preserved Ejection Fraction
Heart failure with preserved ejection fraction (HFpEF) is a major public health problem that has no proven effective treatment. This study will assess the effects of nebulized inhaled nitrite administration on resting and exercise hemodynamics in patients with HFpEF referred to the catheterization lab.
Read the detailed description
Patients referred to the cardiac catheterization laboratory for invasive exercise stress testing will be prospectively recruited. Standard right heart catheterization using high fidelity micromanometers (Millar Instruments) will be performed at rest and during supine exercise with simultaneous expired gas analysis (Medgraphics) as is the investigator's current practice. The protocol is rest-passive leg elevation--20 Watts exercise x 5 minutes, and then graded workload increases in 10Watt increments (3 minute stages) to exhaustion. Hemodynamic, arterial and mixed venous blood gas and expired gas data are acquired at rest, during each exercise stage and at peak exercise. Venous blood samples will be obtained at rest and at peak exercise. Perceived symptoms of dyspnea and fatigue will be quantified using the Borg dyspnea and effort scores at each stage of exercise.
After the initial exercise study and hemodynamics have returned to baseline, previously prepared study drug (normal saline placebo or Sodium Nitrite Inhalation Solution (AIR001) 90mg placed into the medication chamber) will be nebulized utilizing the Aerogen Solo-Idehaler over 10-15 minutes. After a 15 minute observation period post completion of nebulization, resting hemodynamic and expired gas data will be acquired exactly as in the initial run. Subjects will then repeat the leg elevation-20 Watt x 5 minutes exercise phase. Blood samples will be again obtained at rest and with exercise. Subjects will repeat exercise only at the 20 Watt stage, rather repeating the entire study. This is done to increase the feasibility and shorten the time of the case. The investigators have previously observed that the vast majority (>85%) of the elevation in cardiac filling pressures and reduction in venous oxygen content in people with HFpEF occurs at the low 20 Watt workload, so repeating exercise hemodynamic assessment at this load should be sufficient to detect any clinically meaningful treatment effect.
- Conditions
- Heart Failure
- Being tested
- Sodium Nitrite Inhalation Solution, Placebo
- Keywords
- Preserved Ejection Fraction
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sodium Nitrite Inhalation SolutionDrug
Also called AIR001, NaNO2, Sodium Nitrite
90mg of (nebulized) inhaled sodium nitrite will be administered (by inhalation) to participants prior to exercise.
PlaceboOther
Also called Saline
Normal saline will be administered (by inhalation) to participants prior to exercise.
| Study group | Role | What they receive |
|---|---|---|
| Placebo (Saline) | Placebo comparator | Participants receive normal saline, administered by inhalation over 10-15 minutes, using a nebulizer Receives: Other: Placebo |
| Sodium Nitrite | Experimental | Participants receive Sodium Nitrite inhalation solution, administered by inhalation over 10-15 minutes, using a nebulizer Receives: Drug: Sodium Nitrite Inhalation Solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Pulmonary Capillary Wedge Pressure During Exercise
Pulmonary capillary wedge pressure is a measure of cardiac filling pressure, measured in millimeters of mercury (mmHg)
Measured: Baseline, after study drug dosing, approximately 4 minutes after starting exercise
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2014 (estimated)
- Study startOct 2014
- Primary completionDec 2015
- Study completionDec 2015
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 FailureStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- 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
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- Aires Pharmaceuticals, Inc., National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Barry Borlaug, Mayo Clinic
- Investigators
- Barry Borlaug, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02262078
- Sponsor's protocol ID
- 14-005091
- Other IDs
- R01HL128526, U10HL110262
- Status last verified
- Jul 2017
- First submitted
- 30 Sep 2014
- Last updated
- 29 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Borlaug BA, Melenovsky V, Koepp KE. Inhaled Sodium Nitrite Improves Rest and Exercise Hemodynamics in Heart Failure With Preserved Ejection Fraction. Circ Res. 2016 Sep 16;119(7):880-6. doi: 10.1161/CIRCRESAHA.116.309184. Epub 2016 Jul 25.
PubMed 27458234Reddy 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 29 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acute Effects of Inhaled Sodium Nitrite on Cardiovascular Hemodynamics in Heart Failure With Preserved Ejection Fraction
- ClinicalTrials.gov ID
- NCT02262078
- Acronym / sponsor ID
- 14-005091
- Conditions
- Heart Failure
- Keywords
- Preserved Ejection Fraction
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- Aires Pharmaceuticals, Inc., National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Oct 2014
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 10 Oct 2014 (estimated)
- Results
- Posted 19 Jan 2017
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 will assess the effects of nebulized inhaled nitrite administration on resting and exercise hemodynamics in patients with HFpEF referred to the catheterization lab.
Detailed description
Patients referred to the cardiac catheterization laboratory for invasive exercise stress testing will be prospectively recruited. Standard right heart catheterization using high fidelity micromanometers (Millar Instruments) will be performed at rest and during supine exercise with simultaneous expired gas analysis (Medgraphics) as is the investigator's current practice. The protocol is rest-passive leg elevation--20 Watts exercise x 5 minutes, and then graded workload increases in 10Watt increments (3 minute stages) to exhaustion. Hemodynamic, arterial and mixed venous blood gas and expired gas data are acquired at rest, during each exercise stage and at peak exercise. Venous blood samples will be obtained at rest and at peak exercise. Perceived symptoms of dyspnea and fatigue will be quantified using the Borg dyspnea and effort scores at each stage of exercise.
After the initial exercise study and hemodynamics have returned to baseline, previously prepared study drug (normal saline placebo or Sodium Nitrite Inhalation Solution (AIR001) 90mg placed into the medication chamber) will be nebulized utilizing the Aerogen Solo-Idehaler over 10-15 minutes. After a 15 minute observation period post completion of nebulization, resting hemodynamic and expired gas data will be acquired exactly as in the initial run. Subjects will then repeat the leg elevation-20 Watt x 5 minutes exercise phase. Blood samples will be again obtained at rest and with exercise. Subjects will repeat exercise only at the 20 Watt stage, rather repeating the entire study. This is done to increase the feasibility and shorten the time of the case. The investigators have previously observed that the vast majority (>85%) of the elevation in cardiac filling pressures and reduction in venous oxygen content in people with HFpEF occurs at the low 20 Watt workload, so repeating exercise hemodynamic assessment at this load should be sufficient to detect any clinically meaningful treatment effect.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo (Saline) | Placebo comparator | Other: PlaceboParticipants receive normal saline, administered by inhalation over 10-15 minutes, using a nebulizer |
| Sodium Nitrite | Experimental | Drug: Sodium Nitrite Inhalation SolutionParticipants receive Sodium Nitrite inhalation solution, administered by inhalation over 10-15 minutes, using a nebulizer |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Heart Failure with preserved Ejection Fraction (HFpEF) is defined by clinical symptoms of dyspnea and fatigue
- Normal left ventricular ejection fraction (>/=50%)
- And elevated Left Ventricular (LV) filling pressure at cardiac catheterization (defined as resting Pulmonary Capillary Wedge Pressure (PCWP)>15 mmHg and/or PCWP >/=25 mmHg during exercise).
Key exclusion criteria (9 listed)
- Systolic Blood Pressure <120 mmHg (during catheterization)
- 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
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 |
|---|---|---|
| Sodium Nitrite Inhalation SolutionAlso: AIR001, NaNO2, Sodium Nitrite90mg of (nebulized) inhaled sodium nitrite will be administered (by inhalation) to participants prior to exercise. | Drug | Sodium Nitrite |
| PlaceboAlso: SalineNormal saline will be administered (by inhalation) to participants prior to exercise. | Other | Placebo (Saline) |
Primary outcome
Change in Pulmonary Capillary Wedge Pressure During Exercise
Time frame: Baseline, after study drug dosing, approximately 4 minutes after starting exercise
Pulmonary capillary wedge pressure is a measure of cardiac filling pressure, measured in millimeters of mercury (mmHg)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 27458234Borlaug BA, Melenovsky V, Koepp KE. Inhaled Sodium Nitrite Improves Rest and Exercise Hemodynamics in Heart Failure With Preserved Ejection Fraction. Circ Res. 2016 Sep 16;119(7):880-6. doi: 10.1161/CIRCRESAHA.116.309184. Epub 2016 Jul 25.
- 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.
- Individual participant dataSharing planned: No
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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 Sodium Nitrite Inhalation Solution in people with Heart Failure, run by Mayo Clinic 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 3 inclusion and 9 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 29 Aug 2017. 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 19 Jan 2017). 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?
Change in Pulmonary Capillary Wedge Pressure During Exercise (time frame: Baseline, after study drug dosing, approximately 4 minutes after starting exercise). 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 NCT02262078, 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 29 Aug 2017.