Heart FailurePhase 1/2NCT02797184
Inorganic NItrate and EXercise Performance in Heart Failure (iNIX-HF): Dose Response
A Phase 1/2 study testing KNO3, potassium nitrate in people with Heart Failure, run by Washington University School of Medicine at 1 site in United States.
Trial summary
The purpose of this study is to do the work that is necessary and sufficient for setting up an appropriate multi-center, randomized clinical trial (RCT) of a new therapy for heart failure: inorganic nitrate. Read more about this study
- Who is it for?
- Ages 18 to 74 years
- Conditions the study is for
- Heart Failure
- What is being tested?
- KNO3, potassium nitrate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Oct 2017to 15 Dec 2021
- Phase
- Phase 1/2
- 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 to 74 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Sex: females and males
- Age: at least 18 years and less than 75 years
- Diagnosis of heart failure with reduced ejection fraction (NYHA II-IV)
- Ejection fraction <45% as determined on an imaging study within 12 mo of enrollment
- Stable medical therapy - defined by no addition or removal (or change of more than 100%) of the following: beta-adrenergic blockade, angiotensin converting enzyme (ACE) inhibitors, or angiotensin receptor blocker (ARB or aldosterone antagonists) for 30 days prior to enrolment
Who cannot join
- "Vulnerable populations" as defined by the U.S. Department of Health and Human Services, such as prisoners and children
- Pharmacologic, organic nitrate therapy within the last 3 months
- Major orthopedic, psychiatric, neurological, or other conditions that would impair performance of the exercise tests in this study
- Atrial fibrillation/flutter
- Estimated glomerular filtration rate < 50 ml/min on most recent clinical laboratories
- Systolic blood pressure < 95 mmHg or >180 mmHg at consent
Show all 24Show fewer
- Diastolic blood pressure <40 mmHg or >100 mmHg at consent
- Previous adverse reaction to nitrates necessitating withdrawal of therapy
- Treatment with phosphodiesterase inhibitors within the last 3 months (patient must also be willing to not take them for the duration of the trial).
- Ejection fraction > 45%
- Primary hypertrophic cardiomyopathy
- Infiltrative cardiomyopathy (e.g., amyloid)
- Active myocarditis
- Complex congenital heart disease
- Active collagen vascular disease
- Active angina/ischemia from epicardial coronary disease
- Percutaneous coronary intervention, new bi-ventricular pacing, or coronary artery bypass grafting within the past 3 months
- More than mild mitral or aortic stenosis
- Valvular heart disease with severe regurgitation of any valve.
- Acute or chronic severe liver disease as evidenced by encephalopathy, international normalized ratio (INR) >1.7 without anticoagulation therapy, or variceal bleeding
- Patients requiring exogenous oxygen at rest or for exercise
- Terminal disease (other than heart failure) with expected survival < 1 y
- Enrollment in another therapeutic trial during the period of the study
- Pregnancy
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
The purpose of this study is to do the work that is necessary and sufficient for setting up an appropriate multi-center, randomized clinical trial (RCT) of a new therapy for heart failure: inorganic nitrate. The investigators will first determine the effects and palatability of ~12.8mmol KNO3 (an oral pill) as compared to the roughly equivalent amount of nitrate in 2 beetroot juice (BRJ) Sports Shots (by James White Drinks). Next, the investigators will determine the effects of inorganic nitrate (KNO3 in an oral pill format) on blood pressure, blood nitrate levels, breath nitric oxide (NO) levels, and exercise performance in a dose-response study. Third, the investigators will perform a small phase II chronic treatment study that will allow them to determine the best primary endpoint and the numbers of patients the investigators will need to study in the large, multi-center RCT to follow this project. In the small study and in the RCT to follow, the investigators will determine whether inorganic nitrate can improve aerobic exercise capacity, muscle power, and speed of muscle contraction, and lessen the effort of breathing during exercise.
Read the detailed description
- Subjects will be patients with Heart Failure (HF).
- All subjects will be consented.
- All subjects will give permission for the investigators to review their medical records.
- After consenting to participate, subjects will be instructed to refrain from spitting or the use of an antibacterial mouthwash, antacids, proton pump inhibitors, or chewing gum during the morning of each clinic visit.
- Subjects will have a physical examination.
- Subjects will undergo transthoracic echocardiographic imaging at rest (unless they had this performed within the past 6 months).
- Subjects will be asked to undergo a mouth swab for bacterial DNA analyses.
- Subjects will be asked to answer questionnaires regarding their medical health (basic health questionnaire, Minnesota living with heart failure questionnaire, a combined fatigue questionnaire.
- Dose visit 1: Subjects will receive 2 capsules containing either 10 or 20 mmol of potassium nitrate (KNO3).
- Before and at 3 hourly time points after receiving the KNO3, subjects will undergo phlebotomy for plasma nitrite levels, will have their blood pressure measured, and will blow into a small machine to assess the amount of nitric oxide in their breath.
- Exercise Test 1: Subjects will complete measurements of leg muscle power by doing knee extension exercises on a dynamometer (a device that measures voluntary muscle force production while controlling the speed of movement).
- Exercise Test 2: Subjects complete a measurement of peak aerobic capacity (VO2peak) while walking on a treadmill and breathing into a mouthpiece. Blood pressure, heart rate and heart rhythm will be monitored during this test.
- Subjects will undergo a 7 d washout period.
- Dose visit 2: Subjects will receive 2 capsules containing either 10 or 20 mmol of KNO3 (whichever dose they did not receive at dose visit 1). They will repeat the same assessments listed above in 10, 11, and 12.
- Conditions
- Heart Failure
- Being tested
- KNO3, potassium nitrate
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KNO3, potassium nitrateDrug
Also called saltpeter
Potassium nitrate (KNO3) will be given orally in 2 gelatin capsules, which will be compounded by the Barnes-Jewish Hospital Pharmacy. The doses are 10 mmol and 20 mmol KNO3.
| Study group | Role | What they receive |
|---|---|---|
| 10mmol KNO3 | Experimental | Intervention: Subjects with heart failure will receive a single oral dose of potassium nitrate (10 or 20 mmol KNO3) in 2 gelatin capsules during dose visit 1 and the other dose (10 or 20 mmol KNO3) during dose visit 2. The dose order will be randomized. Receives: Drug: KNO3, potassium nitrate |
| 20mmol KNO3 | Experimental | Intervention: Subjects with heart failure will receive a single oral dose of potassium nitrate (10 or 20 mmol KNO3) in 2 gelatin capsules during dose visit 1 and the other dose (10 or 20 mmol KNO3) during dose visit 2. The dose order will be randomized. Receives: Drug: KNO3, potassium nitrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
VO2peak
peak oxygen consumption during treadmill exercise
Measured: acute - 2.5 hours post dose
Secondary outcomes (3)
Peak Muscle Power
Participants completed measurements of leg muscle power by doing knee extension exercises on a dynamometer (a device that measures voluntary muscle force production while controlling the speed of movement).
Measured: acute - 2 hours post dose
Blood Nitrite Levels
concentrations of nitrite in the blood
Measured: time 0 (before receiving the KNO3 dose) and hourly after receiving KNO3 (1, 2, and 3 hours post-dose)
Breath Nitric Oxide (NO) Level
Breath nitric oxide (NO) level will be taken via NIOX breath analyzer
Measured: time 0 (before receiving the KNO3 dose) and hourly after receiving KNO3 (1, 2, and 3 hours post-dose)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2016 (estimated)
- Study start31 Oct 2017
- Primary completion31 Oct 2021
- Study completion15 Dec 2021
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.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Subjects will receive one drug dose on the first dose visit and the second drug dose on the second dose visit. The order of the two drug doses (10 and 20 mmol KNO3) will be randomized, so that some subjects will receive the lower dose first and others will receive the higher dose first
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Linda R Peterson, MD, Principal investigator, Washington University School of MedicineAndrew R Coggan, PhD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02797184
- Sponsor's protocol ID
- 2016_11111
- Other IDs
- 2016
- Status last verified
- May 2025
- First submitted
- 25 May 2016
- Last updated
- 20 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: HIPPA-related data will not be available for publishing. Study results will be published in accordance with journal, institution, and HIPPA guidelines.
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inorganic NItrate and EXercise Performance in Heart Failure (iNIX-HF): Dose Response
- ClinicalTrials.gov ID
- NCT02797184
- Acronym / sponsor ID
- 2016_11111
- Conditions
- Heart Failure
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- 31 Oct 2017 (actual)
- Primary completion
- 31 Oct 2021 (actual)
- Study completion
- 15 Dec 2021 (actual)
- First posted
- 13 Jun 2016 (estimated)
- Results
- Posted 10 Feb 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to do the work that is necessary and sufficient for setting up an appropriate multi-center, randomized clinical trial (RCT) of a new therapy for heart failure: inorganic nitrate. The investigators will first determine the effects and palatability of ~12.8mmol KNO3 (an oral pill) as compared to the roughly equivalent amount of nitrate in 2 beetroot juice (BRJ) Sports Shots (by James White Drinks). Next, the investigators will determine the effects of inorganic nitrate (KNO3 in an oral pill format) on blood pressure, blood nitrate levels, breath nitric oxide (NO) levels, and exercise performance in a dose-response study. Third, the investigators will perform a small phase II chronic treatment study that will allow them to determine the best primary endpoint and the numbers of patients the investigators will need to study in the large, multi-center RCT to follow this project. In the small study and in the RCT to follow, the investigators will determine whether inorganic nitrate can improve aerobic exercise capacity, muscle power, and speed of muscle contraction, and lessen the effort of breathing during exercise.
Detailed description
- Subjects will be patients with Heart Failure (HF).
- All subjects will be consented.
- All subjects will give permission for the investigators to review their medical records.
- After consenting to participate, subjects will be instructed to refrain from spitting or the use of an antibacterial mouthwash, antacids, proton pump inhibitors, or chewing gum during the morning of each clinic visit.
- Subjects will have a physical examination.
- Subjects will undergo transthoracic echocardiographic imaging at rest (unless they had this performed within the past 6 months).
- Subjects will be asked to undergo a mouth swab for bacterial DNA analyses.
- Subjects will be asked to answer questionnaires regarding their medical health (basic health questionnaire, Minnesota living with heart failure questionnaire, a combined fatigue questionnaire.
- Dose visit 1: Subjects will receive 2 capsules containing either 10 or 20 mmol of potassium nitrate (KNO3).
- Before and at 3 hourly time points after receiving the KNO3, subjects will undergo phlebotomy for plasma nitrite levels, will have their blood pressure measured, and will blow into a small machine to assess the amount of nitric oxide in their breath.
- Exercise Test 1: Subjects will complete measurements of leg muscle power by doing knee extension exercises on a dynamometer (a device that measures voluntary muscle force production while controlling the speed of movement).
- Exercise Test 2: Subjects complete a measurement of peak aerobic capacity (VO2peak) while walking on a treadmill and breathing into a mouthpiece. Blood pressure, heart rate and heart rhythm will be monitored during this test.
- Subjects will undergo a 7 d washout period.
- Dose visit 2: Subjects will receive 2 capsules containing either 10 or 20 mmol of KNO3 (whichever dose they did not receive at dose visit 1). They will repeat the same assessments listed above in 10, 11, and 12.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Subjects will receive one drug dose on the first dose visit and the second drug dose on the second dose visit. The order of the two drug doses (10 and 20 mmol KNO3) will be randomized, so that some subjects will receive the lower dose first and others will receive the higher dose first
| Arm | Type | Receives |
|---|---|---|
| 10mmol KNO3 | Experimental | Drug: KNO3, potassium nitrateIntervention: Subjects with heart failure will receive a single oral dose of potassium nitrate (10 or 20 mmol KNO3) in 2 gelatin capsules during dose visit 1 and the other dose (10 or 20 mmol KNO3) during dose visit 2. The dose order will be randomized. |
| 20mmol KNO3 | Experimental | Drug: KNO3, potassium nitrateIntervention: Subjects with heart failure will receive a single oral dose of potassium nitrate (10 or 20 mmol KNO3) in 2 gelatin capsules during dose visit 1 and the other dose (10 or 20 mmol KNO3) during dose visit 2. The dose order will be randomized. |
Who may qualify
- Ages
- 18 to 74 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Sex: females and males
- Age: at least 18 years and less than 75 years
- Diagnosis of heart failure with reduced ejection fraction (NYHA II-IV)
- Ejection fraction <45% as determined on an imaging study within 12 mo of enrollment
- Stable medical therapy - defined by no addition or removal (or change of more than 100%) of the following: beta-adrenergic blockade, angiotensin converting enzyme (ACE) inhibitors, or angiotensin receptor blocker (ARB or aldosterone antagonists) for 30 days prior to enrolment
Key exclusion criteria (24 listed)
- "Vulnerable populations" as defined by the U.S. Department of Health and Human Services, such as prisoners and children
- Pharmacologic, organic nitrate therapy within the last 3 months
- Major orthopedic, psychiatric, neurological, or other conditions that would impair performance of the exercise tests in this study
- Atrial fibrillation/flutter
- Estimated glomerular filtration rate < 50 ml/min on most recent clinical laboratories
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 |
|---|---|---|
| KNO3, potassium nitrateAlso: saltpeterPotassium nitrate (KNO3) will be given orally in 2 gelatin capsules, which will be compounded by the Barnes-Jewish Hospital Pharmacy. The doses are 10 mmol and 20 mmol KNO3. | Drug | 10mmol KNO3, 20mmol KNO3 |
Primary outcome
VO2peak
Time frame: acute - 2.5 hours post dose
peak oxygen consumption during treadmill exercise
3 secondary outcomes
Peak Muscle Power
Time frame: acute - 2 hours post dose
Blood Nitrite Levels
Time frame: time 0 (before receiving the KNO3 dose) and hourly after receiving KNO3 (1, 2, and 3 hours post-dose)
Breath Nitric Oxide (NO) Level
Time frame: time 0 (before receiving the KNO3 dose) and hourly after receiving KNO3 (1, 2, and 3 hours post-dose)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. HIPPA-related data will not be available for publishing. Study results will be published in accordance with journal, institution, and HIPPA guidelines.
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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.
Linda R Peterson, MD principal investigator
Washington University School of Medicine
Andrew R Coggan, PhD principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing KNO3, potassium nitrate in people with Heart Failure, run by Washington University School of Medicine 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 5 inclusion and 24 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 20 May 2025. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 10 Feb 2023). 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?
VO2peak (time frame: acute - 2.5 hours post dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 May 2025.