Heart FailurePhase 2iNIX-HFNCT05562167
The Inorganic Nitrate and eXercise Performance in Heart Failure (iNIX-HF)
A Phase 2 study testing KNO3 in people with Heart Failure, run by Washington University School of Medicine at 1 site in United States.
Trial summary
The goals of this project are to determine the effectiveness of acute (2 hours after a single dose) and chronic (after 6 weeks of once-a-day dosing) KNO3 treatment (10mmol) vs. placebo on quadriceps muscle power and on aerobic exercise performance (V̇O2peak) in patients with HFrEF (left ventricular ejection fraction… Read more about this study
- Who is it for?
- Ages 19 to 79 years
- Conditions the study is for
- Heart Failure
- What is being tested?
- KNO3
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 75 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Mar 2023to 31 Jul 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 19 to 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- To participate in this study, a patient must meet all of the criteria listed below:
- Males and females aged greater than or equal to 18y and less than 80y at time of consent
- Diagnosis of heart failure with reduced ejection fraction
- New York Heart Association (NYHA) Class II-III at Visit 1
- Ejection fraction less than 45%, as evaluated through transthoracic echocardiography at Visit 1
- Stable medical therapy, defined by no addition or removal (or change of more than 100 percent) of the following for 60 days prior to Visit 1: beta-adrenergic blockade and angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blocker (ARB or aldosterone antagonists) or ARNI (ARB + sacubitril)
- Ability and willingness to sign an IRB approved written informed consent form; legally authorized representatives are not allowed in this study
Who cannot join
- To participate in this study, a patient must not meet any of the criteria listed below:
- Vulnerable populations as defined by the U.S. Department of Health and Human Services; prisoners and children will be excluded from this study
- Pharmacologic, organic nitrate therapy within 3 months prior to Visit 1
- Major orthopedic, psychiatric, neurological, or other conditions that would hinder the ability to complete the exercise tests at the time of Visit 1
- Estimated glomerular filtration rate less than 45 mL/min/1.73m2 on screening clinical laboratories measured at Visit 1
- Systolic blood pressure less than 90mmHg or greater than 180mmHg at Visit 1
Show all 31Show fewer
- Diastolic blood pressure less than 40mmHg or greater than 100mmHg at Visit 1
- Previous adverse reaction to nitrate prior to Visit 1
- Treatment with phosphodiesterase inhibitors within the last 3 months prior to Visit 1; Patient must also be willing to not take them for the duration of the trial
- Diagnosis of primary hypertrophic cardiomyopathy, infiltrative cardiomyopathy (e.g., amyloid), active myocarditis, or complex congenital heart disease prior to Visit 1
- Active collagen vascular disease at time of Visit 1
- Percutaneous coronary intervention, new bi-ventricular pacing, or coronary artery bypass grafting within the 3 months prior to Visit 1
- Valvular heart disease with severe regurgitation or stenosis of any valve, as demonstrated on the echocardiogram at Visit 1
- Known severe liver disease as evidenced by encephalopathy or variceal bleeding;
- Terminal disease (other than heart failure) with expected survival less than 1 y at time of Visit 1
- Enrollment in another therapeutic trial at time of Visit 1
- Pregnant and breastfeeding women or postmenopausal women taking exogenous estrogen replacement therapy at time of Visit 1
- To meet this criterion, patients must have a negative urine pregnancy test and provide verbal confirmation that they are not breastfeeding at time of Visit 1.
- Note, post-menopausal is defined as last menstrual period occurring greater than or equal to 12 months prior to Visit 1 or confirmation of prior bilateral oophorectomy at least 6 months prior to first dose of study drug.
- Women of childbearing potential or men with childbearing potential partners must agree that the participant and/or their partner will use at least two of the following highly effective method of birth control from study entry until 48 hours after completing study therapy, if not abstaining from sexual activity:
- Barrier method contraception (e.g., male or female condoms with or without a spermicidal agent, diaphragm, or cervical cap with spermicide)
- Stable dose of injectable, depot, oral, implanted, intravaginal, or transdermal hormonal contraception for at least 30 days before sexual activity
- Intrauterine device (IUD) with or without hormones
- Surgical sterilization
- For women, this includes hysterectomy, bilateral oophorectomy with or without hysterectomy, or bilateral tubal ligation, bilateral salpingectomy, completed at least 6 months before first dose of study drug.
- For men, this includes vasectomy.
- Patients requiring exogenous oxygen at rest or during exercise prior to Visit 1
- Patients with active angina at time of Visit 1 or ischemia due to epicardial coronary disease prior to or at time of Visit 1
- Patients taking xanthine oxidase inhibitors at time of Visit 1
- Individuals taking proton pump inhibitors and/or antacids at time of Visit 1, if unable to stop these medications for the duration of the study.
- Note, while patients will be asked to refrain from taking these medications for the duration of the study, they may take tums. However, patients must discontinue Tums for 5 days prior to study visits 2, 3, and 4.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
Dawson A Haley, B.S., 314-791-4455, dhaley@wustl.edu
Linda R Peterson, MD, 314-362-4577, lpeterso@wustl.edu
About this study
Official title: The Inorganic Nitrate and eXercise Performance in Heart Failure (iNIX-HF) -a Phase II Clinical Trial
The goals of this project are to determine the effectiveness of acute (2 hours after a single dose) and chronic (after 6 weeks of once-a-day dosing) KNO3 treatment (10mmol) vs. placebo on quadriceps muscle power and on aerobic exercise performance (V̇O2peak) in patients with HFrEF (left ventricular ejection fraction <45%). The investigators hypothesize that both acute and chronic dosing of 10mmol of KNO3 will improve exercise performance in HFrEF. To test this hypothesis, the investors will perform a randomized, double-blind, placebo-controlled, parallel-arm design study.
Read the detailed description
Visit 1 - Screening
Visit 1 will be considered the screening visit. Participants will not be required to fast for this visit. This visit will be conducted over approximately 1.5 to 2 hours. The following procedures will be completed during this visit:
- Informed consent, if not already obtained previously.
- Health questionnaire
- Review of medical history and concomitant medication usage
- Review of any patient reported eligibility criteria (e.g., agreeance to using birth control, not using phosphodiesterase, inhibitors, etc.)
- Labs
- As this is the only blood sample collected during this visit, IV placement is not necessary at this visit.
- Urine pregnancy test
- Physical examination
- NYHA classification
- Vital signs measurements
- Height and weight measurements
- Resting TTE with or without contrast
At the conclusion of Visit 1, eligibility criteria for each participant will be reviewed and confirmed by the PI prior to the participant completing Visit 2 procedures.
Visit 2 - Baseline
Visit 2 will be considered the baseline visit. Participants will be required to fast for this visit. This visit will be conducted over approximately 4 to 5 hours. Upon the participant's arrival, the following will occur:
- Review of any changes to medical history and concomitant medication usage
- Review of compliance on restrictions
- IV placement
- Labs
- Vital signs measurements
- Height, weight, hip, and waist circumference measurements
- Low nitrate snack consumption
- PWV and PWA
After these procedures have been completed, the following procedures will occur each hour as follows in the order in which they are listed, if not being completed simultaneously:
- 0 Hour
- Blood sampling for NO3- and NO2- and NT-proBNP
- Breath Nitric Oxide
- Hand grip strength assessment
- KCCQ and MLHFQ
- 1 Hour
- Blood sampling for NO3- and NO2- only
- Vital signs measurements (BP and HR only)
- Breath Nitric Oxide
- PWV and PWA
- DXA Scan
- 2 Hour
- Blood sampling for NO3- and NO2- only
- Vital signs measurements (BP and HR only)
- Breath Nitric Oxide
- Maximal muscle power test
- Aerobic capacity test
- 3 Hour
- Blood sampling for NO3- and NO2- only
- Vital signs measurements (BP and HR only)
- Breath Nitric Oxide
- Hand grip strength assessment
- 4 Hour
- Blood sampling for NO3- and NO2- only
- Vital signs measurements (BP and HR only)
- Breath Nitric Oxide
Note, blood sampling, vital signs, and breath nitric oxide measurements should be collected as close to the beginning of each hourly time point as possible. However, it will not be considered a protocol deviation if they are slightly delayed due to procedures such as exercise testing extending into the next hour. All other procedures can be completed within each hour as time permits.
After completion of the 4 hour time point, the participant will be discharged from the facility.
Visit 3 - Acute Dose Administration
This visit will occur within 1 month after Visit 2. Participants will be required to fast for this visit. This visit will be conducted over approximately 4 to 5 hours. Upon the participant's arrival, the following will occur:
- Review of any changes to medical history and concomitant medication usage
- Review of compliance on restrictions
- IV placement
- Labs
- Vital signs measurements
- Height, weight, hip, and waist circumference measurements
- Low nitrate snack consumption
- PWV and PWA
After these procedures have been completed, the following procedures will occur each hour as follows in the order in which they are listed, if not being completed simultaneously:
- 0 Hour
- Blood sampling for NO3- and NO2- and NT-proBNP
- Breath Nitric Oxide
- Ingestion of investigational product
- Hand grip strength assessment
- KCCQ and MLHFQ
- 1 Hour
- Blood sampling for NO3- and NO2- only
- Vital signs measurements (BP and HR only)
- Breath Nitric Oxide
- PWV and PWA
- 2 Hour
- Blood sampling for NO3- and NO2- only
- Vital signs measurements (BP and HR only)
- Breath Nitric Oxide
- Maximal muscle power test
- Aerobic capacity test
- 3 Hour
- Blood sampling for NO3- and NO2- only
- Vital signs measurements (BP and HR only)
- Breath Nitric Oxide
- Hand grip strength assessment
- 4 Hour
- Blood sampling for NO3- and NO2- only
- Vital signs measurements (BP and HR only)
- Breath Nitric Oxide
- Review of any adverse events specifically associated with investigational medication administration
- Dispense of 6 weeks' worth of investigational medication
Note, blood sampling, vital signs, and breath nitric oxide measurements should be collected as close to the beginning of each hourly time point as possible. However, it will not be considered a protocol deviation if they are slightly delayed due to procedures such as exercise testing extending into the next hour. All other procedures can be completed within each hour as time permits.
After completion of the 4 hour time point, the participant will be discharged from the facility.
Between Visits 3 and 4
Between visits 3 and 4, participants will take the study medication provided daily.
Every 2 weeks, participants will be asked to complete a Bi-weekly Adherence Survey to track compliance between Visits 3 and 4.
Visit 4 - 6 Week Follow Up/End of Study
Participants will be required to fast for this visit. This visit will be conducted over approximately 4 to 5 hours. Upon the participant's arrival, the following will occur:
- Review of any changes to medical history and concomitant medication usage
- Review of compliance on restrictions
- Collection of any remaining investigational product
- IV placement
- Labs
- Vital signs measurements
- Height, weight, hip, and waist circumference measurements
- Physical exam
- Low nitrate snack consumption
- Resting TTE with contrast
- PWV and PWA
After these procedures have been completed, the following procedures will occur each hour as follows in the order in which they are listed, if not being completed simultaneously:
- 0 Hour
- Blood sampling for NO3- and NO2- and NT-proBNP f. Breath Nitric Oxide g. Ingestion of investigational product h. Hand grip strength assessment i. KCCQ and MLHFQ
- 1 Hour
- Blood sampling for NO3- and NO2- only
- Vital signs measurements (BP and HR only)
- Breath Nitric Oxide
- PWV and PWA
- DXA scan
- 2 Hour
- Blood sampling for NO3- and NO2- only
- Vital signs measurements (BP and HR only)
- Breath Nitric Oxide
- Maximal muscle power test
- Aerobic capacity test
- 3 Hour
- Blood sampling for NO3- and NO2- only
- Vital signs measurements (BP and HR only)
- Breath Nitric Oxide
- Hand grip strength assessment
- 4 Hour
- Blood sampling for NO3- and NO2- only
- Vital signs measurements (BP and HR only)
- Breath Nitric Oxide
Note, blood sampling, vital signs, and breath nitric oxide measurements should be collected as close to the beginning of each hourly time point as possible. However, it will not be considered a protocol deviation if they are slightly delayed due to procedures such as exercise testing extending into the next hour. All other procedures can be completed within each hour as time permits.
After completion of the 4 hour time point, the participant will be discharged from the facility. At this time, the participant will be considered to have completed the study.
- Conditions
- Heart Failure
- Being tested
- KNO3, Placebo
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KNO3Drug
Also called Potassium nitrate
10 mmol of KNO3 via a single gel capsule to be consumed orally once per day for 6 weeks.
PlaceboDrug
10 mmol of placebo via a single gel capsule to be consumed orally once per day for 6 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Potassium Nitrate (KNO3) treatment arm | Experimental | 10 mmol of KNO3 via a single gel capsule to be consumed orally once per day for 6 weeks. Receives: Drug: KNO3 |
| Placebo-controlled arm | Placebo comparator | 10 mmol of placebo via a single gel capsule to be consumed orally once per day for 6 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
VO2 Peak Testing
peak oxygen consumption during treadmill exercise
Measured: Determined at Baseline visit, Acute Dose Visit, and Chronic Dose Visit, which will be scheduled throughout 8 weeks.
Maximal muscle power
assessment of quadriceps power
Measured: Determined at Baseline visit, Acute Dose Visit, and Chronic Dose Visit, which will be scheduled throughout 8 weeks.
Secondary outcomes (6)
MLHFQ questionnaire
Minnesota Living with Heart Failure Questionnaire
Measured: Determined at Baseline visit, Acute Dose Visit, and Chronic Dose Visit, which will be scheduled throughout 8 weeks.
KCCQ questionnaire
Kansas City Cardiomyopathy Questionnaire
Measured: Determined at Baseline visit, Acute Dose Visit, and Chronic Dose Visit, which will be scheduled throughout 8 weeks.
Maximal muscle velocity
assessment of quadriceps velocity
Measured: Determined at Baseline visit, Acute Dose Visit, and Chronic Dose Visit, which will be scheduled throughout 8 weeks.
Maximal exercise time on treadmill
Maximum time spent on treadmill during the VO2 peak test
Measured: Determined at Baseline visit, Acute Dose Visit, and Chronic Dose Visit, which will be scheduled throughout 8 weeks.
Plasma nitrate and nitrite
concentrations of nitrate and nitrite in the blood
Measured: Determined at Baseline visit, Acute Dose Visit, and Chronic Dose Visit, which will be scheduled throughout 8 weeks.
Breath nitric oxide (NO) level
breath NO level
Measured: Determined at Baseline visit, Acute Dose Visit, and Chronic Dose Visit, which will be scheduled throughout 8 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2022
- Study start31 Mar 2023
- Primary completion31 May 2027 (estimated)
- Study completion31 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, placebo-controlled, parallel arm design
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 75 participants (estimated)
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 Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05562167
- Sponsor's protocol ID
- 202204141
- Acronym
- iNIX-HF
- Status last verified
- May 2026
- First submitted
- 21 Sep 2022
- Last updated
- 6 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Inorganic Nitrate and eXercise Performance in Heart Failure (iNIX-HF) -a Phase II Clinical Trial
- ClinicalTrials.gov ID
- NCT05562167
- Acronym / sponsor ID
- iNIX-HF / 202204141
- Conditions
- Heart Failure
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 75 participants (estimated)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- 31 Mar 2023 (actual)
- Primary completion
- 31 May 2027 (estimated)
- Study completion
- 31 Jul 2027 (estimated)
- First posted
- 30 Sep 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goals of this project are to determine the effectiveness of acute (2 hours after a single dose) and chronic (after 6 weeks of once-a-day dosing) KNO3 treatment (10mmol) vs. placebo on quadriceps muscle power and on aerobic exercise performance (V̇O2peak) in patients with HFrEF (left ventricular ejection fraction <45%). The investigators hypothesize that both acute and chronic dosing of 10mmol of KNO3 will improve exercise performance in HFrEF. To test this hypothesis, the investors will perform a randomized, double-blind, placebo-controlled, parallel-arm design study.
Detailed description
Visit 1 - Screening
Visit 1 will be considered the screening visit. Participants will not be required to fast for this visit. This visit will be conducted over approximately 1.5 to 2 hours. The following procedures will be completed during this visit:
- Informed consent, if not already obtained previously.
- Health questionnaire
- Review of medical history and concomitant medication usage
- Review of any patient reported eligibility criteria (e.g., agreeance to using birth control, not using phosphodiesterase, inhibitors, etc.)
- Labs
- As this is the only blood sample collected during this visit, IV placement is not necessary at this visit.
- Urine pregnancy test
- Physical examination
- NYHA classification
- Vital signs measurements
- Height and weight measurements
- Resting TTE with or without contrast
At the conclusion of Visit 1, eligibility criteria for each participant will be reviewed and confirmed by the PI prior to the participant completing Visit 2 procedures.
Visit 2 - Baseline
Visit 2 will be considered the baseline visit. Participants will be required to fast for this visit. This visit will be conducted over approximately 4 to 5 hours. Upon the participant's arrival, the following will occur:
- Review of any changes to medical history and concomitant medication usage
- Review of compliance on restrictions
- IV placement
- Labs
- Vital signs measurements
- Height, weight, hip, and waist circumference measurements
- Low nitrate snack consumption
- PWV and PWA
After these procedures have been completed, the following procedures will occur each hour as follows in the order in which they are listed, if not being completed simultaneously:
- 0 Hour
- Blood sampling for NO3- and NO2- and NT-proBNP
- Breath Nitric Oxide
- Hand grip strength assessment
- KCCQ and MLHFQ
- 1 Hour
- Blood sampling for NO3- and NO2- only
- Vital signs measurements (BP and HR only)
- Breath Nitric Oxide
- PWV and PWA
- DXA Scan
- 2 Hour
- Blood sampling for NO3- and NO2- only
- Vital signs measurements (BP and HR only)
- Breath Nitric Oxide
- Maximal muscle power test
- Aerobic capacity test
- 3 Hour
- Blood sampling for NO3- and NO2- only
- Vital signs measurements (BP and HR only)
- Breath Nitric Oxide
- Hand grip strength assessment
- 4 Hour
- Blood sampling for NO3- and NO2- only
- Vital signs measurements (BP and HR only)
- Breath Nitric Oxide
Note, blood sampling, vital signs, and breath nitric oxide measurements should be collected as close to the beginning of each hourly time point as possible. However, it will not be considered a protocol deviation if they are slightly delayed due to procedures such as exercise testing extending into the next hour. All other procedures can be completed within each hour as time permits.
After completion of the 4 hour time point, the participant will be discharged from the facility.
Visit 3 - Acute Dose Administration
This visit will occur within 1 month after Visit 2. Participants will be required to fast for this visit. This visit will be conducted over approximately 4 to 5 hours. Upon the participant's arrival, the following will occur:
- Review of any changes to medical history and concomitant medication usage
- Review of compliance on restrictions
- IV placement
- Labs
- Vital signs measurements
- Height, weight, hip, and waist circumference measurements
- Low nitrate snack consumption
- PWV and PWA
After these procedures have been completed, the following procedures will occur each hour as follows in the order in which they are listed, if not being completed simultaneously:
- 0 Hour
- Blood sampling for NO3- and NO2- and NT-proBNP
- Breath Nitric Oxide
- Ingestion of investigational product
- Hand grip strength assessment
- KCCQ and MLHFQ
- 1 Hour
- Blood sampling for NO3- and NO2- only
- Vital signs measurements (BP and HR only)
- Breath Nitric Oxide
- PWV and PWA
- 2 Hour
- Blood sampling for NO3- and NO2- only
- Vital signs measurements (BP and HR only)
- Breath Nitric Oxide
- Maximal muscle power test
- Aerobic capacity test
- 3 Hour
- Blood sampling for NO3- and NO2- only
- Vital signs measurements (BP and HR only)
- Breath Nitric Oxide
- Hand grip strength assessment
- 4 Hour
- Blood sampling for NO3- and NO2- only
- Vital signs measurements (BP and HR only)
- Breath Nitric Oxide
- Review of any adverse events specifically associated with investigational medication administration
- Dispense of 6 weeks' worth of investigational medication
Note, blood sampling, vital signs, and breath nitric oxide measurements should be collected as close to the beginning of each hourly time point as possible. However, it will not be considered a protocol deviation if they are slightly delayed due to procedures such as exercise testing extending into the next hour. All other procedures can be completed within each hour as time permits.
After completion of the 4 hour time point, the participant will be discharged from the facility.
Between Visits 3 and 4
Between visits 3 and 4, participants will take the study medication provided daily.
Every 2 weeks, participants will be asked to complete a Bi-weekly Adherence Survey to track compliance between Visits 3 and 4.
Visit 4 - 6 Week Follow Up/End of Study
Participants will be required to fast for this visit. This visit will be conducted over approximately 4 to 5 hours. Upon the participant's arrival, the following will occur:
- Review of any changes to medical history and concomitant medication usage
- Review of compliance on restrictions
- Collection of any remaining investigational product
- IV placement
- Labs
- Vital signs measurements
- Height, weight, hip, and waist circumference measurements
- Physical exam
- Low nitrate snack consumption
- Resting TTE with contrast
- PWV and PWA
After these procedures have been completed, the following procedures will occur each hour as follows in the order in which they are listed, if not being completed simultaneously:
- 0 Hour
- Blood sampling for NO3- and NO2- and NT-proBNP f. Breath Nitric Oxide g. Ingestion of investigational product h. Hand grip strength assessment i. KCCQ and MLHFQ
- 1 Hour
- Blood sampling for NO3- and NO2- only
- Vital signs measurements (BP and HR only)
- Breath Nitric Oxide
- PWV and PWA
- DXA scan
- 2 Hour
- Blood sampling for NO3- and NO2- only
- Vital signs measurements (BP and HR only)
- Breath Nitric Oxide
- Maximal muscle power test
- Aerobic capacity test
- 3 Hour
- Blood sampling for NO3- and NO2- only
- Vital signs measurements (BP and HR only)
- Breath Nitric Oxide
- Hand grip strength assessment
- 4 Hour
- Blood sampling for NO3- and NO2- only
- Vital signs measurements (BP and HR only)
- Breath Nitric Oxide
Note, blood sampling, vital signs, and breath nitric oxide measurements should be collected as close to the beginning of each hourly time point as possible. However, it will not be considered a protocol deviation if they are slightly delayed due to procedures such as exercise testing extending into the next hour. All other procedures can be completed within each hour as time permits.
After completion of the 4 hour time point, the participant will be discharged from the facility. At this time, the participant will be considered to have completed the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Randomized, placebo-controlled, parallel arm design
| Arm | Type | Receives |
|---|---|---|
| Potassium Nitrate (KNO3) treatment arm | Experimental | Drug: KNO310 mmol of KNO3 via a single gel capsule to be consumed orally once per day for 6 weeks. |
| Placebo-controlled arm | Placebo comparator | Drug: Placebo10 mmol of placebo via a single gel capsule to be consumed orally once per day for 6 weeks. |
Who may qualify
- Ages
- 19 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Males and females aged greater than or equal to 18y and less than 80y at time of consent
- Diagnosis of heart failure with reduced ejection fraction
- New York Heart Association (NYHA) Class II-III at Visit 1
- Ejection fraction less than 45%, as evaluated through transthoracic echocardiography at Visit 1
- Stable medical therapy, defined by no addition or removal (or change of more than 100 percent) of the following for 60 days prior to Visit 1: beta-adrenergic blockade and angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blocker (ARB or aldosterone antagonists) or ARNI (ARB + sacubitril)
Key exclusion criteria (31 listed)
- Vulnerable populations as defined by the U.S. Department of Health and Human Services; prisoners and children will be excluded from this study
- Pharmacologic, organic nitrate therapy within 3 months prior to Visit 1
- Major orthopedic, psychiatric, neurological, or other conditions that would hinder the ability to complete the exercise tests at the time of Visit 1
- Estimated glomerular filtration rate less than 45 mL/min/1.73m2 on screening clinical laboratories measured at Visit 1
- Systolic blood pressure less than 90mmHg or greater than 180mmHg at Visit 1
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 |
|---|---|---|
| KNO3Also: Potassium nitrate10 mmol of KNO3 via a single gel capsule to be consumed orally once per day for 6 weeks. | Drug | Potassium Nitrate (KNO3) treatment arm |
| Placebo10 mmol of placebo via a single gel capsule to be consumed orally once per day for 6 weeks. | Drug | Placebo-controlled arm |
Primary outcome
VO2 Peak Testing
Time frame: Determined at Baseline visit, Acute Dose Visit, and Chronic Dose Visit, which will be scheduled throughout 8 weeks.
peak oxygen consumption during treadmill exercise
Maximal muscle power
Time frame: Determined at Baseline visit, Acute Dose Visit, and Chronic Dose Visit, which will be scheduled throughout 8 weeks.
assessment of quadriceps power
6 secondary outcomes
MLHFQ questionnaire
Time frame: Determined at Baseline visit, Acute Dose Visit, and Chronic Dose Visit, which will be scheduled throughout 8 weeks.
KCCQ questionnaire
Time frame: Determined at Baseline visit, Acute Dose Visit, and Chronic Dose Visit, which will be scheduled throughout 8 weeks.
Maximal muscle velocity
Time frame: Determined at Baseline visit, Acute Dose Visit, and Chronic Dose Visit, which will be scheduled throughout 8 weeks.
Maximal exercise time on treadmill
Time frame: Determined at Baseline visit, Acute Dose Visit, and Chronic Dose Visit, which will be scheduled throughout 8 weeks.
Plasma nitrate and nitrite
Time frame: Determined at Baseline visit, Acute Dose Visit, and Chronic Dose Visit, which will be scheduled throughout 8 weeks.
Breath nitric oxide (NO) level
Time frame: Determined at Baseline visit, Acute Dose Visit, and Chronic Dose Visit, which will be scheduled throughout 8 weeks.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2026.
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Heart Failure and Reduced Ejection Fraction, Heart Failure Chronic
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.
Linda R Peterson, MD 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 2 study testing KNO3 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 7 inclusion and 31 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: looking for participants now, as of the sponsor's last update on 6 May 2026. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Dawson A Haley, B.S. (3147914455, dhaley@wustl.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
VO2 Peak Testing (time frame: Determined at Baseline visit, Acute Dose Visit, and Chronic Dose Visit, which will be scheduled throughout 8 weeks.). The study lists 2 primary outcomes in all. 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 6 May 2026.