Heart FailurePhase 2NCT02840799
Effect of KNO3 Compared to KCl on Oxygen UpTake in Heart Failure With Preserved Ejection Fraction (KNO3CK OUT HFPEF)
A Phase 2 study testing Potassium Nitrate (KNO3) and Potassium Chloride (KCl) in people with Heart Failure, run by University of Pennsylvania at 3 sites in United States.
Trial summary
This trial seeks to assess if potassium nitrate (KNO3) therapy improves exercise capacity and oxygen uptake in heart failure patients with preserved ejection fraction (HFpEF). Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Heart Failure
- What is being tested?
- Potassium Nitrate (KNO3) and Potassium Chloride (KCl)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 84 participants
- Where
- 3 sitesUnited States
- Study dates
- Aug 2016to Aug 2022
- 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 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults aged 18-90 years of age
- A diagnosis of heart failure with NYHA Class II-III symptoms
- LV ejection fraction >50% during baseline echocardiography
- Stable medical therapy: no addition/removal/changes in antihypertensive medications, or beta-blockers in the preceding 30 days
- Elevated filling pressures as evidenced by at least 1 of the following:
- Mitral E/e' ratio > 8 (either lateral or septal), with low e' velocity (septal e'<7 cm/sec or lateral e'< 10 cm/sec), in addition to one of the following:
Show all 10Show fewer
- i Enlarged left atrium (LA volume index >34 ml/m2) ii Chronic loop diuretic use for control of symptoms iii Elevated natriuretic peptides (BNP levels >100 ng/L or NT-proBNP levels >300 ng/L)
- Mitral E/e' ratio > 14 (either lateral or septal)
- Elevated invasively-determined filling pressures previously (resting LVEDP>16 mmHg or mean pulmonary capillary wedge pressure [PCWP] > 12 mmHg; or PCWP/LVEDP≥25 mmHg with exercise)
- Acute heart failure decompensation requiring IV diuretics
Who cannot join
- Supine systolic blood pressure <100 mm Hg
- Pregnancy: Women of childbearing potential will undergo a pregnancy test during the screening visit
- Orthostatic hypotension defined as >20 mm Hg decrease in systolic blood pressure 3-5 minutes following the transition from the supine to standing position
- Uncontrolled atrial fibrillation, as defined by a resting heart rate>100 beats per minute
- Hemoglobin < 10 g/dL
- Inability/unwillingness to exercise
Show all 25Show fewer
- Moderate or greater left sided valvular disease (mitral regurgitation, aortic stenosis, aortic regurgitation), any degree of mitral stenosis, severe right-sided valvular disease, or presence of a prosthetic valve in the mitral position
- Hypertrophic, infiltrative, or inflammatory cardiomyopathy
- Clinically significant pericardial disease, as per investigator judgement.
- Current angina
- Acute coronary syndrome or coronary intervention within the past 2 months
- Primary pulmonary arteriopathy
- Clinically significant lung disease as defined by: Chronic Obstructive Pulmonary Disease meeting Stage III or greater GOLD criteria, treatment with oral steroids within the past 6 months for an exacerbation of obstructive lung disease, or the use of daytime supplemental oxygen
- Ischemia on stress testing without either (1) subsequent revascularization, or; (2) a subsequent angiogram demonstrating the absence of clinically significant epicardial coronary artery disease, as per investigator judgement.
- Left ventricular ejection fraction <45% in any prior echocardiogram or cardiac MRI, unless this was in the setting of uncontrolled atrial fibrillation.
- Treatment with phosphodiesterase inhibitors that cannot be withheld
- Treatment with organic nitrates
- Significant liver disease impacting synthetic function or volume control (ALT/AST > 3x ULN, Albumin <3.0 g/dL)
- eGFR < 30 mL/min/1.73m2
- G6PD deficiency. In males of African, Asian or Mediterranean decent, this will be formally evaluated by enzyme testing prior to drug administration. A negative screening test for G6PD will be required in these subjects for inclusion in the study. If a quantitative test is being performed, a clinically significant reduction in G6PD activity (<60% of normal) will exclude subjects.
- Methemoglobinemia - baseline methemoglobin level >5%
- Serum K>5.0 mEq/L
- Severe right ventricular dysfunction
- Any medical condition that, in the opinion of the investigator, will interfere with the safe completion of the study.
- Contraindications to MRI (except as noted below), including the presence of a pacemaker, metal implants, claustrophobia, or that have known medical conditions which can be exacerbated by stress such as anxiety or panic attacks. Inability to lie flat in the MRI scanner for 90 minutes is also an exclusion criterion.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Northwestern Medical Center
Evanston, Illinois, 60208
Corporal Michael J Crescenz Veterans Affairs Medical Center (VA)
Philadelphia, Pennsylvania, 19104
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
This trial seeks to assess if potassium nitrate (KNO3) therapy improves exercise capacity and oxygen uptake in heart failure patients with preserved ejection fraction (HFpEF).
Read the detailed description
Approximately 50% of heart failure patients exhibit preserved left ventricular (LV) ejection fraction (EF), and therefore have HF with preserved EF (HFpEF). There are currently no proven effective pharmacologic interventions. Exercise intolerance with reduced aerobic capacity is the hallmark of HFpEF and greatly impairs quality of life (QOL). During exercise, blood vessels within active muscle vasodilator, increasing perfusion to the muscle bed. Nitric oxide is a chief mediator of this process. Inorganic nitrate can ultimately be converted to nitric oxide. This conversion occurs preferentially at the site of exercising muscle, allowing for vasodilation to occur, hence increasing blood flow to the working muscle. Preliminary data suggest that inorganic nitrate improves exercise tolerance in HFpEF. The investigator will aim to test this hypothesis in a larger group.
- Conditions
- Heart Failure
- Being tested
- Potassium Nitrate (KNO3), Potassium Chloride (KCl)
- Keywords
- Heart Failure, Exercise Intolerance, 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.
Potassium Nitrate (KNO3)Drug
The effect of potassium nitrate (KNO3) supplementation on exercise capacity and peak oxygen consumption in HFpEF will be assessed.
Potassium Chloride (KCl)Drug
Potassium Chloride (KCl) is the matching placebo control drug in this trial.
| Study group | Role | What they receive |
|---|---|---|
| Potassium Nitrate (KNO3) | Experimental | Potassium nitrate (KNO3) capsules, providing 6 millimoles of inorganic nitrate per capsule, to be taken three times daily for 6 weeks. Receives: Drug: Potassium Nitrate (KNO3) |
| Potassium Chloride (KCl) | Placebo comparator | Potassium Chloride (KCl) is the placebo (control drug) in this trial.
Potassium Chloride (KCl) capsules administered at a dose of 6 millimoles (1 capsule) three times daily for 6 weeks. Receives: Drug: Potassium Chloride (KCl) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in Peak Oxygen Consumption (Vo2) Between KNO3 and KCl Phases
Subjects will perform a maximal-effort peak oxygen consumption test using a supine bicycle exercise test with expired gas analysis.
Measured: 6 weeks after start of phase 1 (experimental drug or control); 6 weeks after start of phase 2 (experimental drug or control)
Change in Total Work Performed During a Maximal-effort Exercise Test From Phase 1 to Phase 2
Subjects will perform a maximal-effort supine bicycle exercise test.
Measured: 6 weeks after start of phase 1 (experimental drug or control); 6 weeks after start of phase 2 (experimental drug or control)
Secondary outcomes (11)
Effect of Potassium Nitrate (KNO3) on Quality of Life (QOL)
QOL will be assessed with the Kansas City Cardiomyopathy Questionnaire (KCCQ). The overall summary score from the KCCQ ranges from 0-100, where higher scores indicate a better quality of life.
Measured: All three visits: Baseline (first) visit; 6 weeks after start of phase 1 (experimental drug or control); 6 weeks after start of phase 2 (experimental drug or control)
Effect of KNO3 on the Percent Change of Systemic Vasodilatory Response to Exercise: The Change in Systemic Vascular Resistance Reserve During Exercise During a Maximal Effort Exercise Test
We measured the Systematic vasodilatory response at rest and peak maximal exercise using corresponding echo parameters and blood pressures for each visit. This measure depicts the change from rest and exercise.
Measured: 6 weeks after start of phase 1 (experimental drug or control); 6 weeks after start of phase 2 (experimental drug or control)
Effect of Potassium Nitrate (KNO3) on Muscle Phosphocreatine (PCr) Recovery Kinetics Following a Standardized Plantar Flexor Exercise Protocol
Muscle PCr recovery kinetics were measured using MRI and a standardized plantar flexor exercise protocol with a high resolution spatial mapping of creatine in muscle to analyze creatine chemical exchange saturation transfer and quantify the recovery kinetics of creatine levels. Exercise induces increases in the rate of O2 consumption, which upon cessation of exercise, declines towards baseline in a mono-exponential fashion. This is characterized by a time constant (τ, tau) that corresponds to the time constant of PCr recovery kinetics. Muscle PCr is a marker of oxidative capacity. This outcome measure relates to the half-time derived from linear regression, where a lower value depicts a faster PCr recovery.
Measured: 6 weeks after start of phase 1 (experimental drug or control); 6 weeks after start of phase 2 (experimental drug or control)
Effect of Potassium Nitrate (KNO3) on Left Ventricle (LV) Diastolic Function: E/e' Ratio
E/e' ratio is a standard echo parameter that was measured at rest during each visit and calculated using the mitral E, septal e', and lateral e'. This index is parameter for noninvasive left ventricular diastolic function assessment, where an E/e' ratio < 8 is considered to be normal, and a ratio > 15 is considered to reflect an increase in the LV filling pressure.
Measured: All three visits: Baseline (first) visit; 6 weeks after start of phase 1 (experimental drug or control); 6 weeks after start of phase 2 (experimental drug or control)
Effect of Potassium Nitrate (KNO3) on Left Ventricle (LV) Diastolic Function: Left Atrial Volume Index
Left atrial volume index is a standard echo parameter that was measured at rest during each visit and calculated the body surface area (Dubois and Dubois equation) and left atrial volume from both the two chamber and four chamber views.
Measured: All three visits: Baseline (first) visit; 6 weeks after start of phase 1 (experimental drug or control); 6 weeks after start of phase 2 (experimental drug or control)
Effect of Potassium Nitrate (KNO3) on Myocardial Systolic Strain: Peak Global Systolic Myocardial Longitudinal Strain
Peak global systolic myocardial longitudinal strain was evaluated with resting echocardiograms at each visit. Strain was analyzed at the four chamber, two chamber, and three chamber views of the left ventricle and averaged.
Measured: All three visits: Baseline (first) visit; 6 weeks after start of phase 1 (experimental drug or control); 6 weeks after start of phase 2 (experimental drug or control)
Effect of Potassium Nitrate (KNO3) on Late Systolic Wall Stress as Assessed by the Arts Formula Using Echocardiographic and Tonometry Recordings
Late systolic wall stress is assessed via comprehensive aortic pressure-flow relations, using arterial tonometry and Doppler echocardiography. Myocardial wall stress was calculated with the following formula =: Stress = P / [1/3 In (1 + VW/VLV)], where ln is the natural logarithm, P is aortic pressure obtained with arterial tonometry, VW is the volume of the LV wall obtained with echocardiography and VLV is the cavity volume obtained with echocardiography
Measured: All three visits: Baseline (first) visit; 6 weeks after start of phase 1 (experimental drug or control); 6 weeks after start of phase 2 (experimental drug or control)
Effect of Potassium Nitrate (KNO3) on Arterial Wave Reflections as Assessed by Wave Separation Analysis Using Tonometry and Doppler Flow Data
Arterial Wave reflections were assessed via wave separation analysis, using arterial tonometry and Doppler echocardiography.
The pulse wave generated by the left ventricle travels forward in arteries and is partially reflected at sites of impedance mismatch (i.e., bifurcations, points of change in arterial size or wall stiffness, predominantly in middle-sized conduit arteries). Wave reflections travel back to the heart, merging into a discrete reflected wave and arrive while the LV is still ejecting blood in mid-to-late systole. Wave reflections increase the late systolic workload of the LV and profoundly impact the LV loading sequence (late relative to early systolic load).
Measured: All three visits: Baseline (first) visit; 6 weeks after start of phase 1 (experimental drug or control); 6 weeks after start of phase 2 (experimental drug or control)
Effect of Potassium Nitrate (KNO3) on Augmentation Index
Aortic augmentation index was assessed via comprehensive aortic pressure-flow relations, using arterial tonometry and Doppler echocardiography. It is an indirect measure of arterial stiffness, where a higher value would indicate greater arterial stiffness risk.
Measured: All three visits: Baseline (first) visit; 6 weeks after start of phase 1 (experimental drug or control); 6 weeks after start of phase 2 (experimental drug or control)
Effect of Potassium Nitrate (KNO3) on Muscle Blood Flow During Exercise: Muscle Blood Flow During Exercise, Measured With Arterial MRI Spin Labeling During a Standardized Plantar Flexion Exercise Test
MRI studies will be performed at rest and immediately after a standardized plantar flexion exercise. Arterial spin labeling using the flow-sensitive alternating inversion recovery (FAIR) technique will be used to image muscle perfusion with high temporal resolution.
Measured: 6 weeks after start of phase 1 (experimental drug or control); 6 weeks after start of phase 2 (experimental drug or control)
Effect of Potassium Nitrate (KNO3) on Myocardial Systolic Strain: Peak Global Systolic Myocardial Circumferential Strain
Measured: All three visits: Baseline (first) visit; 6 weeks after start of phase 1 (experimental drug or control); 6 weeks after start of phase 2 (experimental drug or control)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2016 (estimated)
- Study startAug 2016
- Primary completionAug 2022
- Study completionAug 2022
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 (1)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 University of PennsylvaniaThe 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
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 84 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- Northwestern University
- Responsible party
- Sponsor
- Investigators
- Julio A Chirinos, MD, PhD, Study chair, University of PennsylvaniaPayman Zamani, MD, Principal investigator, University of PennsylvaniaSanjiv Shah, MD, Principal investigator, Northwestern UniversitySujith Kuruvilla, MD, Principal investigator, Corporal Michael J Crescenz Veterans Affairs Medical Center (VA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02840799
- Sponsor's protocol ID
- 824290
- Status last verified
- Dec 2023
- First submitted
- 13 Jun 2016
- Last updated
- 18 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Zamani P, Shah SJ, Cohen JB, Zhao M, Yang W, Afable JL, Caturla M, Maynard H, Pourmussa B, Demastus C, Mohanty I, Miyake MM, Adusumalli S, Margulies KB, Prenner SB, Poole DC, Wilson N, Reddy R, Townsend RR, Ischiropoulos H, Cappola TP, Chirinos JA. Potassium Nitrate in Heart Failure With Preserved Ejection Fraction: A Randomized Clinical Trial. JAMA Cardiol. 2025 Mar 1;10(3):284-289. doi: 10.1001/jamacardio.2024.4417.
PubMed 39693096
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of KNO3 Compared to KCl on Oxygen UpTake in Heart Failure With Preserved Ejection Fraction (KNO3CK OUT HFPEF)
- ClinicalTrials.gov ID
- NCT02840799
- Acronym / sponsor ID
- 824290
- Conditions
- Heart Failure
- Keywords
- Heart Failure, Exercise Intolerance, Ejection Fraction
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 84 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- Northwestern University
- Study start
- Aug 2016
- Primary completion
- Aug 2022 (actual)
- Study completion
- Aug 2022 (actual)
- First posted
- 21 Jul 2016 (estimated)
- Results
- Posted 18 Dec 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial seeks to assess if potassium nitrate (KNO3) therapy improves exercise capacity and oxygen uptake in heart failure patients with preserved ejection fraction (HFpEF).
Detailed description
Approximately 50% of heart failure patients exhibit preserved left ventricular (LV) ejection fraction (EF), and therefore have HF with preserved EF (HFpEF). There are currently no proven effective pharmacologic interventions. Exercise intolerance with reduced aerobic capacity is the hallmark of HFpEF and greatly impairs quality of life (QOL). During exercise, blood vessels within active muscle vasodilator, increasing perfusion to the muscle bed. Nitric oxide is a chief mediator of this process. Inorganic nitrate can ultimately be converted to nitric oxide. This conversion occurs preferentially at the site of exercising muscle, allowing for vasodilation to occur, hence increasing blood flow to the working muscle. Preliminary data suggest that inorganic nitrate improves exercise tolerance in HFpEF. The investigator will aim to test this hypothesis in a larger group.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Potassium Nitrate (KNO3) | Experimental | Drug: Potassium Nitrate (KNO3)Potassium nitrate (KNO3) capsules, providing 6 millimoles of inorganic nitrate per capsule, to be taken three times daily for 6 weeks. |
| Potassium Chloride (KCl) | Placebo comparator | Drug: Potassium Chloride (KCl)Potassium Chloride (KCl) is the placebo (control drug) in this trial. Potassium Chloride (KCl) capsules administered at a dose of 6 millimoles (1 capsule) three times daily for 6 weeks. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Adults aged 18-90 years of age
- A diagnosis of heart failure with NYHA Class II-III symptoms
- LV ejection fraction >50% during baseline echocardiography
- Stable medical therapy: no addition/removal/changes in antihypertensive medications, or beta-blockers in the preceding 30 days
- Elevated filling pressures as evidenced by at least 1 of the following:
Key exclusion criteria (25 listed)
- Supine systolic blood pressure <100 mm Hg
- Pregnancy: Women of childbearing potential will undergo a pregnancy test during the screening visit
- Orthostatic hypotension defined as >20 mm Hg decrease in systolic blood pressure 3-5 minutes following the transition from the supine to standing position
- Uncontrolled atrial fibrillation, as defined by a resting heart rate>100 beats per minute
- Hemoglobin < 10 g/dL
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 |
|---|---|---|
| Potassium Nitrate (KNO3)The effect of potassium nitrate (KNO3) supplementation on exercise capacity and peak oxygen consumption in HFpEF will be assessed. | Drug | Potassium Nitrate (KNO3) |
| Potassium Chloride (KCl)Potassium Chloride (KCl) is the matching placebo control drug in this trial. | Drug | Potassium Chloride (KCl) |
Primary outcome
Difference in Peak Oxygen Consumption (Vo2) Between KNO3 and KCl Phases
Time frame: 6 weeks after start of phase 1 (experimental drug or control); 6 weeks after start of phase 2 (experimental drug or control)
Subjects will perform a maximal-effort peak oxygen consumption test using a supine bicycle exercise test with expired gas analysis.
Change in Total Work Performed During a Maximal-effort Exercise Test From Phase 1 to Phase 2
Time frame: 6 weeks after start of phase 1 (experimental drug or control); 6 weeks after start of phase 2 (experimental drug or control)
Subjects will perform a maximal-effort supine bicycle exercise test.
11 secondary outcomes
Effect of Potassium Nitrate (KNO3) on Quality of Life (QOL)
Time frame: All three visits: Baseline (first) visit; 6 weeks after start of phase 1 (experimental drug or control); 6 weeks after start of phase 2 (experimental drug or control)
Effect of KNO3 on the Percent Change of Systemic Vasodilatory Response to Exercise: The Change in Systemic Vascular Resistance Reserve During Exercise During a Maximal Effort Exercise Test
Time frame: 6 weeks after start of phase 1 (experimental drug or control); 6 weeks after start of phase 2 (experimental drug or control)
Effect of Potassium Nitrate (KNO3) on Muscle Phosphocreatine (PCr) Recovery Kinetics Following a Standardized Plantar Flexor Exercise Protocol
Time frame: 6 weeks after start of phase 1 (experimental drug or control); 6 weeks after start of phase 2 (experimental drug or control)
Effect of Potassium Nitrate (KNO3) on Left Ventricle (LV) Diastolic Function: E/e' Ratio
Time frame: All three visits: Baseline (first) visit; 6 weeks after start of phase 1 (experimental drug or control); 6 weeks after start of phase 2 (experimental drug or control)
Effect of Potassium Nitrate (KNO3) on Left Ventricle (LV) Diastolic Function: Left Atrial Volume Index
Time frame: All three visits: Baseline (first) visit; 6 weeks after start of phase 1 (experimental drug or control); 6 weeks after start of phase 2 (experimental drug or control)
Effect of Potassium Nitrate (KNO3) on Myocardial Systolic Strain: Peak Global Systolic Myocardial Longitudinal Strain
Time frame: All three visits: Baseline (first) visit; 6 weeks after start of phase 1 (experimental drug or control); 6 weeks after start of phase 2 (experimental drug or control)
Effect of Potassium Nitrate (KNO3) on Late Systolic Wall Stress as Assessed by the Arts Formula Using Echocardiographic and Tonometry Recordings
Time frame: All three visits: Baseline (first) visit; 6 weeks after start of phase 1 (experimental drug or control); 6 weeks after start of phase 2 (experimental drug or control)
Effect of Potassium Nitrate (KNO3) on Arterial Wave Reflections as Assessed by Wave Separation Analysis Using Tonometry and Doppler Flow Data
Time frame: All three visits: Baseline (first) visit; 6 weeks after start of phase 1 (experimental drug or control); 6 weeks after start of phase 2 (experimental drug or control)
Effect of Potassium Nitrate (KNO3) on Augmentation Index
Time frame: All three visits: Baseline (first) visit; 6 weeks after start of phase 1 (experimental drug or control); 6 weeks after start of phase 2 (experimental drug or control)
Effect of Potassium Nitrate (KNO3) on Muscle Blood Flow During Exercise: Muscle Blood Flow During Exercise, Measured With Arterial MRI Spin Labeling During a Standardized Plantar Flexion Exercise Test
Time frame: 6 weeks after start of phase 1 (experimental drug or control); 6 weeks after start of phase 2 (experimental drug or control)
Effect of Potassium Nitrate (KNO3) on Myocardial Systolic Strain: Peak Global Systolic Myocardial Circumferential Strain
Time frame: All three visits: Baseline (first) visit; 6 weeks after start of phase 1 (experimental drug or control); 6 weeks after start of phase 2 (experimental drug or control)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39693096Zamani P, Shah SJ, Cohen JB, Zhao M, Yang W, Afable JL, Caturla M, Maynard H, Pourmussa B, Demastus C, Mohanty I, Miyake MM, Adusumalli S, Margulies KB, Prenner SB, Poole DC, Wilson N, Reddy R, Townsend RR, Ischiropoulos H, Cappola TP, Chirinos JA. Potassium Nitrate in Heart Failure With Preserved Ejection Fraction: A Randomized Clinical Trial. JAMA Cardiol. 2025 Mar 1;10(3):284-289. doi: 10.1001/jamacardio.2024.4417.
- 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.
Julio A Chirinos, MD, PhD study chair
University of Pennsylvania
Payman Zamani, MD principal investigator
University of Pennsylvania
Sanjiv Shah, MD principal investigator
Northwestern University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Potassium Nitrate (KNO3) and Potassium Chloride (KCl) in people with Heart Failure, run by University of Pennsylvania at 3 sites 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 10 inclusion and 25 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 18 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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 18 Dec 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?
Difference in Peak Oxygen Consumption (Vo2) Between KNO3 and KCl Phases (time frame: 6 weeks after start of phase 1 (experimental drug or control); 6 weeks after start of phase 2 (experimental drug or control)). 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?
On the ClinicalTrials.gov record for NCT02840799, which also lists 1 linked publication.
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 18 Dec 2023.