Trial · NCT02840799
Effect of KNO3 Compared to KCl on Oxygen UpTake in Heart Failure With Preserved Ejection Fraction (KNO3CK OUT HFPEF)
NCT02840799, Phase 2, Completed, University of Pennsylvania; results first posted 2023-12-18
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. Effect of KNO3 Compared to KCl on Oxygen UpTake in Heart Failure With Preserved Ejection Fraction (KNO3CK OUT HFPEF). Trials, record NCT02840799. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT02840799
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- Effect of KNO3 Compared to KCl on Oxygen UpTake in Heart Failure With Preserved Ejection Fraction (KNO3CK OUT HFPEF)
- NCT number
- NCT02840799
- Status
- Completed
- Phases
- Phase 2
- Enrollment
- 84 participants, actual
- Lead sponsor
- University of Pennsylvania
- Conditions
- Heart Failure
- Interventions
- Potassium Nitrate (KNO3), Potassium Chloride (KCl)
- First posted
- 2016-07-21
- Last updated
- 2023-12-18
- Results first posted
- 2023-12-18
- Limitations and caveats
Due to dispensing errors, nine participants didn't crossover. Overall study power was maintained. MRI completion varied across sites, leading to the discontinuation of this study component. MRI endpoints have a smaller N; interpret results cautiously. Myocardial circumferential strain wasn't quantified. Instead, longitudinal LV function, crucial for LV relaxation and filling, was quantified.
Source ClinicalTrials.gov
Registered outcomes13
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Difference in Peak Oxygen Consumption (Vo2) Between KNO3 and KCl Phases | 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. |
| Primary | Change in Total Work Performed During a Maximal-effort Exercise Test From Phase 1 to Phase 2 | 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. |
| Secondary | Effect of Potassium Nitrate (KNO3) on Quality of Life (QOL) | 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) | 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. |
| Secondary | 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 | 6 weeks after start of phase 1 (experimental drug or control); 6 weeks after start of phase 2 (experimental drug or control) | 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. |
| Secondary | Effect of Potassium Nitrate (KNO3) on Muscle Phosphocreatine (PCr) Recovery Kinetics Following a Standardized Plantar Flexor Exercise Protocol | 6 weeks after start of phase 1 (experimental drug or control); 6 weeks after start of phase 2 (experimental drug or control) | 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. |
| Secondary | Effect of Potassium Nitrate (KNO3) on Left Ventricle (LV) Diastolic Function: E/e' Ratio | 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) | 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. |
| Secondary | Effect of Potassium Nitrate (KNO3) on Left Ventricle (LV) Diastolic Function: Left Atrial Volume Index | 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) | 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. |
| Secondary | Effect of Potassium Nitrate (KNO3) on Myocardial Systolic Strain: Peak Global Systolic Myocardial Longitudinal Strain | 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) | 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. |
| Secondary | Effect of Potassium Nitrate (KNO3) on Late Systolic Wall Stress as Assessed by the Arts Formula Using Echocardiographic and Tonometry Recordings | 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) | 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 |
| Secondary | Effect of Potassium Nitrate (KNO3) on Arterial Wave Reflections as Assessed by Wave Separation Analysis Using Tonometry and Doppler Flow Data | 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) | 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). |
1 to 10 of 13Source ClinicalTrials.gov
See all 13 registered outcomesOutcomes13
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Difference in Peak Oxygen Consumption (Vo2) Between KNO3 and KCl Phases | 6 weeks after start of phase 1 (experimental drug or control); 6 weeks after start of phase 2 (experimental drug or control) | As this is a crossover trial, participants received both KNO3 and KCl in different phase, and the sequence of which was dependent on a double blinded randomization. Only participants with outcome data were analyzed. The mean, SD, and t-tests were calculated based on the number of completed cases with successful crossover (N=60), but the mixed model included phase 1 data as well (N=74). | L/min/kg | MEAN |
| PRIMARY | Change in Total Work Performed During a Maximal-effort Exercise Test From Phase 1 to Phase 2 | 6 weeks after start of phase 1 (experimental drug or control); 6 weeks after start of phase 2 (experimental drug or control) | Total work was calculated at each phase of the crossover trial. However, the analysis for the t-tests including the reported mean and standard deviation only includes cases in which Phase 1 and Phase 2 were completed. | KJ | MEAN |
| SECONDARY | Effect of Potassium Nitrate (KNO3) on Quality of Life (QOL) | 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) | As this is a crossover trial, participants received both KNO3 and KCl in different phases, the sequence of which was dependent on a double blinded randomization. Only participants with KCCQ results were analyzed. The mean, SD, and t-tests were calculated based on the number of completed cases with successful crossover (N=66), but the mixed model included phase 1 data as well. Baseline scores for all participants were analyzed in the mixed model as a predictive value. | score on a scale | MEAN |
| SECONDARY | 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 | 6 weeks after start of phase 1 (experimental drug or control); 6 weeks after start of phase 2 (experimental drug or control) | % change | MEAN | |
| SECONDARY | Effect of Potassium Nitrate (KNO3) on Muscle Phosphocreatine (PCr) Recovery Kinetics Following a Standardized Plantar Flexor Exercise Protocol | 6 weeks after start of phase 1 (experimental drug or control); 6 weeks after start of phase 2 (experimental drug or control) | MRI was not completed throughout the duration of the study and only completed at one site (University of Pennsylvania). | seconds | MEAN |
| SECONDARY | Effect of Potassium Nitrate (KNO3) on Left Ventricle (LV) Diastolic Function: E/e' Ratio | 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) | All participants were expected to undergo an echocardiogram at each visit (baseline, Phase 1, and Phase 2). | Ratio | MEAN |
| SECONDARY | Effect of Potassium Nitrate (KNO3) on Left Ventricle (LV) Diastolic Function: Left Atrial Volume Index | 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) | mL/m2 | MEAN | |
| SECONDARY | Effect of Potassium Nitrate (KNO3) on Myocardial Systolic Strain: Peak Global Systolic Myocardial Longitudinal Strain | 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) | All participants underwent an echocardiogram at each visit; however, participants in which these echo measures could not be reliably quantified were excluded. | % (change in length) | MEAN |
| SECONDARY | Effect of Potassium Nitrate (KNO3) on Late Systolic Wall Stress as Assessed by the Arts Formula Using Echocardiographic and Tonometry Recordings | 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) | dynes·cm-2·s | MEAN | |
| SECONDARY | Effect of Potassium Nitrate (KNO3) on Arterial Wave Reflections as Assessed by Wave Separation Analysis Using Tonometry and Doppler Flow Data | 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) | unitless | MEAN |
1 to 10 of 13Source ClinicalTrials.gov
See all 13 outcomesResults by group29
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Difference in Peak Oxygen Consumption (Vo2) Between KNO3 and KCl Phases | Potassium Nitrate (KNO3) | 10.31714 | Standard Deviation 3.851249 | L/min/kg | |
| Difference in Peak Oxygen Consumption (Vo2) Between KNO3 and KCl Phases | Potassium Chloride (KCl) | 10.215172 | Standard Deviation 3.823188 | L/min/kg | |
| Change in Total Work Performed During a Maximal-effort Exercise Test From Phase 1 to Phase 2 | Potassium Nitrate (KNO3) | 26.74341 | Standard Deviation 32.15162 | KJ | |
| Change in Total Work Performed During a Maximal-effort Exercise Test From Phase 1 to Phase 2 | Potassium Chloride (KCl) | 23.76294 | Standard Deviation 29.88680 | KJ | |
| Effect of Potassium Nitrate (KNO3) on Quality of Life (QOL) | Potassium Nitrate (KNO3) | 66.06147 | Standard Deviation 18.99883 | score on a scale | |
| Effect of Potassium Nitrate (KNO3) on Quality of Life (QOL) | Potassium Chloride (KCl) | 62.77142 | Standard Deviation 18.95087 | score on a scale | |
| Effect of Potassium Nitrate (KNO3) on Quality of Life (QOL) | Baseline | 61.4335 | Standard Deviation 17.02081 | score on a scale | |
| 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 | Potassium Nitrate (KNO3) | -23.92288 | Standard Deviation 23.39527 | % change | |
| 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 | Potassium Chloride (KCl) | -22.13564 | Standard Deviation 24.67150 | % change | |
| Effect of Potassium Nitrate (KNO3) on Muscle Phosphocreatine (PCr) Recovery Kinetics Following a Standardized Plantar Flexor Exercise Protocol | Potassium Nitrate (KNO3) | 159.5455 | Standard Deviation 99.54442 | seconds |
1 to 10 of 29Source ClinicalTrials.gov
See all 29 results by groupParticipant flow12
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Phase 1 | STARTED | Potassium Nitrate (KNO3), Then Potassium Chloride (KCl) | 41 | |
| Phase 1 | STARTED | Potassium Chloride (KCl) Then Potassium Nitrate (KNO3) | 43 | |
| Phase 1 | COMPLETED | Potassium Nitrate (KNO3), Then Potassium Chloride (KCl) | 36 | |
| Phase 1 | COMPLETED | Potassium Chloride (KCl) Then Potassium Nitrate (KNO3) | 40 | |
| Phase 1 | NOT COMPLETED | Potassium Nitrate (KNO3), Then Potassium Chloride (KCl) | 5 | |
| Phase 1 | NOT COMPLETED | Potassium Chloride (KCl) Then Potassium Nitrate (KNO3) | 3 | |
| Phase 2 (Crossover) | STARTED | Potassium Nitrate (KNO3), Then Potassium Chloride (KCl) | 41 | |
| Phase 2 (Crossover) | STARTED | Potassium Chloride (KCl) Then Potassium Nitrate (KNO3) | 35 | |
| Phase 2 (Crossover) | COMPLETED | Potassium Nitrate (KNO3), Then Potassium Chloride (KCl) | 41 | |
| Phase 2 (Crossover) | COMPLETED | Potassium Chloride (KCl) Then Potassium Nitrate (KNO3) | 33 |
1 to 10 of 12Source ClinicalTrials.gov
See all 12 participant flowAdverse events318
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | abnormal sensation of swallowing | Gastrointestinal disorders | Potassium Nitrate (KNO3) | 1 | 77 | 1 |
| other | abnormal sensation of swallowing | Gastrointestinal disorders | Potassium Chloride (KCl) | 0 | 74 | 0 |
| other | abnormal sensation of swallowing | Gastrointestinal disorders | Baseline Visit | 0 | 84 | 0 |
| other | aches in the joints | Musculoskeletal and connective tissue disorders | Potassium Nitrate (KNO3) | 1 | 77 | 1 |
| other | aches in the joints | Musculoskeletal and connective tissue disorders | Potassium Chloride (KCl) | 0 | 74 | 0 |
| other | aches in the joints | Musculoskeletal and connective tissue disorders | Baseline Visit | 0 | 84 | 0 |
| other | acute exacerbation of bronchiectasis | Respiratory, thoracic and mediastinal disorders | Potassium Nitrate (KNO3) | 0 | 77 | 0 |
| other | acute exacerbation of bronchiectasis | Respiratory, thoracic and mediastinal disorders | Potassium Chloride (KCl) | 1 | 74 | 1 |
| other | acute exacerbation of bronchiectasis | Respiratory, thoracic and mediastinal disorders | Baseline Visit | 0 | 84 | 0 |
| other | atrial fibrillation | Cardiac disorders | Potassium Nitrate (KNO3) | 0 | 77 | 0 |
1 to 10 of 318Source ClinicalTrials.gov
See all 318 adverse eventsAdverse event totals9
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Potassium Nitrate (KNO3) | 0 | 77 |
| Total, all-cause mortality | Potassium Chloride (KCl) | 0 | 74 |
| Total, all-cause mortality | Baseline Visit | 0 | 84 |
| Total, other adverse events | Potassium Nitrate (KNO3) | 43 | 77 |
| Total, other adverse events | Potassium Chloride (KCl) | 45 | 74 |
| Total, other adverse events | Baseline Visit | 61 | 84 |
| Total, serious adverse events | Potassium Nitrate (KNO3) | 1 | 77 |
| Total, serious adverse events | Potassium Chloride (KCl) | 1 | 74 |
| Total, serious adverse events | Baseline Visit | 1 | 84 |
Source ClinicalTrials.gov
Papers1
The papers the trial lists on ClinicalTrials.gov.
| PMID | Listed as |
|---|---|
| 39693096 | DERIVED |
Source PubMed
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons0
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
None in this release.
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
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