Phase 2
Completed N=84
Effect of KNO3 Compared to KCl on Oxygen UpTake in Heart Failure With Preserved Ejection Fraction (KNO3CK OUT HFPEF)
Source: ClinicalTrials.gov NCT02840799 ↗Enrolled (actual)
84
Serious AEs
1.3%
Results posted
Dec 2023
Primary outcomePrimary: Difference in Peak Oxygen Consumption (Vo2) Between KNO3 and KCl Phases — 10.31714; 10.215172 L/min/kg — p=0.6191
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).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Difference in Peak Oxygen Consumption (Vo2) Between KNO3 and KCl Phases |
10.31714; 10.215172 | 0.6191 |
| PRIMARY Change in Total Work Performed During a Maximal-effort Exercise Test From Phase 1 to Phase 2 |
26.74341; 23.76294 | 0.2871 |
| SECONDARY Effect of Potassium Nitrate (KNO3) on Quality of Life (QOL) |
66.06147; 62.77142; 61.4335 | 0.171 |
| 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 |
-23.92288; -22.13564 | 0.4905 |
| SECONDARY Effect of Potassium Nitrate (KNO3) on Muscle Phosphocreatine (PCr) Recovery Kinetics Following a Standardized Plantar Flexor Exercise Protocol |
159.5455; 219.8485 | 0.4017 |
| SECONDARY Effect of Potassium Nitrate (KNO3) on Left Ventricle (LV) Diastolic Function: E/e' Ratio |
11.84599; 11.61516; 11.7999 | 0.5636 |
| SECONDARY Effect of Potassium Nitrate (KNO3) on Left Ventricle (LV) Diastolic Function: Left Atrial Volume Index |
26.63060; 27.65687; 27.4408 | 0.7707 |
| SECONDARY Effect of Potassium Nitrate (KNO3) on Myocardial Systolic Strain: Peak Global Systolic Myocardial Longitudinal Strain |
18.04317; 17.273221; 17.7164 | 0.1680825 |
| SECONDARY Effect of Potassium Nitrate (KNO3) on Late Systolic Wall Stress as Assessed by the Arts Formula Using Echocardiographic and Tonometry Recordings |
32.36347; 34.31358; 33.95494 | 0.07984 |
| SECONDARY Effect of Potassium Nitrate (KNO3) on Arterial Wave Reflections as Assessed by Wave Separation Analysis Using Tonometry and Doppler Flow Data |
0.3681837; 0.372307; 0.3804 | 0.1450 |
| SECONDARY Effect of Potassium Nitrate (KNO3) on Augmentation Index |
122.6139; 122.5160; 126.3574 | 0.44 |
| SECONDARY 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 |
— | — |
| SECONDARY Effect of Potassium Nitrate (KNO3) on Myocardial Systolic Strain: Peak Global Systolic Myocardial Circumferential Strain |
— | — |
Eligibility Criteria
Inclusion Criteria
- 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' 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
Exclusion Criteria
- Supine systolic blood pressure 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 3x ULN, Albumin 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.
Data sourced from ClinicalTrials.gov (NCT02840799). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.