Phase 2
Completed N=12
Pharmacokinetics, Pharmacodynamics, and Impact of Inorganic Nitrate on Exercise in HFpEF
Heart Failure · Diastolic Heart Failure
Source: ClinicalTrials.gov NCT02256345 ↗
Enrolled (actual)
12
Serious AEs
0.0%
Results posted
Oct 2017
Primary outcomePrimary: Change in Peak Oxygen Uptake (VO2) From Baseline Upto 1 Week of Administration for Each Dose — 1.16; 1.49; 1.20; 1.44 L/min
Summary
This study will be performed to determine the safety, tolerability, and dose-response to inorganic nitrate on exercise capacity in HFpEF. There are two primary goals for this study:
1. Determine the population-specific pharmacokinetics and dose of KNO3 that can be safely given to subjects with HFpEF.
2. Determine if there is a dose-response effect of nitrate supplementation on exercise capacity, evidenced by peak oxygen consumption (peak VO2), and physiologic adaptations to exercise.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in Peak Oxygen Uptake (VO2) From Baseline Upto 1 Week of Administration for Each Dose |
1.16; 1.49; 1.20; 1.44; 1.20; 1.44 | — |
| SECONDARY Change in Vasodilatory Reserve for Each Dose |
-25.6; -25.8; -27.1; -30.6; -34.2; -20.0 | — |
| SECONDARY Change in Mitochondrial Oxidative Capacity for Each Dose |
63.2; 106.5; 59.2; 110.4; 62.2; 45.4 | — |
| SECONDARY Change in Aortic Augmentation Index |
3.0; -2.3; -5.4; -11.9; -7.1; -0.2 | — |
Eligibility Criteria
Inclusion Criteria
- NYHA Class II-III symptoms.
- LV EF > 50%.
- Stable medical therapy for at least 1 month.
- Evidence of significant diastolic dysfunction, meeting the European Society of Echocardiography criteria for HFpEF.
Exclusion Criteria
- Any rhythm other than sinus with native conduction.
- Inability to exercise.
- Moderate or greater valvular disease.
- Hypertrophic, infiltrative, or inflammatory cardiomyopathy.
- Pericardial disease.
- Current angina.
- Acute coronary syndrome or coronary intervention within the past 2 months.
- Primary pulmonary arteriopathy.
- Clinically significant lung disease.
- Ischemia on stress testing without subsequent revascularization.
- Treatment with phosphodiesterase inhibitors that cannot be withheld.
- Treatment with organic nitrates or allopurinol.
- Significant liver disease impacting synthetic function or volume control.
- Poor echocardiographic windows.
- eGFR 2.5.
- Current smoking.
- Alcohol dependency.
- History of Barret's esophagus.
- G6PD deficiency
- Methemoglobinemia - baseline methemoglobin level >3% prior to any study medication.
Data sourced from ClinicalTrials.gov (NCT02256345). 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.