Phase 2
Completed N=42
Inorganic NItrate and EXercise Performance in Heart Failure (iNIX-HF): Dose Response
Source: ClinicalTrials.gov NCT02797184 ↗Enrolled (actual)
42
Serious AEs
0.0%
Results posted
Feb 2023
Primary outcomePrimary: VO2peak — 17.7; 18.0 mL/kg/min
Summary
The purpose of this study is to do the work that is necessary and sufficient for setting up an appropriate multi-center, randomized clinical trial (RCT) of a new therapy for heart failure: inorganic nitrate. The investigators will first determine the effects and palatability of ~12.8mmol KNO3 (an oral pill) as compared to the roughly equivalent amount of nitrate in 2 beetroot juice (BRJ) Sports Shots (by James White Drinks). Next, the investigators will determine the effects of inorganic nitrate (KNO3 in an oral pill format) on blood pressure, blood nitrate levels, breath nitric oxide (NO) levels, and exercise performance in a dose-response study. Third, the investigators will perform a small phase II chronic treatment study that will allow them to determine the best primary endpoint and the numbers of patients the investigators will need to study in the large, multi-center RCT to follow this project. In the small study and in the RCT to follow, the investigators will determine whether inorganic nitrate can improve aerobic exercise capacity, muscle power, and speed of muscle contraction, and lessen the effort of breathing during exercise.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY VO2peak |
17.7; 18.0 | — |
| SECONDARY Peak Muscle Power |
469.4; 497.9 | — |
| SECONDARY Blood Nitrite Levels |
0.489; 0.432; 0.568; 0.591; 0.658; 0.864 | — |
| SECONDARY Breath Nitric Oxide (NO) Level |
26; 23; 28; 30; 28; 36 | — |
Eligibility Criteria
Inclusion Criteria
- Sex: females and males
- Age: at least 18 years and less than 75 years
- Diagnosis of heart failure with reduced ejection fraction (NYHA II-IV)
- Ejection fraction 180 mmHg at consent
- Diastolic blood pressure 100 mmHg at consent
- Previous adverse reaction to nitrates necessitating withdrawal of therapy
- Treatment with phosphodiesterase inhibitors within the last 3 months (patient must also be willing to not take them for the duration of the trial).
- Ejection fraction > 45%
- Primary hypertrophic cardiomyopathy
- Infiltrative cardiomyopathy (e.g., amyloid)
- Active myocarditis
- Complex congenital heart disease
- Active collagen vascular disease
- Active angina/ischemia from epicardial coronary disease
- Percutaneous coronary intervention, new bi-ventricular pacing, or coronary artery bypass grafting within the past 3 months
- More than mild mitral or aortic stenosis
- Valvular heart disease with severe regurgitation of any valve.
- Acute or chronic severe liver disease as evidenced by encephalopathy, international normalized ratio (INR) >1.7 without anticoagulation therapy, or variceal bleeding
- Patients requiring exogenous oxygen at rest or for exercise
- Terminal disease (other than heart failure) with expected survival < 1 y
- Enrollment in another therapeutic trial during the period of the study
- Pregnancy
Data sourced from ClinicalTrials.gov (NCT02797184). 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.