The Inorganic Nitrate and eXercise Performance in Heart Failure (iNIX-HF)

• Status: Recruiting
• Trial end date: 2028-01-01
• Target enrollment: 0
• Participant gender: All

Summary

The goals of this project are to determine the effectiveness of acute (2 hours after a single dose) and chronic (after 6 weeks of once-a-day dosing) KNO3 treatment (10mmol) vs. placebo on quadriceps muscle power and on aerobic exercise performance (V̇O2peak) in patients with HFrEF (left ventricular ejection fraction <45%). The investigators hypothesize that both acute and chronic dosing of 10mmol of KNO3 will improve exercise performance in HFrEF. To test this hypothesis, the investors will perform a randomized, double-blind, placebo-controlled, parallel-arm design study.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Washington University School of Medicine

Criteria

Inclusion Criteria:

• Diagnosis of heart failure with reduced ejection fraction; New York Heart Association (NYHA) Class II-III; Ejection fraction less than 45% as determined on an imaging study within 3 months of enrollment.

• Stable medical therapy, defined by no addition or removal (or change of more than 100 percent) of the following: beta-adrenergic blockade and angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blocker (ARB or aldosterone antagonists) or ARNI (ARB + sacubitril) for 60 days.

Exclusion Criteria:

• Vulnerable populations as defined by the U.S. Department of Health and Human Services; prisoners and children will be excluded from this study

• Pharmacologic, organic nitrate therapy within the last 3 months

• Major orthopedic, psychiatric, neurological, or other conditions that would hinder the ability to complete the exercise tests

• Estimated glomerular filtration rate less than 45 mL/min on screening clinical laboratories

• Systolic blood pressure less than 90mmHg or greater than 180mmHg at screening; Diastolic blood pressure less than 40mmHg or greater than 100mmHg at screening

• Previous adverse reaction to nitrate 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 greater than or equal to 45%

• Primary hypertrophic cardiomyopathy; Infiltrative cardiomyopathy (e.g., amyloid); Active myocarditis; Complex congenital heart disease;

• Active collagen vascular disease;

• Percutaneous coronary intervention, new bi-ventricular pacing, or coronary artery bypass grafting within the past 3 months

• Valvular heart disease with severe regurgitation or stenosis of any valve

• Acute or chronic severe liver disease as evidenced by encephalopathy or variceal bleeding

• Terminal disease (other than heart failure) with expected survival less than 1 y

• Enrollment in another therapeutic trial during the period of the study

• Pregnant women; Postmenopausal women taking exogenous estrogen replacement therapy

• Patients requiring exogenous oxygen at rest or during exercise

• Patients with active angina or ischemia due to epicardial coronary disease

• Patients taking xanthine oxidase inhibitors will be excluded

• Individuals taking proton pump inhibitors, antacids will be asked to hold these medications for the duration of the study if approved by his/her physician.