The Inorganic Nitrate and eXercise Performance in Heart Failure (iNIX-HF) -a Phase II Clinical Trial

202204141

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.

2023-03-31

2028-01-01

2028-01-01

Recruiting

Early phase I

75

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.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Randomized, placebo-controlled, parallel arm design', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'DOUBLE', 'maskingDescription': 'Double blind, placebo controlled', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR']}}, 'enrollmentInfo': {'count': 75, 'type': 'ESTIMATED'}}

2024-05-29