The Inorganic Nitrate and eXercise Performance in Heart Failure (iNIX-HF)
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.
Conditions:
🦠 Heart Failure
🗓️ Study Start (Actual) 31 March 2023
🗓️ Primary Completion (Estimated) 1 January 2028
✅ Study Completion (Estimated) 1 January 2028
👥 Enrollment (Estimated) 75
🔬 Study Type INTERVENTIONAL
📊 Phase PHASE2
Locations:
📍 Saint Louis, Missouri, United States

📋 Eligibility Criteria

Description

    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.
Ages Eligible for Study: 19 Years to 79 Years (ADULT, OLDER_ADULT)
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers: No

🗓️ Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

  • First Submitted 21 September 2022
  • First Submitted that Met QC Criteria 29 September 2022
  • First Posted 30 September 2022

Study Record Updates

  • Last Update Submitted that Met QC Criteria 24 May 2024
  • Last Update Posted 29 May 2024
  • Last Verified May 2024