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

NCT05562167 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 202204141
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (2)

• VO2 Peak Testing

  peak oxygen consumption during treadmill exercise

  Determined at Baseline visit, Acute Dose Visit, and Chronic Dose Visit, which will be scheduled throughout 8 weeks.

• Maximal muscle power

  assessment of quadriceps power

  Determined at Baseline visit, Acute Dose Visit, and Chronic Dose Visit, which will be scheduled throughout 8 weeks.

Secondary Outcomes (6)

• MLHFQ questionnaire

  Determined at Baseline visit, Acute Dose Visit, and Chronic Dose Visit, which will be scheduled throughout 8 weeks.

• KCCQ questionnaire

  Determined at Baseline visit, Acute Dose Visit, and Chronic Dose Visit, which will be scheduled throughout 8 weeks.

• Maximal muscle velocity

  Determined at Baseline visit, Acute Dose Visit, and Chronic Dose Visit, which will be scheduled throughout 8 weeks.

• Maximal exercise time on treadmill

  Determined at Baseline visit, Acute Dose Visit, and Chronic Dose Visit, which will be scheduled throughout 8 weeks.

• Plasma nitrate and nitrite

  Determined at Baseline visit, Acute Dose Visit, and Chronic Dose Visit, which will be scheduled throughout 8 weeks.

Study Arms (2)

Potassium Nitrate (KNO3) treatment arm

EXPERIMENTAL

10 mmol of KNO3 via a single gel capsule to be consumed orally once per day for 6 weeks.

Drug: KNO3

Placebo-controlled arm

PLACEBO COMPARATOR

10 mmol of placebo via a single gel capsule to be consumed orally once per day for 6 weeks.

Drug: Placebo

Interventions

KNO3 DRUG

10 mmol of KNO3 via a single gel capsule to be consumed orally once per day for 6 weeks.

Also known as: Potassium nitrate

Potassium Nitrate (KNO3) treatment arm

Placebo DRUG

10 mmol of placebo via a single gel capsule to be consumed orally once per day for 6 weeks.

Placebo-controlled arm

Eligibility Criteria

• Age: 19 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To participate in this study, a patient must meet all of the criteria listed below:
• Males and females aged greater than or equal to 18y and less than 80y at time of consent
• Diagnosis of heart failure with reduced ejection fraction
• New York Heart Association (NYHA) Class II-III at Visit 1
• Ejection fraction less than 45%, as evaluated through transthoracic echocardiography at Visit 1
• Stable medical therapy, defined by no addition or removal (or change of more than 100 percent) of the following for 60 days prior to Visit 1: beta-adrenergic blockade and angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blocker (ARB or aldosterone antagonists) or ARNI (ARB + sacubitril)
• Ability and willingness to sign an IRB approved written informed consent form; legally authorized representatives are not allowed in this study

You may not qualify if:

• To participate in this study, a patient must not meet any of the criteria listed below:
• 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 3 months prior to Visit 1
• Major orthopedic, psychiatric, neurological, or other conditions that would hinder the ability to complete the exercise tests at the time of Visit 1
• Estimated glomerular filtration rate less than 45 mL/min/1.73m2 on screening clinical laboratories measured at Visit 1
• Systolic blood pressure less than 90mmHg or greater than 180mmHg at Visit 1
• Diastolic blood pressure less than 40mmHg or greater than 100mmHg at Visit 1
• Previous adverse reaction to nitrate prior to Visit 1
• Treatment with phosphodiesterase inhibitors within the last 3 months prior to Visit 1; Patient must also be willing to not take them for the duration of the trial
• Diagnosis of primary hypertrophic cardiomyopathy, infiltrative cardiomyopathy (e.g., amyloid), active myocarditis, or complex congenital heart disease prior to Visit 1
• Active collagen vascular disease at time of Visit 1
• Percutaneous coronary intervention, new bi-ventricular pacing, or coronary artery bypass grafting within the 3 months prior to Visit 1
• Valvular heart disease with severe regurgitation or stenosis of any valve, as demonstrated on the echocardiogram at Visit 1
• Known severe liver disease as evidenced by encephalopathy or variceal bleeding;
• Terminal disease (other than heart failure) with expected survival less than 1 y at time of Visit 1

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

MeSH Terms

Conditions

Heart Failure

Interventions

potassium nitrate

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Linda R Peterson, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dawson A Haley, B.S.

CONTACT

3147914455; dhaley@wustl.edu

Susan B Racette, PhD

CONTACT

602-543-1563; Susan.Racette@asu.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double blind, placebo controlled
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, placebo-controlled, parallel arm design

Study Record Dates

• First Submitted: September 21, 2022
• First Posted: September 30, 2022
• Study Start: March 31, 2023
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): July 31, 2027
• Last Updated: May 6, 2026

Record last verified: 2026-05

Locations

US (1)