What side effects are associated with this type of intervention?

Common treatments for heart failure that enhance nitric oxide availability, such as potassium nitrate, may include side effects like headaches, dizziness, and gastrointestinal discomfort. Additionally, treatments like nitrates can cause hypotension (low blood pressure) and reflex tachycardia (increased heart rate). Other common heart failure treatments, such as ACE inhibitors, beta-blockers, and diuretics, can have side effects including cough, hyperkalemia (high potassium levels), fatigue, and electrolyte imbalances.

What prior FDA approvals exist?

FDA-approved treatments for heart failure that enhance nitric oxide availability or have similar mechanisms include nitrates such as isosorbide dinitrate and hydralazine, which are often used in combination to reduce ventricular preload and improve symptoms. These drugs work by dilating blood vessels, thereby decreasing the workload on the heart. Additionally, the use of sildenafil, a phosphodiesterase-5 inhibitor, has shown benefits in improving exercise capacity and hemodynamics in heart failure patients, although its use is more common in pulmonary hypertension. The ongoing iNIX-HF trial is investigating the effects of potassium nitrate (KNO3) on exercise performance in heart failure patients, hypothesizing that it will improve muscle power and aerobic capacity by enhancing nitric oxide availability.

What other types of research exist?

Promising novel alternatives to potassium nitrate for enhancing nitric oxide availability in heart failure patients include L-arginine and L-citrulline, which are amino acids that serve as substrates for nitric oxide production. Additionally, dietary supplementation with inorganic nitrate and nitrite, as well as (poly)phenols and other dietary antioxidants, have shown potential in improving nitric oxide bioavailability and cardiovascular health.

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Inorganic Nitrate

Nitrate Supplementation for Heart Failure (iNIX-HF Trial)

Q: What is the mechanism of action of this treatment?

Common treatments for Heart Failure with Reduced Ejection Fraction (HFrEF) include beta-blockers, ACE inhibitors, ARBs, and diuretics. These medications work by reducing the workload on the heart, lowering blood pressure, and preventing fluid buildup. Potassium nitrate, which enhances nitric oxide availability, is being studied for its potential to improve exercise performance in HFrEF patients. Nitric oxide is a vasodilator that helps relax blood vessels, improving blood flow and reducing the heart's workload. This is crucial for heart failure patients as it can enhance oxygen delivery to tissues, improve exercise capacity, and potentially reduce symptoms and hospitalizations.

Phase 2

Recruiting

Led By Linda R Peterson, MD

Research Sponsored by Washington University School of Medicine

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Must not have

Valvular heart disease with severe regurgitation or stenosis of any valve

Active collagen vascular disease

Timeline

Screening 3 weeks

Treatment Varies

Follow Up determined at visit 1, visit 2, and visit 3, which will be scheduled throughout 8 weeks.

Summary

This trial tests if taking potassium nitrate daily can help people with heart failure improve their muscle strength and exercise ability. The study involves an initial test followed by a period of daily doses. Potassium nitrate may work by improving blood flow in the body.

Who is the study for?

This trial is for adults with heart failure where the heart's left ventricle doesn't pump well (ejection fraction <45%). They should be in a stable condition without recent changes to key medications and not involved in other studies. Excluded are pregnant women, those with severe liver disease, recent major cardiovascular procedures, or conditions that prevent exercise testing.

What is being tested?

The iNIX-HF study tests if KNO3 can improve muscle power and aerobic performance in heart failure patients compared to a placebo. Participants will receive either KNO3 or placebo over six weeks and undergo exercise tests to measure any improvements.

What are the potential side effects?

While specific side effects of KNO3 aren't listed here, nitrates commonly cause headaches, dizziness, flushing, low blood pressure, and may interact with certain medications like phosphodiesterase inhibitors.

Eligibility Criteria

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have severe heart valve disease.

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I have an active collagen vascular disease.

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I have severe liver disease with symptoms like confusion or bleeding from enlarged veins.

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I have a specific heart condition like thickened heart muscle, amyloidosis, heart inflammation, or a complex congenital heart disease.

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I am pregnant or a postmenopausal woman on hormone replacement therapy.

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I have ongoing chest pain or heart issues due to blocked heart arteries.

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My heart pumps well, with an ejection fraction of 45% or higher.

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I need extra oxygen when I'm resting or moving.

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I am not taking medication for gout.

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I have a terminal illness and am expected to live less than one year.

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I don't have any major health issues that would stop me from doing exercise tests.

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My kidney function is reduced, with a filtration rate below 45 mL/min.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ determined at visit 1, visit 2, and visit 3, which will be scheduled throughout 8 weeks.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~determined at visit 1, visit 2, and visit 3, which will be scheduled throughout 8 weeks.

This trial's timeline: 3 weeks for screening, Varies for treatment, and determined at visit 1, visit 2, and visit 3, which will be scheduled throughout 8 weeks. for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Maximal muscle power

VO2 Peak Testing

Secondary study objectives

Breath nitric oxide (NO) level

KCCQ questionnaire

MLHFQ questionnaire

+3 more

Side effects data

From 2016 Phase 2 trial • 12 Patients • NCT02256345

33%

Any side effect

33%

GI symptoms

33%

Mild lower extremity edema

100%

80%

60%

40%

20%

Study treatment Arm

Randomized to KCl

Randomized to KNO3

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Potassium Nitrate (KNO3) treatment armExperimental Treatment1 Intervention

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

Group II: Placebo-controlled armPlacebo Group1 Intervention

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

KNO3

2015

Completed Phase 2

~20

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Heart Failure with Reduced Ejection Fraction (HFrEF) include beta-blockers, ACE inhibitors, ARBs, and diuretics. These medications work by reducing the workload on the heart, lowering blood pressure, and preventing fluid buildup. Potassium nitrate, which enhances nitric oxide availability, is being studied for its potential to improve exercise performance in HFrEF patients. Nitric oxide is a vasodilator that helps relax blood vessels, improving blood flow and reducing the heart's workload. This is crucial for heart failure patients as it can enhance oxygen delivery to tissues, improve exercise capacity, and potentially reduce symptoms and hospitalizations.

Effects of pharmacological treatment of acute myocardial infarction on left ventricular function.Nitrates in myocardial infarction: a current perspective.