The inorganic NItrate and eXercise performance in Heart Failure (iNIX-HF) phase II clinical trial: Rationale and study design

Background: Heart failure (HF) is a debilitating and often fatal disease that affects millions of people worldwide. Diminished nitric oxide synthesis, signaling, and bioavailability are believed to contribute to poor skeletal muscle function and aerobic capacity. The aim of this clinical trial (iNIX...

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Main Authors: Andrew R. Coggan, Lauren K. Park, Susan B. Racette, Victor G. Davila-Roman, Pattie Lenzen, Kathryn Vehe, Peter M. Dore, Kenneth B. Schechtman, Linda R. Peterson
Format: Article
Language:English
Published: Elsevier 2023-12-01
Series:Contemporary Clinical Trials Communications
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2451865423001540
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author Andrew R. Coggan
Lauren K. Park
Susan B. Racette
Victor G. Davila-Roman
Pattie Lenzen
Kathryn Vehe
Peter M. Dore
Kenneth B. Schechtman
Linda R. Peterson
author_facet Andrew R. Coggan
Lauren K. Park
Susan B. Racette
Victor G. Davila-Roman
Pattie Lenzen
Kathryn Vehe
Peter M. Dore
Kenneth B. Schechtman
Linda R. Peterson
author_sort Andrew R. Coggan
collection DOAJ
description Background: Heart failure (HF) is a debilitating and often fatal disease that affects millions of people worldwide. Diminished nitric oxide synthesis, signaling, and bioavailability are believed to contribute to poor skeletal muscle function and aerobic capacity. The aim of this clinical trial (iNIX-HF) is to determine the acute and longer-term effectiveness of inorganic nitrate supplementation on exercise performance in patients with HF with reduced ejection fraction (HFrEF). Methods: This clinical trial is a double-blind, placebo-controlled, randomized, parallel-arm design study in which patients with HFrEF (n = 75) are randomized to receive 10 mmol potassium nitrate (KNO3) or a placebo capsule daily for 6 wk. Primary outcome measures are muscle power determined by isokinetic dynamometry and peak aerobic capacity (VO2peak) determined during an incremental treadmill exercise test. Endpoints include the acute effects of a single dose of KNO3 and longer-term effects of 6 wk of KNO3. The study is adequately powered to detect expected increases in these outcomes at P < 0.05 with 1-β>0.80. Discussion: The iNIX-HF phase II clinical trial will evaluate the effectiveness of inorganic nitrate supplements as a new treatment to ameliorate poor exercise capacity in HFrEF. This study also will provide critical preliminary data for a future ‘pivotal’, phase III, multi-center trial of the effectiveness of nitrate supplements not only for improving exercise performance, but also for improving symptoms and decreasing other major cardiovascular endpoints. The potential public health impact of identifying a new, relatively inexpensive, safe, and effective treatment that improves overall exercise performance in patients with HFrEF is significant.
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spelling doaj.art-70dc2447bd9040f5b0db2d1c6ed583912023-12-16T06:08:34ZengElsevierContemporary Clinical Trials Communications2451-86542023-12-0136101208The inorganic NItrate and eXercise performance in Heart Failure (iNIX-HF) phase II clinical trial: Rationale and study designAndrew R. Coggan0Lauren K. Park1Susan B. Racette2Victor G. Davila-Roman3Pattie Lenzen4Kathryn Vehe5Peter M. Dore6Kenneth B. Schechtman7Linda R. Peterson8Department of Kinesiology, School of Health &amp; Human Sciences, And Indiana Center for Musculoskeletal Health, School of Medicine, Indiana University Purdue University Indianapolis, Indianapolis, IN, USA; Corresponding author. Department of Kinesiology, Indiana University Purdue University Indianapolis, IF 101C, 250 University Boulevard, Indianapolis, IN, 46112, USA.Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USACollege of Health Solutions, Arizona State University, Phoenix, AZ, USADepartment of Medicine, Washington University School of Medicine, Saint Louis, MO, USADepartment of Medicine, Washington University School of Medicine, Saint Louis, MO, USABarnes-Jewish Hospital, Saint Louis, MO, USADivision of Biostatistics, Washington University School of Medicine, Saint Louis, MO, USADivision of Biostatistics, Washington University School of Medicine, Saint Louis, MO, USADepartment of Medicine, Washington University School of Medicine, Saint Louis, MO, USABackground: Heart failure (HF) is a debilitating and often fatal disease that affects millions of people worldwide. Diminished nitric oxide synthesis, signaling, and bioavailability are believed to contribute to poor skeletal muscle function and aerobic capacity. The aim of this clinical trial (iNIX-HF) is to determine the acute and longer-term effectiveness of inorganic nitrate supplementation on exercise performance in patients with HF with reduced ejection fraction (HFrEF). Methods: This clinical trial is a double-blind, placebo-controlled, randomized, parallel-arm design study in which patients with HFrEF (n = 75) are randomized to receive 10 mmol potassium nitrate (KNO3) or a placebo capsule daily for 6 wk. Primary outcome measures are muscle power determined by isokinetic dynamometry and peak aerobic capacity (VO2peak) determined during an incremental treadmill exercise test. Endpoints include the acute effects of a single dose of KNO3 and longer-term effects of 6 wk of KNO3. The study is adequately powered to detect expected increases in these outcomes at P < 0.05 with 1-β>0.80. Discussion: The iNIX-HF phase II clinical trial will evaluate the effectiveness of inorganic nitrate supplements as a new treatment to ameliorate poor exercise capacity in HFrEF. This study also will provide critical preliminary data for a future ‘pivotal’, phase III, multi-center trial of the effectiveness of nitrate supplements not only for improving exercise performance, but also for improving symptoms and decreasing other major cardiovascular endpoints. The potential public health impact of identifying a new, relatively inexpensive, safe, and effective treatment that improves overall exercise performance in patients with HFrEF is significant.http://www.sciencedirect.com/science/article/pii/S2451865423001540Heart failureNitric oxideDietary nitratePeak oxygen consumptionMuscle power
spellingShingle Andrew R. Coggan
Lauren K. Park
Susan B. Racette
Victor G. Davila-Roman
Pattie Lenzen
Kathryn Vehe
Peter M. Dore
Kenneth B. Schechtman
Linda R. Peterson
The inorganic NItrate and eXercise performance in Heart Failure (iNIX-HF) phase II clinical trial: Rationale and study design
Contemporary Clinical Trials Communications
Heart failure
Nitric oxide
Dietary nitrate
Peak oxygen consumption
Muscle power
title The inorganic NItrate and eXercise performance in Heart Failure (iNIX-HF) phase II clinical trial: Rationale and study design
title_full The inorganic NItrate and eXercise performance in Heart Failure (iNIX-HF) phase II clinical trial: Rationale and study design
title_fullStr The inorganic NItrate and eXercise performance in Heart Failure (iNIX-HF) phase II clinical trial: Rationale and study design
title_full_unstemmed The inorganic NItrate and eXercise performance in Heart Failure (iNIX-HF) phase II clinical trial: Rationale and study design
title_short The inorganic NItrate and eXercise performance in Heart Failure (iNIX-HF) phase II clinical trial: Rationale and study design
title_sort inorganic nitrate and exercise performance in heart failure inix hf phase ii clinical trial rationale and study design
topic Heart failure
Nitric oxide
Dietary nitrate
Peak oxygen consumption
Muscle power
url http://www.sciencedirect.com/science/article/pii/S2451865423001540
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