Demonstration of Reverse Remodeling Effects of Entresto. Using Echocardiography Endocardial Surface Analysis

Phase 4

Completed

• Conditions: Heart Failure
• Interventions: Drug: Entresto

• Registration Number: NCT02754518
• Lead Sponsor: University of Chicago

Brief Summary

This study intends to measure the effects of valsartan/sacubitril compared to baseline standard medical heart failure therapy on reverse remodeling using echocardiographic endocardial surface analysis techniques to assess changes in ventricular volume, function, and shape.

Detailed Description

This study intends to measure the effects of valsartan/sacubitril compared to baseline standard medical heart failure therapy on reverse remodeling using echocardiographic endocardial surface analysis techniques to assess changes in ventricular volume, function, and shape. Furthermore, Metaiodobenzylguanidine (MIBG) scintigraphy and the heart to mediastinum ratio will be used to assess Left Ventricle (LV) volume regression and risk reduction. The investigators also intend to measure the effects of valsartan/sacubitril on exercise capacity as assessed by the 6 minute walk test and peak Volume of Oxygen (V02) on cardiopulmonary exercise testing. Additionally, the investigators will examine the impact of valsartan/sacubitril on functional status and quality of life using the Kansas City Cardiomyopathy Questionnaire (KCCQ) and Qualia Health (a novel iPhone application that incorporates Fitbit technology to provide a "real time" daily 6 minute step count and assesses quality of life using a series of short targeted questions. The investigators will also measure Brain Natriuretic Peptide (BNP), N-terminal of the Prohormone Brain Natriuretic Peptide (NT-proBNP), and Rho-kinase (a biomarker associated with heart failure) levels at multiple time-points throughout the study period.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2016-04
• Study First Submitted: 2016-04-22
• Study First Submitted QC: 2016-04-27
• Study First Posted: 2016-04-28
• Primary Completion: 2019-04
• Study Completion: 2019-04
• Results First Submitted: 2019-04-09
• Status Verified: 2021-01
• Results First Submitted QC: 2021-01-05
• Last Update Submitted: 2021-01-05
• Results First Posted: 2021-01-29
• Last Update Posted: 2021-01-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. Males and females aged ≥18 years

2. Congestive Heart Failure (CHF) New York Heart Association (NYHA) class II-IV with 25%≤ Left Ventricular Ejection Fraction (LVEF) ≤40% (ECHO within last 6 months)

   • NT-proBNP ≥ 600 pg/mL OR
   • NT-proBNP ≥ 400 pg/mL and a hospitalization for heart failure within the last 12 months

3. Stable and optimized on an angiotensin-converting-enzyme inhibitor (ACEI) equivalent to enalapril ≥ 10 twice a day (BID) for at least 4 weeks

4. Stable and optimized on a beta-blocker for at least 4 weeks

5. Optimized dosing of aldosterone antagonist at stable dose for at least 4 weeks

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Exclusion Criteria

1. History of angioedema
2. estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73 m2 at screening
3. Serum potassium > 5.2 mmol/L at screening
4. Symptomatic hypotension as defined by Investigator, systolic blood pressure (SBP) < 100 mmHg at screening
5. Current acute decompensated heart failure
6. History of severe pulmonary disease
7. Active malignancy
8. Requirement for treatment with both angiotensin-converting-enzyme inhibitor (ACEI) and angiotensin receptor blockers (ARB)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Open label Entresto	Entresto	All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure. In this study subjects will take this drug as they normally would for their standard of care.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in LV Remodeling Conicity (%)	Baseline,1 year	LV Remodeling Conicity (%)
Change From Baseline in LV Remodeling Sphericity (%)	Baseline,1 year	LV Remodeling Sphericity (%)
Change From Baseline in LV Remodeling 2D End-Diastolic Diameter (cm)	Baseline,1 year	LV Remodeling 2D End-Diastolic Diameter (cm)
Change From Baseline in LV Remodeling 2D End-Systolic Diameter (cm)	Baseline,1 year	LV Remodeling 2D End-Systolic Diameter (cm)
Change From Baseline in LV Remodeling Global Longitudinal Strain (%)	Baseline,1 year	LV Remodeling Global Longitudinal Strain (%)
Change From Baseline in RV Remodeling Free-Wall Curvature (%)	Baseline,1 year	RV Remodeling Free-Wall Curvature (%)
Change From Baseline in LV Remodeling Left Atrial Volume (mL)	Baseline,1 year	LV Remodeling Left Atrial Volume (mL)
Change From Baseline in LV Remodeling 3D End-Diastolic Volume (mL)	Baseline,1 year	LV Remodeling 3D End-Diastolic Volume (mL)
Change From Baseline in LV Remodeling 3D End-Systolic Volume (mL)	Baseline,1 year	LV Remodeling 3D End-Systolic Volume (mL)
Change From Baseline in LV Remodeling LV Ejection Fraction (%)	Baseline,1 year	LV Remodeling LV Ejection Fraction (%)
Change From Baseline in RV Remodeling End-Diastolic Volume (mL)	Baseline,1 year	RV Remodeling End-Diastolic Volume (mL)
Change From Baseline in RV Remodeling End Systolic Volume (mL)	Baseline,1 year	RV Remodeling End Systolic Volume (mL)
Change From Baseline in RV Remodeling Ejection Fraction (%)	Baseline,1 year	RV Remodeling Ejection Fraction (%)
Change From Baseline in RV Remodeling Septal Curvature (%)	Baseline,1 year	RV Remodeling Septal Curvature (%)
Change From Baseline in RV Remodeling Tricuspid Regurgitation	Baseline,1 year	RV Remodeling Tricuspid Regurgitation

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in (MIBG) Late hm Ratio	Baseline,1 year	Cardiac 123Iodine-metaiodobenzylguanidine (MIBG) Late heart/mediastinum ratio (hm) ratio
Change From Baseline in NT-proBNP Levels	Baseline,1 year	NT-proBNP levels (pg/ml)
Change From Baseline in Exercise Performance - 6 Minute Walk	Baseline,1 year	Exercise Performance - 6 Minute Walk
Change From Baseline in Exercise Performance - CPX - Peak VO2 (mL/kg/Min)	Baseline,1 year	Exercise Performance - CPX - Peak VO2 (mL/kg/min)
Change From Baseline in Exercise Performance - CPX - Peak RER	Baseline,1 year	Exercise Performance - CPX - Peak RER (Respiratory Exchange Ratio)
Change From Baseline in Exercise Performance - CPX - VE/VC02	Baseline,1 year	Exercise Performance - CPX - VE/VC02
Change From Baseline in Blood Pressure - Systolic (mmHg)	Baseline,1 year	Blood Pressure - Systolic (mmHg)
Change From Baseline in Blood Pressure - Diastolic (mmHg)	Baseline,1 year	Blood Pressure - Diastolic (mmHg)
Change From Baseline in KCCQ - Physical Limitation	Baseline,1 year	KCCQ is a 23-item instrument that is self-administered. KCCQ measures physical function, symptoms (specifically frequency, severity, and recent change), social function, self-efficacy and knowledge, and quality of life. Subscales and Total Score range from 0-100; higher scores show better health status.; Developed and validated by Dr. John Spertus,MD of University of Missouri-Kansas City.
Change From Baseline in KCCQ - Clinical Summary	Baseline,1 year	KCCQ is a 23-item instrument that is self-administered. KCCQ measures physical function, symptoms (specifically frequency, severity, and recent change), social function, self-efficacy and knowledge, and quality of life. Subscales and Total Score range from 0-100; higher scores show better health status.; Developed and validated by Dr. John Spertus,MD of University of Missouri-Kansas City.
Change From Baseline in Rho-associated Protein Kinase (ROCK)	Baseline,1 year	Rho-associated protein kinase (ROCK)
Change From Baseline in (MIBG) Early hm Ratio	Baseline,1 year	Cardiac 123Iodine-metaiodobenzylguanidine (MIBG) Early heart/mediastinum ratio (hm) ratio
Change From Baseline in KCCQ - Symptom Stability	Baseline,1 year	KCCQ is a 23-item instrument that is self-administered. KCCQ measures physical function, symptoms (specifically frequency, severity, and recent change), social function, self-efficacy and knowledge, and quality of life. Subscales and Total Score range from 0-100; higher scores show better health status.; Developed and validated by Dr. John Spertus,MD of University of Missouri-Kansas City.
Change From Baseline in KCCQ - Symptom Frequency	Baseline,1 year	KCCQ is a 23-item instrument that is self-administered. KCCQ measures physical function, symptoms (specifically frequency, severity, and recent change), social function, self-efficacy and knowledge, and quality of life. Subscales and Total Score range from 0-100; higher scores show better health status.; Developed and validated by Dr. John Spertus,MD of University of Missouri-Kansas City.
Change From Baseline in KCCQ - Symptom Burden	Baseline,1 year	KCCQ is a 23-item instrument that is self-administered. KCCQ measures physical function, symptoms (specifically frequency, severity, and recent change), social function, self-efficacy and knowledge, and quality of life. Subscales and Total Score range from 0-100; higher scores show better health status.; Developed and validated by Dr. John Spertus,MD of University of Missouri-Kansas City.
Change From Baseline in KCCQ - Total Symptom	Baseline,1 year	KCCQ is a 23-item instrument that is self-administered. KCCQ measures physical function, symptoms (specifically frequency, severity, and recent change), social function, self-efficacy and knowledge, and quality of life. Subscales and Total Score range from 0-100; higher scores show better health status.; Developed and validated by Dr. John Spertus,MD of University of Missouri-Kansas City.
Change From Baseline in KCCQ - Self Efficacy	Baseline,1 year	KCCQ is a 23-item instrument that is self-administered. KCCQ measures physical function, symptoms (specifically frequency, severity, and recent change), social function, self-efficacy and knowledge, and quality of life. Subscales and Total Score range from 0-100; higher scores show better health status.; Developed and validated by Dr. John Spertus,MD of University of Missouri-Kansas City.
Change From Baseline in KCCQ - Quality of Life Score	Baseline,1 year	KCCQ is a 23-item instrument that is self-administered. KCCQ measures physical function, symptoms (specifically frequency, severity, and recent change), social function, self-efficacy and knowledge, and quality of life. Subscales and Total Score range from 0-100; higher scores show better health status.; Developed and validated by Dr. John Spertus,MD of University of Missouri-Kansas City.
Change From Baseline in KCCQ - Social Limitation	Baseline,1 year	KCCQ is a 23-item instrument that is self-administered. KCCQ measures physical function, symptoms (specifically frequency, severity, and recent change), social function, self-efficacy and knowledge, and quality of life. Subscales and Total Score range from 0-100; higher scores show better health status.; Developed and validated by Dr. John Spertus,MD of University of Missouri-Kansas City.
Change From Baseline in KCCQ - Overall Summary	Baseline,1 year	KCCQ is a 23-item instrument that is self-administered. KCCQ measures physical function, symptoms (specifically frequency, severity, and recent change), social function, self-efficacy and knowledge, and quality of life. Subscales and Total Score range from 0-100; higher scores show better health status.; Developed and validated by Dr. John Spertus,MD of University of Missouri-Kansas City.

Trial Locations

Locations (1)

University of Chicago Medical Center; 🇺🇸 Chicago, Illinois, United States