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

Demonstration of Reverse Remodeling Effects of Entresto (Valsartan/Sacubitril) Using Echocardiography Endocardial Surface Analysis

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.

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Drug: Entresto

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Open label 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.	Drug: Entresto; Other Names: valsartan/sacubitril

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Rho-associated Protein Kinase (ROCK)	Rho-associated protein kinase (ROCK)	Baseline,1 year
Change From Baseline in (MIBG) Early hm Ratio	Cardiac 123Iodine-metaiodobenzylguanidine (MIBG) Early heart/mediastinum ratio (hm) ratio	Baseline,1 year
Change From Baseline in (MIBG) Late hm Ratio	Cardiac 123Iodine-metaiodobenzylguanidine (MIBG) Late heart/mediastinum ratio (hm) ratio	Baseline,1 year
Change From Baseline in NT-proBNP Levels	NT-proBNP levels (pg/ml)	Baseline,1 year
Change From Baseline in Exercise Performance - 6 Minute Walk	Exercise Performance - 6 Minute Walk	Baseline,1 year
Change From Baseline in Exercise Performance - CPX - Peak VO2 (mL/kg/Min)	Exercise Performance - CPX - Peak VO2 (mL/kg/min)	Baseline,1 year
Change From Baseline in Exercise Performance - CPX - Peak RER	Exercise Performance - CPX - Peak RER (Respiratory Exchange Ratio)	Baseline,1 year
Change From Baseline in Exercise Performance - CPX - VE/VC02	Exercise Performance - CPX - VE/VC02	Baseline,1 year
Change From Baseline in Blood Pressure - Systolic (mmHg)	Blood Pressure - Systolic (mmHg)	Baseline,1 year
Change From Baseline in Blood Pressure - Diastolic (mmHg)	Blood Pressure - Diastolic (mmHg)	Baseline,1 year
Change From Baseline in KCCQ - Physical Limitation	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.	Baseline,1 year
Change From Baseline in KCCQ - Symptom Stability	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.	Baseline,1 year
Change From Baseline in KCCQ - Symptom Frequency	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.	Baseline,1 year
Change From Baseline in KCCQ - Symptom Burden	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.	Baseline,1 year
Change From Baseline in KCCQ - Total Symptom	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.	Baseline,1 year
Change From Baseline in KCCQ - Self Efficacy	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.	Baseline,1 year
Change From Baseline in KCCQ - Quality of Life Score	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.	Baseline,1 year
Change From Baseline in KCCQ - Social Limitation	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.	Baseline,1 year
Change From Baseline in KCCQ - Overall Summary	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.	Baseline,1 year
Change From Baseline in KCCQ - Clinical Summary	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.	Baseline,1 year

Collaborators and Investigators

• Sponsor: University of Chicago
• Investigators: Principal Investigator: Sara Kalantari, MD, University of Chicago

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2016
• Primary Completion (Actual): April 1, 2019
• Study Completion (Actual): April 1, 2019

Study Registration Dates

• First Submitted: April 22, 2016
• First Submitted That Met QC Criteria: April 27, 2016
• First Posted (Estimate): April 28, 2016

Study Record Updates

• Last Update Posted (Actual): January 29, 2021
• Last Update Submitted That Met QC Criteria: January 5, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Valsartan; Sacubitril and valsartan sodium hydrate drug combination
• Other Study ID Numbers: IRB15-1410