Demonstration of Reverse Remodeling Effects of Entresto (Valsartan/Sacubitril) Using Echocardiography Endocardial Surface Analysis
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Sponsor
- University of Chicago
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- Change From Baseline in LV Remodeling 2D End-Diastolic Diameter (cm)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Males and females aged ≥18 years
- •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
- •Stable and optimized on an angiotensin-converting-enzyme inhibitor (ACEI) equivalent to enalapril ≥ 10 twice a day (BID) for at least 4 weeks
- •Stable and optimized on a beta-blocker for at least 4 weeks
- •Optimized dosing of aldosterone antagonist at stable dose for at least 4 weeks
Exclusion Criteria
- •History of angioedema
- •estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73 m2 at screening
- •Serum potassium > 5.2 mmol/L at screening
- •Symptomatic hypotension as defined by Investigator, systolic blood pressure (SBP) < 100 mmHg at screening
- •Current acute decompensated heart failure
- •History of severe pulmonary disease
- •Active malignancy
- •Requirement for treatment with both angiotensin-converting-enzyme inhibitor (ACEI) and angiotensin receptor blockers (ARB)
Arms & Interventions
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.
Intervention: Entresto (Drug)
Outcomes
Primary Outcomes
Change From Baseline in LV Remodeling 2D End-Diastolic Diameter (cm)
Time Frame: Baseline,1 year
LV Remodeling 2D End-Diastolic Diameter (cm)
Change From Baseline in LV Remodeling 2D End-Systolic Diameter (cm)
Time Frame: Baseline,1 year
LV Remodeling 2D End-Systolic Diameter (cm)
Change From Baseline in LV Remodeling Global Longitudinal Strain (%)
Time Frame: Baseline,1 year
LV Remodeling Global Longitudinal Strain (%)
Change From Baseline in RV Remodeling Free-Wall Curvature (%)
Time Frame: Baseline,1 year
RV Remodeling Free-Wall Curvature (%)
Change From Baseline in LV Remodeling Left Atrial Volume (mL)
Time Frame: Baseline,1 year
LV Remodeling Left Atrial Volume (mL)
Change From Baseline in LV Remodeling 3D End-Diastolic Volume (mL)
Time Frame: Baseline,1 year
LV Remodeling 3D End-Diastolic Volume (mL)
Change From Baseline in LV Remodeling 3D End-Systolic Volume (mL)
Time Frame: Baseline,1 year
LV Remodeling 3D End-Systolic Volume (mL)
Change From Baseline in LV Remodeling LV Ejection Fraction (%)
Time Frame: Baseline,1 year
LV Remodeling LV Ejection Fraction (%)
Change From Baseline in LV Remodeling Conicity (%)
Time Frame: Baseline,1 year
LV Remodeling Conicity (%)
Change From Baseline in LV Remodeling Sphericity (%)
Time Frame: Baseline,1 year
LV Remodeling Sphericity (%)
Change From Baseline in RV Remodeling End-Diastolic Volume (mL)
Time Frame: Baseline,1 year
RV Remodeling End-Diastolic Volume (mL)
Change From Baseline in RV Remodeling End Systolic Volume (mL)
Time Frame: Baseline,1 year
RV Remodeling End Systolic Volume (mL)
Change From Baseline in RV Remodeling Ejection Fraction (%)
Time Frame: Baseline,1 year
RV Remodeling Ejection Fraction (%)
Change From Baseline in RV Remodeling Septal Curvature (%)
Time Frame: Baseline,1 year
RV Remodeling Septal Curvature (%)
Change From Baseline in RV Remodeling Tricuspid Regurgitation
Time Frame: Baseline,1 year
RV Remodeling Tricuspid Regurgitation
Secondary Outcomes
- Change From Baseline in (MIBG) Late hm Ratio(Baseline,1 year)
- Change From Baseline in NT-proBNP Levels(Baseline,1 year)
- Change From Baseline in Exercise Performance - 6 Minute Walk(Baseline,1 year)
- Change From Baseline in Exercise Performance - CPX - Peak VO2 (mL/kg/Min)(Baseline,1 year)
- Change From Baseline in Exercise Performance - CPX - Peak RER(Baseline,1 year)
- Change From Baseline in Exercise Performance - CPX - VE/VC02(Baseline,1 year)
- Change From Baseline in Blood Pressure - Systolic (mmHg)(Baseline,1 year)
- Change From Baseline in Blood Pressure - Diastolic (mmHg)(Baseline,1 year)
- Change From Baseline in KCCQ - Physical Limitation(Baseline,1 year)
- Change From Baseline in KCCQ - Clinical Summary(Baseline,1 year)
- Change From Baseline in Rho-associated Protein Kinase (ROCK)(Baseline,1 year)
- Change From Baseline in (MIBG) Early hm Ratio(Baseline,1 year)
- Change From Baseline in KCCQ - Symptom Stability(Baseline,1 year)
- Change From Baseline in KCCQ - Symptom Frequency(Baseline,1 year)
- Change From Baseline in KCCQ - Symptom Burden(Baseline,1 year)
- Change From Baseline in KCCQ - Total Symptom(Baseline,1 year)
- Change From Baseline in KCCQ - Self Efficacy(Baseline,1 year)
- Change From Baseline in KCCQ - Quality of Life Score(Baseline,1 year)
- Change From Baseline in KCCQ - Social Limitation(Baseline,1 year)
- Change From Baseline in KCCQ - Overall Summary(Baseline,1 year)