Clinical trial NCT02754518: Demonstration of Reverse Remodeling Effects of Entresto. Using Echocardiography Endocardial Surface Analysis
Official title: Demonstration of Reverse Remodeling Effects of Entresto (Valsartan/Sacubitril) Using Echocardiography Endocardial Surface Analysis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Heart Failure
Lead sponsor: University of Chicago
Sponsor class: OTHER
First posted: 2016-04-28
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Change From Baseline in LV Remodeling 2D End-Diastolic Diameter (cm)
timeFrame: Baseline,1 year
measure: Change From Baseline in LV Remodeling 2D End-Systolic Diameter (cm)
timeFrame: Baseline,1 year
measure: Change From Baseline in LV Remodeling Global Longitudinal Strain (%)
timeFrame: Baseline,1 year
measure: Change From Baseline in LV Remodeling Left Atrial Volume (mL)
timeFrame: Baseline,1 year
measure: Change From Baseline in LV Remodeling 3D End-Diastolic Volume (mL)
timeFrame: Baseline,1 year
measure: Change From Baseline in LV Remodeling 3D End-Systolic Volume (mL)
timeFrame: Baseline,1 year
measure: Change From Baseline in LV Remodeling LV Ejection Fraction (%)
timeFrame: Baseline,1 year
measure: Change From Baseline in LV Remodeling Conicity (%)
timeFrame: Baseline,1 year
measure: Change From Baseline in LV Remodeling Sphericity (%)
timeFrame: Baseline,1 year
measure: Change From Baseline in RV Remodeling End-Diastolic Volume (mL)
timeFrame: Baseline,1 year
measure: Change From Baseline in RV Remodeling End Systolic Volume (mL)
timeFrame: Baseline,1 year
measure: Change From Baseline in RV Remodeling Ejection Fraction (%)
timeFrame: Baseline,1 year
measure: Change From Baseline in RV Remodeling Septal Curvature (%)
timeFrame: Baseline,1 year
measure: Change From Baseline in RV Remodeling Free-Wall Curvature (%)
timeFrame: Baseline,1 year
measure: Change From Baseline in RV Remodeling Tricuspid Regurgitation
timeFrame: Baseline,1 year
Secondary outcomes:
measure: Change From Baseline in Rho-associated Protein Kinase (ROCK)
timeFrame: Baseline,1 year
measure: Change From Baseline in (MIBG) Early hm Ratio
timeFrame: Baseline,1 year
measure: Change From Baseline in (MIBG) Late hm Ratio
timeFrame: Baseline,1 year
measure: Change From Baseline in NT-proBNP Levels
timeFrame: Baseline,1 year
measure: Change From Baseline in Exercise Performance - 6 Minute Walk
timeFrame: Baseline,1 year
measure: Change From Baseline in Exercise Performance - CPX - Peak VO2 (mL/kg/Min)
timeFrame: Baseline,1 year
measure: Change From Baseline in Exercise Performance - CPX - Peak RER
timeFrame: Baseline,1 year
measure: Change From Baseline in Exercise Performance - CPX - VE/VC02
timeFrame: Baseline,1 year
measure: Change From Baseline in Blood Pressure - Systolic (mmHg)
timeFrame: Baseline,1 year
measure: Change From Baseline in Blood Pressure - Diastolic (mmHg)
timeFrame: Baseline,1 year
measure: Change From Baseline in KCCQ - Physical Limitation
timeFrame: Baseline,1 year
measure: Change From Baseline in KCCQ - Symptom Stability
timeFrame: Baseline,1 year
measure: Change From Baseline in KCCQ - Symptom Frequency
timeFrame: Baseline,1 year
measure: Change From Baseline in KCCQ - Symptom Burden
timeFrame: Baseline,1 year
measure: Change From Baseline in KCCQ - Total Symptom
timeFrame: Baseline,1 year
measure: Change From Baseline in KCCQ - Self Efficacy
timeFrame: Baseline,1 year
measure: Change From Baseline in KCCQ - Quality of Life Score
timeFrame: Baseline,1 year
measure: Change From Baseline in KCCQ - Social Limitation
timeFrame: Baseline,1 year
measure: Change From Baseline in KCCQ - Overall Summary
timeFrame: Baseline,1 year
measure: Change From Baseline in KCCQ - Clinical Summary
timeFrame: Baseline,1 year
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
Study officials:
affiliation: University of Chicago
name: Sara Kalantari, MD
role: PRINCIPAL_INVESTIGATOR
References: