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

Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02754518
• Other study ID #: IRB15-1410
• Status: Completed
• Phase: Phase 4
• Start date: April 2016
• Est. completion date: April 2019

Study information

• Verified date: January 2021
• Source: University of Chicago
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: April 2019
• Est. primary completion date: April 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Heart Failure

Intervention

Drug:
• Entresto

Locations

Country	Name	City	State
United States	University of Chicago Medical Center	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
University of Chicago

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in LV Remodeling 2D End-Diastolic Diameter (cm)	LV Remodeling 2D End-Diastolic Diameter (cm)	Baseline,1 year
Primary	Change From Baseline in LV Remodeling 2D End-Systolic Diameter (cm)	LV Remodeling 2D End-Systolic Diameter (cm)	Baseline,1 year
Primary	Change From Baseline in LV Remodeling Global Longitudinal Strain (%)	LV Remodeling Global Longitudinal Strain (%)	Baseline,1 year
Primary	Change From Baseline in LV Remodeling Left Atrial Volume (mL)	LV Remodeling Left Atrial Volume (mL)	Baseline,1 year
Primary	Change From Baseline in LV Remodeling 3D End-Diastolic Volume (mL)	LV Remodeling 3D End-Diastolic Volume (mL)	Baseline,1 year
Primary	Change From Baseline in LV Remodeling 3D End-Systolic Volume (mL)	LV Remodeling 3D End-Systolic Volume (mL)	Baseline,1 year
Primary	Change From Baseline in LV Remodeling LV Ejection Fraction (%)	LV Remodeling LV Ejection Fraction (%)	Baseline,1 year
Primary	Change From Baseline in LV Remodeling Conicity (%)	LV Remodeling Conicity (%)	Baseline,1 year
Primary	Change From Baseline in LV Remodeling Sphericity (%)	LV Remodeling Sphericity (%)	Baseline,1 year
Primary	Change From Baseline in RV Remodeling End-Diastolic Volume (mL)	RV Remodeling End-Diastolic Volume (mL)	Baseline,1 year
Primary	Change From Baseline in RV Remodeling End Systolic Volume (mL)	RV Remodeling End Systolic Volume (mL)	Baseline,1 year
Primary	Change From Baseline in RV Remodeling Ejection Fraction (%)	RV Remodeling Ejection Fraction (%)	Baseline,1 year
Primary	Change From Baseline in RV Remodeling Septal Curvature (%)	RV Remodeling Septal Curvature (%)	Baseline,1 year
Primary	Change From Baseline in RV Remodeling Free-Wall Curvature (%)	RV Remodeling Free-Wall Curvature (%)	Baseline,1 year
Primary	Change From Baseline in RV Remodeling Tricuspid Regurgitation	RV Remodeling Tricuspid Regurgitation	Baseline,1 year
Secondary	Change From Baseline in Rho-associated Protein Kinase (ROCK)	Rho-associated protein kinase (ROCK)	Baseline,1 year
Secondary	Change From Baseline in (MIBG) Early hm Ratio	Cardiac 123Iodine-metaiodobenzylguanidine (MIBG) Early heart/mediastinum ratio (hm) ratio	Baseline,1 year
Secondary	Change From Baseline in (MIBG) Late hm Ratio	Cardiac 123Iodine-metaiodobenzylguanidine (MIBG) Late heart/mediastinum ratio (hm) ratio	Baseline,1 year
Secondary	Change From Baseline in NT-proBNP Levels	NT-proBNP levels (pg/ml)	Baseline,1 year
Secondary	Change From Baseline in Exercise Performance - 6 Minute Walk	Exercise Performance - 6 Minute Walk	Baseline,1 year
Secondary	Change From Baseline in Exercise Performance - CPX - Peak VO2 (mL/kg/Min)	Exercise Performance - CPX - Peak VO2 (mL/kg/min)	Baseline,1 year
Secondary	Change From Baseline in Exercise Performance - CPX - Peak RER	Exercise Performance - CPX - Peak RER (Respiratory Exchange Ratio)	Baseline,1 year
Secondary	Change From Baseline in Exercise Performance - CPX - VE/VC02	Exercise Performance - CPX - VE/VC02	Baseline,1 year
Secondary	Change From Baseline in Blood Pressure - Systolic (mmHg)	Blood Pressure - Systolic (mmHg)	Baseline,1 year
Secondary	Change From Baseline in Blood Pressure - Diastolic (mmHg)	Blood Pressure - Diastolic (mmHg)	Baseline,1 year
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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