Trial Outcomes & Findings for Demonstration of Reverse Remodeling Effects of Entresto. Using Echocardiography Endocardial Surface Analysis (NCT NCT02754518)

NCT ID: NCT02754518

Last Updated: 2021-01-29

Results Overview

LV Remodeling 2D End-Diastolic Diameter (cm)

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

40 participants

Primary outcome timeframe

Baseline,1 year

Results posted on

2021-01-29

Participant Flow

This is a prospective, single-arm longitudinal study, 40 patients were initiated on valsartan/sacubitril after a two week run in period of ACE or ARB alone.

Participant milestones

Participant milestones
Measure	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. Entresto
Overall Study STARTED	40
Overall Study COMPLETED	40
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Some patients have incomplete data.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Open Label Entresto n=40 Participants 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. Entresto
Age, Continuous	55 Years STANDARD_DEVIATION 12.4 • n=40 Participants
Sex: Female, Male Female	16 Participants n=40 Participants
Sex: Female, Male Male	24 Participants n=40 Participants
Race (NIH/OMB) Ethnicity · American Indian or Alaska Native	0 Participants n=40 Participants
Race (NIH/OMB) Ethnicity · Asian	2 Participants n=40 Participants
Race (NIH/OMB) Ethnicity · Native Hawaiian or Other Pacific Islander	0 Participants n=40 Participants
Race (NIH/OMB) Ethnicity · Black or African American	23 Participants n=40 Participants
Race (NIH/OMB) Ethnicity · White	15 Participants n=40 Participants
Race (NIH/OMB) Ethnicity · More than one race	0 Participants n=40 Participants
Race (NIH/OMB) Ethnicity · Unknown or Not Reported	0 Participants n=40 Participants
Region of Enrollment United States	40 Participants n=40 Participants
New York Heart Association (NYHA) Class Class II	26 Participants n=40 Participants
New York Heart Association (NYHA) Class Class III	13 Participants n=40 Participants
New York Heart Association (NYHA) Class Unknown	1 Participants n=40 Participants
Heart Failure Etiology Ischemic (ICM)	10 Participants n=40 Participants
Heart Failure Etiology Nonischemic (NICM)	24 Participants n=40 Participants
Heart Failure Etiology Unknown	6 Participants n=40 Participants
LV Remodeling LV Ejection Fraction	32 percent STANDARD_DEVIATION 7 • n=40 Participants
LV Remodeling Conicity	0.75 percent STANDARD_DEVIATION 0.03 • n=40 Participants
LV Remodeling Sphericity	0.73 percent STANDARD_DEVIATION 0.05 • n=40 Participants
LV Remodeling-Global Longitudinal Strain (%)	-12.9 percent STANDARD_DEVIATION 2.8 • n=40 Participants
LV Remodeling Left Atrial Volume	90.9 mL n=40 Participants • Some patients have incomplete data.
LV Remodeling 3D End-Diastolic Volume	243.5 mL n=39 Participants • Some patients have incomplete data.
LV Remodeling 3D End-Systolic Volume	159.7 mL n=39 Participants • Some patients have incomplete data.
LV Remodeling 2D End-Diastolic Diameter	6.0 cm STANDARD_DEVIATION 0.8 • n=40 Participants
LV Remodeling 2D End-Systolic Diameter	5.3 cm STANDARD_DEVIATION 0.9 • n=40 Participants
RV Remodeling End-Diastolic Volume	143 cm n=40 Participants
RV Remodeling End Systolic Volume	73 cm n=40 Participants
RV Remodeling Ejection Fraction	50 percent STANDARD_DEVIATION 10 • n=40 Participants
RV Remodeling Septal Curvature	0.86 percent STANDARD_DEVIATION 0.15 • n=40 Participants
RV Remodeling - Free-Wall Curvature	1.17 percent n=40 Participants
RV Remodeling - Tricuspid Regurgitation No	3 Participants n=40 Participants
RV Remodeling - Tricuspid Regurgitation Trace	30 Participants n=40 Participants
RV Remodeling - Tricuspid Regurgitation Mild	4 Participants n=40 Participants
RV Remodeling - Tricuspid Regurgitation Mild-Moderate	2 Participants n=40 Participants
RV Remodeling - Tricuspid Regurgitation Moderate	0 Participants n=40 Participants
RV Remodeling - Tricuspid Regurgitation Moderate-Severe	1 Participants n=40 Participants
RV Remodeling - Tricuspid Regurgitation Severe	0 Participants n=40 Participants
Exercise Performance- 6 Minute Walk	425 Meter STANDARD_DEVIATION 102 • n=40 Participants
Exercise Performance - CPX -Peak RER	1.14 meters STANDARD_DEVIATION 0.1 • n=40 Participants
Exercise Performance - CPX - Peak VO2	17.5 mL/kg/min n=40 Participants
Exercise Performance - CPX - VE/VC02	33 ratio n=40 Participants
Blood Pressure Systolic	127 mmHg STANDARD_DEVIATION 22.6 • n=40 Participants
Blood Pressure Diastolic	76 mmHg STANDARD_DEVIATION 14.6 • n=40 Participants
Rho-kinase (Rock)	1 ng/mL n=40 Participants
hm ratio (MIBG) Early hm ratio	1.54 ratio n=39 Participants • Some patients have incomplete data.
hm ratio (MIBG) Late hm ratio	1.43 ratio n=39 Participants • Some patients have incomplete data.
NT-proBNP levels	333 pg/mL n=40 Participants
Kansas City Cardiomyopathy Questionnaire (KCCQ) Physical limitation	90 scores on a scale n=40 Participants • Clinical Summary Score is the sum of total symptom and physical function, and then rescaled to range from 0-100. Overall Summary Score is sum of total symptom, physical function, social limitations, and quality of life scores, and then rescaled to range from 0-100. Some patients had incomplete data.
Kansas City Cardiomyopathy Questionnaire (KCCQ) Symptom Stability	50 scores on a scale n=40 Participants • Clinical Summary Score is the sum of total symptom and physical function, and then rescaled to range from 0-100. Overall Summary Score is sum of total symptom, physical function, social limitations, and quality of life scores, and then rescaled to range from 0-100. Some patients had incomplete data.
Kansas City Cardiomyopathy Questionnaire (KCCQ) Symptom Frequency	89 scores on a scale n=40 Participants • Clinical Summary Score is the sum of total symptom and physical function, and then rescaled to range from 0-100. Overall Summary Score is sum of total symptom, physical function, social limitations, and quality of life scores, and then rescaled to range from 0-100. Some patients had incomplete data.
Kansas City Cardiomyopathy Questionnaire (KCCQ) Symptom Burden	92 scores on a scale n=40 Participants • Clinical Summary Score is the sum of total symptom and physical function, and then rescaled to range from 0-100. Overall Summary Score is sum of total symptom, physical function, social limitations, and quality of life scores, and then rescaled to range from 0-100. Some patients had incomplete data.
Kansas City Cardiomyopathy Questionnaire (KCCQ) Total Symptom	89 scores on a scale n=40 Participants • Clinical Summary Score is the sum of total symptom and physical function, and then rescaled to range from 0-100. Overall Summary Score is sum of total symptom, physical function, social limitations, and quality of life scores, and then rescaled to range from 0-100. Some patients had incomplete data.
Kansas City Cardiomyopathy Questionnaire (KCCQ) Self Efficacy	88 scores on a scale n=40 Participants • Clinical Summary Score is the sum of total symptom and physical function, and then rescaled to range from 0-100. Overall Summary Score is sum of total symptom, physical function, social limitations, and quality of life scores, and then rescaled to range from 0-100. Some patients had incomplete data.
Kansas City Cardiomyopathy Questionnaire (KCCQ) Quality of Life Score	67 scores on a scale n=40 Participants • Clinical Summary Score is the sum of total symptom and physical function, and then rescaled to range from 0-100. Overall Summary Score is sum of total symptom, physical function, social limitations, and quality of life scores, and then rescaled to range from 0-100. Some patients had incomplete data.
Kansas City Cardiomyopathy Questionnaire (KCCQ) Social Limitation	81 scores on a scale n=39 Participants • Clinical Summary Score is the sum of total symptom and physical function, and then rescaled to range from 0-100. Overall Summary Score is sum of total symptom, physical function, social limitations, and quality of life scores, and then rescaled to range from 0-100. Some patients had incomplete data.
Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary	82 scores on a scale n=40 Participants • Clinical Summary Score is the sum of total symptom and physical function, and then rescaled to range from 0-100. Overall Summary Score is sum of total symptom, physical function, social limitations, and quality of life scores, and then rescaled to range from 0-100. Some patients had incomplete data.
Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary	91 scores on a scale n=40 Participants • Clinical Summary Score is the sum of total symptom and physical function, and then rescaled to range from 0-100. Overall Summary Score is sum of total symptom, physical function, social limitations, and quality of life scores, and then rescaled to range from 0-100. Some patients had incomplete data.

PRIMARY outcome

Timeframe: Baseline,1 year

Population: All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure.

LV Remodeling 2D End-Diastolic Diameter (cm)

Outcome measures

Outcome measures
Measure	Open Label Entresto n=40 Participants 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. Entresto
Change From Baseline in LV Remodeling 2D End-Diastolic Diameter (cm) 1 year	6 cm Standard Deviation 0.7
Change From Baseline in LV Remodeling 2D End-Diastolic Diameter (cm) Baseline	6 cm Standard Deviation 0.8

PRIMARY outcome

Timeframe: Baseline,1 year

Population: All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure.

LV Remodeling 2D End-Systolic Diameter (cm)

Outcome measures

Outcome measures
Measure	Open Label Entresto n=40 Participants 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. Entresto
Change From Baseline in LV Remodeling 2D End-Systolic Diameter (cm) Baseline	5.3 cm Standard Deviation 0.9
Change From Baseline in LV Remodeling 2D End-Systolic Diameter (cm) 1 year	4.5 cm Standard Deviation 0.9

PRIMARY outcome

Timeframe: Baseline,1 year

Population: All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure.

LV Remodeling Global Longitudinal Strain (%)

Outcome measures

Outcome measures
Measure	Open Label Entresto n=40 Participants 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. Entresto
Change From Baseline in LV Remodeling Global Longitudinal Strain (%) Baseline	-12.9 percentage of global longitudinal strain Standard Deviation 2.8
Change From Baseline in LV Remodeling Global Longitudinal Strain (%) 1 year	-15.3 percentage of global longitudinal strain Standard Deviation 3.5

PRIMARY outcome

Timeframe: Baseline,1 year

Population: All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure.

LV Remodeling Left Atrial Volume (mL)

Outcome measures

Outcome measures
Measure	Open Label Entresto n=40 Participants 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. Entresto
Change From Baseline in LV Remodeling Left Atrial Volume (mL) Baseline	90.9 mL Interval 67.7 to 111.1
Change From Baseline in LV Remodeling Left Atrial Volume (mL) 1 year	65.6 mL Interval 49.8 to 90.3

PRIMARY outcome

Timeframe: Baseline,1 year

Population: All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure.

LV Remodeling 3D End-Diastolic Volume (mL)

Outcome measures

Outcome measures
Measure	Open Label Entresto n=39 Participants 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. Entresto
Change From Baseline in LV Remodeling 3D End-Diastolic Volume (mL) Baseline	243.5 mL Interval 190.1 to 302.1
Change From Baseline in LV Remodeling 3D End-Diastolic Volume (mL) 1 year	160.2 mL Interval 118.8 to 214.8

PRIMARY outcome

Timeframe: Baseline,1 year

Population: All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure.

LV Remodeling 3D End-Systolic Volume (mL)

Outcome measures

Outcome measures
Measure	Open Label Entresto n=39 Participants 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. Entresto
Change From Baseline in LV Remodeling 3D End-Systolic Volume (mL) Baseline	159.7 mL Interval 118.9 to 207.9
Change From Baseline in LV Remodeling 3D End-Systolic Volume (mL) 1 year	90.7 mL Interval 66.4 to 130.6

PRIMARY outcome

Timeframe: Baseline,1 year

Population: All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure.

LV Remodeling LV Ejection Fraction (%)

Outcome measures

Outcome measures
Measure	Open Label Entresto n=40 Participants 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. Entresto
Change From Baseline in LV Remodeling LV Ejection Fraction (%) Baseline	32 percentage of ejection fraction Standard Deviation 7
Change From Baseline in LV Remodeling LV Ejection Fraction (%) 1 year	43 percentage of ejection fraction Standard Deviation 9

PRIMARY outcome

Timeframe: Baseline,1 year

Population: All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure.

LV Remodeling Conicity (%)

Outcome measures

Outcome measures
Measure	Open Label Entresto n=40 Participants 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. Entresto
Change From Baseline in LV Remodeling Conicity (%) Baseline	0.75 percentage of conicity Standard Deviation 0.03
Change From Baseline in LV Remodeling Conicity (%) 1 year	0.77 percentage of conicity Standard Deviation 0.02

PRIMARY outcome

Timeframe: Baseline,1 year

Population: All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure.

LV Remodeling Sphericity (%)

Outcome measures

Outcome measures
Measure	Open Label Entresto n=40 Participants 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. Entresto
Change From Baseline in LV Remodeling Sphericity (%) Baseline	0.73 percentage of sphericity Standard Deviation 0.05
Change From Baseline in LV Remodeling Sphericity (%) 1 year	0.71 percentage of sphericity Standard Deviation 0.03

PRIMARY outcome

Timeframe: Baseline,1 year

Population: All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure.

RV Remodeling End-Diastolic Volume (mL)

Outcome measures

Outcome measures
Measure	Open Label Entresto n=27 Participants 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. Entresto
Change From Baseline in RV Remodeling End-Diastolic Volume (mL) Baseline	143 mL Interval 121.0 to 174.0
Change From Baseline in RV Remodeling End-Diastolic Volume (mL) 1 year	104 mL Interval 83.0 to 145.0

PRIMARY outcome

Timeframe: Baseline,1 year

Population: All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure.

RV Remodeling End Systolic Volume (mL)

Outcome measures

Outcome measures
Measure	Open Label Entresto n=40 Participants 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. Entresto
Change From Baseline in RV Remodeling End Systolic Volume (mL) Baseline	73 mL Interval 51.0 to 97.0
Change From Baseline in RV Remodeling End Systolic Volume (mL) 1 year	47 mL Interval 35.4 to 72.3

PRIMARY outcome

Timeframe: Baseline,1 year

Population: All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure.

RV Remodeling Ejection Fraction (%)

Outcome measures

Outcome measures
Measure	Open Label Entresto n=40 Participants 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. Entresto
Change From Baseline in RV Remodeling Ejection Fraction (%) Baseline	50 percentage of ejection fraction Standard Deviation 10
Change From Baseline in RV Remodeling Ejection Fraction (%) 1 year	50 percentage of ejection fraction Standard Deviation 8

PRIMARY outcome

Timeframe: Baseline,1 year

Population: All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure.

RV Remodeling Septal Curvature (%)

Outcome measures

Outcome measures
Measure	Open Label Entresto n=40 Participants 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. Entresto
Change From Baseline in RV Remodeling Septal Curvature (%) Baseline	0.86 percentage of septal curvature Standard Deviation 0.15
Change From Baseline in RV Remodeling Septal Curvature (%) 1 year	0.77 percentage of septal curvature Standard Deviation 0.8

PRIMARY outcome

Timeframe: Baseline,1 year

Population: All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure.

RV Remodeling Free-Wall Curvature (%)

Outcome measures

Outcome measures
Measure	Open Label Entresto n=40 Participants 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. Entresto
Change From Baseline in RV Remodeling Free-Wall Curvature (%) 1 year	1.14 percentage of free-wall curvature Interval 1.1 to 1.17
Change From Baseline in RV Remodeling Free-Wall Curvature (%) Baseline	1.17 percentage of free-wall curvature Interval 1.09 to 1.22

PRIMARY outcome

Timeframe: Baseline,1 year

Population: All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure.

RV Remodeling Tricuspid Regurgitation

Outcome measures

Outcome measures
Measure	Open Label Entresto n=40 Participants 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. Entresto
Change From Baseline in RV Remodeling Tricuspid Regurgitation Baseline · No	3 Participants
Change From Baseline in RV Remodeling Tricuspid Regurgitation Baseline · Trace	30 Participants
Change From Baseline in RV Remodeling Tricuspid Regurgitation Baseline · Mild	4 Participants
Change From Baseline in RV Remodeling Tricuspid Regurgitation Baseline · Mild-Moderate	2 Participants
Change From Baseline in RV Remodeling Tricuspid Regurgitation Baseline · Moderate	0 Participants
Change From Baseline in RV Remodeling Tricuspid Regurgitation Baseline · Moderate-Severe	1 Participants
Change From Baseline in RV Remodeling Tricuspid Regurgitation Baseline · Severe	0 Participants
Change From Baseline in RV Remodeling Tricuspid Regurgitation 1 year · No	8 Participants
Change From Baseline in RV Remodeling Tricuspid Regurgitation 1 year · Trace	16 Participants
Change From Baseline in RV Remodeling Tricuspid Regurgitation 1 year · Mild	9 Participants
Change From Baseline in RV Remodeling Tricuspid Regurgitation 1 year · Mild-Moderate	0 Participants
Change From Baseline in RV Remodeling Tricuspid Regurgitation 1 year · Moderate	0 Participants
Change From Baseline in RV Remodeling Tricuspid Regurgitation 1 year · Moderate-Severe	0 Participants
Change From Baseline in RV Remodeling Tricuspid Regurgitation 1 year · Severe	0 Participants

SECONDARY outcome

Timeframe: Baseline,1 year

Population: All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure.

Rho-associated protein kinase (ROCK)

Outcome measures

Outcome measures
Measure	Open Label Entresto n=40 Participants 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. Entresto
Change From Baseline in Rho-associated Protein Kinase (ROCK) Baseline	1.1 ng/mL Interval 0.7 to 1.4
Change From Baseline in Rho-associated Protein Kinase (ROCK) 1 year	0.7 ng/mL Interval 0.5 to 1.0

SECONDARY outcome

Timeframe: Baseline,1 year

Population: All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure. 0 participants analyzed at 1 year as data were not collected.

Cardiac 123Iodine-metaiodobenzylguanidine (MIBG) Early heart/mediastinum ratio (hm) ratio

Outcome measures

Outcome measures
Measure	Open Label Entresto n=39 Participants 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. Entresto
Change From Baseline in (MIBG) Early hm Ratio Baseline	1.54 ratio Interval 1.34 to 1.61

SECONDARY outcome

Timeframe: Baseline,1 year

Population: All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure. 0 participants analyzed at 1 year as data were not collected

Cardiac 123Iodine-metaiodobenzylguanidine (MIBG) Late heart/mediastinum ratio (hm) ratio

Outcome measures

Outcome measures
Measure	Open Label Entresto n=39 Participants 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. Entresto
Change From Baseline in (MIBG) Late hm Ratio Baseline	1.43 ratio Interval 1.27 to 1.53

SECONDARY outcome

Timeframe: Baseline,1 year

Population: All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure.

NT-proBNP levels (pg/ml)

Outcome measures

Outcome measures
Measure	Open Label Entresto n=37 Participants 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. Entresto
Change From Baseline in NT-proBNP Levels Baseline	333 pg/ml Interval 130.0 to 1003.0
Change From Baseline in NT-proBNP Levels 1 year	290 pg/ml Interval 64.0 to 616.0

SECONDARY outcome

Timeframe: Baseline,1 year

Population: All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure.

Exercise Performance - 6 Minute Walk

Outcome measures

Outcome measures
Measure	Open Label Entresto n=40 Participants 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. Entresto
Change From Baseline in Exercise Performance - 6 Minute Walk Baseline	425 meters Standard Deviation 102
Change From Baseline in Exercise Performance - 6 Minute Walk 1 year	486 meters Standard Deviation 124

SECONDARY outcome

Timeframe: Baseline,1 year

Population: All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure.

Exercise Performance - CPX - Peak VO2 (mL/kg/min)

Outcome measures

Outcome measures
Measure	Open Label Entresto n=40 Participants 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. Entresto
Change From Baseline in Exercise Performance - CPX - Peak VO2 (mL/kg/Min) Baseline	17.5 mL/kg/min Interval 13.7 to 22.4
Change From Baseline in Exercise Performance - CPX - Peak VO2 (mL/kg/Min) 1 year	19.5 mL/kg/min Interval 14.8 to 23.0

SECONDARY outcome

Timeframe: Baseline,1 year

Population: All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure.

Exercise Performance - CPX - Peak RER (Respiratory Exchange Ratio)

Outcome measures

Outcome measures
Measure	Open Label Entresto n=40 Participants 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. Entresto
Change From Baseline in Exercise Performance - CPX - Peak RER Baseline	1.14 ratio Standard Deviation 0.10
Change From Baseline in Exercise Performance - CPX - Peak RER 1 year	1.06 ratio Standard Deviation 0.10

SECONDARY outcome

Timeframe: Baseline,1 year

Population: All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure.

Exercise Performance - CPX - VE/VC02

Outcome measures

Outcome measures
Measure	Open Label Entresto n=40 Participants 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. Entresto
Change From Baseline in Exercise Performance - CPX - VE/VC02 Baseline	33 ratio Interval 29.0 to 38.0
Change From Baseline in Exercise Performance - CPX - VE/VC02 1 year	33 ratio Interval 30.0 to 40.0

SECONDARY outcome

Timeframe: Baseline,1 year

Population: All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure.

Blood Pressure - Systolic (mmHg)

Outcome measures

Outcome measures
Measure	Open Label Entresto n=40 Participants 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. Entresto
Change From Baseline in Blood Pressure - Systolic (mmHg) Baseline	131 mmHg Interval 122.0 to 143.0
Change From Baseline in Blood Pressure - Systolic (mmHg) 1 year	114 mmHg Interval 105.0 to 124.0

SECONDARY outcome

Timeframe: Baseline,1 year

Population: All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure.

Blood Pressure - Diastolic (mmHg)

Outcome measures

Outcome measures
Measure	Open Label Entresto n=40 Participants 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. Entresto
Change From Baseline in Blood Pressure - Diastolic (mmHg) 1 year	76 mmHg Interval 66.0 to 84.0
Change From Baseline in Blood Pressure - Diastolic (mmHg) Baseline	82 mmHg Interval 74.0 to 89.0

SECONDARY outcome

Timeframe: Baseline,1 year

Population: All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure.

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.

Outcome measures

Outcome measures
Measure	Open Label Entresto n=40 Participants 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. Entresto
Change From Baseline in KCCQ - Physical Limitation Baseline	90 score on a scale Interval 71.0 to 100.0
Change From Baseline in KCCQ - Physical Limitation 1 year	96 score on a scale Interval 88.0 to 100.0

SECONDARY outcome

Timeframe: Baseline,1 year

Population: All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure.

Outcome measures

Outcome measures
Measure	Open Label Entresto n=40 Participants 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. Entresto
Change From Baseline in KCCQ - Symptom Stability Baseline	50 score on a scale Interval 50.0 to 50.0
Change From Baseline in KCCQ - Symptom Stability 1 year	50 score on a scale Interval 50.0 to 100.0

SECONDARY outcome

Timeframe: Baseline,1 year

Population: All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure.

Outcome measures

Outcome measures
Measure	Open Label Entresto n=40 Participants 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. Entresto
Change From Baseline in KCCQ - Symptom Frequency Baseline	89 score on a scale Interval 74.0 to 100.0
Change From Baseline in KCCQ - Symptom Frequency 1 year	92 score on a scale Interval 85.0 to 98.0

SECONDARY outcome

Timeframe: Baseline,1 year

Population: All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure.

Outcome measures

Outcome measures
Measure	Open Label Entresto n=40 Participants 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. Entresto
Change From Baseline in KCCQ - Symptom Burden Baseline	92 score on a scale Interval 79.0 to 100.0
Change From Baseline in KCCQ - Symptom Burden 1 year	92 score on a scale Interval 83.0 to 100.0

SECONDARY outcome

Timeframe: Baseline,1 year

Population: All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure.

Outcome measures

Outcome measures
Measure	Open Label Entresto n=40 Participants 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. Entresto
Change From Baseline in KCCQ - Total Symptom Baseline	89 score on a scale Interval 71.5 to 100.0
Change From Baseline in KCCQ - Total Symptom 1 year	92 score on a scale Interval 86.0 to 99.0

SECONDARY outcome

Timeframe: Baseline,1 year

Population: All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure.

Outcome measures

Outcome measures
Measure	Open Label Entresto n=40 Participants 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. Entresto
Change From Baseline in KCCQ - Self Efficacy Baseline	88 score on a scale Interval 75.0 to 100.0
Change From Baseline in KCCQ - Self Efficacy 1 year	100 score on a scale Interval 75.0 to 100.0

SECONDARY outcome

Timeframe: Baseline,1 year

Population: All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure.

Outcome measures

Outcome measures
Measure	Open Label Entresto n=40 Participants 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. Entresto
Change From Baseline in KCCQ - Quality of Life Score Baseline	67 score on a scale Interval 42.0 to 83.0
Change From Baseline in KCCQ - Quality of Life Score 1 year	83 score on a scale Interval 67.0 to 100.0

SECONDARY outcome

Timeframe: Baseline,1 year

Population: All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure.

Outcome measures

Outcome measures
Measure	Open Label Entresto n=39 Participants 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. Entresto
Change From Baseline in KCCQ - Social Limitation Baseline	81 score on a scale Interval 56.0 to 94.0
Change From Baseline in KCCQ - Social Limitation 1 year	94 score on a scale Interval 81.0 to 100.0

SECONDARY outcome

Timeframe: Baseline,1 year

Population: All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure.

Outcome measures

Outcome measures
Measure	Open Label Entresto n=40 Participants 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. Entresto
Change From Baseline in KCCQ - Overall Summary Baseline	82 score on a scale Interval 65.0 to 90.0
Change From Baseline in KCCQ - Overall Summary 1 year	90 score on a scale Interval 79.5 to 97.5

SECONDARY outcome

Timeframe: Baseline,1 year

Population: All subjects will take Entresto, a drug recently approved by the US Food and Drug Administration (FDA) for heart failure.

Outcome measures

Outcome measures
Measure	Open Label Entresto n=40 Participants 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. Entresto
Change From Baseline in KCCQ - Clinical Summary Baseline	91 score on a scale Interval 72.0 to 98.0
Change From Baseline in KCCQ - Clinical Summary 1 year	94.5 score on a scale Interval 87.0 to 98.5

Adverse Events

Open Label Entresto

Serious events: 4 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Open Label Entresto n=40 participants at risk REMODEL is a prospective, single-arm longitudinal study investigating the structural, neurohormonal and functional effects of sacubitril/valsartan. Patients with New York Heart Association (NYHA) Class II-III HFrEF who were on optimal guideline directed medical therapy for at least three months with an LVEF between 20-40% who otherwise met inclusion and exclusion criteria similar to that of the Paradigm Trial were eligible for enrollment.
Cardiac disorders Hypotension	10.0% 4/40 • Number of events 4 • 1 year

Other adverse events

Other adverse events
Measure	Open Label Entresto n=40 participants at risk REMODEL is a prospective, single-arm longitudinal study investigating the structural, neurohormonal and functional effects of sacubitril/valsartan. Patients with New York Heart Association (NYHA) Class II-III HFrEF who were on optimal guideline directed medical therapy for at least three months with an LVEF between 20-40% who otherwise met inclusion and exclusion criteria similar to that of the Paradigm Trial were eligible for enrollment.
Cardiac disorders Hypotension	10.0% 4/40 • Number of events 40 • 1 year

Additional Information

Sara Kalantari, MD

University of Chicago

Phone: 773-834-6853

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place