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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02754518
Recruitment Status : Completed
First Posted : April 28, 2016
Results First Posted : January 29, 2021
Last Update Posted : January 29, 2021
Sponsor:
Information provided by (Responsible Party):
University of Chicago

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.

Condition or disease Intervention/treatment Phase
Heart Failure Drug: Entresto Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Demonstration of Reverse Remodeling Effects of Entresto (Valsartan/Sacubitril) Using Echocardiography Endocardial Surface Analysis
Actual Study Start Date : April 2016
Actual Primary Completion Date : April 2019
Actual Study Completion Date : April 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arm Intervention/treatment
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 Name: valsartan/sacubitril




Primary Outcome Measures :
  1. Change From Baseline in LV Remodeling 2D End-Diastolic Diameter (cm) [ Time Frame: Baseline,1 year ]
    LV Remodeling 2D End-Diastolic Diameter (cm)

  2. Change From Baseline in LV Remodeling 2D End-Systolic Diameter (cm) [ Time Frame: Baseline,1 year ]
    LV Remodeling 2D End-Systolic Diameter (cm)

  3. Change From Baseline in LV Remodeling Global Longitudinal Strain (%) [ Time Frame: Baseline,1 year ]
    LV Remodeling Global Longitudinal Strain (%)

  4. Change From Baseline in LV Remodeling Left Atrial Volume (mL) [ Time Frame: Baseline,1 year ]
    LV Remodeling Left Atrial Volume (mL)

  5. Change From Baseline in LV Remodeling 3D End-Diastolic Volume (mL) [ Time Frame: Baseline,1 year ]
    LV Remodeling 3D End-Diastolic Volume (mL)

  6. Change From Baseline in LV Remodeling 3D End-Systolic Volume (mL) [ Time Frame: Baseline,1 year ]
    LV Remodeling 3D End-Systolic Volume (mL)

  7. Change From Baseline in LV Remodeling LV Ejection Fraction (%) [ Time Frame: Baseline,1 year ]
    LV Remodeling LV Ejection Fraction (%)

  8. Change From Baseline in LV Remodeling Conicity (%) [ Time Frame: Baseline,1 year ]
    LV Remodeling Conicity (%)

  9. Change From Baseline in LV Remodeling Sphericity (%) [ Time Frame: Baseline,1 year ]
    LV Remodeling Sphericity (%)

  10. Change From Baseline in RV Remodeling End-Diastolic Volume (mL) [ Time Frame: Baseline,1 year ]
    RV Remodeling End-Diastolic Volume (mL)

  11. Change From Baseline in RV Remodeling End Systolic Volume (mL) [ Time Frame: Baseline,1 year ]
    RV Remodeling End Systolic Volume (mL)

  12. Change From Baseline in RV Remodeling Ejection Fraction (%) [ Time Frame: Baseline,1 year ]
    RV Remodeling Ejection Fraction (%)

  13. Change From Baseline in RV Remodeling Septal Curvature (%) [ Time Frame: Baseline,1 year ]
    RV Remodeling Septal Curvature (%)

  14. Change From Baseline in RV Remodeling Free-Wall Curvature (%) [ Time Frame: Baseline,1 year ]
    RV Remodeling Free-Wall Curvature (%)

  15. Change From Baseline in RV Remodeling Tricuspid Regurgitation [ Time Frame: Baseline,1 year ]
    RV Remodeling Tricuspid Regurgitation


Secondary Outcome Measures :
  1. Change From Baseline in Rho-associated Protein Kinase (ROCK) [ Time Frame: Baseline,1 year ]
    Rho-associated protein kinase (ROCK)

  2. Change From Baseline in (MIBG) Early hm Ratio [ Time Frame: Baseline,1 year ]
    Cardiac 123Iodine-metaiodobenzylguanidine (MIBG) Early heart/mediastinum ratio (hm) ratio

  3. Change From Baseline in (MIBG) Late hm Ratio [ Time Frame: Baseline,1 year ]
    Cardiac 123Iodine-metaiodobenzylguanidine (MIBG) Late heart/mediastinum ratio (hm) ratio

  4. Change From Baseline in NT-proBNP Levels [ Time Frame: Baseline,1 year ]
    NT-proBNP levels (pg/ml)

  5. Change From Baseline in Exercise Performance - 6 Minute Walk [ Time Frame: Baseline,1 year ]
    Exercise Performance - 6 Minute Walk

  6. Change From Baseline in Exercise Performance - CPX - Peak VO2 (mL/kg/Min) [ Time Frame: Baseline,1 year ]
    Exercise Performance - CPX - Peak VO2 (mL/kg/min)

  7. Change From Baseline in Exercise Performance - CPX - Peak RER [ Time Frame: Baseline,1 year ]
    Exercise Performance - CPX - Peak RER (Respiratory Exchange Ratio)

  8. Change From Baseline in Exercise Performance - CPX - VE/VC02 [ Time Frame: Baseline,1 year ]
    Exercise Performance - CPX - VE/VC02

  9. Change From Baseline in Blood Pressure - Systolic (mmHg) [ Time Frame: Baseline,1 year ]
    Blood Pressure - Systolic (mmHg)

  10. Change From Baseline in Blood Pressure - Diastolic (mmHg) [ Time Frame: Baseline,1 year ]
    Blood Pressure - Diastolic (mmHg)

  11. Change From Baseline in KCCQ - Physical Limitation [ Time Frame: Baseline,1 year ]

    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.


  12. Change From Baseline in KCCQ - Symptom Stability [ Time Frame: Baseline,1 year ]

    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.


  13. Change From Baseline in KCCQ - Symptom Frequency [ Time Frame: Baseline,1 year ]

    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.


  14. Change From Baseline in KCCQ - Symptom Burden [ Time Frame: Baseline,1 year ]

    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.


  15. Change From Baseline in KCCQ - Total Symptom [ Time Frame: Baseline,1 year ]

    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.


  16. Change From Baseline in KCCQ - Self Efficacy [ Time Frame: Baseline,1 year ]

    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.


  17. Change From Baseline in KCCQ - Quality of Life Score [ Time Frame: Baseline,1 year ]

    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.


  18. Change From Baseline in KCCQ - Social Limitation [ Time Frame: Baseline,1 year ]

    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.


  19. Change From Baseline in KCCQ - Overall Summary [ Time Frame: Baseline,1 year ]

    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.


  20. Change From Baseline in KCCQ - Clinical Summary [ Time Frame: Baseline,1 year ]

    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.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02754518


Locations
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United States, Illinois
University of Chicago Medical Center
Chicago, Illinois, United States, 60637
Sponsors and Collaborators
University of Chicago
Investigators
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Principal Investigator: Sara Kalantari, MD University of Chicago
  Study Documents (Full-Text)

Documents provided by University of Chicago:
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Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT02754518    
Other Study ID Numbers: IRB15-1410
First Posted: April 28, 2016    Key Record Dates
Results First Posted: January 29, 2021
Last Update Posted: January 29, 2021
Last Verified: January 2021
Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardiovascular Diseases
Valsartan
Sacubitril and valsartan sodium hydrate drug combination
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action