Phase 4
N=40
Demonstration of Reverse Remodeling Effects of Entresto. Using Echocardiography Endocardial Surface Analysis
Heart Failure
Bottom Line
View on ClinicalTrials.gov: NCT02754518 ↗Enrolled (actual)
40
Serious AEs
10.0%
Results posted
Jan 2021
Primary outcome: Primary: Change From Baseline in LV Remodeling 2D End-Diastolic Diameter (cm) — 6; 6 cm — p=<0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 4
- Interventions
- Entresto (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- University of Chicago
- Primary completion
- Apr 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in LV Remodeling 2D End-Diastolic Diameter (cm) |
6; 6 | <0.001 sig |
| PRIMARY Change From Baseline in LV Remodeling 2D End-Systolic Diameter (cm) |
5.3; 4.5 | <0.001 sig |
| PRIMARY Change From Baseline in LV Remodeling Global Longitudinal Strain (%) |
-12.9; -15.3 | <0.001 sig |
| PRIMARY Change From Baseline in LV Remodeling Left Atrial Volume (mL) |
90.9; 65.6 | <0.001 sig |
| PRIMARY Change From Baseline in LV Remodeling 3D End-Diastolic Volume (mL) |
243.5; 160.2 | <0.001 sig |
| PRIMARY Change From Baseline in LV Remodeling 3D End-Systolic Volume (mL) |
159.7; 90.7 | <0.001 sig |
| PRIMARY Change From Baseline in LV Remodeling LV Ejection Fraction (%) |
32; 43 | <0.001 sig |
| PRIMARY Change From Baseline in LV Remodeling Conicity (%) |
0.75; 0.77 | 0.13 |
| PRIMARY Change From Baseline in LV Remodeling Sphericity (%) |
0.73; 0.71 | 0.95 |
| PRIMARY Change From Baseline in RV Remodeling End-Diastolic Volume (mL) |
143; 104 | <0.001 sig |
| PRIMARY Change From Baseline in RV Remodeling End Systolic Volume (mL) |
73; 47 | <0.001 sig |
| PRIMARY Change From Baseline in RV Remodeling Ejection Fraction (%) |
50; 50 | 0.65 |
| PRIMARY Change From Baseline in RV Remodeling Septal Curvature (%) |
0.86; 0.77 | 0.06 |
| PRIMARY Change From Baseline in RV Remodeling Free-Wall Curvature (%) |
1.17; 1.14 | 0.76 |
| PRIMARY Change From Baseline in RV Remodeling Tricuspid Regurgitation |
3; 30; 4; 2; 0; 1 | 0.07 |
| SECONDARY Change From Baseline in Rho-associated Protein Kinase (ROCK) |
1.1; 0.7 | 0.001 sig |
| SECONDARY Change From Baseline in (MIBG) Early hm Ratio |
1.54 | — |
| SECONDARY Change From Baseline in (MIBG) Late hm Ratio |
1.43 | — |
| SECONDARY Change From Baseline in NT-proBNP Levels |
333; 290 | 0.03 sig |
| SECONDARY Change From Baseline in Exercise Performance - 6 Minute Walk |
425; 486 | <0.001 sig |
| SECONDARY Change From Baseline in Exercise Performance - CPX - Peak VO2 (mL/kg/Min) |
17.5; 19.5 | 0.02 sig |
| SECONDARY Change From Baseline in Exercise Performance - CPX - Peak RER |
1.14; 1.06 | <0.001 sig |
| SECONDARY Change From Baseline in Exercise Performance - CPX - VE/VC02 |
33; 33 | 0.82 |
| SECONDARY Change From Baseline in Blood Pressure - Systolic (mmHg) |
131; 114 | <0.001 sig |
| SECONDARY Change From Baseline in Blood Pressure - Diastolic (mmHg) |
82; 76 | 0.01 sig |
| SECONDARY Change From Baseline in KCCQ - Physical Limitation |
90; 96 | 0.11 |
| SECONDARY Change From Baseline in KCCQ - Symptom Stability |
50; 50 | 0.17 |
| SECONDARY Change From Baseline in KCCQ - Symptom Frequency |
89; 92 | 0.035 sig |
| SECONDARY Change From Baseline in KCCQ - Symptom Burden |
92; 92 | 0.059 |
| SECONDARY Change From Baseline in KCCQ - Total Symptom |
89; 92 | 0.054 |
| SECONDARY Change From Baseline in KCCQ - Self Efficacy |
88; 100 | 0.28 |
| SECONDARY Change From Baseline in KCCQ - Quality of Life Score |
67; 83 | 0.002 sig |
| SECONDARY Change From Baseline in KCCQ - Social Limitation |
81; 94 | 0.008 sig |
| SECONDARY Change From Baseline in KCCQ - Overall Summary |
82; 90 | 0.005 sig |
| SECONDARY Change From Baseline in KCCQ - Clinical Summary |
91; 94.5 | 0.056 |
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.
Eligibility Criteria
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) 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)
Data sourced from ClinicalTrials.gov (NCT02754518). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.