To determine whether treatment with sacubitril/valsartan provides a superior effect on aortic characteristic impedance compared to enalapril in patients with heart failure and reduced ejection fraction (left ventricular ejection fraction \[LVEF\] ≤ 40%) after 12 weeks of treatment. The primary endpoint is the change in aortic characteristic impedance (Zc = dP/dQ in early systole) between baseline and Week 12.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
465
24/26mg, 49/51mg and 97/103mg oral, tablets.
2.5mg, 5mg, and 10mg, oral, tablets
matching placebo (2.5mg, 5mg and 10mg) oral, tablets
Change From Baseline in Aortic Characteristic Impedance at Week 12
Aortic characteristic impedance, Zc, is the ratio of the change in pressure (dP)produced by a given change in flow (dQ) in early systole, i.e., Zc = dP/dQ. Zc is related directly to aortic wall stiffness and inversely to lumen area.
Time frame: Baseline, Week 12
Pearson Correlation Coefficient Between Change From Baseline in Aortic Characteristic Impedance and Biomarker Levels: B-type Natriuretic Peptide (BNP) During Both Trough and 4 Hours Post-dose at Week 4
Pearson correlation coefficients between changes from baseline in aortic characteristic impedance (dyne x sec/cm5) and biomarker levels such as BNP (pg/ML) during both trough and 4 hours post-dose at Week 4
Time frame: Pre-dose and 4 hours post dose at week 4
Pearson Correlation Coefficient Between Change From Baseline in Aortic Characteristic Impedance and Biomarker Levels: cGMP/U-creatinine During Both Trough and 4 Hours Post-dose at Week 4
Pearson correlation coefficient between changes from baseline in aortic characteristic impedance (dyne x sec/cm5) and biomarker levels such as U-cGMP/U-creatinine ratio (nmol/mmol) during both trough and 4 hours post-dose at Week 4
Time frame: pre-dose and 4 hours post dose at week 4
Change From Baseline in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)
Change from baseline in N-terminal pro-brain natriuretic peptide (NT-proBNP)
Time frame: Baseline, Week 12
Change From Baseline in Echocardiographic Measure: Global Longitudinal Strain
Parameter measured by echocardiography.
Time frame: Baseline, Week 12
Change From Baseline in Echocardiographic Measure: Left Atrial Volume Index (LAVi)
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matching placebo (24/26mg, 49/51mg and 97/103mg) oral, tablets
Novartis Investigative Site
Birmingham, Alabama, United States
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Little Rock, Arkansas, United States
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Beverly Hills, California, United States
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Huntington Beach, California, United States
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Newport Beach, California, United States
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Northridge, California, United States
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Santa Ana, California, United States
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Van Nuys, California, United States
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Greenwich, Connecticut, United States
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Norwalk, Connecticut, United States
...and 71 more locations
Parameter measured by echocardiography
Time frame: Baseline, Week 12
Change From Baseline in Echocardiographic Measure: Mitral Annular E' Velocity (Doppler Tissue Imaging)
Parameter measured by echocardiography
Time frame: Baseline, Week 12
Change From Basekine in Echocardiographic Measure: Mitral E/E'
Parameter measured by echocardiography
Time frame: Baseline, Week 12
Change From Baseline in Echocardiographic Measure: Left Ventricular Ejection Fraction (LVEF)
Parameter measured by echocardiography
Time frame: Baseline, Week 12
Change From Baseline in Echocardiographic Measure: Ventricular-vascular Coupling (Ea/Ees)
Parameter measured by echocardiography
Time frame: Baseline, Week 12
Change From Baseline in Echocardiographic Measure: Left Ventricular End Systolic Volume Index (LVESVi)
Parameter measured by echocardiography
Time frame: Baseline, Week 12
Change From Baseline in Echocardiographic Measure: Left Ventricular End Diastolic Volume Index (LVEDVi)
Parameter measured by echocardiography
Time frame: Baseline, Week 12