Phase 4
Completed N=465
Study of Effects of Sacubitril/Valsartan vs. Enalapril on Aortic Stiffness in Patients With Mild to Moderate HF With Reduced Ejection Fraction
Heart Failure and Reduced Ejection Fraction
Source: ClinicalTrials.gov NCT02874794 ↗
Enrolled (actual)
465
Serious AEs
8.5%
Results posted
Mar 2020
Primary outcomePrimary: Change From Baseline in Aortic Characteristic Impedance at Week 12 — -0.7; -2.9 dyne x sec/cm5 — p=0.7827
◆ Published Evidence
Highly cited
320citations · ~46 / year
Effect of Sacubitril-Valsartan vs Enalapril on Aortic Stiffness in Patients With Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial.
Summary
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.
Linked Publications (5)
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Effect of Sacubitril-Valsartan vs Enalapril on Aortic Stiffness in Patients With Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial.
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Early B-Type Natriuretic Peptide Change in HFrEF Patients Treated With Sacubitril/Valsartan: A Pooled Analysis of EVALUATE-HF and PROVE-HF.
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Changes in cardiac biomarkers in association with alterations in cardiac structure and function, and health status in heart failure with reduced ejection fraction: the EVALUATE-HF trial.
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Hemodynamic Effects of Sacubitril-Valsartan Versus Enalapril in Patients With Heart Failure in the EVALUATE-HF Study: Effect Modification by Left Ventricular Ejection Fraction and Sex.
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Changes in cardiac structure and function are associated with health-related quality of life in heart failure patients with reduced ejection fraction: Results from the EVALUATE-HF trial.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Aortic Characteristic Impedance at Week 12 |
-0.7; -2.9 | 0.7827 |
| SECONDARY 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 |
0.022; 0.070; -0.127; 0.016 | — |
| SECONDARY 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 |
0.087; 0.098; 0.110; 0.157 | — |
| SECONDARY Change From Baseline in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) |
0.9500; 0.6334 | <.0001 sig |
| SECONDARY Change From Baseline in Echocardiographic Measure: Global Longitudinal Strain |
-0.21; -0.34 | 0.5792 |
| SECONDARY Change From Baseline in Echocardiographic Measure: Left Atrial Volume Index (LAVi) |
0.63; -2.17 | <.0001 sig |
| SECONDARY Change From Baseline in Echocardiographic Measure: Mitral Annular E' Velocity (Doppler Tissue Imaging) |
-0.00; -0.03 | 0.8617 |
| SECONDARY Change From Basekine in Echocardiographic Measure: Mitral E/E' |
0.32; -1.43 | 0.0007 sig |
| SECONDARY Change From Baseline in Echocardiographic Measure: Left Ventricular Ejection Fraction (LVEF) |
1.30; 1.94 | 0.2354 |
| SECONDARY Change From Baseline in Echocardiographic Measure: Ventricular-vascular Coupling (Ea/Ees) |
0.03; 0.02 | 0.8215 |
| SECONDARY Change From Baseline in Echocardiographic Measure: Left Ventricular End Systolic Volume Index (LVESVi) |
-3.28; -4.86 | 0.0452 sig |
| SECONDARY Change From Baseline in Echocardiographic Measure: Left Ventricular End Diastolic Volume Index (LVEDVi) |
-3.18; -5.15 | 0.0242 sig |
Eligibility Criteria
Inclusion Criteria
- History of HTN and one of the following at BOTH screening and pre-randomization:
- SBP >105 mm Hg on antihypertensive medication.
- SBP >/= 140 mm Hg and NOT on antihypertensive medication.
- NYHA class I-III heart failure and with reduced ejection fraction </= 40%, as determined by any local measurement made within the past 12 months using echocardiography, MUGA, CT scanning, MRI, ventricular angiography or single-photon emission computed tomography (SPECT), provided no subsequent measurement above 40%. Patients who have had an intervening medical event (e.g. myocardial infarction) or procedure (e.g. revascularization, cardiac resynchronization), must have a reassessment of EF ≥ 3 months following the event to ensure that eligibility criteria are still met.
- On stable doses of treatment with guideline-directed therapy, other than ACEis and ARBs prior to randomization.
- If the patient is currently taking an ACEi, a 36-hour washout is required prior to randomization (Visit 2).
- If the patient is currently taking an ARB, they must discontinue the ARB before initiation of study treatment however washout is not required.
- On an optimal medical regiment of diuretics and background medications to effectively treat co-morbidities such as HTN, DM, and coronary artery disease.
Key Exclusion Criteria
- History of hypersensitivity to any of the study drigs, including history of hypersensitivity to drugs of similar chemical classes, or allergy to ACEis, ARBs, or NEP inhibitors as well as known or suspected contraindications to the study drugs.
- Previous history of intolerance to sacubitril and valsartan, ACEi or ARB standard of care doses despite appropriate and gradual up-titration.
- History of angioedema, drug-related or otherwise.
- Requirement of treatment with both ACE inhibitor and ARB.
- Current or prior treatment with sacubitril and valsartan.
Data sourced from ClinicalTrials.gov (NCT02874794) and the linked publication. 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. Informational only — not medical advice.