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Completed

NCT Number: NCT02874794

Study of Effects of Sacubitril/Valsartan vs. Enalapril on Aortic Stiffness in Patients With Mild to Moderate HF With Reduced Ejection Fraction

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.

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Key information

Conditions

Heart Failure and Reduced Ejection Fraction Cardiovascular Diseases Heart Diseases Heart Failure Heart Failure, Systolic

Age range

50 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Novartis Investigative Site, Birmingham, Alabama, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

LCZ696 (Sacubitril/Valsartan)

Drug

24/26mg, 49/51mg and 97/103mg oral, tablets.

Other names: LCZ696

Enalapril

Drug

2.5mg, 5mg, and 10mg, oral, tablets

Placebo of Enalapril

Drug

matching placebo (2.5mg, 5mg and 10mg) oral, tablets

Placebo of LCZ696

Drug

matching placebo (24/26mg, 49/51mg and 97/103mg) oral, tablets

Primary outcomes

  1. Change From Baseline in Aortic Characteristic Impedance at Week 12

    Time frame: Baseline, 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.

Secondary outcomes

  1. 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

    Time frame: Pre-dose 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

  2. 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

    Time frame: pre-dose 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

  3. Change From Baseline in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)

    Time frame: Baseline, Week 12

    Change from baseline in N-terminal pro-brain natriuretic peptide (NT-proBNP)

  4. Change From Baseline in Echocardiographic Measure: Global Longitudinal Strain

    Time frame: Baseline, Week 12

    Parameter measured by echocardiography.

  5. Change From Baseline in Echocardiographic Measure: Left Atrial Volume Index (LAVi)

    Time frame: Baseline, Week 12

    Parameter measured by echocardiography

  6. Change From Baseline in Echocardiographic Measure: Mitral Annular E' Velocity (Doppler Tissue Imaging)

    Time frame: Baseline, Week 12

    Parameter measured by echocardiography

  7. Change From Basekine in Echocardiographic Measure: Mitral E/E'

    Time frame: Baseline, Week 12

    Parameter measured by echocardiography

  8. Change From Baseline in Echocardiographic Measure: Left Ventricular Ejection Fraction (LVEF)

    Time frame: Baseline, Week 12

    Parameter measured by echocardiography

  9. Change From Baseline in Echocardiographic Measure: Ventricular-vascular Coupling (Ea/Ees)

    Time frame: Baseline, Week 12

    Parameter measured by echocardiography

  10. Change From Baseline in Echocardiographic Measure: Left Ventricular End Systolic Volume Index (LVESVi)

    Time frame: Baseline, Week 12

    Parameter measured by echocardiography

  11. Change From Baseline in Echocardiographic Measure: Left Ventricular End Diastolic Volume Index (LVEDVi)

    Time frame: Baseline, Week 12

    Parameter measured by echocardiography

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

A Multicenter, Randomized, Double-blind, Double-dummy, Parallel Group, Active-controlled, Forced-titration, 12-week Comparison of Combined Angiotensin-neprilysin Inhibition With Sacubitril and Valsartan Versus Enalapril on Changes in Central Aortic Stiffness in Patients With Heart Failure and Reduced Ejection Fraction (HFrEF)

Acronym: EVALUATE-HF

Important dates

Study start
2016
Primary completion
2018
Study completion
2019
First posted
Aug 22, 2016
Registry last updated
Jan 5, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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