Study of Effects of Sacubitril/Valsartan vs. Enalapril on Aortic Stiffness in Patients With Mild to Moderate HF With Reduced Ejection Fraction
Condition: Heart Failure and Reduced Ejection Fraction
MeSH terms: Heart Failure
Intervention: LCZ696 (sacubitril/valsartan); Enalapril; Placebo of Enalapril; Placebo of LCZ696
Intervention description: 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; matching placebo (24/26mg, 49/51mg and 97/103mg) oral, tablets
Intervention MeSH terms: Valsartan; Enalapril; Enalaprilat; Sacubitril and valsartan sodium hydrate drug combination
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 465.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: No
Keywords: Heart Failure; Reduced Ejection Fraction; Central Aortic Stiffness; Vascular; Echocardiogram; Aortic Stiffness

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  History of HTN and one of the following at BOTH screening and pre-randomization:

               1. SBP >105 mm Hg on antihypertensive medication.

               2. 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.

               1. If the patient is currently taking an ACEi, a 36-hour washout is required prior
                  to randomization (Visit 2).

               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.