LCZ696 Compared to Valsartan in Patients With Chronic Heart Failure and Preserved Left-ventricular Ejection Fraction
Condition: Chronic Heart Failure
MeSH terms: Heart Failure
Intervention: LCZ696; Valsartan; Placebo
Intervention description: 50 mg, 100 mg and 200 mg tablets; 40 mg, 80 mg and 160 mg tablets; matching placebo to LCZ696 and Valsartan
Intervention MeSH terms: Valsartan; Sacubitril and valsartan sodium hydrate drug combination
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 307.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No
Keywords: Chronic heart failure; preserved ejection fraction; cardiovascular disease; NT-proBNP; biomarkers; Heart failure with preserved left-ventricular ejection; fraction

Summary:

      The study will assess the effects of 36 weeks of treatment with LCZ696 compared to valsartan
      on N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) in patients with chronic heart
      failure and preserved left-ventricular ejection fraction.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with documented stable chronic heart failure (NYHA II-IV):

               -  LVEF ≥ 45% (local measurement, assessed by echocardiography, MUGA, CT scan, MRI
                  or ventricular angiography)

               -  the ejection fraction must have been obtained within 6 months prior to
                  randomization or after any MI or other event that would affect ejection fraction.

          -  Plasma NT-proBNP > 500 pg/ml at Visit 1.

          -  Patients with documented stable chronic heart failure (NYHA II-IV).

          -  Patients receiving ACE inhibitors (ACEi), an angiotensin receptor blockers (ARB)
             and/or a beta blockers must be on a stable dose of these medications stable for the 1
             month period prior to Visit 1.

          -  Patients must be on diuretic therapy prior to Visit 1 (flexible dosing is permitted).

          -  Patients with a controlled systolic BP, defined as a target systolic BP less than 140
             mm Hg; participants with BP up to and including 160 mm Hg are eligible for enrollment
             if they are on three or more medications to control BP at randomization (Visit 2).

          -  Patients with at least one of the following symptoms at the time of screening (Visit
             1):

               -  Dyspnea on exertion

               -  Orthopnea

               -  Paroxysmal nocturnal dyspnea

               -  Peripheral edema

          -  Patients must have an eGFR ≥ 30 ml/min/1.73 m2 at Visit 1 (calculated by the
             Modification of Diet in Renal Disease formula).

          -  Patients with a potassium ≤5.2 mmol/l at Visit 1.

        Exclusion Criteria:

          -  Patients with a prior LVEF reading <45%, at any time.

          -  Patients who require treatment with both an ACE inhibitor and an ARB.

          -  Isolated right heart failure due to pulmonary disease.

          -  Dyspnea and/or edema from non-cardiac causes, such as lung disease, anemia, or severe
             obesity.

          -  Presence of hemodynamically significant mitral and /or aortic valve disease.

          -  Presence of hemodynamically significant obstructive lesions of left ventricular
             outflow tract, including aortic stenosis.

          -  Presence of hypertrophic obstructive cardiomyopathy.

          -  Other protocol-defined inclusion/exclusion criteria may apply