Comparison of Sacubitril/Valsartan Versus Enalapril on Effect on NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode.
Condition: Acute Heart Failure
MeSH terms: Heart Failure
Intervention: sacubitril/valsartan (LCZ696); Enalapril; sacubitril/valsartan (LCZ696) matching placebo; enalapril matching placebo
Intervention description: sacubitril/valsartan (LCZ696) tablet with minimum dose 24/26 mg, maximum dose 97/103 mg twice daily administered orally.; Enalapril tablet with minimum dose 2.5 mg, maximum dose 10 mg twice daily administered orally.; matching placebo of sacubitril/valsartan (LCZ696) tablet with minimum dose 24/26 mg, maximum dose 97/103 mg twice daily administered orally.; enalapril matching placebo tablet with minimum dose 2.5 mg, maximum dose 10 mg twice daily administered orally.
Intervention MeSH terms: Valsartan; Enalapril; Enalaprilat; Sacubitril and valsartan sodium hydrate drug combination
Phase: Phase 4
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 887.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Acute; Heart Failure; reduced ejection fraction; NTproBNP; Heart failure with reduced ejection fraction (HFREF)

Summary:

      The purpose of this study was to assess the effect of in-hospital initiation of
      sacubitril/valsartan (LCZ696) vs. enalapril on time averaged proportional change in NT-proBNP
      in patients who have been stabilized following hospitalization for acute decompensated heart
      failure (ADHF) and reduced ejection fraction (left ventricular ejection fraction (LVEF) ≤
      40%).
    

Eligibility criteria:

        Key Inclusion Criteria:

          1. Possess the capacity to provide written informed consent which must be obtained before
             any assessment is performed.

          2. Currently hospitalized for ADHF. Patients with a diagnosis of acute heart failure had
             to have symptoms and signs of fluid overload (i.e. jugular venous distention, edema or
             rales on auscultation or pulmonary congestion on chest x-ray) at time of
             hospitalization.

          3. Eligible patients will be randomized no earlier than 24 hours and up to ten days after
             presentation while still hospitalized as long as meet the following definition of
             stable status:

               -  SBP ≥100mm Hg for the preceding 6 hours prior to randomization; no symptomatic
                  hypotension

               -  No increase (intensification) in i.v. diuretic dose within last 6 hours prior to
                  randomization

               -  No i.v. inotropic drugs for 24 hours prior to randomization

               -  No i.v. vasodilators including nitrates within last 6 hours prior to
                  randomization

          4. LVEF ≤40% within the past 6 months (including current hospitalization) using
             echocardiography, multi gated acquisition scan (MUGA), CT scanning, MRI or ventricular
             angiography, provided no subsequent study documented an EF of >40%.

          5. Elevated NT-proBNP ≥ 1600pg/mL OR BNP ≥400 pg/mL during current hospitalization.

        Key Exclusion Criteria:

          1. Currently taking sacubitril/valsartan tablets or any use within the past 30 days.

          2. Enrollment in any other clinical trial involving an investigational agent or
             investigational device.

          3. History of hypersensitivity, known or suspected contraindications, or intolerance to
             any of the study drugs, including ACEIs, ARBs, or Sacubitril (NEP inhibitor).

          4. Patients with a known history of angioedema related to previous ACE inhibitor or ARB
             therapy.

          5. Requirement of treatment with both ACE inhibitor and ARB.

          6. eGFR < 30 ml/min/1.73 m2 as measured by the simplified Modification of Diet in Renal
             Disease (MDRD) formula at screening.

          7. Serum potassium > 5.2 mEq/L at screening.

          8. Known hepatic impairment (as evidenced by total bilirubin > 3 mg/dL, or increased
             ammonia levels, if performed), or history of cirrhosis with evidence of portal
             hypertension such as varices

          9. Acute coronary syndrome, stroke, transient ischemic attack; cardiac, carotid or other
             major CV surgery; percutaneous coronary intervention (PCI) or carotid angioplasty,
             within one month prior to Visit 1.

         10. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a
             female after conception and until the termination of gestation, confirmed by a
             positive hCG laboratory test.

         11. Women of child-bearing potential, defined as all women physiologically capable of
             becoming pregnant, including women whose career, lifestyle, or sexual orientation
             precludes intercourse with a male partner and women whose partners have been
             sterilized by vasectomy or other means, UNLESS they are using two birth control
             methods.