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%).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE
Enrollment
887
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.
N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) Values and Time-averaged Change From Baseline
To assess the effect of in-hospital initiation of sacubitril/valsartan vs. enalapril on the time-averaged percentage change of NT-proBNP from baseline in patients who have been stabilized following hospitalization for ADHF and reduced ejection fraction (left ventricular ejection fraction \[LVEF\] ≤ 40%) between week 4 and 8. Number of patients with both a baseline value and a value at Week 4 or Week 8. Plasma NT-proBNP (pg/mL) values were averaged from Week 4 and Week 8 visits. N-terminal pro b-type natriuretic peptide (NTproBNP) are peptide (small proteins) that are either hormones or part of the peptide that contained the hormone at one time. They are continually produced in small quantities in the heart and released in larger quantities when the heart senses that it needs to work harder, as in heart failure.
Time frame: Baseline, Week 4 and Week 8
Number of Patients With Incidences of Symptomatic Hypotension
Examine the effect of LCZ696 vs. enalapril on incidence of symptomatic hypotension during 8 weeks of treatment Hypotension is low blood pressure. Patients with hypotension may experience symptoms when their blood pressure drops, compared to the patient's normal values. Symptoms of hypotension can include dizziness, lightheadedness, blurred vision, weakness, fatigue, nausea, palpitations, and headache.
Time frame: 8 weeks of treatment
Number of Patients With Incidences of Hyperkalemia
Hyperkalemia is defined as Potassium level \>5.5 mEq/L. Hyperkalemia is the medical term that describes a potassium level in your blood that's higher than normal. Potassium is a chemical that is critical to the function of nerve and muscle cells, including those in your heart.
Time frame: 8 weeks of treatment
Number of Patients With Incidences of Angioedema
Angioedema is a type of abrupt swelling that occurs under the skin and/or mucous membranes and is often localized to the head, neck, throat, and/or tongue, but may occur elsewhere, including the genitalia and intestines. Severe cases may be associated with difficulty in breathing.
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enalapril matching placebo tablet with minimum dose 2.5 mg, maximum dose 10 mg twice daily administered orally.
Novartis Investigative Site
Birmingham, Alabama, United States
Novartis Investigative Site
Fort Smith, Arkansas, United States
Novartis Investigative Site
Little Rock, Arkansas, United States
Novartis Investigative Site
Bakersfield, California, United States
Novartis Investigative Site
Fresno, California, United States
Novartis Investigative Site
Long Beach, California, United States
Novartis Investigative Site
Los Angeles, California, United States
Novartis Investigative Site
Los Angeles, California, United States
Novartis Investigative Site
Orange, California, United States
Novartis Investigative Site
Pasadena, California, United States
...and 113 more locations
Time frame: 8 weeks of treatment
Change From Baseline in High Sensitivity Troponin (Hs-Troponin)
time-averaged (Weeks 4 and 8) change from baseline in hs-troponin T. hs-Troponin-T is a biomarker that is released from the heart under stress or injury conditions.
Time frame: Baseline, Week 4/Week 8
Change From Baseline in Urinary cGMP
Time-averaged (Weeks 4 and 8) change from baseline in urinary cGMP. Urinary Cyclic GMP (cGMP) is a biomarker measured in the urine that reflects the activity of biomarkers such as BNP (Brain Natriuretic Peptide)
Time frame: Baseline, Week 4 and Week 8
Change From Baseline in Urinary cGMP to Urinary Creatinine Ratio
Time-averaged (Weeks 4 and 8) change from baseline in urinary cGMP to urinary creatinine ratio. Urinary cGMP to urinary creatinine ratio is how much urinary cGMP (which reflects natriuretic peptide activity) compared to a compound in the urine called creatinine (which helps your doctor evaluate how well your kidneys are functioning).
Time frame: Baseline, Week 4 and Week 8
Change From Baseline in BNP to NTproBNP Ratio
Time-averaged (Weeks 4 and 8) change from baseline in BNP to NT-proBNP ratio. BNP and NT-proBNP are small proteins produced in large amounts when the heart senses it needs to work harder, such as in heart failure. The test measuring BNP to NT-proBNP is measuring how much of each of these biomarkers are present in order to evaluate heart failure.
Time frame: baseline, Week 4 and Week 8
N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) Values and Change From Baseline at Week 8
BNP and NT-proBNP are small proteins produced in large amounts when the heart senses it needs to work harder, such as in heart failure. The test measuring BNP to NT-proBNP is measuring how much of each of these biomarkers are present in order to evaluate heart failure. Plasma NT-proBNP (pg/mL) values were Week 8 visit.
Time frame: Baseline, Week 8