The purpose of this study is to evaluate the effect of sacubitril/valsartan 200 mg BID compared with enalapril 10 mg BID, in addition to conventional heart failure (HF) treatment, in improving a hierarchical composite of cardiovascular (CV) events (i.e. CV death or the occurrence of first HF hospitalization) and causing a greater reduction in n terminal prohormone of brain natriuretic peptide (NT-proBNP, at Week 12 from Baseline) in participants with HF with reduced ejection fraction (HFrEF) caused by CCC.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
918
50 (24/26) mg, 100 (49/51) mg and 200 (97/103) mg will be available for dose adjustments.
5 mg and 10 mg will be available for dose adjustments.
Novartis Investigative Site
CABA, Buenos Aires, Argentina
Novartis Investigative Site
CABA, Buenos Aires, Argentina
Novartis Investigative Site
Ramos Mejía, Buenos Aires, Argentina
Novartis Investigative Site
San Martín, Buenos Aires, Argentina
Novartis Investigative Site
Temperley, Buenos Aires, Argentina
Hierarchical composite endpoint composed of time to CV death, time to first HF hospitalization, relative change in NT-proBNP from baseline to Week 12
The primary efficacy endpoint will be analyzed using the win ratio approach comparing every participant in the sacubitril/valsartan arm to every participant in the enalapril arm to determine a winner. The estimated win ratio (the total number of winners in the sacubitril/valsartan arm divided by the total number of winners in the enalapril arm) will be provided. A winner in the pair-wise comparison has a delayed time to the occurrence of CV death; if time to the occurrence of CV death is censored, a winner has a delayed time to the occurrence of first HF hospitalization event; if the times to both CV events are censored, a winner has a more favorable (less increase or more decrease) change in NT-proBNP between Baseline and Week 12.
Time frame: Total follow up time up to approximately 36 months
Time to the first occurrence of a composite of CV events
Time from randomization to the first occurrence of HF hospitalization or CV death
Time frame: From the date of randomization to the first occurrence (total follow up time up to approximately 36 months)
Time to all-cause mortality
The time to all-cause mortality will be determined.
Time frame: From date of randomization until the date of death from any cause assessed up to the end of the study, which is estimated to be up to approximately 36 months
Time to sudden death or resuscitated sudden cardiac arrest
The time to sudden death or resuscitated sudden cardiac arrest will be determined.
Time frame: From date of randomization until the date of the sudden death or resuscitated sudden cardiac arrest assessed up to the end of the study, which is estimated to be up to approximately 36 months
Number of visits to an ER due to HF (where intravenous therapy is required)
The rate of visits to an emergency room (ER) due to HF (where intravenous therapy is required) will be determined.
Time frame: From the date of randomization up to End of Study (EOS) assessment. Total follow up time up to approximately 36 months.
Number of days alive out of the hospital
The number of days alive out of the hospital will be determined.
Time frame: From the date of randomization up to End of Study (EOS) assessment. Total follow up time up to approximately 36 months.
Number of ventricular fibrillation or sustained ventricular tachycardia
The number of ventricular fibrillation or sustained ventricular tachycardia needing specific pharmacological, electrical or other treatment will be determined.
Time frame: From the date of randomization up to End of Study (EOS) assessment. Total follow up time up to approximately 36 months.
Number of anti-tachycardia pacing or shock therapies
This will be determined in a subset on a subset of participants who have an ICD or CRT-D at Randomization.
Time frame: From the date of randomization up to End of Study (EOS) assessment. Total follow up time up to approximately 36 months.
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Novartis Investigative Site
Villa María, Córdoba Province, Argentina
Novartis Investigative Site
Salta, Salta Province, Argentina
Novartis Investigative Site
San Miguel de Tucumán, San Miguel de Tucuman, Argentina
Novartis Investigative Site
Rosario, Santa Fe Province, Argentina
Novartis Investigative Site
Rosario, Santa Fe Province, Argentina
...and 69 more locations