Circulating NEP and NEP Inhibition Study in Heart Failure With Preserved Ejection Fraction

Phase 4

Completed

Brief Summary: To determine biomarker responses to Entresto™in patients with Heart Failure with preserved Ejection Fraction (HFpEF) and who have high or low serum neprilysin (NEP) levels.

Detailed Description: This is a proof of concept single arm study in which 40 subjects with HFpEF will be assigned to Entresto™ 49/51 mg (sacubitril/valsartan) twice-daily for a total duration of up to 5 weeks of treatment. Blood will be drawn prior to and at completion of treatment. The primary endpoint measured is change in biomarkers with Entresto™ administration that reflect NEP activity and myocardial stress (NT pro-ANP, -BNP, -CNP) and drug action (cGMP). This endpoint has been well validated as a measure of Entresto™ drug response.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Low Serum Neprilysin (sNEP) levels	Entresto™ 49Mg-51 mg tablet	Subjects with baseline sNEP levels less than or equal to 0.9 ng/ml
High Serum Neprilysin (sNEP) levels	Entresto™ 49Mg-51 mg tablet	Subjects with baseline sNEP greater than or equal to 0.9 ng/ml

Primary Outcome Measures

Name	Time	Method
Change in Plasma N-terminal Proatrial Natriuretic Peptide (NT proANP)	baseline, 5 weeks	Change in plasma NT pro-ANP value levels as measured in pg/mL. NT-pro ANP means N-terminal polypeptide of ANP (atrial natriuretic peptide) precursor. Natriuretic peptides are substances made by the heart. Elevated levels can mean the heart isn't pumping as much blood the body needs.
Change in Plasma N-terminal Brain Natriuretic Peptide (BNP)	baseline, 5 weeks	Change in plasma BNP biomarker value levels as measured in pg/mL. Brain natriuretic peptide is a hormone secreted by cardiomyocytes in the heart ventricles in response to stretching caused by increased ventricular blood volume. Elevated levels can mean the heart isn't pumping as much blood the body needs.
Change in Plasma Cyclic Guanine Monophosphate (cGMP)	baseline, 5 weeks	Change in Plasma cGMP biomarker value levels as measured in nmol/L. Cyclic guanosine monophosphate is a cyclic nucleotide derived from guanosine triphosphate. cGMP acts as a second messenger to tissue and cellular responses.
Change in Plasma N-terminal Pro B-type Natriuretic Peptide (NT-proBNP)	baseline, 5 weeks	Change in plasma NT pro-ANP value levels as measured in pg/mL. Natriuretic peptides are substances made by the heart. Two main types of these substances are brain natriuretic peptide (BNP) and N-terminal pro b-type natriuretic peptide (NT-proBNP). Elevated levels can mean the heart isn't pumping as much blood the body needs.