Trial Outcomes & Findings for Circulating NEP and NEP Inhibition Study in Heart Failure With Preserved Ejection Fraction (NCT NCT03506412)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

40 participants

Primary outcome timeframe

baseline, 5 weeks

Results posted on

2022-02-04

Participant Flow

Total of 40 subject enrolled. Enrolled subjects were assigned to an arm based on their Baseline serum Neprilysin (sNEP) levels. Baseline sNEP levels were only available for 37 subjects. Data not collected for 3 subjects.

Participant milestones

Participant milestones
Measure	Low Serum Neprilysin (sNEP) Levels Subjects with baseline sNEP levels less than or equal to 0.9 ng/ml Entresto™ 49Mg-51 mg tablet: Entresto™ 49 Mg-51 mg will be given twice daily orally for 5 weeks	High Serum Neprilysin (sNEP) Levels Subjects with baseline sNEP greater than or equal to 0.9 ng/ml Entresto™ 49Mg-51 mg tablet: Entresto™ 49 Mg-51 mg will be given twice daily orally for 5 weeks
Overall Study STARTED	18	19
Overall Study COMPLETED	18	19
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Low Serum Neprilysin (sNEP) Levels n=18 Participants Subjects with baseline sNEP levels less than or equal to 0.9 ng/ml Entresto™ 49Mg-51 mg tablet: Entresto™ 49Mg-51 mg will be given twice daily orally for 5 weeks	High Serum Neprilysin (sNEP) Levels n=19 Participants Subjects with baseline sNEP greater than or equal to 0.9 ng/ml Entresto™ 49Mg-51 mg tablet: Entresto™ 49Mg-51 mg will be given twice daily orally for 5 weeks	Total n=37 Participants Total of all reporting groups
Age, Continuous	77.0 years n=18 Participants	74.0 years n=19 Participants	76 years n=37 Participants
Sex: Female, Male Female	10 Participants n=18 Participants	7 Participants n=19 Participants	17 Participants n=37 Participants
Sex: Female, Male Male	8 Participants n=18 Participants	12 Participants n=19 Participants	20 Participants n=37 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment United States	18 participants n=18 Participants	19 participants n=19 Participants	37 participants n=37 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Low Serum Neprilysin (sNEP) Levels n=18 Participants Subjects with baseline sNEP levels less than or equal to 0.9 ng/ml Entresto™ 49Mg-51 mg tablet: Entresto™ 49Mg-51 mg will be given twice daily orally for 5 weeks	High Serum Neprilysin (sNEP) Levels n=19 Participants Subjects with baseline sNEP greater than or equal to 0.9 ng/ml Entresto™ 49Mg-51 mg tablet: Entresto™ 49Mg-51 mg will be given twice daily orally for 5 weeks
Change in Plasma N-terminal Proatrial Natriuretic Peptide (NT proANP)	47.4 pg/mL Interval -4.6 to 129.9	46.4 pg/mL Interval 6.4 to 139.5

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Low Serum Neprilysin (sNEP) Levels n=18 Participants Subjects with baseline sNEP levels less than or equal to 0.9 ng/ml Entresto™ 49Mg-51 mg tablet: Entresto™ 49Mg-51 mg will be given twice daily orally for 5 weeks	High Serum Neprilysin (sNEP) Levels n=19 Participants Subjects with baseline sNEP greater than or equal to 0.9 ng/ml Entresto™ 49Mg-51 mg tablet: Entresto™ 49Mg-51 mg will be given twice daily orally for 5 weeks
Change in Plasma N-terminal Pro B-type Natriuretic Peptide (NT-proBNP)	-11.5 pg/mL Interval -50.0 to 66.0	45.0 pg/mL Interval -16.0 to 107.0

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Low Serum Neprilysin (sNEP) Levels n=18 Participants Subjects with baseline sNEP levels less than or equal to 0.9 ng/ml Entresto™ 49Mg-51 mg tablet: Entresto™ 49Mg-51 mg will be given twice daily orally for 5 weeks	High Serum Neprilysin (sNEP) Levels n=19 Participants Subjects with baseline sNEP greater than or equal to 0.9 ng/ml Entresto™ 49Mg-51 mg tablet: Entresto™ 49Mg-51 mg will be given twice daily orally for 5 weeks
Change in Plasma N-terminal Brain Natriuretic Peptide (BNP)	-301.5 pg/mL Interval -684.0 to -20.0	-100.0 pg/mL Interval -405.0 to 69.0

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Low Serum Neprilysin (sNEP) Levels n=18 Participants Subjects with baseline sNEP levels less than or equal to 0.9 ng/ml Entresto™ 49Mg-51 mg tablet: Entresto™ 49Mg-51 mg will be given twice daily orally for 5 weeks	High Serum Neprilysin (sNEP) Levels n=19 Participants Subjects with baseline sNEP greater than or equal to 0.9 ng/ml Entresto™ 49Mg-51 mg tablet: Entresto™ 49Mg-51 mg will be given twice daily orally for 5 weeks
Change in Plasma Cyclic Guanine Monophosphate (cGMP)	4.2 nmol/L Interval 2.4 to 8.5	1.0 nmol/L Interval -0.9 to 6.3

Adverse Events

Low Serum Neprilysin (sNEP) Levels

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

High Serum Neprilysin (sNEP) Levels

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Naveen L. Pereira, M.D.

Mayo Clinic

Phone: 507-284-8612

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place