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

NCT03506412 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: 18-000044R21AG053512
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Heart Failure With Preserved Ejection Fraction

Keywords

Heart Failure; HFpEF; Entresto™; Neprilysin; Diastolic Heart Failure

Outcome Measures

Primary Outcomes (4)

• Change in Plasma N-terminal Proatrial Natriuretic Peptide (NT proANP)

  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.

  baseline, 5 weeks

• Change in Plasma N-terminal Pro B-type Natriuretic Peptide (NT-proBNP)

  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.

  baseline, 5 weeks

• Change in Plasma N-terminal Brain Natriuretic Peptide (BNP)

  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.

  baseline, 5 weeks

• Change in Plasma Cyclic Guanine Monophosphate (cGMP)

  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.

  baseline, 5 weeks

Study Arms (2)

Low Serum Neprilysin (sNEP) levels

EXPERIMENTAL

Subjects with baseline sNEP levels less than or equal to 0.9 ng/ml

Drug: Entresto™ 49Mg-51 mg tablet

High Serum Neprilysin (sNEP) levels

EXPERIMENTAL

Subjects with baseline sNEP greater than or equal to 0.9 ng/ml

Drug: Entresto™ 49Mg-51 mg tablet

Interventions

Entresto™ 49Mg-51 mg tablet DRUG

Entresto™ 49Mg-51 mg will be given twice daily orally for 5 weeks

High Serum Neprilysin (sNEP) levels; Low Serum Neprilysin (sNEP) levels

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 50 years
• LVEF ≥ 45% assessed by echocardiography, nuclear scan, MRI or left ventriculogram within the past 24 months
• Current New York Heart Association (NYHA) class 2-4 symptoms of heart failure (HF)
• Stable medical therapy for 30 days as defined by:
• No addition or removal of ACE, ARB, beta-blockers, calcium channel blockers (CCBs) or aldosterone antagonists
• No change in dosage of ACE, ARBs, beta-blockers, CCBs or aldosterone antagonists of more than 100%
• One of the following within the last 24 months
• Previous hospitalization for HF with radiographic evidence of pulmonary congestion (pulmonary venous hypertension, vascular congestion, interstitial edema, pleural effusion) or
• Catheterization documented elevated filling pressures at rest (LVEDP≥15 or PCWP≥20) or with exercise (PCWP≥25) or
• Elevated NT-proBNP (\> 400 pg/ml) or BNP (\> 200 pg/ml) or
• Echo evidence of diastolic dysfunction / elevated filling pressures (at least two)
• i. E/A \> 1.5 + decrease in E/A of \> 0.5 with valsalva
• ii. Deceleration time ≤ 140 ms
• iii. Pulmonary vein velocity in systole \< diastole (PVs\<PVd) (sinus rhythm)
• iv. E/e'≥15

You may not qualify if:

• History of hypersensitivity or allergy to ACE inhibitors (ACEIs), ARBs, or NEP inhibitors
• Known history of angioedema
• Previous LVEF \< 40% at any time
• Systolic blood pressure \< 100 mmHg or \> 180 mmHg
• Current acute decompensated HF (exacerbation of chronic HF manifested by signs and symptoms that may require intravenous therapy)
• Unstable angina, myocardial infarction, stroke, transient ischemic attack, or cardiovascular surgery or urgent percutaneous coronary intervention (PCI) within 3 months of screening or elective PCI within 30 days of entry
• Significant valvular stenosis or regurgitation (greater than moderate in severity), hypertrophic, restrictive or obstructive cardiomyopathy including amyloidosis, constrictive pericarditis, primary pulmonary hypertension, or biopsy proven active myocarditis
• Severe congenital heart disease
• History of heart transplant or with LV assist device
• Evidence of severe hepatic disease as determined by any one of the following: history of hepatic encephalopathy, history of esophageal varices, or history of porto-caval shunt.
• Glomerular filtration rate \< 20 ml/min/1.73 m2 on most recent clinical laboratories\*
• Serum potassium of \> 5.5 mEq/dL on most recent clinical laboratories\*
• Concomitant use of aliskiren in patients with diabetes
• Currently receiving an investigational drug
• Inability to comply with planned study procedures

Sponsors & Collaborators

• Mayo Clinic: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Heart Failure; Heart Failure, Diastolic

Interventions

sacubitril and valsartan sodium hydrate drug combination

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Naveen L. Pereira, M.D.
• Organization: Mayo Clinic

Pereira.Naveen@mayo.edu

507-284-8612

Study Officials

• Naveen L Pereira, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: Entresto™ will be administered to subjects with high and low circulating neprilysin (NEP) levels.

Study Record Dates

• First Submitted: April 11, 2018
• First Posted: April 24, 2018
• Study Start: June 25, 2018
• Primary Completion: March 23, 2021
• Study Completion: March 23, 2021
• Last Updated: February 4, 2022
• Results First Posted: February 4, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)