Heart Failure With Preserved Ejection Fraction Clinical Trial
— CNEPiOfficial title:
A Proof of Concept Study to Determine the Efficacy of Entresto™ in HFpEF Based on Circulating Neprilysin Levels: The Circulating NEP and NEP Inhibition (CNEPi) Study
Verified date | January 2022 |
Source | Mayo Clinic |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 40 |
Est. completion date | March 23, 2021 |
Est. primary completion date | March 23, 2021 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 50 Years and older |
Eligibility | Inclusion Criteria 1. Age = 50 years 2. LVEF = 45% assessed by echocardiography, nuclear scan, MRI or left ventriculogram within the past 24 months 3. Current New York Heart Association (NYHA) class 2-4 symptoms of heart failure (HF) 4. Stable medical therapy for 30 days as defined by: 1. No addition or removal of ACE, ARB, beta-blockers, calcium channel blockers (CCBs) or aldosterone antagonists 2. No change in dosage of ACE, ARBs, beta-blockers, CCBs or aldosterone antagonists of more than 100% 5. One of the following within the last 24 months 1. Previous hospitalization for HF with radiographic evidence of pulmonary congestion (pulmonary venous hypertension, vascular congestion, interstitial edema, pleural effusion) or 2. Catheterization documented elevated filling pressures at rest (LVEDP=15 or PCWP=20) or with exercise (PCWP=25) or 3. Elevated NT-proBNP (> 400 pg/ml) or BNP (> 200 pg/ml) or 4. 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 v. Left atrial enlargement (= moderate) vi. Pulmonary artery systolic pressure > 40 mmHg vii. Evidence of left ventricular hypertrophy 1. LV mass/BSA = 96 (?) or = 116 (?) g/m2 2. Relative wall thickness = 0.43 (? or ?) [(IVS+PW)/LVEDD] 3. Posterior wall thickness = 0.9 (?) or 1.0 (?) cm Exclusion Criteria 1. History of hypersensitivity or allergy to ACE inhibitors (ACEIs), ARBs, or NEP inhibitors 2. Known history of angioedema 3. Previous LVEF < 40% at any time 4. Systolic blood pressure < 100 mmHg or > 180 mmHg 5. Current acute decompensated HF (exacerbation of chronic HF manifested by signs and symptoms that may require intravenous therapy) 6. 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 7. 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 8. Severe congenital heart disease 9. History of heart transplant or with LV assist device 10. 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. 11. Glomerular filtration rate < 20 ml/min/1.73 m2 on most recent clinical laboratories* 12. Serum potassium of > 5.5 mEq/dL on most recent clinical laboratories* 13. Concomitant use of aliskiren in patients with diabetes 14. Currently receiving an investigational drug 15. Inability to comply with planned study procedures 16. Female subject who is pregnant or breastfeeding - Performed within 90 days of enrollment |
Country | Name | City | State |
---|---|---|---|
United States | Mayo Clinic in Rochester | Rochester | Minnesota |
Lead Sponsor | Collaborator |
---|---|
Mayo Clinic | National Institute on Aging (NIA) |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | |
Primary | 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 | |
Primary | 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 | |
Primary | 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 |
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