Heart Failure Clinical Trial
Circulating NEP and NEP Inhibition Study in Heart Failure With Preserved Ejection Fraction
To determine biomarker responses to Entrestoâ„¢in patients with Heart Failure with preserved Ejection Fraction (HFpEF) and who have high or low serum neprilysin (NEP) levels.
This is a proof of concept single arm study in which 40 subjects with HFpEF will be assigned to Entrestoâ„¢ 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 Entrestoâ„¢ 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 Entrestoâ„¢ drug response.
Age â‰¥ 50 years
LVEF â‰¥ 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 (LVEDPâ‰¥15 or PCWPâ‰¥20) or with exercise (PCWPâ‰¥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 â‰¤ 140 ms
iii. Pulmonary vein velocity in systole < diastole (PVs
v. Left atrial enlargement (â‰¥ moderate)
vi. Pulmonary artery systolic pressure > 40 mmHg
vii. Evidence of left ventricular hypertrophy
LV mass/BSA â‰¥ 96 (â™€) or â‰¥ 116 (â™‚) g/m2
Relative wall thickness â‰¥ 0.43 (â™‚ or â™€) [(IVS+PW)/LVEDD]
Posterior wall thickness â‰¥ 0.9 (â™€) or 1.0 (â™‚) cm
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
Female subject who is pregnant or breastfeeding
Performed within 90 days of enrollment
Check Your Eligibility
Let’s see if you might be eligible for this study.
What is your age and gender ?
There is 1 Location for this study
Rochester Minnesota, 55905, United States
How clear is this clinincal trial information?
Introducing, the Journey Bar
Use this bar to access information about the steps in your cancer journey.