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About
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.
Full 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.
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Inclusion and exclusion criteria
Inclusion Criteria
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:
One of the following within the last 24 months
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
Exclusion Criteria
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
Primary purpose
Allocation
Interventional model
Masking
40 participants in 2 patient groups
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Data sourced from clinicaltrials.gov
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