Heart Failure
Conditions
Keywords
Nervous System, Cardiac disease
Brief summary
The hyperactivation of the sympathetic nervous system is a feature of the heart failure and the determinants of disease progression and risk of sudden cardiac death. This research project aims to study, in the drug use conditions provided in the summary of product characteristics based on European marketing authorization (indications and dosage), the effect of the Entresto® on the activity of sympathic nervous system using the reference method, the microneurographic recording of sympathetic activity in muscle destiny (MSNA). This study will try to determine if the double inhibition of AT1 receptor and neprilysin activity result in lower sympathic nervous system burst rate versus single AT1 receptor inhibition using angiotensin-converting-enzyme inhibitor or AT1 receptor of angiotensin II inhibitor.
Interventions
DRUGvalsartan/sacubitril 100 mg
Treatment with 100 mg tablets during 2 to 4 weeks
DRUGvalsartan/sacubitril 200 mg
Treatment with 200 mg tablets during 2 to 4 weeks
PROCEDUREMicroneurography
Microneurography recording of sympathetic nervous system activity in muscle destiny
Sponsors
University Hospital, Toulouse
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men or women with heart failure with symptomatic left ventricular systolic dysfunction (left ventricular ejection fraction ≤ 40 %) with : * Functional class New York Heart Association II and at least 2 hospitalizations for cardiac decompensation in the year with N terminal pro brain-type natriuretic peptide ≥300 pg/ml (or brain-type natriuretic peptide ≥100 pg/ml) or usage of intravenous diuretics, * Functional class New York Heart Association III-IV, * Insufficiently controlled by alternative drug-free therapies (surgery, cardiac resynchronization ...) or well managed drug therapies: angiotensin-converting-enzyme inhibitor, AT1 receptor of angiotensin II inhibitor diuretics or beta blockers. * Treated by maximum dosage of AT1 receptor of angiotensin II inhibitor or angiotensin-converting-enzyme inhibitor for New York Heart Association II patient or 50% of the recommended dose for New York Heart Association III-IV patients or New York Heart Association II patients with clinical manifestation restricting the use of maximum dosage, like orthostatic hypotension. * Patient member of his home social security scheme
Exclusion criteria
* Patient who are receiving direct renin inhibitor like aliskiren * Patient who are receiving phosphodiesterase V inhibitors * Patient who are receiving a potassium-sparing drug * Patient with medical history of angioedema with previous treatment by angiotensin-converting-enzyme inhibitor or AT1 receptor of angiotensin II inhibitor * Hypersensitivity to any component of Entresto® * Adult protected by the law * Severe renal impairment (DFGe \<30 ml/min/1,73 m2) * Severe hepatic impairment, cirrhosis or cholestasis (Child-Pugh C class) * Patient with are receiving anticoagulant therapies or suffering from known hemostatic trouble * Patient participating in another biomedical research or with an active exclusion period * Pregnancy * Breast-feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of sympathetic nervous system activity as assessed by microneurography recording recording of sympathetic activity in muscle destiny | Up to 8 weeks | Evaluation of sympathetic nervous system activity in burst/minute |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of severity of heart failure | Day 0 | assessed by New York Heart Association stage |
| Comparison of treatment effect on pro-brain natriuretic peptide serum levels at baseline and at the end of treatment period | Day 0 and up to 8 weeks | pro-brain natriuretic peptide serum levels |
Countries
France
Outcome results
None listed