Evaluation of the Entresto Effect on Sympathic Nervous System in Patient With Heart Failure

Phase 4

Terminated

• Conditions: Heart Failure
• Interventions: Drug: valsartan/sacubitril 100 mg; Drug: valsartan/sacubitril 200 mg; Procedure: Microneurography

• Registration Number: NCT02787798
• Lead Sponsor: University Hospital, Toulouse

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-05-26
• Study First Submitted QC: 2016-05-26
• Study First Posted: 2016-06-01
• Study Start: 2016-10
• Primary Completion: 2018-01
• Study Completion: 2018-01
• Status Verified: 2019-02
• Last Update Submitted: 2019-02-05
• Last Update Posted: 2019-02-07

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 4

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Entresto	valsartan/sacubitril 200 mg	* Stop of all angiotensin-converting-enzyme inhibitor or antagonist of angiotensin II receptor during 2 days. * valsartan/sacubitril 100 mg tablets (51 and 49 mg) during 2 to 4 weeks twice a day. * valsartan/sacubitril 200 mg tablets (103 and 97 mg) during 2 to 4 weeks twice a day. * Microneurography recording of sympathetic activity in muscle destiny (MSNA)
Entresto	valsartan/sacubitril 100 mg	* Stop of all angiotensin-converting-enzyme inhibitor or antagonist of angiotensin II receptor during 2 days. * valsartan/sacubitril 100 mg tablets (51 and 49 mg) during 2 to 4 weeks twice a day. * valsartan/sacubitril 200 mg tablets (103 and 97 mg) during 2 to 4 weeks twice a day. * Microneurography recording of sympathetic activity in muscle destiny (MSNA)
Entresto	Microneurography	* Stop of all angiotensin-converting-enzyme inhibitor or antagonist of angiotensin II receptor during 2 days. * valsartan/sacubitril 100 mg tablets (51 and 49 mg) during 2 to 4 weeks twice a day. * valsartan/sacubitril 200 mg tablets (103 and 97 mg) during 2 to 4 weeks twice a day. * Microneurography recording of sympathetic activity in muscle destiny (MSNA)
Control	Microneurography	* Hearth failure treatment as usual (angiotensin-converting-enzyme inhibitor or antagonist of angiotensin II receptor) * Microneurography recording of sympathetic activity in muscle destiny (MSNA) will be done

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
Evaluation of severity of heart failure	Up to 8 weeks	assessed by New York Heart Association stage

Trial Locations

Locations (1)

CHU de Toulouse; 🇫🇷 Toulouse, France