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

NCT02787798 | Terminated Phase 4 DMC

• 1 other identifier: RC31/15/7746
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Heart Failure

Keywords

Nervous System; Cardiac disease

Outcome Measures

Primary Outcomes (1)

• Evaluation of sympathetic nervous system activity as assessed by microneurography recording recording of sympathetic activity in muscle destiny

  Evaluation of sympathetic nervous system activity in burst/minute

  Up to 8 weeks

Secondary Outcomes (5)

• Evaluation of severity of heart failure

  Day 0

• Evaluation of severity of heart failure

  Day 2

• Evaluation of severity of heart failure

  Up to 4 weeks

• Evaluation of severity of heart failure

  Up to 8 weeks

• 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

Study Arms (2)

Entresto

EXPERIMENTAL

* 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)

Drug: valsartan/sacubitril 100 mg; Drug: valsartan/sacubitril 200 mg; Procedure: Microneurography

Control

PLACEBO COMPARATOR

* 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

Procedure: Microneurography

Interventions

valsartan/sacubitril 100 mg DRUG

Treatment with 100 mg tablets during 2 to 4 weeks

Also known as: Entresto 100 mg

Entresto

valsartan/sacubitril 200 mg DRUG

Treatment with 200 mg tablets during 2 to 4 weeks

Also known as: Entresto 200 mg

Entresto

Microneurography PROCEDURE

Microneurography recording of sympathetic nervous system activity in muscle destiny

Also known as: MSNA

Control; Entresto

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Pregnancy
• Breast-feeding

Sponsors & Collaborators

• University Hospital, Toulouse: lead

Study Sites (1)

CHU de Toulouse

Toulouse, France

Location

MeSH Terms

Conditions

Heart Failure; Neurologic Manifestations; Heart Diseases

Interventions

Valsartan; sacubitril; sacubitril and valsartan sodium hydrate drug combination

Condition Hierarchy (Ancestors)

Cardiovascular Diseases; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Study Officials

• Michel Galinier, MD

  University Hospital, Toulouse

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2016
• First Posted: June 1, 2016
• Study Start: October 1, 2016
• Primary Completion: January 1, 2018
• Study Completion: January 1, 2018
• Last Updated: February 7, 2019

Record last verified: 2019-02

Locations

FR (1)