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Evaluation of the Entresto Effect on Sympathic Nervous System in Patient With Heart Failure (B2AN-SNS)

Primary Purpose

Heart Failure

Status
Terminated
Phase
Phase 4
Locations
France
Study Type
Interventional
Intervention
valsartan/sacubitril 100 mg
valsartan/sacubitril 200 mg
Microneurography
Sponsored by
University Hospital, Toulouse
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure focused on measuring Nervous System, Cardiac disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • CHU de Toulouse

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Entresto

Control

Arm Description

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)

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Evaluation of severity of heart failure
assessed by New York Heart Association stage
Evaluation of severity of heart failure
assessed by New York Heart Association stage
Evaluation of severity of heart failure
assessed by New York Heart Association stage
Evaluation of severity of heart failure
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
pro-brain natriuretic peptide serum levels

Full Information

First Posted
May 26, 2016
Last Updated
February 5, 2019
Sponsor
University Hospital, Toulouse
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1. Study Identification

Unique Protocol Identification Number
NCT02787798
Brief Title
Evaluation of the Entresto Effect on Sympathic Nervous System in Patient With Heart Failure
Acronym
B2AN-SNS
Official Title
Evaluation of the Effect of Double Inhibition of Angiotensin II AT1 Receptor and Neprilysin Activity on Sympathic Nervous System Activity in Patient With Heart Failure
Study Type
Interventional

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Terminated
Why Stopped
Today Entresto treatment has marketing authorization and is available for all patients, that is the reason why study was halted prematurely.
Study Start Date
October 2016 (Actual)
Primary Completion Date
January 2018 (Actual)
Study Completion Date
January 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Toulouse

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure
Keywords
Nervous System, Cardiac disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
4 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Entresto
Arm Type
Experimental
Arm Description
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)
Arm Title
Control
Arm Type
Placebo Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
valsartan/sacubitril 100 mg
Other Intervention Name(s)
Entresto 100 mg
Intervention Description
Treatment with 100 mg tablets during 2 to 4 weeks
Intervention Type
Drug
Intervention Name(s)
valsartan/sacubitril 200 mg
Other Intervention Name(s)
Entresto 200 mg
Intervention Description
Treatment with 200 mg tablets during 2 to 4 weeks
Intervention Type
Procedure
Intervention Name(s)
Microneurography
Other Intervention Name(s)
MSNA
Intervention Description
Microneurography recording of sympathetic nervous system activity in muscle destiny
Primary Outcome Measure Information:
Title
Evaluation of sympathetic nervous system activity as assessed by microneurography recording recording of sympathetic activity in muscle destiny
Description
Evaluation of sympathetic nervous system activity in burst/minute
Time Frame
Up to 8 weeks
Secondary Outcome Measure Information:
Title
Evaluation of severity of heart failure
Description
assessed by New York Heart Association stage
Time Frame
Day 0
Title
Evaluation of severity of heart failure
Description
assessed by New York Heart Association stage
Time Frame
Day 2
Title
Evaluation of severity of heart failure
Description
assessed by New York Heart Association stage
Time Frame
Up to 4 weeks
Title
Evaluation of severity of heart failure
Description
assessed by New York Heart Association stage
Time Frame
Up to 8 weeks
Title
Comparison of treatment effect on pro-brain natriuretic peptide serum levels at baseline and at the end of treatment period
Description
pro-brain natriuretic peptide serum levels
Time Frame
Day 0 and up to 8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michel Galinier, MD
Organizational Affiliation
CHU Toulouse
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU de Toulouse
City
Toulouse
Country
France

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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

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