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

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ClinicalTrials.gov Identifier: NCT02787798
Recruitment Status : Terminated (Today Entresto treatment has marketing authorization and is available for all patients, that is the reason why study was halted prematurely.)
First Posted : June 1, 2016
Last Update Posted : February 7, 2019
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Heart Failure Drug: valsartan/sacubitril 100 mg Drug: valsartan/sacubitril 200 mg Procedure: Microneurography Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : October 2016
Actual Primary Completion Date : January 2018
Actual Study Completion Date : January 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arm Intervention/treatment
Experimental: Entresto
  • 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
Treatment with 100 mg tablets during 2 to 4 weeks
Other Name: Entresto 100 mg

Drug: valsartan/sacubitril 200 mg
Treatment with 200 mg tablets during 2 to 4 weeks
Other Name: Entresto 200 mg

Procedure: Microneurography
Microneurography recording of sympathetic nervous system activity in muscle destiny
Other Name: MSNA

Placebo Comparator: Control
  • 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
Microneurography recording of sympathetic nervous system activity in muscle destiny
Other Name: MSNA




Primary Outcome Measures :
  1. Evaluation of sympathetic nervous system activity as assessed by microneurography recording recording of sympathetic activity in muscle destiny [ Time Frame: Up to 8 weeks ]
    Evaluation of sympathetic nervous system activity in burst/minute


Secondary Outcome Measures :
  1. Evaluation of severity of heart failure [ Time Frame: Day 0 ]
    assessed by New York Heart Association stage

  2. Evaluation of severity of heart failure [ Time Frame: Day 2 ]
    assessed by New York Heart Association stage

  3. Evaluation of severity of heart failure [ Time Frame: Up to 4 weeks ]
    assessed by New York Heart Association stage

  4. Evaluation of severity of heart failure [ Time Frame: Up to 8 weeks ]
    assessed by New York Heart Association stage

  5. Comparison of treatment effect on pro-brain natriuretic peptide serum levels at baseline and at the end of treatment period [ Time Frame: Day 0 and up to 8 weeks ]
    pro-brain natriuretic peptide serum levels



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02787798


Locations
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France
CHU de Toulouse
Toulouse, France
Sponsors and Collaborators
University Hospital, Toulouse
Investigators
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Principal Investigator: Michel Galinier, MD CHU Toulouse

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Responsible Party: University Hospital, Toulouse
ClinicalTrials.gov Identifier: NCT02787798     History of Changes
Other Study ID Numbers: RC31/15/7746
First Posted: June 1, 2016    Key Record Dates
Last Update Posted: February 7, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by University Hospital, Toulouse:
Nervous System
Cardiac disease

Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardiovascular Diseases
Valsartan
LCZ 696
Enzyme Inhibitors
Angiotensinogen
Angiotensin II
Giapreza
Angiotensin-Converting Enzyme Inhibitors
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Vasoconstrictor Agents
Serine Proteinase Inhibitors
Protease Inhibitors