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

• ClinicalTrials.gov Identifier: NCT02787798
• Recruitment Status: Terminated
• First Posted: June 1, 2016
• Last Update Posted: February 7, 2019
• Sponsor: University Hospital, Toulouse
• Information provided by (Responsible Party): University Hospital, Toulouse

Tracking Information

• First Submitted Date: May 26, 2016
• First Posted Date: June 1, 2016
• Last Update Posted Date: February 7, 2019
• Actual Study Start Date: October 2016
• Actual Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 26, 2016)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 25, 2017)

• Evaluation of severity of heart failure [ Time Frame: Day 0 ]
  assessed by New York Heart Association stage
• Evaluation of severity of heart failure [ Time Frame: Day 2 ]
  assessed by New York Heart Association stage
• Evaluation of severity of heart failure [ Time Frame: Up to 4 weeks ]
  assessed by New York Heart Association stage
• Evaluation of severity of heart failure [ Time Frame: Up to 8 weeks ]
  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 [ Time Frame: Day 0 and up to 8 weeks ]
  pro-brain natriuretic peptide serum levels

Original Secondary Outcome Measures (submitted: May 26, 2016)

• Evaluation of severity of heart failure as assessed by New York Heart Association stage [ Time Frame: Day 0 ]
• Evaluation of severity of heart failure as assessed by New York Heart Association stage [ Time Frame: Day 2 ]
• Evaluation of severity of heart failure as assessed by New York Heart Association stage [ Time Frame: Up to 4 weeks ]
• Evaluation of severity of heart failure as assessed by New York Heart Association stage [ Time Frame: Up to 8 weeks ]
• 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 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Evaluation of the Entresto Effect on Sympathic Nervous System in Patient With Heart Failure
• 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment
• Condition: Heart Failure

Intervention

• 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

Study Arms

• 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)
  Interventions:

  • Drug: valsartan/sacubitril 100 mg
  • Drug: valsartan/sacubitril 200 mg
  • Procedure: Microneurography
• 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
  Intervention: Procedure: Microneurography

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: February 5, 2019): 4
• Original Estimated Enrollment (submitted: May 26, 2016): 50
• Actual Study Completion Date: January 2018
• Actual Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT02787798
• Other Study ID Numbers: RC31/15/7746
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: University Hospital, Toulouse
• Study Sponsor: University Hospital, Toulouse
• Collaborators: Not Provided

Investigators

• Principal Investigator: Michel Galinier, MD; CHU Toulouse

• PRS Account: University Hospital, Toulouse
• Verification Date: February 2019