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
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Evaluation of sympathetic nervous system activity as assessed by microneurography recording recording of sympathetic activity in muscle destiny
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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)
干预措施: valsartan/sacubitril 100 mg (Drug)
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)
干预措施: valsartan/sacubitril 200 mg (Drug)
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)
干预措施: Microneurography (Procedure)
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
干预措施: Microneurography (Procedure)
结局指标
主要结局
Evaluation of sympathetic nervous system activity as assessed by microneurography recording recording of sympathetic activity in muscle destiny
时间窗: Up to 8 weeks
Evaluation of sympathetic nervous system activity in burst/minute
次要结局
- 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)
- Evaluation of severity of heart failure(Up to 8 weeks)