NATriuretic Response to Expansion and dIUretics in huMans With Heart Failure
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 229
- 试验地点
- 13
- 主要终点
- Natriuretic response to intravascular volume expansion
研究概览
简要总结
NATRIUM-HF is a multicenter, non-randomized, pre-post intervention study designed to assess renal response to intravascular fluid expansion and diuretics after sacubitril/valsartan (Entresto®) in euvolemic heart failure patients with reduced ejection fraction. Approximately 230 eligible patients will attend one visit prior to and visits 2 and 3 months after starting Entresto®. At each visit, the patient's responses to extravascular fluid expansion with Ringer's solution and to a loop diuretic bolus will be measured. Biomarkers measured in blood and urine samples will include natriuretic peptides (NP) B-type NP (BNP) and N-terminal proBNP (NT-proBNP), NP fragments, neprilysin activity and concentration, and other biomarkers related to heart failure.
详细描述
NATRIUM-HF is a multicenter, non-randomized, pre-post intervention study designed to assess renal response to intravascular fluid expansion and diuretics after sacubitril/valsartan (Entresto®) in euvolemic heart failure patients with reduced ejection fraction.
Ambulatory patients with HFrEF who remain symptomatic despite optimal treatment for more than 3 months with an ACEi or ARB, a beta-blocker and a mineralocorticoid receptor antagonist (MRA) for whom sacubitril/valsartan is indicated and is about to be initiated will be enrolled. Approximately 230 patients will attend three outpatient visits: before, and 2 months and 3 months after initiation of, or switch from treatment with angiotensin-converting-enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB) to, oral treatment with the angiotensin receptor-neprilysin inhibitor (ARNi) sacubitril/valsartan (Entresto®). Patient's responses to fluid expansion and diuretic administration will be assessed at each study visit.
The same procedures will be followed at each visit. First, baseline vital signs, clinical assessments (dyspnea score, jugular vein distension, peripheral edema score, pulmonary rales), and blood samples will be obtained. Urine will be collected over a period of 3 hours and urine samples will be obtained from the collected urine at the end of the 3-hour collection period, and vital signs and clinical assessments will be obtained.
This will be followed by an infusion of 0.5 liter Ringer's (8.6 g/L sodium chloride, 0.33 g/L calcium chloride, 0.3 g/L potassium chloride) solution infused in 10 min followed by an infusion of 0.5 liter over 1 hour 50 minutes. Of note 1liter Ringer's contains 8.6 g or 374 mmol of sodium. 1 hour after the end of the infusion, clinical assessments (dyspnea score, jugular vein distension, peripheral edema score, pulmonary rales) and blood samples will be obtained. Urine will be collected over a period of 3 hours and urine samples will be obtained from the collected urine at the end of the 3-hour collection period.
After the second set of blood and urine samples are obtained, 40 mg of furosemide will be given IV and blood samples will be obtained thereafter hourly for 3 hours. Urine will be collected over a period of 3 hours and urine samples will be obtained from the collected urine at the end of the 3-hour collection period, and vital signs and clinical assessments will be obtained.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Fluid Expansion and Diuretic Challenge
Subject receive intravenous infusion of Ringer's (8.6 g/L sodium chloride, 0.33 g/L calcium chloride, 0.3 g/L potassium chloride) solution, followed by diuretic challenge with 40mg Furosemide intravenous bolus.
干预措施: Ringer's (8.6 g/L sodium chloride, 0.33 g/L calcium chloride, 0.3 g/L potassium chloride) Solution (Drug)
Fluid Expansion and Diuretic Challenge
Subject receive intravenous infusion of Ringer's (8.6 g/L sodium chloride, 0.33 g/L calcium chloride, 0.3 g/L potassium chloride) solution, followed by diuretic challenge with 40mg Furosemide intravenous bolus.
干预措施: Intravenous Bolus Furosemide (Drug)
结局指标
主要结局
Natriuretic response to intravascular volume expansion
时间窗: 2 and 3 months
The average change in natriuretic response to intravascular volume expansion from before to 2 and 3 months after initiation of sacubitril/valsartan therapy. Natriuretic response is defined as the cumulative sodium excretion over the 3 hours of intravascular volume expansion and follow up.
Natriuretic response to IV diuretic administration
时间窗: 2 and 3 months
The average change in cumulative natriuresis during the first 3 h following the bolus IV furosemide administration from before to 2 and 3 months after initiation of sacubitril/valsartan therapy.
次要结局
- 4. Changes in dyspnea as measured by a 1-10 scale in response to intravascular fluid expansion, and diuretic administration(2 and 3 months)
- Natriuretic peptide (NP) response to intravascular volume expansion(2 and 3 months)
- Natriuretic peptide response to IV diuretic administration(2 and 3 months)
- Diuretic response(2 and 3 months)