NATriuretic Response to Expansion and dIUretics in huMans With Heart Failure
Condition: Heart Failure
MeSH terms: Heart Failure
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.

      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.

      The aim of NATRIUM-HF is to assess the change in natriuretic response to intravascular fluid
      expansion and diuretics in euvolemic patients with heart failure and reduced ejection
      fraction (HFrEF) after initiation of, or switch from ACEi/ARB to, sacubitril/valsartan
      (Entresto®) therapy.
    

Intervention name(s): Ringer's (8.6 g/L sodium chloride, 0.33 g/L calcium chloride, 0.3 g/L potassium chloride) Solution; Intravenous Bolus Furosemide
Intervention type(s): Drug; Drug
Intervention description(s): A 2-hour of infusion of Ringer's (8.6 g/L sodium chloride, 0.33 g/L calcium chloride, 0.3 g/L potassium chloride) solution will be given following completion of the first 3-hour urine collection period: 0.5 liter infused over 10 min followed by 0.5 liter infused over 1 hour 50 minutes.; Following completion of the second 3-hour urine collection period and after the second set of blood and urine samples are obtained, 40 mg of furosemide will be given as an IV bolus.
Other intervention name(s): Intravascular fluid expansion; Loop diuretic administration
Intervention MeSH terms: Furosemide; Calcium; Diuretics; Sodium Potassium Chloride Symporter Inhibitors
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science