NATriuretic Response to Expansion and dIUretics in huMans With Heart Failure
- Conditions
- Heart Failure
- Interventions
- Drug: Ringer's (8.6 g/L sodium chloride, 0.33 g/L calcium chloride, 0.3 g/L potassium chloride) Solution
- Registration Number
- NCT04235062
- Lead Sponsor
- Momentum Research, Inc.
- Brief 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 229
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Fluid Expansion and Diuretic Challenge Ringer's (8.6 g/L sodium chloride, 0.33 g/L calcium chloride, 0.3 g/L potassium chloride) Solution 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. Fluid Expansion and Diuretic Challenge Intravenous Bolus Furosemide 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.
- Primary Outcome Measures
Name Time Method Natriuretic response to intravascular volume expansion 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 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.
- Secondary Outcome Measures
Name Time Method Natriuretic peptide response to IV diuretic administration 2 and 3 months Change from before to 2 and 3 months after initiation of sacubitril/valsartan therapy in the average change in NP level from the end of the Ringer's infusion to 3 hours following the bolus IV furosemide administration
4. Changes in dyspnea as measured by a 1-10 scale in response to intravascular fluid expansion, and diuretic administration 2 and 3 months Change from before to 2 and 3 months after initiation of sacubitril/valsartan therapy in the average change from just prior to the Ringer's infusion start to one hour following the 2-hour Ringer's infusion and from just prior to the IV bolus furosemide administration to 3 hours following the bolus IV furosemide administration
Diuretic response 2 and 3 months Change from before to 2 and 3 months after initiation of sacubitril/valsartan therapy in the urine volume excreted over the 3 hours following the bolus IV furosemide administration
Natriuretic peptide (NP) response to intravascular volume expansion 2 and 3 months Change from from before to 2 and 3 months after initiation of sacubitril/valsartan therapy in the average change over the 2-hour Ringer's infusion and follow up in plasma NP levels from just prior to the start of the infusion.
Trial Locations
- Locations (13)
University Clinical Center Republic of Srpska, Banja Luka Department of Cardiology
🇧🇦Banja Luka, Bosnia and Herzegovina
Erebouni Medical Center CJSC
🇦🇲Yerevan, Armenia
Institute of Cardiology named after L.A. Hovhannisyan
🇦🇲Yerevan, Armenia
Nairi Medical Center
🇦🇲Yerevan, Armenia
Yerevan State Medical University
🇦🇲Yerevan, Armenia
Moscow State Budgetary Institution of Healthcare of Moscow "City Clinical Hospital named after V.V. Vinogradov of the Department of Healthcare of Moscow"
🇷🇺Moscow, Russian Federation
University Clinical Center Mostar
🇧🇦Mostar, Bosnia and Herzegovina
Regional budget Healthcare Institution "Cardiological dispensary"
🇷🇺Ivanovo, Russian Federation
State Budgetary Healthcare Institution of Moscow "City clinical hospital #51 of the Department of Healthcare of Moscow"
🇷🇺Moscow, Russian Federation
State Budgetary Healthcare Institution of Moscow "Moscow City Clinical Hospital named after V.M. Buyanov" of the Department of Healthcare of Moscow"
🇷🇺Moscow, Russian Federation
State Budgetary Healthcare Institution of Moscow "City Clinical Hospital named after V.V. Veresaev of the Department of Healthcare of Moscow"
🇷🇺Moscow, Russian Federation
State Budgetary Healthcare Institution of Vladimir region "Vladimir City Hospital # 4"
🇷🇺Vladimir, Russian Federation
MedFort LLC
🇷🇺Saint Petersburg, Russian Federation