Hypertonic Saline Therapy in Ambulatory Heart Failure Unit.

Study Overview
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Brief Summary
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The purpose of this study is to compare intravenous furosemide (125 to 250 mg), isolated or in combination with hypertonic saline solution (2.6% to 3.4%) in the outpatient heart failure patient. The hypothesis is that the combination therapy will increase the diuresis volume at 3 hours and improve congestion parameters at 7 days.

Detailed Description
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This is a randomized, double-blind, multicenter study of all consecutive patients with decompensated heart failure and signs of volume overload who do not require hospital admission but require intravenous diuretic for relief of congestion. Patients meeting the inclusion criteria, with prior informed consent, will be randomized to treatment with furosemide with hypertonic saline versus isolated furosemide (control group). Complete clinical evaluation, echocardiography, and blood and urinary tests will be performed before the treatment. After 3 hours, diuresis volume, weight and urinary parameters will be evaluated. Efficacy and safety visits will be performed at 7 and 30 days.

Official Title
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Efficacy and Safety of Ambulatory Hypertonic Saline Therapy in Outpatient Heart Failure Units.

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: Hypertonic saline solution plus intravenous furosemide
* Drug: Intravenous furosemide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previous heart failure diagnosis (according to current European Guidelines) Stable treatment in the previous 4 weeks (except diuretic). Home oral treatment of ≥80 mg of furosemide/day or equivalent (40 mg furosemide = 20 mg of torasemide). Transthoracic echocardiogram performed in the last year. Congestive signs.The presence of two of the following congestion criteria will be required: jugular pressure> 10 cm, lower limb edema, ascites, or pleural effusion Elevation of natriuretic peptides (NTproBNP> 1000 pg / mL or B-type natriuretic peptide> 250 pg / ml) performed in a previous period of no more than 24 hours. Need for intravenous diuretic therapy to relieve congestion according to the responsible physician. Exclusion Criteria: Hospital admission criteria in the opinion of the responsible physician. Systolic blood pressure <90 mmHg or> 180 mmHg. Heart rate> 150 bpm or < 40 bpm Basal oxygen saturation less than 90%. Cardiogenic shock. Acute Pulmonary Edema. Clinically significant arrhythmia. Acute myocardial ischemia. Patients in hemodialysis or peritoneal dialysis program. Serum sodium <125 milliequivalent / L or> 145 milliequivalent / L. Serum potassium < 3.5 milliequivalent/ L. Hemoglobin < 9 g / dL Acute coronary syndrome or cardiological procedure in the previous 2 weeks. Severe uncorrected valve disease except tricuspid regurgitation. Moderate or severe dementia, active delirium or psychiatric problems. Patients in whom cardiac surgery or device implantation is planned in the following 30 days. Pregnancy or breastfeeding. Inability to give informed consent in the absence of a legal officer. Patients on tolvaptan. Inability to collect the urine.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomization 1:1 to treatment with a 1-hour infusion of IV furosemide plus HSS (2.6-3.4% NaCl depending on plasmatic sodium levels) versus a 1-hour infusion of IV furosemide at the same dose (125-250 mg, depending on basal loop diuretic dose).
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intravenous furosemide<br> | Drug: Intravenous furosemide<br>* Intravenous 60-minutes infusion of furosemide: 125 mg if home oral furosemide ≤ 160 mg, 250 mg if home oral furosemide > 160 mg<br>|
| Experimental: Hypertonic saline solution plus intravenous furosemide<br> | Drug: Hypertonic saline solution plus intravenous furosemide<br>* Intravenous 60-minutes of hypertonic saline therapy plus furosemide: Furosemide: 125 mg if home oral furosemide ≤160 mg, 250 mg if home oral furosemide > 160 mg Hypertonic saline solution: Na+ 125-134: 3.4%, Na+ 135-145: 2.6%<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diuresis volume (ml) | Total diuresis volume after 3 hours of therapy administration | 3 hours after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight difference (kg) | Difference of weight 3 hours after the start of treatment | 3 hours | 
| Weight difference (kg) | Difference of weight 7 days after the start of treatment | 7 days | 
| Change in composite congestion score | Composite of orthopnoea (0-3), jugular venous distension (0-3), lower limb oedema (0-3). Higher score: worse congestion | 7 days | 
| Change in Inferior cava vein diameter (mm) | Change in Inferior cava vein diameter (mm) 7 days after treatment | 7 days | 
| Change in Number of fields with more than 3 B-lines in lung ultrasound | Change in Number of fields with more than 3 B-lines in lung ultrasound 7 days after treatment | 7 days | 
| Change in New York Heart Association and Visual Analogue Scale | Visual Analogue Scale from 0 (worst state of health) to 100 (best state of health) | 7 days | 
| Change in NTproBNP and Cancer Antigen 125 levels | Change in NTproBNP and Cancer Antigen 125 levels 7 days after treatment | 7 days | 
| Change in Hemoconcentration Parameters | Hematocrit, Albumin and total Proteins | 7 days | 
| Change in Urinary Sodium | Change in Urinary Sodium measured in a spot urinary sample | 7 days | 
| Adverse Events | Need of new intravenous diuretic (outpatient clinic or emergency department). Heart Failure hospitalization. Cardiovascular mortality. All-Cause mortality or hospitalization. Worsening of kidney function: defined as an increase in creatinine ≥ 0.3 mg / dl. Electrolyte abnormalities defined as hypokalemia (K+ less than 3.5 milliequivalent / L) or hyperkalemia (K+ greater than 5.5 milliequivalent /L) | 7 days | 
| Adverse Events | Need of new intravenous diuretic (outpatient clinic or emergency department). Heart Failure hospitalization. Cardiovascular mortality. All-Cause mortality or hospitalization. | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertonic Saline Solution, Outpatient Heart Failure