Hypertonic Saline Therapy in Ambulatory Heart Failure Unit.

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

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.

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Drug: Intravenous furosemide; Drug: Hypertonic saline solution plus intravenous furosemide

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 167
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08907
    • Hospital Universitari de Bellvitge
  • Barcelona, Spain, 08041
    • Hospital de la Santa Creu i Santa Pau (Fundación Privada Hospital de la Santa Creu i Sant Pau
  • Cáceres, Spain, 10003
    • Hospital San Pedro de Alcantara
  • Lérida, Spain, 25198
    • Hospital Universitario Arnau de Vilanova
  • Madrid, Spain, 28006
    • Hospital Universitario La Princesa
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28040
    • Hospital Clinico Universitario San Carlos
  • Madrid, Spain, 28041
    • Hospital Universitario Doce de Octubre
  • Málaga, Spain, 29010
    • Hospital Universitario Virgen de la Victoria
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
  • Valencia, Spain, 46014
    • Hospital General Universitario de Valencia
  • Zaragoza, Spain, 50009
    • Hospital Clínico Universitario Lozano de Blesa
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro
    • Móstoles, Madrid, Spain, 28933
      • Hospital Universitario Rey Juan Carlos

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intravenous furosemide	Drug: Intravenous furosemide; Intravenous 60-minutes infusion of furosemide: 125 mg if home oral furosemide ≤ 160 mg, 250 mg if home oral furosemide > 160 mg
Experimental: Hypertonic saline solution plus intravenous furosemide	Drug: Hypertonic saline solution plus intravenous furosemide; 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%

What is the study measuring?

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
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
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
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 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

Collaborators and Investigators

• Sponsor: Puerta de Hierro University Hospital
• Collaborators: Instituto de Salud Carlos III; Spanish Society of Cardiology
• Investigators: Principal Investigator: Marta Cobo Marcos, MD, Hospital Universitario Puerta de Hierro. Madrid. Spain

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Actual): May 10, 2023
• Study Completion (Actual): September 30, 2023

Study Registration Dates

• First Submitted: August 23, 2020
• First Submitted That Met QC Criteria: August 26, 2020
• First Posted (Actual): September 1, 2020

Study Record Updates

• Last Update Posted (Estimated): November 9, 2023
• Last Update Submitted That Met QC Criteria: November 7, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Hypertonic Saline Solution; Outpatient Heart Failure
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Furosemide
• Other Study ID Numbers: SALT-HF TRIAL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No