Outpatient Hypertonic Saline and Loop Diuretic Combination Therapy in Cardiorenal (SALT-HF)

Outpatient Hypertonic Saline and Loop Diuretic Combination Therapy in Cardiorenal Syndrome: The SALT-HF Randomized Double-Blind Trial

Congestive heart failure (CHF) remains a major cause of morbidity, rehospitalization, and mortality worldwide, particularly among elderly and polymorbid patients. Systemic congestion is its most characteristic clinical manifestation and the leading cause of hospitalization for acute heart failure. Standard treatment relies on loop diuretics, primarily furosemide, to reduce fluid overload and alleviate congestive symptoms. However, in clinical practice, many patients exhibit an inadequate diuretic response or resistance to furosemide, particularly in the context of cardiorenal syndrome (CRS), where cardiac and renal dysfunction mutually exacerbate each other. This profile, frequently observed in advanced stages of heart failure, significantly limits the effectiveness of guideline-directed medical therapies (GDMTs), particularly SGLT2 inhibitors, mineralocorticoid receptor antagonists, and angiotensin-converting enzyme (ACE) inhibitors, whose use is often restricted by hypotension, hyperkalemia, or impaired renal function.

Thus, in this subgroup of patients, conventional pharmacological approaches encounter a therapeutic barrier, necessitating the search for alternative or complementary strategies targeting sodium and water depletion without compromising renal perfusion. In this context, the combined administration of hypertonic saline (HS) and furosemide has been proposed as a pathophysiologically sound approach to break the vicious cycle of cardiorenal syndrome. Hypertonic saline solution (HSS) acts by restoring effective intravascular volume, improving renal perfusion, and promoting more efficient natriuresis through better furosemide delivery to the distal nephron. Pioneering studies by Paterna et al. showed that the concomitant administration of HSS (1.4-3% NaCl, 150-250 mL) and intravenous furosemide increased diuresis, improved the hemodynamic profile, and reduced the length of hospital stay and readmission rates without deterioration of renal function.

Study Overview

• Status: Not yet recruiting
• Conditions: Heart Failure; Renal Disease, Chronic
• Intervention / Treatment: Drug: Hypertonic sodium chloride 10%; Drug: Furosemide intravenous solution; Drug: Sodium Chloride 0.9%

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years
• Chronic renal insufficiency (serum creatinine > 150 µg/ml)
• Diagnosis of heart failure (preserved or reduced LVEF)
• Signed informed consent

Exclusion Criteria:

• Severe hyponatremia (<130 mmol/L) or hypernatremia (>150 mmol/L),
• History of allergic reaction to HSS or furosemide
• Shock or hemodynamic instability
• Pregnancy or breastfeeding
• Chronic dialysis treatment
• Patient refusal or withdrawal of consent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HSS group; 50 mL of 10% hypertonic sodium chloride (NaCl) administered intravenously over 60 minutes once weekly for 2 months.; Furosemide 250 mg administered intravenously over 60 minutes once weekly for 2 months.	Drug: Hypertonic sodium chloride 10%; 50 mL of 10% hypertonic sodium chloride (NaCl); Drug: Furosemide intravenous solution; Furosemide 250 mg administered intravenously over 60 minutes once weekly for 2 months.
Placebo Comparator: placebo group; 50 mL of 0.9% sodium chloride (NaCl) administered intravenously over 60 minutes once weekly for 2 months.; Furosemide 250 mg administered intravenously over 60 minutes once weekly for 2 months.	Drug: Furosemide intravenous solution; Furosemide 250 mg administered intravenously over 60 minutes once weekly for 2 months.; Drug: Sodium Chloride 0.9%; 50 mL of 0.9% sodium chloride (NaCl)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants rehospitalized for heart failure	Description: Number of participants requiring rehospitalization for heart failure during follow-up.	30 days and 60 days
All-cause mortality	Description: Number of deaths from any cause during follow-up.	30 days and 60 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum creatinine level	Evaluation of serum creatinine levels.	30 days 60 days
Blood urea level	Evaluation of blood urea levels.	30 days 60 days
BNP or NT-proBNP concentration	Evaluation of BNP or NT-proBNP levels.	30days 60 days
Quality of life and patient satisfaction score assessed using a Likert scale	Description: Assessment of quality of life and patient satisfaction using a 5-point Likert scale ranging from 1 to 5, where: 1 = very dissatisfied/very poor quality of life 5 = very satisfied/excellent quality of life Higher scores indicate better patient satisfaction and quality of life.	30 days and 60 days

Collaborators and Investigators

• Sponsor: University of Monastir

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: February 24, 2026
• First Submitted That Met QC Criteria: May 18, 2026
• First Posted (Actual): May 19, 2026

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Cardiovascular Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Heart Diseases; Chronic Disease; Disease Attributes; Renal Insufficiency; Pathological Conditions, Signs and Symptoms; Heart Failure; Renal Insufficiency, Chronic; Inorganic Chemicals; Chlorine Compounds; Sodium Compounds; Chlorides; Hydrochloric Acid; Sodium Chloride
• Other Study ID Numbers: SALT-HF study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: PD will not be shared due to concerns related to patient confidentiality and data privacy

Drug and device information, study documents

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