Outpatient Hypertonic Saline and Loop Diuretic Combination Therapy in Cardiorenal

NCT07596329 | Not Yet Recruiting Phase 3

• 1 other identifier: SALT-HF study
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Heart Failure; Renal Disease, Chronic

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Serum creatinine level

  30 days 60 days

• Blood urea level

  30 days 60 days

• BNP or NT-proBNP concentration

  30days 60 days

• Quality of life and patient satisfaction score assessed using a Likert scale

  30 days and 60 days

Study Arms (2)

HSS group

EXPERIMENTAL

* 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%; Drug: Furosemide intravenous solution

placebo group

PLACEBO COMPARATOR

* 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: Sodium Chloride 0.9%; Drug: Furosemide intravenous solution

Interventions

Hypertonic sodium chloride 10% DRUG

50 mL of 10% hypertonic sodium chloride (NaCl)

HSS group

Sodium Chloride 0.9% DRUG

50 mL of 0.9% sodium chloride (NaCl)

placebo group

Furosemide intravenous solution DRUG

Furosemide 250 mg administered intravenously over 60 minutes once weekly for 2 months.

HSS group; placebo group

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Monastir: lead

MeSH Terms

Conditions

Heart Failure; Renal Insufficiency, Chronic

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Participants will be randomized into two parallel groups. The HSS group will receive 50 mL of 10% hypertonic sodium chloride (NaCl) combined with 250 mg of furosemide administered as a slow intravenous infusion over 60 minutes, once weekly for 2 months. The placebo group will receive 50 mL of 0.9% sodium chloride (NaCl) combined with 250 mg of furosemide administered as a slow intravenous infusion over 60 minutes, once weekly for 2 months.

Study Record Dates

• First Submitted: February 24, 2026
• First Posted: May 19, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: May 19, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share