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Outpatient Hypertonic Saline and Loop Diuretic Combination Therapy in Cardiorenal

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

Status
Not yet recruiting
Phases
Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT07596329
Acronym
SALT-HF
Enrollment
60
Registered
2026-05-19
Start date
2026-09-01
Completion date
2027-12-30
Last updated
2026-07-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Heart Failure, Renal Disease, Chronic

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.

Interventions

DRUGHypertonic sodium chloride 10%

50 mL of 10% hypertonic sodium chloride (NaCl)

DRUGSodium Chloride 0.9%

50 mL of 0.9% sodium chloride (NaCl)

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

Sponsors

University of Monastir
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Caregiver)

Intervention model description

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.

Eligibility

Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
Number of participants rehospitalized for heart failure30 days and 60 daysDescription: Number of participants requiring rehospitalization for heart failure during follow-up.
All-cause mortality30 days and 60 daysDescription: Number of deaths from any cause during follow-up.

Secondary

MeasureTime frameDescription
Serum creatinine level30 days 60 daysEvaluation of serum creatinine levels.
Blood urea level30 days 60 daysEvaluation of blood urea levels.
BNP or NT-proBNP concentration30days 60 daysEvaluation of BNP or NT-proBNP levels.
Quality of life and patient satisfaction score assessed using a Likert scale30 days and 60 daysDescription: 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.

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Jul 16, 2026