Outpatient Hypertonic Saline and Loop Diuretic Combination Therapy in Cardiorenal

Official title

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

Overview

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

• Drug Hypertonic sodium chloride 10%
  50 mL of 10% hypertonic sodium chloride (NaCl)
• Drug Sodium Chloride 0.9%
  50 mL of 0.9% sodium chloride (NaCl)
• Drug Furosemide intravenous solution
  Furosemide 250 mg administered intravenously over 60 minutes once weekly for 2 months.

Primary outcome measures

• Number of participants rehospitalized for heart failure [Time frame: 30 days and 60 days]
• All-cause mortality [Time frame: 30 days and 60 days]

Secondary outcome measures (4)

• Serum creatinine level [Time frame: 30 days 60 days]
• Blood urea level [Time frame: 30 days 60 days]
• BNP or NT-proBNP concentration [Time frame: 30days 60 days]
• Quality of life and patient satisfaction score assessed using a Likert scale [Time frame: 30 days and 60 days]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07596329 · SALT-HF study

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗