NCT07528365

Urea for Treatment of Hyponatremia in Patients With SIAD Unresponsive to Fluid Restriction

Efficacy of Oral Urea Supplementation in Patients With SIAD Not Adequately Controlled With Fluid Restriction

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: University of Turin, Italy · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Hyponatremia due to SIAD is frequently insufficiently corrected by fluid restriction alone, which remains the first-line therapy but is often poorly tolerated. Urea supplementation is recommended as second-line therapy. This prospective study evaluates the effectiveness of oral urea supplementation in patients with chronic SIAD and persistent hyponatremia despite fluid restriction.

Detailed description

Hyponatremia (serum sodium, s-Na \<135 mmol/L) is the most common electrolyte disorder in hospitalized patients, with prevalence increasing with length of hospital stay. Among hypotonic euvolemic hyponatremias, the syndrome of inappropriate antidiuresis (SIAD) is the most frequent cause and is characterized by impaired free water excretion. SIAD may result from central nervous system disorders, pulmonary diseases, malignancies, or medications, and remains a diagnosis of exclusion. When possible, treating the underlying cause can resolve the syndrome; however, in many cases the cause remains unknown and therapeutic options are limited. First-line treatment is fluid restriction, which is often insufficient and difficult to maintain in the long term. AVP receptor antagonists, such as tolvaptan, are effective but expensive and may carry a risk of overly rapid correction of serum sodium. Second-line therapy recommended by current guidelines is urea supplementation, which has shown safety and efficacy in normalizing serum sodium. However, most available evidence derives from retrospective studies, and prospective data are limited. This study aims to evaluate the effectiveness of urea supplementation in patients with chronic, mildly symptomatic SIAD-related hyponatremia not adequately controlled by fluid restriction (≤1500 mL/day), and to explore its effects on neuroendocrine adaptation, body fluid composition, and bone metabolism.

Conditions

• SIAD - Syndrome of Inappropriate Antidiuresis

Interventions

Type	Name	Description
DIETARY_SUPPLEMENT	urea	Patients with persistent hyponatremia (sodium corrected for glucose \<135 mmol/L) after ≥1 week of fluid restriction (≤1500 mL/day) will receive urea 30 g/day (2 sachets; 1 in the morning and 1 in the evening) dissolved in water, while maintaining fluid restriction ≤1500 mL/day. Blood and urine evaluations will be performed at day 1, day 21±4 and day 42±4, with additional assessments (Montreal Cognitive Assessment \[MoCA\] questionnaire and bioelectrical impedance vector analysis \[BIVA\]) at selected visits. Urea dose adjustments will be based on serum sodium at day 21±4: 45 g/day if Na 130-134 mmol/L, or 60 g/day if Na \<130 mmol/L (maximum 60 g/day). In case of intolerance, the dose will be reduced by one sachet from the planned dose. After day 42±4, urea will be discontinued. A final evaluation will be performed 10±2 days after discontinuation.

Timeline

• Start date: 2024-09-12
• Primary completion: 2027-11-01
• Completion: 2027-12-01
• First posted: 2026-04-14
• Last updated: 2026-04-14

Locations

1 site across 1 country: Italy