Tolvaptan vs Fluid Restriction in Moderate-Profound Hyponatremia: An Open-Label Randomized Clinical Trial.

Area of Science:

• Nephrology
• Endocrinology
• Internal Medicine

Background:

• Fluid restriction (FR) is the standard first-line therapy for hyponatremia but often proves ineffective.
• Tolvaptan, a vasopressin V2-receptor antagonist, offers an effective treatment for hyponatremia.
• Concerns regarding the risk of plasma sodium (pNa) overcorrection have limited the widespread adoption of tolvaptan.

Purpose of the Study:

• To compare the efficacy of tolvaptan against fluid restriction (FR) in treating hyponatremia.
• To evaluate a pre-specified protocol for dextrose 5% intervention to manage potential sodium overcorrection during tolvaptan therapy.

Main Methods:

• An open-label, randomized controlled trial was conducted.
• 54 hospitalized patients with syndrome of inappropriate antidiuresis (SIAD) and pNa 115-130 mmol/L were enrolled.
• Participants received either tolvaptan (7.5mg daily) or FR (<1000ml/day) for 3 days, with daily titration based on pNa response.

Main Results:

• Tolvaptan treatment resulted in a significantly greater increase in plasma sodium compared to FR over 3 days (p<0.001).
• The mean adjusted difference in pNa between groups ranged from 2.5 to 3.5 mmol/L from Day 2 to Day 4.
• Nineteen percent of tolvaptan recipients required IV dextrose 5% to manage rapid sodium rise, successfully preventing overcorrection (>10mmol/L at 24 hours).

Conclusions:

• Tolvaptan demonstrates superior efficacy in increasing plasma sodium levels over 3 days compared to fluid restriction.
• A dextrose intervention protocol is effective in preventing and treating tolvaptan-associated sodium overcorrection.
• Despite improved sodium correction, tolvaptan did not show benefits in secondary outcomes like length of stay or symptom improvement.