Tolvaptan vs Fluid Restriction in Moderate-Profound Hyponatremia: An Open-Label Randomized Clinical Trial.
In an open-label randomized trial of hospitalized patients with moderate-to-profound hyponatremia, tolvaptan raised plasma sodium faster than fluid restriction over 3 days, but a substantial minority needed dextrose 5% to prevent overcorrection and there was no benefit in symptoms or length of stay.
Background
Fluid restriction is the standard first-line therapy for hyponatremia but is frequently ineffective. The vasopressin V2-receptor antagonist tolvaptan is more effective at raising sodium, yet fears of overcorrection have limited its use. This trial paired tolvaptan with a prespecified dextrose-5% rescue protocol to test efficacy while guarding against overcorrection.
Study design
Single-center, open-label randomized trial at a tertiary hospital. Fifty-four hospitalized patients with plasma sodium 115–130 mmol/L (mean 124) were randomized 1:1 to oral tolvaptan 7.5 mg daily or fluid restriction <1000 mL/day for 3 days, with daily titration to sodium response. The primary outcome was the change in plasma sodium from day 1 to day 4.
Key findings
Plasma sodium rose significantly more with tolvaptan (overall P<0.001); the adjusted between-group difference was 3.5 mmol/L at day 3 and 2.5 mmol/L at day 4. Five tolvaptan recipients (19%) required dextrose 5% to treat a rapid sodium increase — with this rescue, no patient exceeded a 10 mmol/L rise at 24 hours. There was no difference in length of stay or symptoms.
Clinical implications
Tolvaptan corrects hyponatremia faster than fluid restriction, but the need for rescue dextrose in nearly one in five patients and the lack of symptomatic or length-of-stay benefit underscore that it requires close sodium monitoring. The study provides the first prospectively validated protocol to detect and prevent tolvaptan-related overcorrection.
Category
Research
Source
Journal of Clinical Endocrinology & Metabolism
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