Aims: Arginine vasopressin (AVP) V(2) receptor antagonism is a new approach to the management of hyponatraemia in congestive heart failure (CHF). The aim of this study was to investigate the efficacy and safety of satavaptan, an oral AVP V(2)-receptor antagonist, in patients with dilutional hyponatraemia.
Methods and results: A total of 118 patients (90 with CHF) with dilutional hyponatraemia (serum sodium 115-132 mmol/L) were randomized to double-blind treatment with placebo or to 25 or 50 mg/day of satavaptan for 4 days, followed by non-comparative open-label satavaptan therapy for up to 343 days. The response rate (sodium ≥ 135 mmol/L and/or an increase in ≥ 5 mmol/L above baseline) was significantly higher with satavaptan 50 mg than with placebo (61.0 vs. 26.8%; P= 0.0035), with a trend towards significance with satavaptan 25 mg (48.6%, P= 0.0599). Median times to response were 3.30 and 2.79 days with satavaptan 25 and 50 mg/day, respectively, both shorter than placebo (>4 days; P= 0.0278 and P= 0.0004, respectively). Satavaptan therapy was effective in CHF patients, with response rates higher with both satavaptan 25 mg/day (53.6%) and 50 mg/day (57.1%) than with placebo (23.5%; P= 0.019 and P= 0.009, respectively). Sodium responses were maintained during open-label therapy after a temporary study drug discontinuation period. Higher rates of adverse events occurred with the 50 mg/day dose, including rapid correction of hyponatraemia.
Conclusions: In patients with dilutional hyponatraemia, V(2) receptor antagonism with satavaptan was effective in increasing serum sodium concentrations. The long-term open-label treatment results demonstrate sustained efficacy of satavaptan in maintaining normal sodium levels. Trial Registration clinicaltrials.gov Identifier: NCT00274326.