Short- and long-term treatment of dilutional hyponatraemia with satavaptan, a selective arginine vasopressin V2-receptor antagonist: the DILIPO study

Aims Arginine vasopressin (AVP) V2 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 V2‐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, V2 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