Efficacy and Safety of Oral Conivaptan, a Vasopressin-Receptor Antagonist, Evaluated in a Randomized, Controlled Trial in Patients With Euvolemic or Hypervolemic Hyponatremia

Background: In most cases of hyponatremia, arginine vasopressin secretion is inappropriately high. This placebo-controlled, randomized, double-blind multicenter study evaluated the efficacy and safety of oral conivaptan, a V-1A/V-2-receptor antagonist, in patients with euvolemic or hypervolemic hyponatremia. Methods: Eighty-three patients with serum [Na+] less than 130 mEq/L were stratified by volume status and randomly assigned to placebo or conivaptan 40 or 80 mg/d for 5 days. Results: Conivaptan increased the baseline-adjusted area under the serum [Na+]-time curve significantly more than placebo (P = 0.0001). Patients given either dose of conivaptan demonstrated a serum [Na+] of 4 mEq/L or greater above baseline significantly faster than those given placebo (P < 0.001) and maintained that increase for a greater total time (P = 0.0001). The least squares mean change in serum [Na+] from baseline to end of treatment was also significantly greater with conivaptan 40 and 80 mg/d (6.8 and 8.8 mEq/L, respectively) (P = 0.0001) than that with placebo (1.2 mEq/L). The percentage of patients who obtained an increase from baseline in serum [Na+] of 6 mEq/L or greater or normal serum [Na+] was significantly higher among patients given conivaptan 40 and 80 mg/d (67% and 88%, respectively) than among those given placebo (20%; P < 0.001). Conivaptan was well tolerated; the most frequent adverse events were urinary tract infection, anemia, pyrexia, cardiac failure, hypotension, and hypokalemia. Conclusion: Oral conivaptan was effective in increasing serum [Na+] in patients with euvolemic or hypervolemic hyponatremia and had a favorable safety profile.