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 V1A/V2-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.


CONCLUSIONS
Oral conivaptan was effective in increasing serum [Na] in patients with euvolemic or hypervolemic hyponatremia and had a favorable safety profile.
Annane
Djillali
D
Department of General Critical Care Medicine/Division of Acute Medicine and Surgery, University of Versailles SQY Raymond Poincaré Hospital, Garches, France. djillali.annane@rpc.aphp.fr
Decaux
Guy
G
Smith
Neila
N
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007010:Hyponatremia / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012964:Sodium / Q000097:blood
D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; C106389:conivaptan; D012964:Sodium