Assessment of the efficacy and safety of intravenous conivaptan in euvolemic and hypervolemic hyponatremia

Am J Nephrol. 2007;27(5):447-57. doi: 10.1159/000106456. Epub 2007 Jul 26.


Background: Most cases of hyponatremia--serum sodium concentration ([Na+]) < 135 mEq/l (< 135 mM)--are associated with an elevated plasma arginine vasopressin level. This study investigated the efficacy and tolerability of intravenous conivaptan (YM087), a vasopressin V1A/V2-receptor antagonist, in treating euvolemic and hypervolemic hyponatremia.

Methods: Eighty-four hospitalized patients with euvolemic or hypervolemic hyponatremia (serum [Na+] 115 to < 130 mEq/l) were randomly assigned to receive intravenous placebo or conivaptan administered as a 30-min, 20-mg loading dose followed by a 96-hour infusion of either 40 or 80 mg/day. The primary efficacy measure was change in serum [Na+], measured by the baseline-adjusted area under the [Na+]-time curve. The secondary measures included time from first dose to a confirmed > or = 4 mEq/l serum [Na+] increase, total time patients had serum [Na+] > or = 4 mEq/l higher than baseline, change in serum [Na+] from baseline to the end of treatment, and number of patients with a confirmed > or = 6 mEq/l increase in serum [Na+] or normal [Na+] (> or = 135 mEq/l).

Results: Both conivaptan doses increased area under the [Na+]-time curve during the 4-day treatment (p < 0.0001 vs. placebo). From baseline to the end of treatment, the least-squares mean +/- standard error serum [Na+] increase associated with placebo was 0.8 +/- 0.8 mEq/l; with conivaptan 40 mg/day, 6.3 +/- 0.7 mEq/l; and with conivaptan 80 mg/day, 9.4 +/- 0.8 mEq/l. Conivaptan significantly improved all secondary efficacy measures (p < 0.001 vs. placebo, both doses). Conivaptan was generally well tolerated, although infusion-site reactions led to the withdrawal of 1 (3%) and 4 (15%) of patients given conivaptan 40 and 80 mg/day, respectively.

Conclusion: Among patients with euvolemic or hypervolemic hyponatremia, 4-day intravenous infusion of conivaptan 40 mg/day significantly increased serum [Na+] and was well tolerated.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Antidiuretic Hormone Receptor Antagonists
  • Benzazepines / administration & dosage*
  • Benzazepines / adverse effects*
  • Benzazepines / therapeutic use
  • Blood Volume*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Hyponatremia / blood
  • Hyponatremia / drug therapy*
  • Hyponatremia / physiopathology*
  • Infusion Pumps
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Single-Blind Method
  • Sodium / blood
  • Time Factors
  • Treatment Outcome


  • Antidiuretic Hormone Receptor Antagonists
  • Benzazepines
  • conivaptan
  • Sodium