Therapy of hyponatremia in cirrhosis with a vasopressin receptor antagonist: a randomized double-blind multicenter trial

Gastroenterology. 2003 Apr;124(4):933-9. doi: 10.1053/gast.2003.50143.


Background & aims: Dilutional hyponatremia is a frequent complication of cirrhosis partly because of nonosmotic vasopressin release. No effective therapy exists for this complication. Therefore, we investigated the effects of VPA-985, an orally active vasopressin V2 receptor antagonist, in patients with cirrhosis and dilutional hyponatremia. Primary endpoint was normalization of serum sodium (serum sodium >or=136 mmol/L).

Methods: Sixty patients with cirrhosis and dilutional hyponatremia were randomly assigned to 100 or 200 mg/day of VPA-985 or placebo in a double-blind study. Treatment was given with fluid restriction (1000 mL/day) until normalization of serum sodium or for 7 days.

Results: Normalization of serum sodium concentration was achieved in 27% and 50% of patients in the VPA-985 100 mg/day and 200 mg/day groups, respectively, but in none of the patients in the placebo group (P < 0.05 and P < 0.001, respectively). Treatment with VPA-985 was associated with a significant reduction in urine osmolality and body weight. Thirst sensation increased significantly in the VPA 200 mg group but not in the VPA 100 mg or placebo group. Serious adverse events were similar among the 3 groups.

Conclusions: An orally active vasopressin receptor antagonist can correct hyponatremia in patients with cirrhosis and ascites. This represents a novel therapy of water retention in cirrhosis.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antidiuretic Hormone Receptor Antagonists
  • Ascites / complications
  • Ascites / metabolism
  • Azepines / administration & dosage*
  • Azepines / adverse effects
  • Benzamides / administration & dosage*
  • Benzamides / adverse effects
  • Blood Pressure / drug effects
  • Double-Blind Method
  • Female
  • Glomerular Filtration Rate / drug effects
  • Humans
  • Hyponatremia / drug therapy*
  • Hyponatremia / etiology*
  • Hyponatremia / metabolism
  • Kidney / metabolism
  • Liver Cirrhosis / complications*
  • Liver Cirrhosis / metabolism
  • Male
  • Middle Aged
  • Pyrroles
  • Sodium / blood
  • Treatment Outcome
  • Water / metabolism


  • Antidiuretic Hormone Receptor Antagonists
  • Azepines
  • Benzamides
  • Pyrroles
  • Water
  • lixivaptan
  • Sodium