title: Therapy of hyponatremia in cirrhosis with a vasopressin receptor antagonist: a randomized double-blind multicenter trial.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Medicine II, Klinikum Grosshadern, University of Munich, Germany.
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Gerbes
authors.forename: Veit
authors.initials: V
authors.lastname: Gülberg
authors.forename: Pere
authors.initials: P
authors.lastname: Ginès
authors.forename: Guy
authors.initials: G
authors.lastname: Decaux
authors.forename: Peter
authors.initials: P
authors.lastname: Gross
authors.forename: Hassan
authors.initials: H
authors.lastname: Gandjini
authors.forename: Jacques
authors.initials: J
authors.lastname: Djian
mesh_terms: D065092:Antidiuretic Hormone Receptor Antagonists; D001201:Ascites / Q000150:complications / Q000378:metabolism; D001381:Azepines / Q000008:administration & dosage* / Q000009:adverse effects; D001549:Benzamides / Q000008:administration & dosage* / Q000009:adverse effects; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007010:Hyponatremia / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008103:Liver Cirrhosis / Q000150:complications* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011758:Pyrroles; D012964:Sodium / Q000097:blood; D016896:Treatment Outcome; D014867:Water / Q000378:metabolism; D001569:Benzodiazepines
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001381:Azepines; D001549:Benzamides; D011758:Pyrroles; D012964:Sodium; D014867:Water; C409452:lixivaptan; D001569:Benzodiazepines