title: Short- and long-term treatment of dilutional hyponatraemia with satavaptan, a selective arginine vasopressin V2-receptor antagonist: the DILIPO study.
abstract: OBJECTIVE
  Arginine vasopressin (AVP) V(2) receptor antagonism is a new approach to the management of hyponatraemia in congestive heart failure (CHF). The aim of this study was to investigate the efficacy and safety of satavaptan, an oral AVP V(2)-receptor antagonist, in patients with dilutional hyponatraemia.
  
  
  RESULTS
  A total of 118 patients (90 with CHF) with dilutional hyponatraemia (serum sodium 115-132 mmol/L) were randomized to double-blind treatment with placebo or to 25 or 50 mg/day of satavaptan for 4 days, followed by non-comparative open-label satavaptan therapy for up to 343 days. The response rate (sodium ≥ 135 mmol/L and/or an increase in ≥ 5 mmol/L above baseline) was significantly higher with satavaptan 50 mg than with placebo (61.0 vs. 26.8%; P= 0.0035), with a trend towards significance with satavaptan 25 mg (48.6%, P= 0.0599). Median times to response were 3.30 and 2.79 days with satavaptan 25 and 50 mg/day, respectively, both shorter than placebo (>4 days; P= 0.0278 and P= 0.0004, respectively). Satavaptan therapy was effective in CHF patients, with response rates higher with both satavaptan 25 mg/day (53.6%) and 50 mg/day (57.1%) than with placebo (23.5%; P= 0.019 and P= 0.009, respectively). Sodium responses were maintained during open-label therapy after a temporary study drug discontinuation period. Higher rates of adverse events occurred with the 50 mg/day dose, including rapid correction of hyponatraemia.
  
  
  CONCLUSIONS
  In patients with dilutional hyponatraemia, V(2) receptor antagonism with satavaptan was effective in increasing serum sodium concentrations. The long-term open-label treatment results demonstrate sustained efficacy of satavaptan in maintaining normal sodium levels. Trial Registration clinicaltrials.gov Identifier: NCT00274326.
authors.affiliation: Department of Cardiology, Rambam Medical Center, and Rappaport Faculty of Medicine and Research Institute, Technion, Israel Institute of Technology, Haifa, Israel.
authors.forename: Doron
authors.initials: D
authors.lastname: Aronson
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Verbalis
authors.forename: Matthias
authors.initials: M
authors.lastname: Mueller
authors.forename: Henry
authors.initials: H
authors.lastname: Krum
mesh_terms: D000328:Adult; D000368:Aged; D065092:Antidiuretic Hormone Receptor Antagonists; D001835:Body Weight; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000150:complications*; D006801:Humans; D007010:Hyponatremia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000009:adverse effects / Q000627:therapeutic use*; D012964:Sodium / Q000097:blood; D013141:Spiro Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014667:Vasopressins / Q000097:blood; D055815:Young Adult
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D009025:Morpholines; D013141:Spiro Compounds; D014667:Vasopressins; D012964:Sodium; C103281:satavaptan