title: Oral lixivaptan effectively increases serum sodium concentrations in outpatients with euvolemic hyponatremia.
abstract: Hyponatremia is the most common electrolyte disorder in clinical practice. Its incidence increases with age and it is associated with increased morbidity and mortality. Recently, the vaptans, antagonists of the arginine vasopressin pathway, have shown promise for safe treatment of hyponatremia. Here we evaluated the efficacy, safety, and tolerability of oral lixivaptan, a selective vasopressin V2-receptor antagonist, for treatment of nonhospitalized individuals with euvolemic hyponatremia (sodium less than 135 mmol/l) in a multicenter, randomized, double-blind, placebo-controlled, phase III study. About half of the 206 patients were elderly in a chronic care setting. Of these patients, 52 were given a placebo and 154 were given 25-100 mg per day lixivaptan, titrated based on the daily serum sodium measurements. Compared with placebo (0.8 mmol/l), the serum sodium concentration significantly increased by 3.2 mmol/l from baseline to day 7 (primary efficacy endpoint) with lixivaptan treatment. A significantly greater proportion of patients that received lixivaptan achieved normal serum sodium (39.4%) by day 7 relative to placebo (12.2%). Overall, lixivaptan was considered safe and well-tolerated. Thus, oral lixivaptan can be safely initiated in the outpatient setting and effectively increases serum sodium concentrations in outpatients with euvolemic hyponatremia.
authors.affiliation: Division of Cardiovascular Medicine, Ohio State University, Columbus, Ohio 43210-1252, USA. william.abraham@osumc.edu
authors.forename: William T
authors.initials: WT
authors.lastname: Abraham
authors.forename: Guy
authors.initials: G
authors.lastname: Decaux
authors.forename: Richard C
authors.initials: RC
authors.lastname: Josiassen
authors.forename: Yoram
authors.initials: Y
authors.lastname: Yagil
authors.forename: Nelson
authors.initials: N
authors.lastname: Kopyt
authors.forename: Hemant P
authors.initials: HP
authors.lastname: Thacker
authors.forename: Massimo
authors.initials: M
authors.lastname: Mannelli
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Bichet
authors.forename: Cesare
authors.initials: C
authors.lastname: Orlandi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007010:Hyponatremia / Q000097:blood / Q000188:drug therapy*; D008134:Long-Term Care; D008297:Male; D008875:Middle Aged; D009735:Nursing Homes; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D012964:Sodium / Q000097:blood*; D016896:Treatment Outcome; D055815:Young Adult; D001569:Benzodiazepines
chemical_list: D001549:Benzamides; D011758:Pyrroles; D012964:Sodium; C409452:lixivaptan; D001569:Benzodiazepines