OBJECTIVE:Tolvaptan, an oral antagonist of the vasopressin V(2) receptor, has been found to improve hyponatremia in patients with mixed etiologies. This study analyzed a subgroup of patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) to evaluate the efficacy and safety of tolvaptan in this group. DESIGN AND PATIENTS: Hyponatremic patients in the SALT-1 and SALT-2 studies with a diagnosis of SIADH were identified based on clinical diagnosis by individual study investigators. Subjects were randomized to receive oral placebo (n=52) or tolvaptan 15 mg daily, with further titration to 30 and 60 mg daily, if necessary, based on the response of serum [Na(+)] (n=58). RESULTS: In patients with SIADH, improvement in serum [Na(+)] was significantly greater (P<0.0001) with tolvaptan than placebo over the first 4 days of therapy as well as the entire 30-day study, with minimal side effects of increased thirst, dry mouth, and urination. Only 5.9% of tolvaptan-treated patients had overly rapid correction of hyponatremia as defined by current guidelines. After discontinuation of tolvaptan, serum [Na(+)] declined to values similar to placebo. A significant positive treatment effect favoring tolvaptan on the physical component, and a near-significant trend on the mental component, was found using the SF-12 Health Survey. Tolvaptan was associated with a significantly reduced incidence of fluid restriction. CONCLUSIONS: Results for the SIADH subgroup were analogous to those of the combined SALT population regarding efficacy and safety but demonstrated a greater improvement in the physical component of the SF-12 Health Survey than in the full mixed etiology SALT patient group.
RCT Entities:
OBJECTIVE:Tolvaptan, an oral antagonist of the vasopressin V(2) receptor, has been found to improve hyponatremia in patients with mixed etiologies. This study analyzed a subgroup of patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) to evaluate the efficacy and safety of tolvaptan in this group. DESIGN AND PATIENTS: Hyponatremic patients in the SALT-1 and SALT-2 studies with a diagnosis of SIADH were identified based on clinical diagnosis by individual study investigators. Subjects were randomized to receive oral placebo (n=52) or tolvaptan 15 mg daily, with further titration to 30 and 60 mg daily, if necessary, based on the response of serum [Na(+)] (n=58). RESULTS: In patients with SIADH, improvement in serum [Na(+)] was significantly greater (P<0.0001) with tolvaptan than placebo over the first 4 days of therapy as well as the entire 30-day study, with minimal side effects of increased thirst, dry mouth, and urination. Only 5.9% of tolvaptan-treated patients had overly rapid correction of hyponatremia as defined by current guidelines. After discontinuation of tolvaptan, serum [Na(+)] declined to values similar to placebo. A significant positive treatment effect favoring tolvaptan on the physical component, and a near-significant trend on the mental component, was found using the SF-12 Health Survey. Tolvaptan was associated with a significantly reduced incidence of fluid restriction. CONCLUSIONS: Results for the SIADH subgroup were analogous to those of the combined SALT population regarding efficacy and safety but demonstrated a greater improvement in the physical component of the SF-12 Health Survey than in the full mixed etiology SALTpatient group.
Authors: A Ohnishi; Y Orita; R Okahara; H Fujihara; T Inoue; Y Yamamura; Y Yabuuchi; T Tanaka Journal: J Clin Invest Date: 1993-12 Impact factor: 14.808
Authors: Tomas Berl; Friederike Quittnat-Pelletier; Joseph G Verbalis; Robert W Schrier; Daniel G Bichet; John Ouyang; Frank S Czerwiec Journal: J Am Soc Nephrol Date: 2010-02-25 Impact factor: 10.121
Authors: Joseph G Verbalis; Stephen R Goldsmith; Arthur Greenberg; Robert W Schrier; Richard H Sterns Journal: Am J Med Date: 2007-11 Impact factor: 4.965
Authors: E Sbardella; A M Isidori; G Arnaldi; M Arosio; C Barone; A Benso; R Berardi; G Capasso; M Caprio; F Ceccato; G Corona; S Della Casa; L De Nicola; M Faustini-Fustini; E Fiaccadori; L Gesualdo; S Gori; A Lania; G Mantovani; P Menè; G Parenti; C Pinto; R Pivonello; P Razzore; G Regolisti; C Scaroni; F Trepiccione; A Lenzi; A Peri Journal: J Endocrinol Invest Date: 2017-11-20 Impact factor: 4.256