학술논문
Short- and long-term treatment of dilutional hyponatraemia with satavaptan, a selective arginine vasopressin V2-receptor antagonist: the DILIPO study
Document Type
Academic Journal
Author
Aronson, Doron; Verbalis, Joseph G.; Mueller, Matthias; Krum, Henry; Alvarisqueta, A.; Blüguermann, J.; Guerrero, R.A. Ahuad; Howes, L.; Krum, H.; Sindone, A.; Decaux, G; Soupart, A.; El Allaf, D.; Baillie, F.; Racine, N.; Logsetty, S.; Morales, Á.; Gutierrez, F.; Gadsbøll, N.; Dervenis, C.; Manolis, A.; Tsiftsis, D.; Forster, T.; Újszászy, L.; Farsang, C.; Aronson, D.; Efrati, S.; Freimark, D.; Zeltser, D.; Gaciong, Z.; Skoneczna, I.; Drzewiecki, A.; Miekus, P.; Piepiorka, M.; Providência, L; Fonseca, C.; Lousada, N.; Dorobantu, M.; Dimulescu, D.; Vintila, M.; Dan, A.G.; Rotaru, L.; Minescu, B.; Zdrenghea, D.; de Vries Basson, M.M.; Roos, J.S.; Roodt, A.; Wikström, G.; Chung, E.S.; Gottlieb, S.S.; Jain, A.; Pan, D.C.
Source
European Journal of Heart Failure. Mar 01, 2011 13(3):327-336
Subject
Language
English
ISSN
1388-9842
Abstract
AIMS: Arginine vasopressin (AVP) V2 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 V2-receptor antagonist, in patients with dilutional hyponatraemia. METHODS AND 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, V2 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