Effects of satavaptan, a selective vasopressin V2 receptor antagonist, on ascites and serum sodium in cirrhosis with hyponatremia: A randomized trial

Authors

  • Pere Ginès,

    Corresponding author
    1. Liver Unit, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi-Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Catalunya, Spain
    • Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalunya, Spain
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    • Potential conflict of interest: Dr. Ginès is a consultant for Sanofi-Aventis. He received grants from Ordman and Ferring Pharmaceuticals. Dr. Wong is a consultant for Sanofi-Aventis. Dr. Watson owns stock in Sanofi-Aventis.

    • fax: 34-93-451.55.22.

  • Florence Wong,

    1. Department of Medicine, Toronto General Hospital, Ontario, Canada
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    • Potential conflict of interest: Dr. Ginès is a consultant for Sanofi-Aventis. He received grants from Ordman and Ferring Pharmaceuticals. Dr. Wong is a consultant for Sanofi-Aventis. Dr. Watson owns stock in Sanofi-Aventis.

  • Hugh Watson,

    1. Sanofi-Aventis Research and Development, Chilly Mazarin, France
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  • Slobodan Milutinovic,

    1. General Hospital Sveti Duh, Zagreb, Croatia
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    • Deceased.

  • Luis Ruiz del Arbol,

    1. Hepatic Hemodynamic Unit, Department of Gastroenterology, Hospital Ramón y Cajal, Madrid, Spain
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  • Dan Olteanu

    1. University Hospital, Bucharest, Romania
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  • Clinical Trial Registration Number: NCT00501722.

  • The list of the HypoCAT study investigators is provided in the Appendix.

Abstract

Hyponatremia in cirrhosis is associated with significant morbidity and mortality and complicates ascites management. Vasopressin receptor antagonists improve serum sodium concentration by increasing renal solute-free water excretion, but their effects on the management of ascites have not been assessed. Our aim was to investigate the effects of satavaptan, a highly selective vasopressin V2 receptor antagonist, on ascites management and serum sodium in hyponatremic patients with cirrhosis. A total of 110 patients with cirrhosis, ascites, and hyponatremia (serum sodium ≤130 mmol/L) were included in a multicenter, double-blind, randomized, controlled study comparing three fixed doses of satavaptan (5 mg, 12.5 mg, or 25 mg once daily) versus placebo. Duration of treatment was 14 days and all patients received spironolactone at 100 mg/day. Satavaptan treatment was associated with improved control of ascites, as indicated by a reduction in body weight (mean change at Day 14 was +0.49 kg [±4.99] for placebo versus +0.15 kg [±4.23], −1.59 kg [±4.60] and −1.68 kg [±4.98] for the 5 mg, 12.5 mg, and 25 mg doses, respectively; P = 0.05 for a dose-effect relationship overall) and a parallel reduction in abdominal girth. This beneficial effect on ascites was associated with improvements in serum sodium (mean change from baseline to day 5 was 1.3 ± 4.2, 4.5 ± 3.5, 4.5 ± 4.8, and 6.6 ± 4.3 mmol/L for the placebo group and the groups on satavaptan at 5 mg, 12.5 mg, and 25 mg/day, respectively; P < 0.01 for all compared to placebo). Thirst was significantly more common in patients treated with satavaptan compared to those treated with placebo, whereas the frequency of other adverse events was similar among groups. Conclusion: The V2 receptor antagonist satavaptan improves the control of ascites and increases serum sodium in patients with cirrhosis, ascites, and hyponatremia under diuretic treatment. (HEPATOLOGY 2008.)

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