Effects of satavaptan, a selective vasopressin V(2) receptor antagonist, on ascites and serum sodium in cirrhosis with hyponatremia: a randomized trial.

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.
Hepatology (Impact Factor: 11.19). 08/2008; 48(1):204-13. DOI: 10.1002/hep.22293
Source: PubMed

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 V(2) 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 < or =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 V(2) receptor antagonist satavaptan improves the control of ascites and increases serum sodium in patients with cirrhosis, ascites, and hyponatremia under diuretic treatment.

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    ABSTRACT: Hyponatremia is an important and common clinical problem. The etiology is multifactorial. Hyponatremia may be euvolemic, hypovolemic or hypervolemic. Proper interpretation of the various laboratory tests helps to differentiate the various types of hyponatremia. Treatment varies with the nature of onset -acute or chronic, severity and symptoms. Normal saline forms the mainstay of treatment for hypovolemic hyponatremia while 3% NaCl and fluid restriction are important for euvolemic hyponatremia. Hypervolemic hyponatremia responds well to fluid restriction and diuretics. There have been several recent advances in the last year with revision in the guidelines for treatment and availability of vaptans. Judicious use of vaptans may help in treatment of hyponatremia.
    11/2014; 18(6):760-71. DOI:10.4103/2230-8210.141320
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    ABSTRACT: Ascites and hyponatremia are the most common complications in patients with liver cirrhosis and develop as a consequence of a severe impairment of liver function and portal hypertension. Increasing evidences support the central role of renal function alterations in the pathogenesis of hydroelectrolytic imbalances in cirrhotic patients, thus implying a dense cross-talk between liver and kidney in the systemic and splanchnic vascular homeostasis in such subjects. Since Arginin Vasopressin (AVP) hyperincretion occurs at late stage of cirrhosis and plays an important role in the development of refractory ascites, dilutional hyponatremia and finally hepato-renal syndrome (HRS), selective antagonists of AVP receptors V2 (vaptans) have been recently introduced in the therapeutic algorithm of advanced cirrhotic patients. Despite the promising results of earlier phase-two studies, randomized controlled trials failed to find significant results in terms of efficacy of such drugs both in refractory ascites and hyponatremia. Moreover, concerns on their safety profile arise, due to the number of potentially severe side effects of vaptans in the clinical setting, such as hypernatremia, dehydration, renal impairment, and osmotic demyelination syndrome. More robust data from randomized controlled trials are needed in order to confirm the potential role of vaptans in the management of advanced cirrhotic patients.
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    ABSTRACT: Dilutional hyponatremia is common in decompensated cirrhosis and can be successfully treated by tolvaptan, a vasopressin V2-receptor antagonist. Data were lacking regarding the effects of tolvaptan on cirrhotic patients with a Child-Pugh score of >10 and a serum sodium concentration of <120 mmol/L. We report a case of forties man with a 20-year history of chronic hepatitis B presenting with yellow urine and skin. Laboratory tests demonstrated prolonged prothrombin time, markedly elevated total bilirubin, severe hyponatremia, and a Child-Pugh score of >10. The patient was diagnosed with dilutional hyponatremia and was treated with recommended dosage tolvaptan at first. The serum concentration of sodium recover but the patient felt obviously thirsty. As the dosage of tolvaptan was decreased accordingly from 15 mg to 5 mg, the patient still maintained the ideal concentration of serum sodium. This case emphasizes that cirrhotic patient with higher Child-Pugh scores and serum sodium concentration of <120 mmol/L can be treated with lower dose of tolvaptan.

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Oct 14, 2014