Effects of a selective vasopressin V-2 receptor antagonist, satavaptan, on ascites recurrence after paracentesis in patients with cirrhosis

BACKGROUND &#38; AIMS: Cirrhotic patients with recurrent ascites frequently require paracentesis despite diuretic therapy. Vasopressin receptor antagonists, by increasing free water clearance, may reduce the recurrence of ascites. To investigate the effects of the addition of a vasopressin V(2) receptor antagonist, satavaptan, to 100mg spironolactone on ascites recurrence after a large volume paracentesis in patients with liver cirrhosis irrespective of the presence of hyponatraemia. METHODS: One hundred and fifty one cirrhotic patients with recurrent ascites with or without hyponatraemia, and normal to mildly abnormal renal function were randomised in a double-blind study to receive either 5mg (n=39), 12.5mg (n=36), 25mg (n=40) of satavaptan or placebo (n=36) for 12 weeks. Their Child-Pugh scores were 9.2+/-1.3, 8.7+/-1.7, 8.8+/-1.3, and 9.0+/-1.5, respectively. RESULTS: Median time to first paracentesis was 23, 26, and 17 days with satavaptan 5, 12.5, and 25mg, respectively, versus 14 days with placebo (ns for all doses). The frequency of paracenteses was decreased significantly (p<0.05) in all satavaptan groups versus placebo. Mean increase in ascites was 2.82+/-0.48 L/week for placebo versus 2.12+/-0.40, 2.14+/-0.33, and 2.06+/-0.40 L/week for the 5, 12.5, and 25mg of satavaptan, respectively (ns for all doses). Similar numbers of patients experienced major adverse events in all groups. Increases in serum creatinine, orthostatic changes in systolic pressure and thirst were more common with satavaptan. CONCLUSIONS: Satavaptan has the potential to reduce recurrence of ascites after a large volume paracentesis at doses from 5 to 25mg in cirrhotic patients with ascites.