Effects of a selective vasopressin V₂ receptor antagonist, satavaptan, on ascites recurrence after paracentesis in patients with cirrhosis☆

Background & 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 V₂ 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 12weeks. 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 17days with satavaptan 5, 12.5, and 25mg, respectively, versus 14days 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±0.48L/week for placebo versus 2.12±0.40, 2.14±0.33, and 2.06±0.40L/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.

Abbreviations: AST, aspartate transaminase, ALT, alanine transaminases, ALP, alkaline phosphatase, CI, confidence interval, dDAVP, 1-desamino-8-d-arginine vasopressin, INR, international normalized ratio, ITT, intention to treat, LVP, large volume paracentesis, MELD, model for end-stage liver disease, QTcF, QT interval corrected by the Fridericia formula, TIPS, transjugular intrahepatic portosystemic stent shunt

Keywords: Cirrhosis, Ascites, V₂ receptor antagonist, Large volume paracentesis