Dose-finding trial of tolvaptan in liver cirrhosis patients with hepatic edema: A randomized, double-blind, placebo-controlled trial.

Aim: Liver cirrhosis represents the end stage of any chronic liver disease, and it is associated with hepatic edema such as ascites. Many patients with ascites do not respond to diuretic therapy or require administration of diuretics at high doses that can cause adverse events. This 7-day, multicenter, double-blind trial of tolvaptan was designed to determine the optimal dose of tolvaptan for producing the intended pharmacological effect in hepatic edema.

A multicenter, open-label, dose-ranging study to exploratively evaluate the efficacy, safety, and dose-response of tolvaptan in patients with decompensated liver cirrhosis.

Objectives: We examined the efficacy of tolvaptan, an orally effective nonpeptide vasopressin V(2) receptor antagonist, in a Japanese clinical study in patients with intractable ascites and/or lower limb edema associated with decompensated liver cirrhosis.

Methods: Tolvaptan was orally administrated at titrated doses of 15, 30, and 60 mg once daily after breakfast for 3 days at each dose to 18 liver cirrhosis patients with persistent ascites and/or lower limb edema despite receiving oral furosemide at 40 mg/day or higher.

Results: Decreased body weight and abdominal circumference and improvement of ascites and edema were observed following tolvaptan administration beginning from 15 mg.