Tolvaptan for improvement of hepatic edema: A phase 3, multicenter, randomized, double-blind, placebo-controlled trial

作者：Sakaida Isao^*; Kawazoe Seiji; Kajimura Kozo; Saito Takafumi; Okuse Chiaki; Takaguchi Koichi; Okada Mitsuru; Okita Kiwamu

来源：Hepatology Research, 2014, 44(1): 73-82.

DOI：10.1111/hepr.12098

• add-on therapy
• ascites-related clinical symptoms
• conventional diuretics
• hepatic edema
• liver cirrhosis
• tolvaptan

AimHepatic edema is manifested by ascites, lower limb edema and intolerable symptoms. Some patients insufficiently respond to the conventional diuretic therapy. Therefore, a novel therapeutic option is required. We conducted a phase 3 study to confirm therapeutic effect of tolvaptan on hepatic edema associated with liver cirrhosis. %26lt;br%26gt;MethodsIn our multicenter, randomized, double-blind, placebo-controlled trial, liver cirrhosis patients who showed insufficient response to conventional diuretics were randomly assigned to 7-day administration of either tolvaptan at 7.5mg/day or placebo as an add-on therapy to conventional diuretics. The primary outcome was change in bodyweight from baseline. %26lt;br%26gt;ResultsOf 164 eligible patients, 84 were assigned to tolvaptan and 80 to placebo. Change in bodyweight from baseline on the final dosing day was -0.44kg (standard deviation [SD], 1.93) in the placebo group and -1.95kg (SD, 1.77) in the tolvaptan group (P%26lt;0.0001). Improvement rates for lower limb edema and ascites-related clinical symptoms were higher with tolvaptan than with placebo. Even in patients with low serum albumin (%26lt;2.5g/dL), decrease in bodyweight was greater with tolvaptan than with placebo (P=0.0163). In addition, tolvaptan significantly increased serum sodium concentration from baseline. %26lt;br%26gt;ConclusionAdd-on therapy with tolvaptan was effective for the treatment of hepatic edema and ascites-related clinical symptoms. Furthermore, tolvaptan is expected to improve low serum sodium concentration and to exert its effect regardless of serum albumin level. Add-on therapy with tolvaptan is therefore considered to be a novel therapeutic option for hepatic edema.

• 出版日期2014-1