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

Abstract

AIM:

Hepatic 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.

METHODS:

In 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 7.5 mg/day or placebo as an add-on therapy to conventional diuretics. The primary outcome was change in bodyweight from baseline.

RESULTS:

Of 164 eligible patients, 84 were assigned to tolvaptan and 80 to placebo. Change in bodyweight from baseline on the final dosing day was -0.44 kg (standard deviation [SD], 1.93) in the placebo group and -1.95 kg (SD, 1.77) in the tolvaptan group (P < 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 (<2.5 g/dL), decrease in bodyweight was greater with tolvaptan than with placebo (P = 0.0163). In addition, tolvaptan significantly increased serum sodium concentration from baseline.

CONCLUSION:

Add-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.

• Authors: Isao Sakaida, Seiji Kawazoe, Kozo Kajimura, Takafumi Saito, Chiaki Okuse, Koichi Takaguchi, Mitsuru Okada, Kiwamu Okita, ASCITES-DOUBLEBLIND Study Group
• Journal: Hepatology research : the official journal of the Japan Society of Hepatology (Hepatol Res) Vol. 44 Issue 1 Pg. 73-82 (Jan 2014) ISSN: 1386-6346 [Print] Netherlands
• PMID: 23551935 (Publication Type: Journal Article)
• Copyright: © 2013 The Japan Society of Hepatology.