title: Tolvaptan for improvement of hepatic edema: A phase 3, multicenter, randomized, double-blind, placebo-controlled trial.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi.
authors.forename: Isao
authors.initials: I
authors.lastname: Sakaida
authors.forename: Seiji
authors.initials: S
authors.lastname: Kawazoe
authors.forename: Kozo
authors.initials: K
authors.lastname: Kajimura
authors.forename: Takafumi
authors.initials: T
authors.lastname: Saito
authors.forename: Chiaki
authors.initials: C
authors.lastname: Okuse
authors.forename: Koichi
authors.initials: K
authors.lastname: Takaguchi
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Okada
authors.forename: Kiwamu
authors.initials: K
authors.lastname: Okita
keywords: add-on therapy; ascites-related clinical symptoms; conventional diuretics; hepatic edema; liver cirrhosis; tolvaptan