Tolvaptan for hyponatremia in patients with cirrhosis: a post hoc subgroup analysis of a multicenter, randomized, double-blind, placebo-controlled trial.

OBJECTIVES

The objective of this study was to investigate the efficacy and safety of oral tolvaptan for hyponatremia in patients with cirrhosis in China.

PATIENTS AND

METHODS

In this post hoc subgroup analysis of a phase 2 clinical trial of oral tolvaptan for hyponatremia due to cirrhosis, heart failure, and syndrome of inappropriate antidiuretic hormone secretion in China, patients with hyponatremia due to cirrhosis received placebo or tolvaptan for 7 days (15 mg titrated to 30 or 60 mg/day). The primary endpoint was the average daily change in serum sodium level from baseline to days 4 and 7.

RESULTS

We enrolled 131 patients (90 males, 41 females) with cirrhosis mainly due to CHB (70.2%). Compared with placebo (N = 65), the tolvaptan group (N = 66) showed a significantly greater daily increase in serum sodium from baseline through day 4 (3.99 ± 2.70 vs. 0.32 ± 2.45 mmol/L; p < 0.0001) and 7 (4.72 ± 2.94 vs. 0.67 ± 3.05 mmol/L; p < 0.0001). The time to normalization of serum sodium levels was significantly shorter in the tolvaptan group (p < 0.0001). The serum sodium normalization rates on days 4 and 7 in the tolvaptan group were 59.09% and 68.18%, respectively, versus 18.46% and 24.62% in placebo (p < 0.0001). Seven days after tolvaptan cessation, the serum sodium levels were comparable to the placebo group. Tolvaptan was generally well tolerated, and the most common adverse events were dry mouth and thirst.

CONCLUSIONS

This study demonstrates that short-term oral tolvaptan is effective and safe for hyponatremia in patients with cirrhosis in China.