Randomized, double blinded, placebo-controlled trial to evaluate the efficacy and safety of tolvaptan in Chinese patients with hyponatremia caused by SIADH

J Clin Pharmacol. 2014 Dec;54(12):1362-7. doi: 10.1002/jcph.342.

Abstract

To study the effect of tolvaptan on non-acute, non-hypovolemic hyponatremia in inappropriate secretion of antidiuretic hormone (SIADH) syndrome in Chinese patients. Hyponatremic SIADH patients received placebo (N = 18) or tolvaptan (N = 19) at an initial dose of 15 mg/day with further titration to 30 mg/day and 60 mg/day based on serum sodium concentrations. Randomized, double-blind, placebo-controlled trial. Primary endpoint was the change of the serum sodium from baseline to days 4 and 7. Analysis of covariance (ANCOVA) was used for statistical analysis. At day 4, average daily changes in serum sodium levels from baseline was 1.9 ± 2.9 mmol/L (1.9 ± 2.9 mEq/L) in the placebo group and 8.1 ± 3.6 mmol/L (8.1 ± 3.6 mEq/L) in the tolvaptan group; at day 7, the values were 2.5 ± 3.9 mmol/L (2.5 ± 3.9 mEq/L) and 8.6 ± 3.9 mmol/L (8.6 ± 3.9 mmEq/L) for the placebo and tolvaptan groups (ANCOVA, P < 0.001). At days 4 and 7, daily urine output and proportions of patients with normalized serum sodium were significantly superior in the tolvaptan group. The most common adverse events occurring in the tolvaptan group were dry mouth and thirst. Tolvaptan demonstrated superiority to placebo in the treatment of Chinese SIADH patients with hyponatremia by elevating serum sodium concentration with acceptable safety profile.

Trial registration: ClinicalTrials.gov NCT00664014.

Keywords: hyponatremia; syndrome of inappropriate antidiuretic hormone; tolvaptan.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antidiuretic Hormone Receptor Antagonists / adverse effects
  • Antidiuretic Hormone Receptor Antagonists / therapeutic use*
  • Benzazepines / adverse effects
  • Benzazepines / therapeutic use*
  • Double-Blind Method
  • Female
  • Humans
  • Hyponatremia / blood
  • Hyponatremia / drug therapy*
  • Hyponatremia / etiology
  • Inappropriate ADH Syndrome / blood
  • Inappropriate ADH Syndrome / complications
  • Inappropriate ADH Syndrome / drug therapy*
  • Male
  • Middle Aged
  • Sodium / blood
  • Tolvaptan
  • Treatment Outcome
  • Young Adult

Substances

  • Antidiuretic Hormone Receptor Antagonists
  • Benzazepines
  • Tolvaptan
  • Sodium

Associated data

  • ClinicalTrials.gov/NCT00664014