1.
Tolvaptan therapy of Chinese cirrhotic patients with ascites after insufficient diuretic routine medication responses: a phase III clinical trial.
Tang, J, Wang, Y, Han, T, Mao, Q, Cheng, J, Ding, H, Shang, J, Zhang, Q, Niu, J, Ji, F, et al
BMC gastroenterology. 2020;(1):391
Abstract
BACKGROUND To determine the safety and efficacy of different doses of tolvaptan for treating Chinese cirrhotic patients with or without hyponatraemia who still had ascites after routine therapy with diuretics. METHODS In the present placebo-controlled, randomized, double-blinded, multicentre clinical trial, patients with cirrhotic ascites who failed to adequately respond to a combination of an aldosterone antagonist plus an orally administered loop diuretic were randomly placed at a 4:2:1 ratio into 3 groups [the 15 mg/day tolvaptan group (N = 301), 7.5 mg/day tolvaptan group (N = 153) and placebo group (N = 76)] for 7 days of treatment. The effects and safety were evaluated on days 4 and 7. A change in body weight from baseline on day 7 of treatment was the primary endpoint. RESULTS The administration of 7.5 or 15 mg/day tolvaptan significantly decreased body weight from baseline on day 7 of treatment compared to that with placebo treatment (P = 0.026; P = 0.001). For the secondary endpoints, changes in abdominal circumference from baseline and improvements in ascites were markedly different in the treatment groups and the placebo group on day 7 (P7.5 = 0.05, P15.0 = 0.002 and P7.5 = 0.037, P15.0 = 0.003), but there was no difference between the 7.5 mg/day and 15 mg/day dosage groups. The 24-h cumulative urine volume was higher in the 7.5 mg/day and 15 mg/day tolvaptan groups than the placebo group (P = 0.002, P < 0.001) and was greater in the 15 mg/day tolvaptan group than the 7.5 mg/day tolvaptan group (P = 0.004). Sodium serum concentrations were higher in patients with hyponatraemia after tolvaptan treatment, with no significant difference between the two dosage groups. The incidence of serious adverse drug reactions was not different between the groups (P = 0.543). CONCLUSIONS Tolvaptan treatment at 7.5 mg per day might be a good therapeutic choice for Chinese cirrhotic patients with ascites who did not achieve satisfactory clinical responses to previous treatment regimens with combination therapy with an aldosterone antagonist and an orally administered loop diuretic. TRIAL REGISTRATION NCT01349348. Retrospectively registered May 2011.
2.
Tolvaptan treatment improves survival of cirrhotic patients with ascites and hyponatremia.
Wang, S, Zhang, X, Han, T, Xie, W, Li, Y, Ma, H, Liebe, R, Weng, H, Ding, HG
BMC gastroenterology. 2018;(1):137
Abstract
BACKGROUND Although tolvaptan treatment improves hyponatremia, only few studies have investigated whether tolvaptan actually benefits the survival of cirrhotic patients. This study evaluated the impact of tolvaptan on six-month survival of decompensated cirrhotic patients with and without hyponatremia. METHODS Two hundred forty-nine decompensated cirrhotic patients with or without hyponatremia were enrolled in a multicenter cohort study. Patients were divided into two groups according to receiving either tolvaptan or placebo treatment for 7-day. Subsequently, the patients were followed up for 6 months. RESULTS Two hundred thirty patients, including 98 with hyponatremia (tolvaptan vs. placebo: 69 vs. 29) finished the study. Tolvaptan did not alter serum sodium levels and survival outcome of decompensated cirrhotic patients without hyponatremia. However, tolvaptan treatment remarkably improved serum sodium levels and six-month survival in patients with hyponatremia. Following tolvaptan treatment, serum sodium levels were restored to normal in 63.8% of patients, whereas in patients receiving placebo, only 36.2% showed the same effect (P < 0.05). Compared to a six-month survival rate of 68.97% in patients receiving placebo, the survival rate in tolvapatan-treated patients was 89.94% (P < 0.05). Furthermore, six-month survival rate in the tolvaptan-treated hyponatremia patients with resolved serum sodium was 81.32%, whereas the survival in those with unresolved serum sodium was only 24% (P < 0.05). CONCLUSIONS Tolvaptan improves short term survival in most decompensated cirrhotic hyponatremia patients with resolved serum sodium. TRIALS REGISTRATION Clinical trial one: ClinicalTrials.gov ID: NCT00664014 , Registered on April 14, 2008. Clinical trial two: ClinicalTrials.gov ID: NCT01349335 , Registered on March 5, 2010. Clinical trial three: ClinicalTrials.gov ID: NCT01349348 , Registered on May 4, 2011.