Phase III Study of Tolvaptan Tablet to Treat Cirrhosis Ascites
To evaluate the efficacy and safety of Tolvaptan 7.5mg and 15mg in treatment of patients with cirrhosis ascites who fail to response adequately to treatment with common diuretics.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Randomized, Double-blinded, Multicenter, Placebo Controlled, Parallel Designed Study, to Evaluate the Efficacy and Safety of Tolvaptan Tablet in Treatment of Patients With Cirrhosis Ascites, Using Diuretics as Initial Treatment|
- Change from baseline in body weight after 7 days randomized treatment (Day 8). [ Time Frame: 7 days ] [ Designated as safety issue: No ]
- Change from baseline in body weight after 4 days randomized treatment (Day 5); [ Time Frame: 4days ] [ Designated as safety issue: No ]
- The rate of change from baseline in body weight after 4, 7 days randomized treatment (Day 5, Day 8); [ Time Frame: 4 and 7 days ] [ Designated as safety issue: No ]
|Study Start Date:||October 2010|
|Study Completion Date:||July 2012|
|Primary Completion Date:||May 2012 (Final data collection date for primary outcome measure)|
Experimental: Tolvaptan 15mg
tablet, 15 mg, Qd, for 7 days
Other Name: SAMSCA
Experimental: Tolvaptan 7.5mg
tablet, 7.5 mg, Qd, for 7 days
Other Name: SAMSCA
Placebo Comparator: Placebo
tablet, 7.5/15mg , Qd, 7days.
Other Name: Blank tablet
For symptoms of fluid retention due to liver diseases (ascites and/or lower extremity edema, i.e. hepatic edema), treatment generally starts with bed rest and a low-salt diet. Aldosterone antagonists and loop diuretics are commonly used diuretics in the treatment of fluid retention due to liver diseases. In aldosterone antagonists' therapy, nevertheless, hyperkalemia is frequently reported, slow onset of action and dose escalation needed also impair its effect. If aldosterone antagonists' therapy is ineffective, loop diuretics as strong diuretics are usually added up. However, Dose escalation of loop diuretics also boost the occurrence of hyponatremia and hypokalemia, and combination of the two drugs provided fastest onset of effectiveness with less adverse events. While, because both diuretics can cause sodium lose which is difficult to prevent and treat, hyponatremia is easy to occur. The combination of aldosterone antagonists and K-sparing diuretics reduces the occurrence of hypokalemia but have little effect on the prevention and treatment of hyponatremia. In addition, there are still some patients who are resistent to loop diuretics or intolerant of an effective diuretic dosage due to adverse events.
Tolvaptan increases the excretion of electrolyte-free water (aquaretic) without changing electrolytes excretion by inhibiting the water reabsorption of collecting duct in kidney. It is demonstrated that Tolvaptan increased urine volume without impairing renal function.
|Renji Hospital, Shanghai Jiaotong University School of Medicine|
|Shanghai, Shanghai, China, 200001|
|Principal Investigator:||Minde Zeng||Renji hospital, Shanghai Jiaotong University School of Medicine|