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Phase III Study of Tolvaptan Tablet to Treat Cirrhosis Ascites

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01349348
Recruitment Status : Completed
First Posted : May 6, 2011
Last Update Posted : October 12, 2012
Sponsor:
Information provided by (Responsible Party):
Otsuka Beijing Research Institute

Tracking Information
First Submitted Date  ICMJE May 4, 2011
First Posted Date  ICMJE May 6, 2011
Last Update Posted Date October 12, 2012
Study Start Date  ICMJE October 2010
Actual Primary Completion Date May 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 5, 2011)
Change from baseline in body weight after 7 days randomized treatment (Day 8). [ Time Frame: 7 days ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 5, 2011)
  • Change from baseline in body weight after 4 days randomized treatment (Day 5); [ Time Frame: 4days ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase III Study of Tolvaptan Tablet to Treat Cirrhosis Ascites
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Ascites
  • Hepatic Cirrhosis
Intervention  ICMJE
  • Drug: Tolvaptan
    tablet, 15 mg, Qd, for 7 days
    Other Name: SAMSCA
  • Drug: Tolvaptan
    tablet, 7.5 mg, Qd, for 7 days
    Other Name: SAMSCA
  • Drug: placebo
    tablet, 7.5/15mg , Qd, 7days.
    Other Name: Blank tablet
Study Arms  ICMJE
  • Experimental: Tolvaptan 15mg
    Tablet;15mg/tab
    Intervention: Drug: Tolvaptan
  • Experimental: Tolvaptan 7.5mg
    Tablet;7.5mg/tab
    Intervention: Drug: Tolvaptan
  • Placebo Comparator: Placebo
    Tolvaptan 0mg/tab
    Intervention: Drug: placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 10, 2012)
535
Original Estimated Enrollment  ICMJE
 (submitted: May 5, 2011)
525
Actual Study Completion Date  ICMJE July 2012
Actual Primary Completion Date May 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria:

  1. Patients diagnosed with liver cirrhosis clinically or pathologically;
  2. Patients with ascites confirmed by Type-B ultrasound scan after receiving combination therapies of oral loop diuretics and aldosterone antagonists for at least 4 days with the fixed usage and dosage
  3. Inpatients or patients who can be hospitalized for this study from Day -3 (Screening) to Day 8 (the day for efficacy evaluation);
  4. Patients with body weight change within ±1.0 kg in the 2 days prior to initiation of treatment (Day -2 and Day -1)
  5. Age: 18 to 75 years, inclusive(at the time informed consent is obtained);
  6. Genders: men or women;
  7. Patients who have signed informed consent form.

Exclusion criteria:

  1. Patients with any of the following diseases, complications or symptoms:

    • Hepatic encephalopathy (hepatic coma of grade II or higher1));
    • Malignant ascites (patients have tumor cells detected in ascites if malignant ascites be highly suspected);
    • Uncontrolled spontaneous bacterial peritonitis;
    • Patients who are likely to experience alimentary tract hemorrhage during the study;
    • Heart failure (NYHA2) grade III or IV);
    • Anuresis (daily urine volume is less than 100mL);
    • Dysuria due to urinary tract stricture, urinary calculus, tumor in the urinary tract or other cause.
  2. Patients with history of :

    • Alimentary tract hemorrhage within 10 days prior to screening;
    • Cerebral accident suffered within 30 days prior to screening;
    • Past history of hypersensitivity or idiosyncratic reaction to benzazepine derivatives (Benazepril).
  3. Patients with systolic pressure below 90mmHg at screening;
  4. Patients with any of the following abnormal laboratory parameters at screening:

    • Serum creatinine >1.5x upper limit of normal range;
    • Serum Na+>145mmol/L (or higher than upper limit of normal range);
    • Serum K+>5.5mmol/L;
  5. Patients with Child-pugh score3)>12;
  6. Patients who are unable to take medicine orally;
  7. Female patients who are pregnant, lactating, or who are at child-bearing age without using acceptable contraceptive means;
  8. Patients who received blood products including albumin within 4 days prior to the initiation of treatment
  9. Patients who participated in any clinical trial other than tolvaptan within one month prior to screening;
  10. Patients who participated in Tolvaptan trials and took Tolvaptan previously;
  11. Patients otherwise judged by the investigator, to be inappropriate for inclusion in the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01349348
Other Study ID Numbers  ICMJE 156-08-805-01
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Otsuka Beijing Research Institute
Study Sponsor  ICMJE Otsuka Beijing Research Institute
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Minde Zeng RenJi Hospital
PRS Account Otsuka Beijing Research Institute
Verification Date October 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP