Dose Exploring and Setting Study for Tolvaptan to Treat Hepatic Cirrhosis With Ascites

Ascites Clinical Trial

Official title:

A Phase 2 Randomized, Double-blinded, Multicenter and Placebo-controlled Clinical Trial to Evaluate the Safety and Efficacy of Different Doses of Tolvaptan Tablet in Patients With Cirrhotic Ascites

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01349335
• Other study ID #: 156-08-804-01
• Status: Completed
• Phase: Phase 2
• First received: March 5, 2010
• Last updated: October 10, 2012
• Start date: April 2009
• Est. completion date: April 2010

Study information

• Verified date: May 2011
• Source: Otsuka Beijing Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

To observe the safety/efficacy of tolvaptan for treatment of patients with hepatic cirrhosis with ascites and exploring the dosage-effect relations of the drug.

Description:

Tolvaptan is able to exert hydragogue diuretic effects (water diuresis) via inhibition of water reabsorption by renal collecting ducts without corresponding increase in electrolyte excretion. It has been confirmed that tolvaptan is able to increase urine volume without any adverse effects on renal functions.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 180
• Est. completion date: April 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. hepatic cirrhosis patients after 7days treatment of loop diuretics and aldosterone antagonist but still with ascites

2. Hospitalized patients or those who can be hospitalized in this trial between observation period and posttherapeutic observation (Visits at clinic will be allowed after day 8);

3. During the observation period (-3 day to -1 day ), subjects whose body weight difference fall within ±1.0 kg range 2 days (day-2 and day -1) prior to initiation of trial drug treatment;

4. Ages: =18 and =75 years of age;

5. Genders: men or women;

6. Signed the Informed Consent Form.

Exclusion Criteria:

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

• Hepatic encephalopathy (Coma scale Note 1) grade 2 or higher);

• Malignant ascites;

• Uncontrolled spontaneous bacterial peritonitis;

• Patients are likely to experience alimentary tract hemorrhage during the trial;

• Heart failure (NYHA cardiac function scale Note 2) stages 3 and 4);

• Anuria (daily urine volume below 100mL);

• Dysuria resulting from urethral stricture, calculus and tumors.

2. Patients with the following medical history:

• Alimentary tract hemorrhage within 10 days prior to screening;

• Cerebrovascular accident within 1 month prior to screening;

• Gout attack within 1 month prior to screening;

• Past allergy or hypersensitive reactions to benzodiazepines (e.g. benazepril hydrochloride)

3. Systolic pressure below 90mmHg at screening;

4. Patients with the following abnormalities in laboratory examinations at screening:

Serum creatinine exceeds 2.5X upper limits of normal, serum Na+>145mmol/L (or exceeds upper limits of normal), serum K+>5.5mmol/L, uric acid>8.0mg/dL (476µmol/L), Child-pugh scale greater than 12.

5. Patients cannot take drugs orally;

6. Pregnant or breast-feeding patients or women at child-bearing ages without taking acceptable contraceptive measures;

7. Patients received albumin or other blood preparations within 4 days prior to trial drug administration;

8. Patients participated in clinical trials of other drugs within 1 month prior to screening;

9. Patients participated in tolvaptan trials and took tolvaptan previously;

10. Patients are unsuitable to participate in this trial in investigators' opinion.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ascites
• Hepatic Cirrhosis
• Liver Cirrhosis

Intervention

Drug:
• Tolvaptan
tablet, 15 mg, Qd, for 7 days
• Tolvaptan
tablet, 30 mg, Qd, 7 days
• placebo
tablet, 30 mg, Qd, 7days.

Locations

Country	Name	City	State
China	Renji hospital, Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Otsuka Beijing Research Institute

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Body weight changes after 7 days of treatment (quantity of changes)		from day1 to day7	No
Secondary	Body weight change after 4 days of treatment (quantity of changes)		from day1 to day4	No
Secondary	Waist circumference after 4 and 7 days of treatment (quantity and rate of changes)		from day1 to day7	No