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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Otsuka Beijing Research Institute
ClinicalTrials.gov Identifier:
NCT01349335
First received: March 5, 2010
Last updated: October 10, 2012
Last verified: May 2011
  Purpose

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.


Condition Intervention Phase
Ascites
Hepatic Cirrhosis
Drug: Tolvaptan
Drug: placebo
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Otsuka Beijing Research Institute:

Primary Outcome Measures:
  • Body weight changes after 7 days of treatment (quantity of changes) [ Time Frame: from day1 to day7 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Body weight change after 4 days of treatment (quantity of changes) [ Time Frame: from day1 to day4 ] [ Designated as safety issue: No ]
  • Waist circumference after 4 and 7 days of treatment (quantity and rate of changes) [ Time Frame: from day1 to day7 ] [ Designated as safety issue: No ]

Enrollment: 180
Study Start Date: April 2009
Study Completion Date: April 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1. tolvaptan
15 mg, P.O., Qd, for 7 days,
Drug: Tolvaptan
tablet, 15 mg, Qd, for 7 days
Other Name: SAMSCA
Experimental: 2 tolvaptan
30 mg, P.O., Qd, for 7 days,
Drug: Tolvaptan
tablet, 30 mg, Qd, 7 days
Other Name: SAMSCA
Experimental: 3. Placebo
30mg,P.O.,Qd, for 7 days.
Drug: placebo
tablet, 30 mg, Qd, 7days.
Other Name: blank tablet

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01349335

Locations
China, Shanghai
Renji hospital, Shanghai Jiaotong University School of Medicine
Shanghai, Shanghai, China, 200001
Sponsors and Collaborators
Otsuka Beijing Research Institute
Investigators
Principal Investigator: Minde Zeng Renji hospital, Shanghai Jiaotong University School of Medicine
  More Information

No publications provided

Responsible Party: Otsuka Beijing Research Institute
ClinicalTrials.gov Identifier: NCT01349335     History of Changes
Other Study ID Numbers: 156-08-804-01
Study First Received: March 5, 2010
Last Updated: October 10, 2012
Health Authority: China: Food and Drug Administration

Additional relevant MeSH terms:
Ascites
Liver Cirrhosis
Fibrosis
Pathologic Processes
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on July 24, 2014