Clinical trial NCT01349335: Dose Exploring and Setting Study for Tolvaptan to Treat Hepatic Cirrhosis With Ascites
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ascites
Hepatic Cirrhosis
Lead sponsor: Otsuka Beijing Research Institute
Sponsor class: INDUSTRY
First posted: 2011-05-06
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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.

Primary outcomes:
measure: Body weight changes after 7 days of treatment (quantity of changes)
timeFrame: from day1 to day7
Secondary outcomes:
measure: Body weight change after 4 days of treatment (quantity of changes)
timeFrame: from day1 to day4
measure: Waist circumference after 4 and 7 days of treatment (quantity and rate of changes)
timeFrame: from day1 to day7
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Renji hospital, Shanghai Jiaotong University School of Medicine
state: Shanghai
Study officials:
affiliation: RenJi Hospital
name: Minde Zeng
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wang S, Zhang X, Han T, Xie W, Li Y, Ma H, Liebe R, Weng H, Ding HG. Tolvaptan treatment improves survival of cirrhotic patients with ascites and hyponatremia. BMC Gastroenterol. 2018 Sep 4;18(1):137. doi: 10.1186/s12876-018-0857-0.