Effect of Samsca on Control of Hyponatremia and Extracellular Fluid in Cirrhotic Patients With Ascites

Study Overview
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Brief Summary
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This study is to evaluate the efficacy of a 2-week course of tolvaptan in improving serum sodium and the excretion of extracellular fluid in liver cirrhotic patients with ascites and hyponatremia

Official Title
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Effect of Samsca on Control of Hyponatremia and Extracellular Fluid in Cirrhotic Patients With Ascites

Conditions
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Hyponatremia and Extracellular Fluid in Cirrhotic

Intervention / Treatment
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* Drug: Tolvaptan
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects aged ≥ 20 years Subjects who have been diagnosed with hyponatremia [serum sodium < 125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction] Subjects who have been diagnosed with an ascites on the abdominal ultrasound. Subjects who have diagnosed with cirrhosis. Subject or their legally acceptable representatives are able to provide informed consent/assent. Exclusion Criteria: Subject who has ascites by other causes (Tbc, CHF, malignancy, or renal disease) acute severe hyponatemia : Serum Na level < 120 mmol/L and Doubt of symptom caused by hyponatremia and the case which should raise serum Na level urgently based on the investigator's judgment international normalized ratio (INR) >3.0 serum sodium ≥135 mmol/L serum potassium > 5.5 mmol/L Creatinine ≥ 2.0 mg/dL Hepatorenal syndrome defined as 'New International Ascites Club's diagnostic criteria' systolic arterial pressure of < 80 mmHg recent myocardial infarction (< 6 month) spontaneous bacterial peritonitis gastrointestinal bleed ( ≤7 days from randomization) ongoing hepatic encephalopathy of > grade1 known hepatocellular carcinoma intractable ascites Subject who requiring urgent intervention to raise serum sodium acutely Subject who are unable to sense or to respond appropriately to thirst Subject with hypovolemic hyponatremia Subject who should take strong CYP3A inhibitors (clarithromycin, ketoconazole, itraconazole, ritonavir, indinavir, nelfinavir, saquinavir, nefazodone, and telithromycin) Subject who are anuric as no benefit is expected Subject who has genetic defects such as galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption Subject who has fluid depletion Female subjects who are pregnant or lactating Subject judged by the investigator to be inappropriate for inclusion in the trial for any other reason

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tolvaptan<br>Tablet, QD, 2 weeks | Drug: Tolvaptan<br> <br> |
| Placebo Comparator: Placebo<br>Tablet, QD, 2 weeks | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Na |  | 2 weeks (Baseline, Day 14) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BCM (body composition monitoring) |  | 7 days | 
| body weight |  | 7 days | 
| A composite endpoint of ascites worsening |  | in case | 
| Serum Na normalization rate |  | 14 days | 
| Biochemistry | Total protein, Albumin, ALP, ALT, AST, r-GT, BUN, Creatinine, Glucose, Cl, K, Na, Ca, Total bilirubin, Uric acid), Hematology (WBC count, Hemoglobin, Hematocrit, Platelets, Serum osm, NT pro-BNP | 7 days | 
| ECG |  | 7 days | 
| Adverse event |  | Daily | 
| Physical examination | HEENT, Thorax, Abdomen, Urogenital, Extremities, Neurological, Skin and Mucosae | 7 days | 
| Vital signs |  | Daily | 
| Blood coagulation | PT, INR | 7 days | 
| Urinalysis | Protein, pH, Glucose, Blood, Bilirubin, Urobilinogen, Random urine Na/K, Urine osm | 7 days |