Hyponatremia and Extracellular Fluid in Cirrhotic
Conditions
Brief summary
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
Interventions
DRUGTolvaptan
DRUGPlacebo
Sponsors
Korea Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subjects aged ≥ 20 years 2. Subjects who have been diagnosed with hyponatremia \[serum sodium \< 125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction\] 3. Subjects who have been diagnosed with an ascites on the abdominal ultrasound. 4. Subjects who have diagnosed with cirrhosis. 5. Subject or their legally acceptable representatives are able to provide informed consent/assent.
Exclusion criteria
1. 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 2. Subject who requiring urgent intervention to raise serum sodium acutely 3. Subject who are unable to sense or to respond appropriately to thirst 4. Subject with hypovolemic hyponatremia 5. Subject who should take strong CYP3A inhibitors (clarithromycin, ketoconazole, itraconazole, ritonavir, indinavir, nelfinavir, saquinavir, nefazodone, and telithromycin) 6. Subject who are anuric as no benefit is expected 7. Subject who has genetic defects such as galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption 8. Subject who has fluid depletion 9. Female subjects who are pregnant or lactating 10. Subject judged by the investigator to be inappropriate for inclusion in the trial for any other reason
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Serum Na | 2 weeks (Baseline, Day 14) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| body weight | 7 days | — |
| A composite endpoint of ascites worsening | in case | — |
| Serum Na normalization rate | 14 days | — |
| Biochemistry | 7 days | 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 |
| ECG | 7 days | — |
| BCM (body composition monitoring) | 7 days | — |
| Physical examination | 7 days | HEENT, Thorax, Abdomen, Urogenital, Extremities, Neurological, Skin and Mucosae |
| Vital signs | Daily | — |
| Blood coagulation | 7 days | PT, INR |
| Urinalysis | 7 days | Protein, pH, Glucose, Blood, Bilirubin, Urobilinogen, Random urine Na/K, Urine osm |
| Adverse event | Daily | — |
Countries
South Korea
Outcome results
None listed