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

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

Study Overview

• Status: Terminated
• Conditions: Hyponatremia and Extracellular Fluid in Cirrhotic
• Intervention / Treatment: Drug: Placebo; Drug: Tolvaptan

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Bucheon, Korea, Republic of
    • Soonchunhyang Univ. Bucheon Hospital
  • Bucheon, Korea, Republic of
    • HALLYM UNIV. Chuncheon Sacred Heart Hospital
  • Wonju, Korea, Republic of
    • Wonju Christian Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Tolvaptan; Tablet, QD, 2 weeks	Drug: Tolvaptan
Placebo Comparator: Placebo; Tablet, QD, 2 weeks	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Korea Otsuka Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: February 21, 2012
• First Submitted That Met QC Criteria: March 9, 2012
• First Posted (Estimate): March 13, 2012

Study Record Updates

• Last Update Posted (Actual): March 4, 2022
• Last Update Submitted That Met QC Criteria: February 17, 2022
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Water-Electrolyte Imbalance; Ascites; Hyponatremia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Antidiuretic Hormone Receptor Antagonists; Tolvaptan
• Other Study ID Numbers: 156-KOB-1101i