Ascites, Cirrhosis
Conditions
Keywords
Cirrhotic, Tolvaptan, v2 receptor antagonist
Brief summary
Open Label Study evaluating the safety and efficacy of tolvaptan in the treatment of ascites in liver cirrhosis. Tolvaptan will be administered in combination with current ascites management.
Detailed description
This is an open label, 12 week dose escalating pilot study of tolvaptan (initiating at 15 mg a day and increasing to 30 mg a day as tolerated in addition to standard ascites treatment) of 10 cirrhotic subjects meeting all inclusion/exclusion criteria. Subjects are monitored for changes in frequency of paracentesis, quantity of ascites removed, and body weight. Additionally, subjects laboratory values were checked frequently during the first days of dosing to ensure tolerability and slow correction/increase in serum sodium.
Interventions
DRUGTolvaptan
Oral administration once daily Dosage will range from 15 mg to 30 mg
Sponsors
Otsuka America Pharmaceutical
University of Florida
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Patients with cirrhosis of liver confirmed by histology and/or combination of ultrasound or endoscopic examination with laboratory evidence * Clinically evident ascites treated by diet and/or diuretics * History of 1 or more therapeutic paracentesis in the previous 6 months.
Exclusion criteria
* History of variceal bleeding * Current or history of Gastrointestinal bleeding within 10 days of screening * Ascites from another cause other than liver cirrhosis (i.e. cardiac origin, peritoneal infection, or peritoneal carcinoma) * INR (International normalized ratio) \> 3.0, neutrophils \<1500 cell/μl, platelets \< 40,000/μl * serum bilirubin \> 3 mg/dl * serum sodium \< 125 meQ (milliequivalent)/L * serum potassium \<3.5 meQ/L
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Worsening Ascites (Increase in Number of Paracentesis Procedures to Remove 2 Liters of Ascites Fluid) | Week 12 | Increase in number of therapeutic paracentesis (removal of \> 2 litres of ascites fluid) during 12 weeks of study drug dosing versus 12 weeks before study drug dosing |
| Number of Subjects With Worsening Ascites (Defined as Greater Than 2 kg Weight Gain) | 12 weeks of study drug | This outcome will provide the number of subjects with a weight increase of \> 2kg from baseline (worsening ascites) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Reduction of Ascites (Weight Loss of 2 kg or More) | 12 weeks | Number of patients with reduction of ascites is defined as reduction of weight by at least 2 kg during study drug dosing |
| Number of Patients With Abnormally Low Levels of Sodium (Sodium Levels Between 130 mmol/L and 135 mmol/L) | 12 weeks | Number of Patients with new episodes of hyponatremia (abnormally low levels of sodium) defined as sodium \>130 mmol/L and \<135 mmol/L |
| Time From Baseline to Worsening Ascites (Requiring 1 or More Therapeutic Paracentesis to Remove Ascites Fluid) | 12 weeks of study drug | This outcome will describe the average time from baseline for subjects to require a therapeutic paracentesis to remove ascites fluid. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tolvaptan Tolvaptan 15 mg tablet once daily for 7 days followed by Tolvaptan 30 mg (two 15 mg tablets) once daily according to efficacy and tolerability
Tolvaptan: Oral administration once daily Dosage will range from 15 mg to 30 mg | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Tolvaptan |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Age, Continuous | 62.5 years |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 9 / 10 |
| serious Total, serious adverse events | 1 / 10 |
Outcome results
Primary
Number of Participants With Worsening Ascites (Increase in Number of Paracentesis Procedures to Remove 2 Liters of Ascites Fluid)
Increase in number of therapeutic paracentesis (removal of \> 2 litres of ascites fluid) during 12 weeks of study drug dosing versus 12 weeks before study drug dosing
Time frame: Week 12
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tolvaptan | Number of Participants With Worsening Ascites (Increase in Number of Paracentesis Procedures to Remove 2 Liters of Ascites Fluid) | 0 participants |
Primary
Number of Subjects With Worsening Ascites (Defined as Greater Than 2 kg Weight Gain)
This outcome will provide the number of subjects with a weight increase of \> 2kg from baseline (worsening ascites)
Time frame: 12 weeks of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tolvaptan | Number of Subjects With Worsening Ascites (Defined as Greater Than 2 kg Weight Gain) | 7 participants |
Secondary
Number of Patients With Abnormally Low Levels of Sodium (Sodium Levels Between 130 mmol/L and 135 mmol/L)
Number of Patients with new episodes of hyponatremia (abnormally low levels of sodium) defined as sodium \>130 mmol/L and \<135 mmol/L
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tolvaptan | Number of Patients With Abnormally Low Levels of Sodium (Sodium Levels Between 130 mmol/L and 135 mmol/L) | 1 participants |
Secondary
Number of Patients With Reduction of Ascites (Weight Loss of 2 kg or More)
Number of patients with reduction of ascites is defined as reduction of weight by at least 2 kg during study drug dosing
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tolvaptan | Number of Patients With Reduction of Ascites (Weight Loss of 2 kg or More) | 0 participants |
Secondary
Time From Baseline to Worsening Ascites (Requiring 1 or More Therapeutic Paracentesis to Remove Ascites Fluid)
This outcome will describe the average time from baseline for subjects to require a therapeutic paracentesis to remove ascites fluid.
Time frame: 12 weeks of study drug
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tolvaptan | Time From Baseline to Worsening Ascites (Requiring 1 or More Therapeutic Paracentesis to Remove Ascites Fluid) | 27 Days |