Tolvaptan for Ascites in Cirrhotic Patients

• Sponsor: University of Florida (Other)
• Overall Status: Completed
• CT.gov ID: NCT01292304
• Collaborator: Otsuka America Pharmaceutical (Industry)
• Enrollment: 10
• Location: 1
• Arm: 1
• Duration (Months): 34
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Ascites; Cirrhosis	Drug: Tolvaptan	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Single Center, Open Labeled Pilot Study Evaluating the Safety and Efficacy of Tolvaptan in Patients With Cirrhotic Ascites
• Study Start Date: Mar 1, 2012
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Jan 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Drug: Tolvaptan; Oral administration once daily Dosage will range from 15 mg to 30 mg; Other Names: (SAMSCA)

Outcome Measures

Primary Outcome Measures

1. 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

2. 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 Outcome Measures

1. 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

2. 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

3. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Florida Hepatology	Gainesville	Florida	United States	32610-0277

Sponsors and Collaborators

• University of Florida
• Otsuka America Pharmaceutical

Investigators

• Principal Investigator: Giuseppe (Joseph) Morelli, MD, University of Florida

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Florida
• ClinicalTrials.gov Identifier: NCT01292304
• Other Study ID Numbers: 156-IST-10-06
• First Posted: Feb 9, 2011
• Last Update Posted: Jul 27, 2015
• Last Verified: Jun 1, 2015

• Keywords provided by University of Florida: Cirrhotic; Tolvaptan; v2 receptor antagonist
• Additional relevant MeSH terms: Ascites; Tolvaptan

Study Results

Participant Flow

Arm/Group Title	Tolvaptan
Arm/Group Description	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
Period Title: Overall Study
STARTED	10
COMPLETED	10
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Tolvaptan
Arm/Group Description	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
Overall Participants	10
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	6 60%
>=65 years	4 40%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	62.5
Sex: Female, Male (Count of Participants)
Female	5 50%
Male	5 50%
Region of Enrollment (participants) [Number]
United States	10 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Worsening Ascites (Increase in Number of Paracentesis Procedures to Remove 2 Liters of Ascites Fluid)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tolvaptan
Arm/Group Description	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
Measure Participants	10
Number [participants]	0 0%

2. Secondary Outcome

Title	Number of Patients With Reduction of Ascites (Weight Loss of 2 kg or More)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tolvaptan
Arm/Group Description	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
Measure Participants	10
Number [participants]	0 0%

3. Secondary Outcome

Title	Number of Patients With Abnormally Low Levels of Sodium (Sodium Levels Between 130 mmol/L and 135 mmol/L)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tolvaptan
Arm/Group Description	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
Measure Participants	10
Number [participants]	1 10%

4. Primary Outcome

Title	Number of Subjects With Worsening Ascites (Defined as Greater Than 2 kg Weight Gain)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tolvaptan
Arm/Group Description	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
Measure Participants	10
Number [participants]	7 70%

5. Secondary Outcome

Title	Time From Baseline to Worsening Ascites (Requiring 1 or More Therapeutic Paracentesis to Remove Ascites Fluid)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tolvaptan
Arm/Group Description	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
Measure Participants	10
Median (Full Range) [Days]	27

Adverse Events

Time Frame	Adverse events collected from baseline day 1 of study drug through day 99 (2 weeks after last dose)
Arm/Group Title	Tolvaptan
Arm/Group Description	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
All Cause Mortality
	Tolvaptan
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Tolvaptan
	Affected / at Risk (%)	# Events
Total	1/10 (10%)
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	1/10 (10%)	2
Other (Not Including Serious) Adverse Events
	Tolvaptan
	Affected / at Risk (%)	# Events
Total	9/10 (90%)
Blood and lymphatic system disorders
Elevated serum creatinine	1/10 (10%)	1
Hyopmagnesemia	1/10 (10%)	1
Hyperkalemia	1/10 (10%)	1
Hypernatrimia	2/10 (20%)	2
Cardiac disorders
Hypertension	1/10 (10%)	2
Gastrointestinal disorders
Abdominal pain	1/10 (10%)	1
Bloating	1/10 (10%)	1
Constipation	1/10 (10%)	2
Nausea	1/10 (10%)	2
Stomach cramps	1/10 (10%)	1
General disorders
Cold Sensitivity	1/10 (10%)	1
Dry mouth	2/10 (20%)	2
Fever	1/10 (10%)	1
Lethargy	1/10 (10%)	1
Polydipsia	8/10 (80%)	8
Infections and infestations
Urinary tract infection	1/10 (10%)	1
Metabolism and nutrition disorders
Polyphagia	1/10 (10%)	1
Musculoskeletal and connective tissue disorders
Back pain	2/10 (20%)	2
Nervous system disorders
Asterixis	1/10 (10%)	1
Headache	1/10 (10%)	1
Nighttime blackouts	1/10 (10%)	1
Vertigo	1/10 (10%)	1
Psychiatric disorders
Depression	1/10 (10%)	1
Stress	1/10 (10%)	1
Renal and urinary disorders
Polyuria	1/10 (10%)	1
Respiratory, thoracic and mediastinal disorders
Lung pain	1/10 (10%)	1
Pleuritic chest pain	1/10 (10%)	1
Skin and subcutaneous tissue disorders
Mouth soreness	1/10 (10%)	1
Pruritus	1/10 (10%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.