Tolvaptan for Ascites in Cirrhotic Patients

Single Center, Open Labeled Pilot Study Evaluating the Safety and Efficacy of Tolvaptan in Patients With Cirrhotic Ascites

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.

Study Overview

• Status: Completed
• Conditions: Cirrhosis; Ascites
• Intervention / Treatment: Drug: Tolvaptan

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 Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610-0277
      • University Of Florida Hepatology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Week 12
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)	12 weeks of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	12 weeks
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	12 weeks
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.	12 weeks of study drug

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: Otsuka America Pharmaceutical
• Investigators: Principal Investigator: Giuseppe (Joseph) Morelli, MD, University of Florida

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): January 1, 2015

Study Registration Dates

• First Submitted: February 7, 2011
• First Submitted That Met QC Criteria: February 7, 2011
• First Posted (Estimate): February 9, 2011

Study Record Updates

• Last Update Posted (Estimate): July 27, 2015
• Last Update Submitted That Met QC Criteria: June 30, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: Cirrhotic; Tolvaptan; v2 receptor antagonist
• Additional Relevant MeSH Terms: Pathologic Processes; Ascites; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Antidiuretic Hormone Receptor Antagonists; Tolvaptan
• Other Study ID Numbers: 156-IST-10-06