Clinical Trial: Tolvaptan to Reduce Length of Stay in Hospitalized Patients With Cirrhosis and Hyponatremia

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Tolvaptan to Reduce Length of Stay in Hospitalized Patients With Cirrhosis and Hyponatremia

Brief Summary:

Hyponatremia is a condition in which there is a low sodium level in the blood. Individuals with cirrhosis may develop low blood sodium as a complication of their liver disease. In these patients, the presence of low blood sodium may exacerbate other complications such as encephalopathy, resulting in confusion, drowsiness, or coma. It may also affect the ability of the body to fight infection. In certain cases, cirrhotic patients may be hospitalized for the treatment of their low blood sodium.

The drug tolvaptan is currently FDA approved for the treatment of hyponatremia in patients with cirrhosis. Although it has been shown to increase the sodium level, the clinical trials that led to its approval did not otherwise assess clinical benefit of the drug.

This study is designed to determine whether patients with cirrhosis derive a clinical benefit when they receive tolvaptan for the treatment of hyponatremia within 2 days of admission. Specifically, whether it is associated with shortened length of stay and improvement in other complications of cirrhosis.

Detailed Summary:

As per hyponatremia standard treatment of care, all patients considered for the study will have had diuretic therapy discontinued for at least 1 day prior to the screening visit and received volume expansion with 25% salt poor albumin, if clinically indicated to ensure adequate intravascular volume expansion as standard of care for a patient hospitalized for complications of cirrhosis.

Patients will be approached and presented with a written consent form during the first 24 hours of their admission to NYUMC (Tisch Hospital). They will be verbally informed about the purpose and procedures of the study, as well as its potential risks and benefits. Following written consent, the patients will undergo a series of screening procedures, including physical examination, medical history, blood work, and hepatic encephalopathy assessment, to determine their eligibility.

After screening and determination that the patient fulfills all inclusion and exclusion criteria, the patients will be randomized the following day on Day 0 to receive oral tolvaptan or placebo once daily. Patients in the treatment arm will receive oral tolvaptan at an initial dose of 15mg once daily. The placebo arm will be used as a comparison group to determine whether long-term, ambulatory tolvaptan administration is associated with clinical benefits to patients with cirrhosis and hyponatremia. Patients in the placebo arm will receive current standard of treatment for patients with cirrhosis and hyponatremia. Current standard treatment of hyponatremia in cirrhotic patients involves fluid restriction in the diet (1L fluid daily), discontinuation of diuretic therapy (such as furosemide, spironolactone), and frequent monitoring of the sodium level. Severe hyponatremia (Na<120mEq/L) involves infusion of hypertonic saline.

Same as current

Current Secondary Outcome:

• Severity of Hepatic Encephalopathy [ Time Frame: Day 2 ]
  Change from baseline of Hepatic Encephalopathy
• Severity of Hepatic Encephalopathy [ Time Frame: Day 4 ]
  Change from baseline of Hepatic Encephalopathy
• Severity of Hepatic Encephalopathy [ Time Frame: Day 6 ]
  Change from baseline of Hepatic Encephalopathy
• Severity of Hepatic Encephalopathy [ Time Frame: Day 8 ]
  Change from baseline of Hepatic Encephalopathy
• Severity of Hepatic Encephalopathy [ Time Frame: participants will be followed for the duration of hospital stay, an expected average of 2 weeks ]
  Change from baseline of Hepatic Encephalopathy
• Severity of Hepatic Encephalopathy [ Time Frame: Week 1-4 Post-discharge ]
  Change from baseline of Hepatic Encephalopathy
• Severity of Hepatic Encephalopathy [ Time Frame: Months 2-6 post-discharge ]
  Change from baseline of Hepatic Encephalopathy
• Ascites [ Time Frame: Day 1 to Post-discharge (6 months) ]
  Improved control of ascites
• Renal Function [BUN and Creatinine Laboratory Results] [ Time Frame: Day 1 to Post-discharge (6 months) ]
  Improved renal function from baseline
• Hospital Readmission Rate [ Time Frame: Post-Discharge (6 months) ]
  Lower readmission rate
• Survival [ Time Frame: Post-discharge (6 months) ]
  Improved chances of survival when receiving Tolvaptan vs. standard of care
• Neutrophil Function [Results From the Assay of Neutrophils] [ Time Frame: Day 1 to Post-discharge (6 months) ]
  Improved neutrophil function from baseline
• Tolerability of Diuretic Therapy [ Time Frame: Day 1 until Discharge (participants will be followed for the duration of hospital stay, an expected average of 2 weeks) ]
  Improved ability to tolerate diuretic therapy, as evidenced by reduced adverse events to diuretic therapy and reduced risk of re-hospitalization.

Original Secondary Outcome:

• Severity of Hepatic Encephalopathy [ Time Frame: Day 2 ]
  Change from baseline of Hepatic Encephalopathy
• Severity of Hepatic Encephalopathy [ Time Frame: Day 4 ]
  Change from baseline of Hepatic Encephalopathy
• Severity of Hepatic Encephalopathy [ Time Frame: Day 6 ]
  Change from baseline of Hepatic Encephalopathy
• Severity of Hepatic Encephalopathy [ Time Frame: Day 8 ]
  Change from baseline of Hepatic Encephalopathy
• Severity of Hepatic Encephalopathy [ Time Frame: participants will be followed for the duration of hospital stay, an expected average of 2 weeks ]
  Change from baseline of Hepatic Encephalopathy
• Severity of Hepatic Encephalopathy [ Time Frame: Week 1-4 Post-discharge ]
  Change from baseline of Hepatic Encephalopathy
• Severity of Hepatic Encephalopathy [ Time Frame: Months 2-6 post-discharge ]
  Change from baseline of Hepatic Encephalopathy
• Ascites [ Time Frame: Day 1 to Post-discharge (6 months) ]
  Improved control of ascites
• Renal function [ Time Frame: Day 1 to Post-discharge (6 months) ]
  Improved renal function from baseline
• Hospital Readmission Rate [ Time Frame: Post-Discharge (6 months) ]
  Lower readmission rate
• Survival [ Time Frame: Post-discharge (6 months) ]
  Improved survival
• Neutrophil function [ Time Frame: Day 1 to Post-discharge (6 months) ]
  Improved neutrophil function from baseline
• Tolerability of Diuretic Therapy [ Time Frame: Day 1 until Discharge (participants will be followed for the duration of hospital stay, an expected average of 2 weeks) ]
  Improved ability to tolerate diuretic therapy

Information By: New York University School of Medicine

Dates:
Date Received: June 20, 2012
Date Started: March 2012
Date Completion:
Last Updated: October 26, 2016
Last Verified: October 2016