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

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ClinicalTrials.gov Identifier: NCT01890694
Recruitment Status : Terminated
First Posted : July 2, 2013
Results First Posted : April 11, 2016
Last Update Posted : December 11, 2017
Sponsor:
Collaborator:
Otsuka America Pharmaceutical
Information provided by (Responsible Party):
New York University School of Medicine

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.


Condition or disease Intervention/treatment Phase
Hyponatremia Drug: Tolvaptan Drug: Placebo Behavioral: Hepatic Encephalopathy Assessment Behavioral: Quality of Life Assessment Biological: Vital signs Biological: Blood laboratory tests Procedure: Ascites Evaluation Procedure: Edema Phase 4

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Tolvaptan to Reduce Length of Stay in Hospitalized Patients With Cirrhosis and Hyponatremia
Study Start Date : March 2012
Actual Primary Completion Date : March 2015
Actual Study Completion Date : March 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cirrhosis
Drug Information available for: Tolvaptan

Arm Intervention/treatment
Placebo Comparator: Placebo

Subjects will receive placebo once daily.

They will undergo the following procedures in every visit: Vitals (blood pressure, heart rate, respiration, temperature, weight, height), Laboratory Tests (chemistry, hematology, liver function, urine electrolytes, renin, and copeptin), ascites assessment, evaluation for edema. Quality of life assessments (SF-36, and LDQOL 1.0) will be administered on Day 1, Discharge day, Weeks 1-4 post-discharge, and months 2-6 post-discharge. Hepatic encephalopathy assessment (Number Connection Test, Digit symbol test, Constructional apraxia, Inhibitory control test, Repeatable Battery for the Assessment of Neuropsychological Status) will be administered on Days 1, 2, 4, 6, and 8; discharge day; Weeks 1-4 post-discharge; and Months 2-6 post-discharge.

Drug: Placebo
15 mg once daily

Behavioral: Hepatic Encephalopathy Assessment
The Number connection test, Digit symbol test, Constructional apraxia, Inhibitory control test, Repeatable Battery for the Assessment of Neuropsychological Status will be administered on Days 1, 2, 4, 6, and 8; discharge day; Weeks 1-4 post-discharge; and Months 2-6 post-discharge.

Behavioral: Quality of Life Assessment
The SF-36 and Liver Disease Questionnaire will be administered on Day 1, Discharge day, Weeks 1-4 post-discharge, and months 2-6 post-discharge

Biological: Vital signs
Vital signs (blood pressure, heart rate, respiration, temperature, weight, height) will be recorded at every visit.

Biological: Blood laboratory tests
Blood laboratory tests (chemistry, hematology, liver function, urine electrolytes, renin, and copeptin) will be recorded at every visit.

Procedure: Ascites Evaluation
Ascites will be assessed at every visit.

Procedure: Edema
Edema will be assessed at every visit.

Experimental: Tolvaptan

Subjects will receive Tolvaptan once daily.

They will undergo the following procedures in every visit: Vitals (blood pressure, heart rate, respiration, temperature, weight, height), Laboratory Tests (chemistry, hematology, liver function, urine electrolytes, renin, and copeptin), ascites assessment, evaluation for edema. Quality of life assessments (SF-36, and LDQOL 1.0) will be administered on Day 1, Discharge day, Weeks 1-4 post-discharge, and months 2-6 post-discharge. Hepatic encephalopathy assessment (Number Connection Test, Digit symbol test, Constructional apraxia, Inhibitory control test, Repeatable Battery for the Assessment of Neuropsychological Status) will be administered on Days 1, 2, 4, 6, and 8; discharge day; Weeks 1-4 post-discharge; and Months 2-6 post-discharge.

Drug: Tolvaptan
15 mg once daily

Behavioral: Hepatic Encephalopathy Assessment
The Number connection test, Digit symbol test, Constructional apraxia, Inhibitory control test, Repeatable Battery for the Assessment of Neuropsychological Status will be administered on Days 1, 2, 4, 6, and 8; discharge day; Weeks 1-4 post-discharge; and Months 2-6 post-discharge.

Behavioral: Quality of Life Assessment
The SF-36 and Liver Disease Questionnaire will be administered on Day 1, Discharge day, Weeks 1-4 post-discharge, and months 2-6 post-discharge

Biological: Vital signs
Vital signs (blood pressure, heart rate, respiration, temperature, weight, height) will be recorded at every visit.

Biological: Blood laboratory tests
Blood laboratory tests (chemistry, hematology, liver function, urine electrolytes, renin, and copeptin) will be recorded at every visit.

Procedure: Ascites Evaluation
Ascites will be assessed at every visit.

Procedure: Edema
Edema will be assessed at every visit.




Primary Outcome Measures :
  1. Length of Hospital Stay [ Time Frame: participants will be followed for the duration of hospital stay, an expected average of 2 weeks ]
    Performance period for sponsored trial expired and not enough subjects were enrolled in study. Funding sponsor did not continue support.


Secondary Outcome Measures :
  1. Severity of Hepatic Encephalopathy [ Time Frame: Day 2 ]
    Change from baseline of Hepatic Encephalopathy

  2. Severity of Hepatic Encephalopathy [ Time Frame: Day 4 ]
    Change from baseline of Hepatic Encephalopathy

  3. Severity of Hepatic Encephalopathy [ Time Frame: Day 6 ]
    Change from baseline of Hepatic Encephalopathy

  4. Severity of Hepatic Encephalopathy [ Time Frame: Day 8 ]
    Change from baseline of Hepatic Encephalopathy

  5. 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

  6. Severity of Hepatic Encephalopathy [ Time Frame: Week 1-4 Post-discharge ]
    Change from baseline of Hepatic Encephalopathy

  7. Severity of Hepatic Encephalopathy [ Time Frame: Months 2-6 post-discharge ]
    Change from baseline of Hepatic Encephalopathy

  8. Ascites [ Time Frame: Day 1 to Post-discharge (6 months) ]
    Improved control of ascites

  9. Renal Function [BUN and Creatinine Laboratory Results] [ Time Frame: Day 1 to Post-discharge (6 months) ]
    Improved renal function from baseline

  10. Hospital Readmission Rate [ Time Frame: Post-Discharge (6 months) ]
    Lower readmission rate

  11. Survival [ Time Frame: Post-discharge (6 months) ]
    Improved chances of survival when receiving Tolvaptan vs. standard of care

  12. Neutrophil Function [Results From the Assay of Neutrophils] [ Time Frame: Day 1 to Post-discharge (6 months) ]
    Improved neutrophil function from baseline

  13. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Cirrhosis
  • Screening within 24 hours of admission
  • Na level less than 130mEq/L
  • Presence of fluid overload with either history of ascites or edema
  • Cr < 2.0mg/dl
  • Planned length of stay after randomization of at least 24 hours
  • Anticipated survival of at least 8 days
  • Ability to provide informed consent

Exclusion Criteria:

  • Hospitalization greater than 24 hours at screening
  • Depletional hyponatremia
  • Hyponatremia due to hyperglycemia
  • Acute and transient hyponatremia associated with head trauma or post-operative states
  • Hyponatremia due to primary polydipsia, adrenal insufficiency, or hypothyroidism
  • Urgent need for treatment of hyponatremia with saline or hypertonic saline
  • Treatment with demeclocycline, lithium chloride, and urea
  • Cr greater than 2.0mg/dl
  • Stage 3 or 4 hepatic encephalopathy
  • Inability to provide informed consent
  • Planned discharge within 24 hours
  • Anticipated survival less than 8 days
  • GI bleeding within one month of enrollment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01890694


Locations
United States, New York
NYU Langone Medical Center
New York, New York, United States, 10016
Sponsors and Collaborators
New York University School of Medicine
Otsuka America Pharmaceutical
Investigators
Principal Investigator: Samuel Sigal, MD NYU School of Medicine

Responsible Party: New York University School of Medicine
ClinicalTrials.gov Identifier: NCT01890694     History of Changes
Other Study ID Numbers: 10-02496
First Posted: July 2, 2013    Key Record Dates
Results First Posted: April 11, 2016
Last Update Posted: December 11, 2017
Last Verified: November 2017

Keywords provided by New York University School of Medicine:
Hyponatremia
Dilutional Hyponatremia
Euvolemic Hyponatremia
Hypervolemic Hyponatremia
Fluid Restriction
Tolvaptan

Additional relevant MeSH terms:
Hyponatremia
Water-Electrolyte Imbalance
Metabolic Diseases
Tolvaptan
Antidiuretic Hormone Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Natriuretic Agents
Physiological Effects of Drugs