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

NCT01890694 | Terminated Phase 4 Results DMC

• 1 other identifier: 10-02496
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Hyponatremia

Keywords

Hyponatremia; Dilutional Hyponatremia; Euvolemic Hyponatremia; Hypervolemic Hyponatremia; Fluid Restriction; Tolvaptan

Outcome Measures

Primary Outcomes (1)

• Length of Hospital Stay

  Performance period for sponsored trial expired and not enough subjects were enrolled in study. Funding sponsor did not continue support.

  participants will be followed for the duration of hospital stay, an expected average of 2 weeks

Secondary Outcomes (13)

• Severity of Hepatic Encephalopathy

  Day 2

• Severity of Hepatic Encephalopathy

  Day 4

• Severity of Hepatic Encephalopathy

  Day 6

• Severity of Hepatic Encephalopathy

  Day 8

• Severity of Hepatic Encephalopathy

  participants will be followed for the duration of hospital stay, an expected average of 2 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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; Behavioral: Hepatic Encephalopathy Assessment; Behavioral: Quality of Life Assessment; Biological: Vital signs; Biological: Blood laboratory tests; Procedure: Ascites Evaluation; Procedure: Edema

Tolvaptan

EXPERIMENTAL

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; Behavioral: Hepatic Encephalopathy Assessment; Behavioral: Quality of Life Assessment; Biological: Vital signs; Biological: Blood laboratory tests; Procedure: Ascites Evaluation; Procedure: Edema

Interventions

Tolvaptan DRUG

15 mg once daily

Tolvaptan

Placebo DRUG

15 mg once daily

Placebo

Hepatic Encephalopathy Assessment BEHAVIORAL

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.

Placebo; Tolvaptan

Quality of Life Assessment BEHAVIORAL

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

Placebo; Tolvaptan

Vital signs BIOLOGICAL

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

Placebo; Tolvaptan

Blood laboratory tests BIOLOGICAL

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

Placebo; Tolvaptan

Ascites Evaluation PROCEDURE

Ascites will be assessed at every visit.

Placebo; Tolvaptan

Edema PROCEDURE

Edema will be assessed at every visit.

Placebo; Tolvaptan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• NYU Langone Health: lead
• Otsuka America Pharmaceutical: collaborator

Study Sites (1)

NYU Langone Medical Center

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Hyponatremia

Interventions

Tolvaptan

Condition Hierarchy (Ancestors)

Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Due to the small sample size, data was not able to be analyzed.

Results Point of Contact

• Title: Office of Clinical Trials
• Organization: NYU Langone Medical Center

clinicaltrials@nyumc.org

646-754-7431

Study Officials

• Samuel Sigal, MD

  NYU School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2012
• First Posted: July 2, 2013
• Study Start: March 1, 2012
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: December 11, 2017
• Results First Posted: April 11, 2016

Record last verified: 2017-11

Locations

US (1)