Safety and Efficacy of Conivaptan for the Correction of Hyponatremia in Neurological Patients

Safety and Efficacy of Conivaptan for the Correction of Euvolemic and Hypervolemic Hyponatremia in Critically Ill Neurological Patients

Low sodium levels (hyponatremia) are a frequent occurrence in medically ill patients, and in particular those with neurological injury. Hyponatremia has been associated with worse outcome, problems with memory and concentration and impaired balance. Standard treatment for low sodium (salt) levels is to give the patient a salt containing solution thru a catheter (small flexible tube) in a vein in the arm or leg. One of the major complications of this treatment is excess body fluid which may cause heart problems or accumulation of fluid in the lungs and may require additional medications to remove extra water from the body.

FDA approval has recently been granted for a new drug - Conivaptan - for use in hyponatremic conditions. Conivaptan works by excreting free water from the body and thereby produce concurrent rise in serum sodium concentrations. Conivaptan has not been evaluated specifically in patients with brain injuries. The primary objective of this study is to demonstrate the safety and efficacy of intravenous Conivaptan for the treatment of hyponatremia in patients with brain injury. If effective, Conivaptan may represent a safe treatment option.

Study Overview

• Status: Withdrawn
• Conditions: Hyponatremia
• Intervention / Treatment: Drug: Conivaptan; Other: D5

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Acute neurological injury
• Euvolemia or hypervolemia (defined clinically by examination, recent I+Os, BUN/creatinine ratio and CVP [if available])
• Serum sodium less than or equal to 132 mEq/L (confirmed as hypoosmolar hyponatremia by a concurrent source: osmolality measurements [<280 mosoms/L] or by a preceding serum Na+ value <135 mEq/L0

Exclusion Criteria:

• Patients who have uncontrolled hypertension; significant orthostatic hypotension or supine systolic blood pressure less than 85 mm Hg;
• Uncontrolled arrhythmias;
• Untreated severe hypothyroidism, hyperthyroidism, or adrenal insufficiency;
• Estimated creatinine clearance less than 20 ml/min;
• Urinary outflow obstruction unless catheterized;
• Alanine aminotransferase (ALT) >3x ULN
• Aspartate aminotransferase (AST) >3x ULN
• Serum albumin of 1.5 g/dl or less;
• Prothrombin time greater than 22 sec or an international normalized ratio (INR) greater than 2.0 without anticoagulant therapy or 3.0 or more with therapy; a white blood cell count less than 3000/µl;
• HIV infection;
• Active hepatitis.
• Pregnant or nursing
• Participation in a clinical trial of an investigational drug or device within 30 days of screening
• Unable to obtain written consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Subjects in the treatment group will receive standard medical treatment plus Conivaptan administered as a 20mg bolus over 30 min, and then as a 20mg infusion over 24 hours for up to 4 days - or until the study endpoint of sodium ≥135mEq/L is reached.	Drug: Conivaptan; 20mg bolus over 30 min, and then as a 20mg infusion over 24 hours for up to 4 days; Other Names: VAPRISOL
Placebo Comparator: 2; Subjects in the placebo control group will receive an equivalent volume loading dose of D5 followed by an infusion of D5 in the same manner as the experimental group.	Other: D5; Volume loading dose of D5 followed by an infusion of D5 over 24 hours for up to 4 days - or until the study endpoint of sodium ≥135mEq/L is reached.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean change in serum sodium over the duration of treatment between the two treatment arms.	From beginning of treatment to return of sodium level to greater than or equal to 135 mEq/L, up to 4 days of treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of patients requiring study drug discontinuation for any reason other than reaching the sodium endpoint, including those with too rapid a rise in serum sodium (>12 mEq rise over 24 hours) or an infusion site reaction	From the initiation of treatment to the end of treatment, up to 4 days

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: Astellas Pharma Inc
• Investigators: Principal Investigator: Stephan A. Mayer, MD, Columbia University

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Anticipated): November 1, 2009
• Study Completion (Anticipated): June 1, 2010

Study Registration Dates

• First Submitted: May 22, 2008
• First Submitted That Met QC Criteria: May 22, 2008
• First Posted (Estimate): May 26, 2008

Study Record Updates

• Last Update Posted (Estimate): March 6, 2015
• Last Update Submitted That Met QC Criteria: March 5, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Euvolemic Hyponatremia; Hypervolemic Hyponatremia; Neurological injury
• Additional Relevant MeSH Terms: Metabolic Diseases; Water-Electrolyte Imbalance; Hyponatremia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Antidiuretic Hormone Receptor Antagonists; Conivaptan
• Other Study ID Numbers: AAAC6833