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

This study has been withdrawn prior to enrollment.
(Unable to complete a contract with the Sponsor.)
Sponsor:
Collaborator:
Astellas Pharma Inc
Information provided by:
Columbia University
ClinicalTrials.gov Identifier:
NCT00684164
First received: May 22, 2008
Last updated: February 10, 2009
Last verified: February 2009
  Purpose

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.


Condition Intervention Phase
Hyponatremia
Drug: Conivaptan
Other: D5
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Safety and Efficacy of Conivaptan for the Correction of Euvolemic and Hypervolemic Hyponatremia in Critically Ill Neurological Patients

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Mean change in serum sodium over the duration of treatment between the two treatment arms. [ Time Frame: From beginning of treatment to return of sodium level to greater than or equal to 135 mEq/L, up to 4 days of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The 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 [ Time Frame: From the initiation of treatment to the end of treatment, up to 4 days ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 50
Study Start Date: May 2008
Estimated Study Completion Date: June 2010
Estimated Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00684164

Locations
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
Sponsors and Collaborators
Columbia University
Astellas Pharma Inc
Investigators
Principal Investigator: Stephan A. Mayer, MD Columbia University
  More Information

No publications provided

Responsible Party: Stephan A. Mayer, MD, Columbia University Medical Center
ClinicalTrials.gov Identifier: NCT00684164     History of Changes
Other Study ID Numbers: AAAC6833
Study First Received: May 22, 2008
Last Updated: February 10, 2009
Health Authority: United States: Institutional Review Board

Keywords provided by Columbia University:
Euvolemic Hyponatremia
Hypervolemic Hyponatremia
Neurological injury

Additional relevant MeSH terms:
Hyponatremia
Water-Electrolyte Imbalance
Metabolic Diseases

ClinicalTrials.gov processed this record on October 16, 2014