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

Primary Purpose

Hyponatremia

Status
Withdrawn
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Conivaptan
D5
Sponsored by
Columbia University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hyponatremia focused on measuring Euvolemic Hyponatremia, Hypervolemic Hyponatremia, Neurological injury

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Columbia University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

1

2

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Mean change in serum sodium over the duration of treatment between the two treatment arms.

Secondary Outcome Measures

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

Full Information

First Posted
May 22, 2008
Last Updated
March 5, 2015
Sponsor
Columbia University
Collaborators
Astellas Pharma Inc
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1. Study Identification

Unique Protocol Identification Number
NCT00684164
Brief Title
Safety and Efficacy of Conivaptan for the Correction of Hyponatremia in Neurological Patients
Official Title
Safety and Efficacy of Conivaptan for the Correction of Euvolemic and Hypervolemic Hyponatremia in Critically Ill Neurological Patients
Study Type
Interventional

2. Study Status

Record Verification Date
March 2015
Overall Recruitment Status
Withdrawn
Why Stopped
Unable to complete a contract with the Sponsor
Study Start Date
May 2008 (undefined)
Primary Completion Date
November 2009 (Anticipated)
Study Completion Date
June 2010 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor
Columbia University
Collaborators
Astellas Pharma Inc

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hyponatremia
Keywords
Euvolemic Hyponatremia, Hypervolemic Hyponatremia, Neurological injury

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
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.
Arm Title
2
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Conivaptan
Other Intervention Name(s)
VAPRISOL
Intervention Description
20mg bolus over 30 min, and then as a 20mg infusion over 24 hours for up to 4 days
Intervention Type
Other
Intervention Name(s)
D5
Intervention Description
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.
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephan A. Mayer, MD
Organizational Affiliation
Columbia University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States

12. IPD Sharing Statement

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

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