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

NCT ID: NCT00684164

Last Updated: 2015-03-06

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-05-31
• Study Completion Date: 2010-06-30

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.

Conditions

Hyponatremia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Conivaptan

Intervention Type: DRUG

20mg bolus over 30 min, and then as a 20mg infusion over 24 hours for up to 4 days

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.

Group Type: PLACEBO_COMPARATOR

D5

Intervention Type: OTHER

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.

Interventions

Conivaptan

20mg bolus over 30 min, and then as a 20mg infusion over 24 hours for up to 4 days

Intervention Type: DRUG

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.

Intervention Type: OTHER

Other Intervention Names

VAPRISOL

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Astellas Pharma Inc

INDUSTRY

Sponsor Role: collaborator

Columbia University

OTHER

Sponsor Role: lead

Responsible Party

Columbia University Medical Center

Principal Investigators

Stephan A. Mayer, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Columbia University Medical Center

New York, New York, United States

Countries

United States

Other Identifiers

AAAC6833

Identifier Type: -

Identifier Source: org_study_id