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

NCT00684164 | Withdrawn Phase 3 DMC

• 1 other identifier: AAAC6833
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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

Keywords

Euvolemic Hyponatremia; Hypervolemic Hyponatremia; Neurological injury

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• 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

Study Arms (2)

1

EXPERIMENTAL

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

2

PLACEBO COMPARATOR

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

Interventions

Conivaptan DRUG

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

Also known as: VAPRISOL

1

D5 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.

2

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Columbia University: lead
• Astellas Pharma Inc: collaborator

Study Sites (1)

Columbia University Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Hyponatremia; Trauma, Nervous System

Interventions

conivaptan

Condition Hierarchy (Ancestors)

Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases; Nervous System Diseases; Wounds and Injuries

Study Officials

• Stephan A. Mayer, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: May 22, 2008
• First Posted: May 26, 2008
• Study Start: May 1, 2008
• Primary Completion: November 1, 2009
• Study Completion: June 1, 2010
• Last Updated: March 6, 2015

Record last verified: 2015-03

Locations

US (1)