Use of Conivaptan (Vaprisol) for Hyponatremic Neuro-ICU Patients

Conivaptan (Vaprisol) is FDA-Approved for the treatment of low serum sodium (hyponatremia), but there are few data in patients with neurologic disease. Very low serum sodium in patients with brain injury can be life-threatening and is associated with cerebral edema (swelling of brain tissue). This can be important in patients with brain hemorrhage, brain tumors, or stroke (cerebral infarction).

This is a pilot study to test the hypothesis that conivaptan (Vaprisol) leads to a greater increase in sodium than usual care. Patients will be randomly assigned to usual care or the lower FDA-approved dose of conivaptan (Vaprisol). We will track the use of other interventions, such as the use of hypertonic saline (concentrated salt solution), diuretics and salt tablets. A blinded co-investigator will record neurologic examination results (NIH Stroke Scale and Glasgow Coma Scale).

Study Overview

• Status: Terminated
• Conditions: Hyponatremia
• Intervention / Treatment: Drug: Conivaptan

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• severe hyponatremia (Na < 130 mmol/L) or
• symptomatic hyponatremia - Na < 135 mmol/L for at least six hours with Glasgow Coma Scale < 15

Exclusion Criteria:

• Enrollment in the NMH high-risk spine protocol. These patients receive large amounts of fluids, have rapid changes in electrolytes, and are typically corrected in 48 hours
• Expected death from any cause
• Known sensitivity or allergy to conivaptan
• Renal failure (baseline creatinine > 1.5 mg/dL)
• Clinical diagnosis of hypovolemia, or by central venous pressure (CVP) < 5 mm Hg if a central venous catheter is in place
• Concomitant use of potent inhibitors of cytochrome P-450 isoenzyme 3A4 (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir). These agents are not commonly used in the Neuro-ICU
• Clinical diagnosis of liver failure or insufficiency
• Pregnancy (must be excluded before entry)
• Lack of informed consent from the patient or a legally authorized representative (LAR)
• Use of intra-arterial vasodilators (e.g. verapamil, nicardipine) within 24 hours (e.g. for vasospasm after SAH)
• Concern by the Neuro-ICU pharmacist of a drug-drug interaction that would meaningfully impact care (the Neuro-ICU pharmacist will review the medication regimen before recruitment)
• Patients with a diagnosis of diabetes insipidus or treated with vasopressin, since these patients are already treated for abnormal free water balance
• Patients with congestive heart failure, since this is an approved use of the drug (these patients are typically not cared for in the Neuro-ICU)
• Age<18 years (these patients are not cared for at NMH)
• Inclusion declined by the attending physician or consulting study nephrologist

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1; Conivaptan in addition to usual care at the discretion of the attending medical staff	Drug: Conivaptan; Conivaptan 20 mg once, followed by conivaptan 20 mg over 24 hours; Other Names: Vaprisol
NO_INTERVENTION: 2; Usual care by the attending physician staff

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Serum Sodium From Baseline to 6 Hours	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NIH Stroke Scale	Standardized neurologic examination, ranging from 0 (best) to 42 (worst possible).	48 hours
Glasgow Coma Scale	Standardized examination of mental status ranging from 3 (worst) to 15 (best possible)	48 hours

Other Outcome Measures

Outcome Measure	Time Frame
Change in Serum Sodium From Baseline to 12 Hours	12 hours
Change in Serum Sodium From Baseline to 18 Hours	18 hours
Change in Serum Sodium From Baseline to 24 Hours	24 hours
Change in Serum Sodium From Baseline to 36 Hours	36 hours
Change in Serum Sodium From Baseline to 48 Hours	48 hours

Collaborators and Investigators

• Sponsor: Northwestern University
• Collaborators: Astellas Pharma US, Inc.
• Investigators: Principal Investigator: Andrew M Naidech, MD, MSPH, Northwestern University

Publications and helpful links

General Publications

• Naidech AM, Paparello J, Liebling SM, Bassin SL, Levasseur K, Alberts MJ, Bernstein RA, Muro K. Use of Conivaptan (Vaprisol) for hyponatremic neuro-ICU patients. Neurocrit Care. 2010 Aug;13(1):57-61. doi: 10.1007/s12028-010-9379-5. Erratum In: Neurocrit Care. 2011 Aug;15(1):210. Leibling, Storm M [corrected to Liebling, Storm M].

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (ACTUAL): January 1, 2010
• Study Completion (ACTUAL): February 1, 2010

Study Registration Dates

• First Submitted: July 30, 2008
• First Submitted That Met QC Criteria: July 30, 2008
• First Posted (ESTIMATE): August 1, 2008

Study Record Updates

• Last Update Posted (ACTUAL): March 28, 2022
• Last Update Submitted That Met QC Criteria: March 2, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• 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: 1507-10