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

• ClinicalTrials.gov Identifier: NCT00727090
• Recruitment Status: Terminated
• First Posted: August 1, 2008
• Results First Posted: September 27, 2010
• Last Update Posted: May 6, 2013
• Sponsor: Northwestern University
• Collaborator: Astellas Pharma US, Inc.
• Information provided by (Responsible Party): Andrew Naidech, Northwestern University

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Hyponatremia	Drug: Conivaptan	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 6 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Use of Conivaptan (Vaprisol) for Hyponatremic Neuro-ICU Patients
• Study Start Date: August 2008
• Actual Primary Completion Date: January 2010
• Actual Study Completion Date: February 2010

Arms and Interventions

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 Name: Vaprisol
No Intervention: 2; Usual care by the attending physician staff

Outcome Measures

Primary Outcome Measures :

1. Change in Serum Sodium From Baseline to 6 Hours [ Time Frame: 48 hours ]

Secondary Outcome Measures :

1. NIH Stroke Scale [ Time Frame: 48 hours ]
   Standardized neurologic examination, ranging from 0 (best) to 42 (worst possible).
2. Glasgow Coma Scale [ Time Frame: 48 hours ]
   Standardized examination of mental status ranging from 3 (worst) to 15 (best possible)

Other Outcome Measures:

1. Change in Serum Sodium From Baseline to 12 Hours [ Time Frame: 12 hours ]
2. Change in Serum Sodium From Baseline to 18 Hours [ Time Frame: 18 hours ]
3. Change in Serum Sodium From Baseline to 24 Hours [ Time Frame: 24 hours ]
4. Change in Serum Sodium From Baseline to 36 Hours [ Time Frame: 36 hours ]
5. Change in Serum Sodium From Baseline to 48 Hours [ Time Frame: 48 hours ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Sponsors and Collaborators

Northwestern University

Astellas Pharma US, Inc.

Investigators

• Principal Investigator: Andrew M Naidech, MD, MSPH; Northwestern University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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].

• Responsible Party: Andrew Naidech, Associate Professor, Northwestern University
• ClinicalTrials.gov Identifier: NCT00727090
• Other Study ID Numbers: 1507-10
• First Posted: August 1, 2008
• Results First Posted: September 27, 2010
• Last Update Posted: May 6, 2013
• Last Verified: April 2013

Additional relevant MeSH terms:

Hyponatremia; Water-Electrolyte Imbalance; Metabolic Diseases; Conivaptan; Antidiuretic Hormone Receptor Antagonists; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Physiological Effects of Drugs