Safety of Dexmedetomidine in Severe Traumatic Brain Injury

This study has been withdrawn prior to enrollment.
(Study will not be intiated)
Sponsor:
Collaborator:
Hospira, Inc.
Information provided by:
University of Maryland
ClinicalTrials.gov Identifier:
NCT01007773
First received: November 2, 2009
Last updated: July 30, 2010
Last verified: July 2010
  Purpose

The aim of this study is to assess the safety and feasibility of dexmedetomidine as an adjunct to conventional sedative therapy compared to conventional sedative therapy alone in patients with severe traumatic brain injury.


Condition Intervention Phase
Traumatic Brain Injury
Drug: Precedex
Drug: Propofol
Drug: Fentanyl
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: Safety of Dexmedetomidine in Severe Traumatic Brain Injury

Resource links provided by NLM:


Further study details as provided by University of Maryland:

Primary Outcome Measures:
  • Intracranial pressure [ Time Frame: one week ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Doses of other sedatives [ Time Frame: one week ] [ Designated as safety issue: No ]
  • Mortality [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • GOS-E [ Time Frame: 12 weeks, 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: January 2010
Estimated Study Completion Date: January 2012
Estimated Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dexmedetomidine
In conjunction with conventional sedative and analgesic agents.
Drug: Precedex
Once this patient is deemed stable on the propofol infusion, the patient will be started on a dexmedetomidine infusion at 0.4 mcg/kg/hr. The dexmedetomidine infusion will be titrated to a Richmond Agitation Sedation Scale (RASS) of 0 to -1 (maximum rate of 1.5 mcg/kg/hr). In the meantime, once sustained ICP control has been achieved, the initial sedative agent (usually propofol) will be weaned. Dexmedetomidine will be infused for up to 7 days or until removal of the ICP or when mechanical ventilation is discontinued. When the patient is ready to come off sedation, the dexmedetomidine will be weaned by 50% every hour over a 4-hour period to off.
Other Name: Dexmedetomidine
Drug: Propofol
Propofol will be titrated to an ICP < 20 mm Hg until achievement of sustained ICP control.
Other Name: Diprivan
Active Comparator: Standard of Care
Patients randomized to conventional sedation will have as the main pharmacologic agents to achieve sedation and analgesia propofol and fentanyl, respectively.
Drug: Propofol
Propofol will be initiated at 25 mcg/kg/min and titrated to achieve an ICP < 20 mm Hg (up to a maximum of 75 mcg/kg/min). Propofol will be continued for up to 7 days or until removal of the ICP or when mechanical ventilation is discontinued.
Other Name: Diprivan
Drug: Fentanyl
Fentanyl will be initiated and titrated to achieve adequate pain control.
Other Names:
  • Actiq
  • Fentora
  • Instanyl

Detailed Description:

Approximately 52,000 deaths occur from traumatic brain injury (TBI) every year. TBI is a major cause of disability, death, and economic cost to our society. When the brain experiences injury, there is direct damage to the brain tissue causing local bleeding and bruising. This is called the primary injury. Additional damage, called secondary brain injury, can occur as a result of swelling of the brain, lack of oxygen to the brain, lowered blood pressure, and the release of inflammatory mediators. The type and degree of insults are major determinants in the final neurologic outcome of the patient who has sustained a TBI. Management of TBI is aimed at the prevention and treatment of these secondary insults.

The swelling of the brain following injury causes an increase in the pressure within the cranium. Increased pressure can reduce blood flow to parts of the brain, leading to further brain damage. An intracranial pressure (ICP) monitor measures the pressure surrounding the brain, and may be placed following traumatic brain injury to help evaluate swelling.

Agitation of the patient or exposure to painful stimuli may significantly increase ICP, and therefore, the use of sedative agents is important in ICP management. A variety of pharmacological agents have been suggested to treat agitation in the TBI patient. Unfortunately, no optimal sedative regimen has been identified for use in this patient population. One prospect is dexmedetomidine (Precedex®), which is FDA-approved for short-term (≤24 hours) sedation in the intensive care unit. Currently, to our knowledge, dexmedetomidine has not been studied prospectively in adults with traumatic brain injury. The safety and efficacy of dexmedetomidine are therefore unknown in severe TBI. Propofol is employed as a first-line sedative agent in neurotrauma patients due to its favorable pharmacokinetic profile. However, some patients require prolonged infusions and high rates of propofol. This has been shown increase their risk for development of a severe propofol-related infusion syndrome, which can be fatal.

Dexmedetomidine as an adjunct to existing conventional sedative therapy may help to facilitate decreasing the amount of other agents used, such as propofol. Therefore, the aim of this study is to assess the safety and feasibility of dexmedetomidine as an adjunct to conventional sedative therapy compared to conventional sedative therapy alone in patients with severe TBI.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of severe traumatic brain injury, as defined by AIS score >2 for the head.
  • Glasgow Coma Score (GCS) <9 on admission, or deterioration of GCS to <9 within 48 hours of admission due to traumatic brain injury.
  • Placement of an intracranial pressure (ICP) monitor or intraventricular catheter (IVC) at the discretion of the Neurosurgical staff as part of standard of care.
  • Patient is between 18 and 80 years of age, inclusive.

Exclusion Criteria:

  • A body region, other than the brain, with an AIS score >2, or multiple system injury at the investigator's discretion.
  • Glasgow Coma Score (GCS) >8 on admission or no decrease of GCS to <9 within 48 hours of admission.
  • Placement of an ICP monitor or IVC not clinically indicated by Neurosurgical staff.
  • Patient is under the age of 18, or over the age of 80.
  • Determination of non-survivability due to the severity of brain injury.
  • Non-English speaking, consentable LAR, or patient is non-English speaking.
  • Patient is pregnant.
  • Unable to obtain consent from a legally authorized representative (LAR).
  • Patient is a prisoner, on parole or probation.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01007773

Locations
United States, Maryland
University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
Sponsors and Collaborators
University of Maryland
Hospira, Inc.
Investigators
Principal Investigator: Deborah Stein, MD University of Maryland
  More Information

No publications provided

Responsible Party: Deborah Stein, University of Maryland
ClinicalTrials.gov Identifier: NCT01007773     History of Changes
Other Study ID Numbers: HP-00042821, PRE-08-019
Study First Received: November 2, 2009
Last Updated: July 30, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Maryland:
Dexmedetomidine
Intracranial Pressure
Traumatic Brain Injury

Additional relevant MeSH terms:
Brain Injuries
Wounds and Injuries
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Fentanyl
Propofol
Dexmedetomidine
Adjuvants, Anesthesia
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Analgesics, Opioid
Hypnotics and Sedatives
Analgesics, Non-Narcotic
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents

ClinicalTrials.gov processed this record on July 23, 2014