Safety of Dexmedetomidine in Severe Traumatic Brain Injury

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01007773
Recruitment Status : Withdrawn (Study will not be intiated)
First Posted : November 4, 2009
Last Update Posted : May 27, 2015
Hospira, now a wholly owned subsidiary of Pfizer
Information provided by:
University of Maryland

Brief Summary:
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 or disease Intervention/treatment Phase
Traumatic Brain Injury Drug: Precedex Drug: Propofol Drug: Fentanyl Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: Safety of Dexmedetomidine in Severe Traumatic Brain Injury
Study Start Date : January 2010
Estimated Primary Completion Date : January 2011
Estimated Study Completion Date : January 2012

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. Intracranial pressure [ Time Frame: one week ]

Secondary Outcome Measures :
  1. Doses of other sedatives [ Time Frame: one week ]
  2. Mortality [ Time Frame: 6 months ]
  3. GOS-E [ Time Frame: 12 weeks, 6 months ]

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01007773

United States, Maryland
University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
Sponsors and Collaborators
University of Maryland
Hospira, now a wholly owned subsidiary of Pfizer
Principal Investigator: Deborah Stein, MD University of Maryland

Responsible Party: Deborah Stein, University of Maryland Identifier: NCT01007773     History of Changes
Other Study ID Numbers: HP-00042821
First Posted: November 4, 2009    Key Record Dates
Last Update Posted: May 27, 2015
Last Verified: July 2010

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

Additional relevant MeSH terms:
Wounds and Injuries
Brain Injuries
Brain Injuries, Traumatic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anesthetics, Intravenous
Anesthetics, General
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Analgesics, Opioid
Adjuvants, Anesthesia