Safety of Dexmedetomidine in Severe Traumatic Brain Injury
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|ClinicalTrials.gov Identifier: NCT01007773|
Recruitment Status : Withdrawn (Study will not be intiated)
First Posted : November 4, 2009
Last Update Posted : May 27, 2015
|Condition or disease||Intervention/treatment||Phase|
|Traumatic Brain Injury||Drug: Precedex Drug: Propofol Drug: Fentanyl||Phase 2|
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|
|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|
In conjunction with conventional sedative and analgesic agents.
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: DexmedetomidineDrug: 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.
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: DiprivanDrug: Fentanyl
Fentanyl will be initiated and titrated to achieve adequate pain control.
- Intracranial pressure [ Time Frame: one week ]
- Doses of other sedatives [ Time Frame: one week ]
- Mortality [ Time Frame: 6 months ]
- GOS-E [ Time Frame: 12 weeks, 6 months ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01007773
|United States, Maryland|
|University of Maryland Medical Center|
|Baltimore, Maryland, United States, 21201|
|Principal Investigator:||Deborah Stein, MD||University of Maryland|