Clinical trial NCT01007773: Safety of Dexmedetomidine in Severe Traumatic Brain Injury
Official title: Safety of Dexmedetomidine in Severe Traumatic Brain Injury
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Traumatic Brain Injury
Keywords: Dexmedetomidine
Intracranial Pressure
Traumatic Brain Injury
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: Hospira, now a wholly owned subsidiary of Pfizer
First posted: 2009-11-04
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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 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.

Primary outcomes:
measure: Intracranial pressure
timeFrame: one week
Secondary outcomes:
measure: Doses of other sedatives
timeFrame: one week
measure: Mortality
timeFrame: 6 months
measure: GOS-E
timeFrame: 12 weeks, 6 months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
Study officials:
affiliation: University of Maryland
name: Deborah Stein, MD
role: PRINCIPAL_INVESTIGATOR
References: