Clinical trial NCT06620393: Effects of Dexmedetomidine on Agitation in Critically Ill TBI Patients
Official title: Effects of Dexmedetomidine on Agitation in Critically Ill TBI Patients (DEX-TBI)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Traumatic Brain Injury
Agitation,Psychomotor
Lead sponsor: Centre Integre Universitaire de Sante et Services Sociaux du Nord de l'ile de Montreal
Sponsor class: OTHER
Collaborators: name: Canadian Critical Care Trials Group
First posted: 2024-10-01
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Agitation is a frequent complication following traumatic braing injury in patients admitted to the intensive care unit. This agitation frequently results in the liberal use of rescue drugs such as antipsychotics, sedatives and opiates, which in turn may delay rehabilitation, liberation from mechanical ventilation and emergence from posttraumatic amnesia. Dexmedetomidine may be a better agent given it's light sedative properties. The main objective is to assess the feasibility of conducting a multicenter randomized controlled trial of dexmedetomidine following TBI in the ICU.

Detailed description: Following a traumatic brain injury, agitation is reported in 53-57% of patients in the intensive care unit. As it is associated with accidental removal of catheters, tubes and dressings as well as self-extubation, agitation poses a threat to patient safety. In addition, agitation can be accompanied by aggressive behaviors that pose a threat to clinician safety. This agitation frequently results in the liberal use of rescue drugs such as antipsychotics, sedatives and opiates, which in turn may delay rehabilitation, liberation from mechanical ventilation and emergence from posttraumatic amnesia. Dexmedetomidine is a highly selective alpha-2 adrenergic receptor agonist used for sedation and also has co-analgesic and withdrawal syndrome alleviating properties. Unlike other sedatives, patients remain easily roused when under dexmedetomidine, facilitating contact and removal from mechanical ventilation. In addition, dexmedetomidine does not induce respiratory depression in critically ill patients. The addition of dexmedetomidine may have the potential to reduce the incidence agitation while reducing the use of agitation rescue drugs such as antipsychotics, the use of physical restraints, as well as the time to cessation of mechanical ventilation and consequently, reduce the time to emergence for post-traumatic amnesia. Duration of posttraumatic amnesia is an important outcome as it is a predictor of cognitive and functional outcomes as well as community integration, psychosocial functioning and employment. The main objective is to assess the feasibility of conducting a multicenter randomized controlled trial of dexmedetomidine following TBI in the ICU. To evaluate the feasibility of conducting a large trial and to refine study procedures, a multicenter randomized double-blind placebo-controlled pilot study comparing dexmedetomidine to placebo will be conducted. The feasibility outcomes will include protocol adherence, trial recruitment and time-in-motion evaluation for study procedures. Clinical outcomes will include agitation, exposure to antipsychotics, time to emergence from post-traumatic amnesia, physical restraint use, ventilator days, and time to ICU and hospital discharge as well as ICU and hospital mortality.

Eligibility criteria: Inclusion Criteria:

1. Adults (≥18 years) admitted to ICU with a critically ill moderate or severe TBI patients. Severity of TBI will be determined with the first Glasgow Coma Score (GCS). TBI patients with polytrauma and patients undergoing neurosurgical interventions will be eligible.
2. Undergoing mechanically ventilation (of any duration) at the time of assessment.
3. Anticipated ICU stay of 48 hours or more.

Exclusion Criteria:

1. Patients at very high risk of short-term mortality (e.g., GCS of 3 without sedation, or unreactive pupils, or declared brain-dead when assessed for eligibility and patients in whom there is a lack of commitment to ongoing life support
2. Patients unable to communicate in English or French (interfering with posttraumatic amnesia assessments)
3. Patients with cognitive impairment as per family evaluation
4. Pregnant or breastfeeding
5. Patients currently receiving DEX or clonidine
6. Allergy, bradycardia or hypotension precluding use of dexmedetomidine as per treating physician

Primary outcomes:
measure: Protocol adherence
timeFrame: Through study completion, an average of 2 years
Secondary outcomes:
measure: Trial recruitment
timeFrame: Through study completion, an average of 2 years
measure: Blinding maintenance
timeFrame: Through study completion, an average of 2 years
measure: Proportion of data collection completed
timeFrame: Through study completion, an average of 2 years
Other outcomes:
measure: ICU-days free of agitation or coma within 14 days following randomization
timeFrame: During ICU stay up to 14 days
measure: Agitation-related event during the ICU stay
timeFrame: Through study completion, an average of 2 years
measure: Proportion of patients and the number of days exposed to antipsychotics, benzodiazepines and physical restraints
timeFrame: Through study completion, an average of 2 years
measure: Time to mechanical ventilation liberation (extubation), time to ICU and hospital discharge
timeFrame: Through study completion, an average of 2 years
measure: Time to emergence from posttraumatic amnesia
timeFrame: Through study completion, an average of 2 years
measure: Cognitive recovery
timeFrame: Through study completion, an average of 2 years
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