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| Name | Class |
|---|---|
| Canadian Critical Care Trials Group | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dexmedetomidine | Experimental | DEX (4 mcg/100 ml supplied by Juno Pharmaceuticals) will be initiated at a starting dose of 0.6 mcg/kg/hour and increased by 0.2 mcg/kg/hour every 30 minutes up to final dose of 1.4 mcg/kg/hour. |
|
| Placebo | Placebo Comparator | Matching placebo (NS 0.9% 100ml) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dexmedetomidine | Drug | DEX 4 mcg/100 ml at a starting dose of 0.6 mcg/kg/hour and increased by 0.2 mcg/kg/hour every 30 minutes up to final dose of 1.4 mcg/kg/hour. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Protocol adherence | Proportion of hours the drug was administered | Through study completion, an average of 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Trial recruitment | Recruitment rate and randomization/activation process (consent rate, proportion of recruited patients who receive the study drug) | Through study completion, an average of 2 years |
| Blinding maintenance |
| Measure | Description | Time Frame |
|---|---|---|
| ICU-days free of agitation or coma within 14 days following randomization | Number of ICU-days without agitation or coma within 14 days following randomization | During ICU stay up to 14 days |
| Agitation-related event during the ICU stay |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Virginie Williams, PhD | Contact | 514-338-2222 | virginie.williams.cnmtl@ssss.gouv.qc.ca |
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| ID | Term |
|---|---|
| D000070642 | Brain Injuries, Traumatic |
| D011595 | Psychomotor Agitation |
| ID | Term |
|---|---|
| D001930 | Brain Injuries |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D020927 | Dexmedetomidine |
| ID | Term |
|---|---|
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Placebo | Drug | NaCl 0.9% 100ml |
|
Proportion of intensivists and nurses predicting study group assignment at the end of the study intervention and proportion of patients receiving propofol
| Through study completion, an average of 2 years |
| Proportion of data collection completed | Data collection completeness for agitation-related events, posttraumatic amnesia and cognitive recovery | Through study completion, an average of 2 years |
Accidental device removal, self-extubation following randomization in the ICU
| Through study completion, an average of 2 years |
| Proportion of patients and the number of days exposed to antipsychotics, benzodiazepines and physical restraints | Exposure to antipsychotics, benzodiazepines and physical restraints after randomization during ICU stay | Through study completion, an average of 2 years |
| Time to mechanical ventilation liberation (extubation), time to ICU and hospital discharge | Time to mechanical ventilation liberation (extubation), time to ICU and hospital discharge | Through study completion, an average of 2 years |
| Time to emergence from posttraumatic amnesia | Time from randomisation to emergence from posttraumatic amnesia | Through study completion, an average of 2 years |
| Cognitive recovery | Brief cognitive assessment in traumatology (EXACT) score (0-100 points); higher scores reflect better function | Through study completion, an average of 2 years |
| D006259 |
| Craniocerebral Trauma |
| D020196 | Trauma, Nervous System |
| D014947 | Wounds and Injuries |
| D020820 | Dyskinesias |
| D009461 | Neurologic Manifestations |
| D011596 | Psychomotor Disorders |
| D019954 | Neurobehavioral Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000096762 | Aberrant Motor Behavior in Dementia |
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |