Effects of Dexmedetomidine on Agitation in Critically Ill TBI Patients

NCT ID: NCT06620393

Last Updated: 2024-10-01

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-10-01
• Study Completion Date: 2026-12-01

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.

Conditions

Traumatic Brain Injury; Agitation,Psychomotor

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Dexmedetomidine

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.

Group Type: EXPERIMENTAL

Dexmedetomidine

Intervention Type: 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.

Placebo

Matching placebo (NS 0.9% 100ml)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

NaCl 0.9% 100ml

Interventions

Dexmedetomidine

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.

Intervention Type: DRUG

Placebo

NaCl 0.9% 100ml

Intervention Type: DRUG

Other Intervention Names

Precedex

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Critical Care Trials Group

OTHER

Sponsor Role: collaborator

Centre Integre Universitaire de Sante et Services Sociaux du Nord de l'ile de Montreal

OTHER

Sponsor Role: lead

Responsible Party

David Williamson

Full Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Virginie Williams, PhD

Role: CONTACT

virginie.williams.cnmtl@ssss.gouv.qc.ca

514-338-2222

Other Identifiers

MP-32-2024-2732

Identifier Type: -

Identifier Source: org_study_id