Clinical trial NCT05097261: Ketamine in Acute Brain Injury Patients.
Official title: Brain Injury and Ketamine: a Prospective, Randomized Controlled Double Blind Clinical Trial to Study the Effects of Ketamine on Sedative Sparing and Intracranial Pressure in Traumatic Brain Injury Patients.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Brain Injuries, Traumatic
Lead sponsor: KU Leuven
Sponsor class: OTHER
Collaborators: name: University of Liege
name: Centre Hospitalier Régional de la Citadelle
name: AZ Delta
name: AZ Sint-Jan AV
name: AZ Turnhout
name: Imelda Hospital, Bonheiden
First posted: 2021-10-28
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: Although, in the past years, an increasing use of ketamine in Traumatic Brain injury (TBI) has been reported as an adjunct to other sedatives, there is no evidence from randomized clinical trial to support this practice.

The BIKe (Brain Injury and Ketamine) study is a double-blind placebo controlled randomized multicenter clinical trial to examine the safety and feasibility of using ketamine as an adjunct to a standard sedative strategy in TBI patients.

Detailed description: In this study the effects of ketamine as an adjunct to an standard sedation regime in adult TBI patients will be investigated on the therapy intensity level and intracranial pressure. All patients will receive propofol for sedation to control ICP, to a maximum dose of 4 mg/kg/h. If the ICP is not controlled at the maximum dose of propofol, midazolam will be added, to a maximum dose of 0.3 mg/kg/h, as part of the current standard of care in the Participating Sites. All patients will receive remifentanil, fentanyl or sufentanil infusions for pain relief. The study medication (ketamine or placebo) will be started after randomization.

As part of the current standard of care in the Participating Sites, the decision for decompressive craniectomy and/or barbiturate coma will be taken after multidisciplinary consultation between the treating intensivist and neurosurgeon.

The decision to stop or reduce sedation, lies with the treating physician, based on the level of ICP control, the absence of clinical or radiological signs of deterioration of the neurologic state. In the case of barbiturate coma, the study drug will be discontinued. During and following decompressive craniectomy, the sedative regime (propofol/midazolam/study drug/ opioids) will be continued. In case of suspected or threatening Propofol-Related Infusion syndrome, propofol will be stopped and switched to midazolam. In case of hypertriglyceridemia \>200 mg/dL, propofol will be reduced and if necessary, midazolam will be associated to allow control of sedation. During surgical procedures related to the traumatic brain injury or not, the study drug will not be discontinued. The use of open label administration of ketamine is not allowed during the course of the trial, i.e until hospital discharge.

Eligibility criteria: Inclusion Criteria:

* Traumatic brain injury patients
* Age \>= 18 years
* Admitted to the ICU
* Within 72 hours after admission to the initial hospital:

  * ICP monitoring in place (parenchymal probe, ventricular catheter, or both)
  * Requiring sedation

Exclusion Criteria:

* Known pregnancy and/or lactation
* Imminent or actual brain death upon inclusion
* Allergy or intolerance to the study medication
* Pre-existing neurocognitive disorders, pre-existing congenital or non-congenital brain dysfunction.
* Inability to obtain informed consent
* Inclusion in an interventional randomised controlled trial of which the PI indicates that co-inclusion specifically in the BIKe study is prohibited.
* Therapy restriction code upon inclusion.
* Porphyria
* Glaucoma

Primary outcomes:
measure: Change in therapeutic intensity of intracranial pressure (ICP) reducing measures, assessed by the TIL score (Therapy Intensity Level)
timeFrame: From date of randomization (and start study drug) until study drug discontinuation or date of death from any cause, whichever came first, assessed up to 6 months.
Secondary outcomes:
measure: Intracranial pressure (ICP)
timeFrame: From date of randomization until study drug discontinuation or or date of death from any cause, whichever came first, assessed up to 6 months.
measure: Duration of sedation
timeFrame: defined as the start of the first infusion of either propofol, midazolam and/or dexmedetomidine to the cessation of the last uninterrupted infusion of either propofol, midazolam, opioids and/or dexmedetomidine, assessed up to 6 months.
measure: Propofol
timeFrame: From date of randomization until study drug discontinuation or date of death from any cause, whichever came first, assessed at ICU discharge, assessed up to 6 months.
measure: Mechanical ventilation
timeFrame: From date of randomization until study drug discontinuation or date of death from any cause, whichever came first, assessed up to 6 months.
measure: Midazolam
timeFrame: From date of randomization until study drug discontinuation or date of death from any cause, whichever came first, assessed up to 6 months.
measure: ICU length of stay
timeFrame: From ICU admission until ICU discharge (end of stay is defined as application for discharge in the hospital computer system, or death), assessed up to 6 months.
measure: Hospital length of stay
timeFrame: From admission to hospital until end of stay in hospital (dead or alive), assessed up to 6 months.
measure: Richmond Agitation-Sedation scale (RASS)
timeFrame: From date of randomization until study drug discontinuation or date of death from any cause, whichever came first, assessed up to 6 months.
measure: Delirium
timeFrame: From date of randomization until study drug discontinuation or date of death from any cause, whichever came first, assessed up to 6 months.
measure: eGOS
timeFrame: 6 months after the onset of TBI
measure: ICU mortality
timeFrame: From date of randomization until ICU discharge, assessed up to 6 months.
measure: In-hospital mortality
timeFrame: From date of randomization until hospital discharge, assessed up to 6 months.
measure: Barbiturate coma incidence
timeFrame: From date of randomization until study drug discontinuation or date of death from any cause, whichever came first, assessed up to 6 months.
measure: Barbiturate coma duration
timeFrame: From date of randomization until study drug discontinuation or date of death from any cause, whichever came first, assessed up to 6 months.
measure: Decompressive craniectomy
timeFrame: From date of randomization until study drug discontinuation or date of death from any cause, whichever came first, assessed up to 6 months, assessed up to 6 months.
measure: Propofol Infusion Syndrome (PRIS)
timeFrame: From date of randomization until study drug discontinuation or date of death from any cause, whichever came first, assessed up to 6 months.
Other outcomes:
Locations:
city: Bonheiden
country: Belgium
facility: Imelda Bonheiden
city: Brugge
country: Belgium
facility: AZ Sint-Jan
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis
city: Leuven
country: Belgium
facility: UZLeuven
city: Liège
country: Belgium
facility: CHR de la Citadelle Liège
city: Liège
country: Belgium
facility: CHU de Liège
city: Roeselare
country: Belgium
facility: AZ Delta
city: Turnhout
country: Belgium
facility: AZ Turnhout
Study officials:
affiliation: Associate Professor of Medicine
name: Geert Meyfroidt, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: