Ketamine in Acute Brain Injury Patients.

NCT05097261 | Recruiting Phase 4 DMC

• 2 other identifiers: S608592017-004698-15
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 8

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.

Conditions

Brain Injuries, Traumatic

Outcome Measures

Primary Outcomes (1)

• Change in therapeutic intensity of intracranial pressure (ICP) reducing measures, assessed by the TIL score (Therapy Intensity Level)

  The primary efficacy endpoint will be the reduction in daily Therapy Intensity Level (TIL) score, based on the highest score in each item per day until study drug discontinuation (calculated every day on the available data at 7:00 AM). Scales for TIL score range from 0 (minimum) to 38 (maximum). Higher scores are related to worse outcome.

  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 (16)

• Intracranial pressure (ICP)

  From date of randomization until study drug discontinuation or or date of death from any cause, whichever came first, assessed up to 6 months.

• Duration of sedation

  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.

• Propofol

  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.

• Mechanical ventilation

  From date of randomization until study drug discontinuation or date of death from any cause, whichever came first, assessed up to 6 months.

• Midazolam

  From date of randomization until study drug discontinuation or date of death from any cause, whichever came first, assessed up to 6 months.

Study Arms (2)

Ketamine

EXPERIMENTAL

Racemic ketamine® will be administered by continuous infusion in a prefilled 50 ml syringe at a concentration of 50 mg/ml, undiluted. The ketamine dose is 1 mg/kg/h, to a maximum dose of 120 mg/hour, which corresponds to an infusion rate of 0.02 ml/kg/h to a maximum rate of 2.4 ml/h. Study patients weighing over 120 kg will not exceed the maximum dose of 120mg/kg of ketamine. The study medication will be started within 6 hours after randomization. The IMP, ketamine, will be provided directly to each Participating Site by the official supplier of ketamine for Belgium (Pfizer).

Drug: Ketamine

Placebo

ACTIVE COMPARATOR

The placebo (NaCl 0.9%) will be provided in the same type syringes and administered at the same infusion rate as the IMP (0.02 ml/kg/h to a maximum rate of 2.4 ml/h).

Drug: Placebo

Interventions

Ketamine DRUG

Racemic ketamine® will be administered by continuous infusion in a prefilled 50 ml syringe at a concentration of 50 mg/ml, undiluted. The ketamine dose is 1 mg/kg/h, to a maximum dose of 120 mg/hour, which corresponds to an infusion rate of 0.02 ml/kg/h to a maximum rate of 2.4 ml/h.

Also known as: Ketalar

Ketamine

Placebo DRUG

Placebo (NaCl 0.9%) will be provided in the same type syringes and administered at the same infusion rate as the IMP (0.02 ml/kg/h to a maximum rate of 2.4 ml/h).

Also known as: Saline

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Known pregnancy and/or lactation
• Allergy or intolerance to the study medication
• Pre-existing neurocognitive disorders, pre-existing congenital or non-congenital brain dysfunction.
• Inability to obtain informed consent
• Porphyria
• Glaucoma

Sponsors & Collaborators

• Geert Meyfroidt, MD, PhD: lead
• University of Liege: collaborator
• Centre Hospitalier Régional de la Citadelle: collaborator
• AZ Delta: collaborator
• AZ Sint-Jan AV: collaborator
• AZ Turnhout: collaborator
• Imelda Hospital, Bonheiden: collaborator

Study Sites (8)

Imelda Bonheiden

Bonheiden, Belgium

RECRUITING

AZ Sint-Jan

Bruges, Belgium

RECRUITING

Jessa Ziekenhuis

Hasselt, 3500, Belgium

RECRUITING

UZLeuven

Leuven, 3001, Belgium

RECRUITING

CHR de la Citadelle Liège

Liège, Belgium

RECRUITING

CHU de Liège

Liège, Belgium

RECRUITING

AZ Delta

Roeselare, Belgium

RECRUITING

AZ Turnhout

Turnhout, Belgium

RECRUITING

Related Publications (1)

• De Sloovere V, Mebis L, Wouters P, Guiza F, Boonen E, Bourgeois M, Dubois J, Ledoux D, Lormans P, Marechal H, Van der Hauwaert E, Depreitere B, Meyfroidt G. Brain Injury and Ketamine study (BIKe): a prospective, randomized controlled double blind clinical trial to study the effects of ketamine on therapy intensity level and intracranial pressure in severe traumatic brain injury patients. Trials. 2025 May 28;26(1):177. doi: 10.1186/s13063-025-08835-5.

  PMID: 40437634 DERIVED

MeSH Terms

Conditions

Brain Injuries, Traumatic

Interventions

Ketamine; Sodium Chloride

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Geert Meyfroidt, MD PhD

  Associate Professor of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Liese Mebis, PhD

CONTACT

003216343125; liese.mebis@uzleuven.be

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: September 8, 2020
• First Posted: October 28, 2021
• Study Start: September 6, 2021
• Primary Completion: December 31, 2025
• Study Completion (Estimated): June 30, 2026
• Last Updated: August 22, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

BE (8)