Ketamine in Acute Brain Injury Patients.

NCT ID: NCT05097261

Last Updated: 2024-08-22

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-06
• Study Completion Date: 2026-06-30

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.

Conditions

Brain Injuries, Traumatic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: DOUBLE

Study Groups

Ketamine

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).

Group Type: EXPERIMENTAL

Ketamine

Intervention Type: 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.

Placebo

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).

Group Type: ACTIVE_COMPARATOR

Placebo

Intervention Type: 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).

Interventions

Ketamine

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.

Intervention Type: DRUG

Placebo

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).

Intervention Type: DRUG

Other Intervention Names

Ketalar; Saline

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

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

Sponsors

University of Liege

OTHER

Sponsor Role: collaborator

Centre Hospitalier Régional de la Citadelle

OTHER

Sponsor Role: collaborator

AZ Delta

OTHER

Sponsor Role: collaborator

AZ Sint-Jan AV

OTHER

Sponsor Role: collaborator

AZ Turnhout

OTHER

Sponsor Role: collaborator

Imelda Hospital, Bonheiden

OTHER

Sponsor Role: collaborator

Geert Meyfroidt, MD, PhD

OTHER

Sponsor Role: lead

Responsible Party

Geert Meyfroidt, MD, PhD

Associate Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Geert Meyfroidt, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Associate Professor of Medicine

Locations

Imelda Bonheiden

Bonheiden, , Belgium

Site Status: RECRUITING

AZ Sint-Jan

Bruges, , Belgium

Site Status: RECRUITING

Jessa Ziekenhuis

Hasselt, , Belgium

Site Status: RECRUITING

UZLeuven

Leuven, , Belgium

Site Status: RECRUITING

CHR de la Citadelle Liège

Liège, , Belgium

Site Status: RECRUITING

CHU de Liège

Liège, , Belgium

Site Status: RECRUITING

AZ Delta

Roeselare, , Belgium

Site Status: RECRUITING

AZ Turnhout

Turnhout, , Belgium

Site Status: RECRUITING

Countries

Belgium

Central Contacts

Liese Mebis, PhD

Role: CONTACT

liese.mebis@uzleuven.be

003216343125

Facility Contacts

Emmanuel Van Der Hauwaert, MD

Role: primary

Marc Bourgeois, MD

Role: primary

Jasperina Dubois, MD

Role: primary

jasperina.dubois@jessazh.be

Liese Mebis, PhD, MSc

Role: primary

liese.mebis@uzleuven.be

+3216343125

Hugues Maréchal, MD

Role: primary

Didier Ledoux, MD

Role: primary

Peiter Lormans, MD

Role: primary

Eva Boonen, MD, PhD

Role: primary

References

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.

Reference Type: DERIVED

PMID: 40437634 (View on PubMed)

Other Identifiers

2017-004698-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

S60859

Identifier Type: -

Identifier Source: org_study_id