Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Ketamine in Acute Brain Injury Patients. (BIKe)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05097261
Recruitment Status : Recruiting
First Posted : October 28, 2021
Last Update Posted : October 28, 2021
Sponsor:
Collaborators:
University of Liege
Centre Hospitalier Régional de la Citadelle
AZ Delta
AZ Sint-Jan AV
AZ Turnhout
Information provided by (Responsible Party):
Geert Meyfroidt, MD, PhD, KU Leuven

Tracking Information
First Submitted Date  ICMJE September 8, 2020
First Posted Date  ICMJE October 28, 2021
Last Update Posted Date October 28, 2021
Actual Study Start Date  ICMJE September 6, 2021
Estimated Primary Completion Date June 30, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 15, 2021)
Change in therapeutic intensity of intracranial pressure (ICP) reducing measures, assessed by the TIL score (Therapy Intensity Level) [ Time Frame: 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. ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: October 15, 2021)
  • Intracranial pressure (ICP) [ Time Frame: From date of randomization until study drug discontinuation or or date of death from any cause, whichever came first, assessed up to 6 months. ]
    The average of hourly validated intracranial pressure (mmHg) measurements per 24 hours
  • Duration of sedation [ Time Frame: 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. ]
    Total duration of the first period of sedative treatments (propofol, midazolam and/or dexmedetomidine)
  • Propofol [ Time Frame: 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. ]
    Total dose of propofol in mg per 24 hours
  • Mechanical ventilation [ Time Frame: From date of randomization until study drug discontinuation or date of death from any cause, whichever came first, assessed up to 6 months. ]
    Total duration of mechanical ventilation, defined as all types of ventilation where positive end expiratory pressure is applied, expressed in cm H2O (5 cm H2O minimum).
  • Midazolam [ Time Frame: From date of randomization until study drug discontinuation or date of death from any cause, whichever came first, assessed up to 6 months. ]
    Total dose of midazolam in mg per 24 hours
  • ICU length of stay [ Time Frame: 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. ]
    Length of stay (number of days) in ICU
  • Hospital length of stay [ Time Frame: From admission to hospital until end of stay in hospital (dead or alive), assessed up to 6 months. ]
    Length of stay in hospital (days)
  • Richmond Agitation-Sedation scale (RASS) [ Time Frame: From date of randomization until study drug discontinuation or date of death from any cause, whichever came first, assessed up to 6 months. ]
    Average daily RASS. Scale ranges from +4 (combative) until -5 (Unarousable).
  • Delirium [ Time Frame: From date of randomization until study drug discontinuation or date of death from any cause, whichever came first, assessed up to 6 months. ]
    Number of delirium-free days, assessed 3 times per day with the Intensive Care Delirium Screening Checklist (ICDSC) or Confusion Assessment Method for the ICU (CAM-ICU delirium scale).
  • eGOS [ Time Frame: 6 months after the onset of TBI ]
    extended Glasgow Outcome Scale (eGOS)
  • ICU mortality [ Time Frame: From date of randomization until ICU discharge, assessed up to 6 months. ]
    Mortality during ICU stay
  • In-hospital mortality [ Time Frame: From date of randomization until hospital discharge, assessed up to 6 months. ]
    Mortality during hospital stay
  • Barbiturate coma incidence [ Time Frame: From date of randomization until study drug discontinuation or date of death from any cause, whichever came first, assessed up to 6 months. ]
    The incidence of barbiturate coma
  • Barbiturate coma duration [ Time Frame: From date of randomization until study drug discontinuation or date of death from any cause, whichever came first, assessed up to 6 months. ]
    The duration of barbiturate coma
  • Decompressive craniectomy [ Time Frame: 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. ]
    The incidence of decompressive craniectomy
  • Propofol Infusion Syndrome (PRIS) [ Time Frame: From date of randomization until study drug discontinuation or date of death from any cause, whichever came first, assessed up to 6 months. ]
    Incidence of PRIS documented and diagnosed by the attending physician and defined as:
    • Cardiac manifestations, not explained by a coronary ischemic event:
      • Acute refractory bradycardia leading to asystole, or
      • ECG: widening of QRS-complex, or Brugada-syndrome-like patterns (particularly Type 1: Coved-type ST-segment elevation >2mm in >1 of V1-V3 followed by a negative T-wave), or ventricular tachy-arrhythmias
    • Combined with one or more of the following:
      • Unexplained metabolic acidosis (base deficit > 10 mmol/L)
      • Rhabdomyolysis (Creatinine kinase at least five times the upper limit of normal)
      • Hyperlipidaemia (triglyceride levels > 150 mg/dl)
      • Enlarged or fatty liver, apparent on CT or echography
    • All occurring in patients receiving propofol for > 24h
    • Diagnosed by the attending physician
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ketamine in Acute Brain Injury Patients.
Official Title  ICMJE 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Supportive Care
Condition  ICMJE Brain Injuries, Traumatic
Intervention  ICMJE
  • Drug: 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.
    Other Name: Ketalar
  • 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).
    Other Name: Saline
Study Arms  ICMJE
  • Experimental: 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).

    Intervention: Drug: Ketamine
  • Active Comparator: 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).
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 15, 2021)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2024
Estimated Primary Completion Date June 30, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Liese Mebis, PhD 003216343125 liese.mebis@uzleuven.be
Listed Location Countries  ICMJE Belgium
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05097261
Other Study ID Numbers  ICMJE S60859
2017-004698-15 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Geert Meyfroidt, MD, PhD, KU Leuven
Study Sponsor  ICMJE Geert Meyfroidt, MD, PhD
Collaborators  ICMJE
  • University of Liege
  • Centre Hospitalier Régional de la Citadelle
  • AZ Delta
  • AZ Sint-Jan AV
  • AZ Turnhout
Investigators  ICMJE
Principal Investigator: Geert Meyfroidt, MD PhD Associate Professor of Medicine
PRS Account KU Leuven
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP