E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Traumatic Brain Injury patients requiring sedation to control the intracranial pressure (ICP).
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E.1.1.1 | Medical condition in easily understood language |
Patients who have experienced a brain trauma and are hospitalized in the ICU. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Injuries, poisonings, and occupational diseases [C21] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate that associating ketamine to the sedative regime for ICP control in TBI, results in a reduction of the therapeutic intensity of ICP reducing measures, assessed by the TIL score. |
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E.2.2 | Secondary objectives of the trial |
To demonstrate that ketamine does not cause an increase in ICP. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
* Traumatic brain injury patients * Age ≥ 18 years * Admitted to the ICU * Within 72 hours after admission to the initial hospital: 1)ICP monitor in place (parenchymal probe, ventricular catheter, or both) 2)Requiring sedation
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E.4 | Principal 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 IMP-RCT of which the PI indicates that co-inclusion specifically in the BIKe study is prohibited. * Therapy restriction code upon inclusion. * Porphyria * Glaucoma
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy endpoint: Reduction in cumulative daily TIL score. Primary safety endpoint: The number of high intracranial pressure episodes defined as an ICP >22 mmHg for >20 minutes [1,2].
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
* The average intracranial pressure (mmHg) per 24h * Total duration of the first episode of sedative treatment (hours) * Total duration of the first episode of mechanical ventilation * Total dose of propofol in mg per 24 hours * Total dose of midazolam in mg per 24 hours * Length of stay in the Intensive Care Unit (ICU) * Length of stay in the hospital (days) * Average daily Richmond agitation and sedation score (RASS) (addendum 2) per hour * Delirium-free days, defined with the Intensive Care Delirium Screening Checklist (ICDSC) or Confusion Assessment Method-ICU (CAM-ICU) every 8 hours (ICDSC) * Extended Glasgow Outcome Score (GOSE) at 6 months after the onset of brain injury * The incidence of barbiturate coma * Incidence of decompressive craniectomy * Incidence of Propofol-Related Infusion Syndrome (PRIS)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Trial is ended after follow-up last patient (i.e. 6 months after TBI onset) |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |