Brain Injury and Ketamine: a prospective, randomized controlled double blind clinical trial to study the effects of ketamine on therapy intensity level and intracranial pressure in acute brain injury patients.

2023-505319-19-00 Protocol S60859 Phase III and Phase IV (Integrated) Ongoing, recruiting

Start 1 Sep 2021 · Status Ongoing, recruiting · 1 EU/EEA countries · 8 sites · Protocol S60859

Overview

Sponsor-declared trial summary

Phase Phase III and Phase IV (Integrated)
Status Ongoing, recruiting
Participants planned 100
Countries 1
Sites 8

Traumatic brain injury

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.

Key facts

Sponsor
UZ Leuven
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03]
Trial duration
1 Sep 2021 → ongoing
Decision date (initial)
2024-02-21
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
Yes
Funding sources
Pfizer Belgium

External identifiers

EU CT number
2023-505319-19-00
EudraCT number
2017-004698-15
ClinicalTrials.gov
NCT05097261

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

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.

Secondary objectives 1

  1. To demonstrate that ketamine does not cause an increase in ICP.

Conditions and MedDRA coding

Traumatic brain injury

VersionLevelCodeTermSystem organ class
26.1 LLT 10060690 Traumatic brain injury 10022117

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

  1. Traumatic brain injury patients
  2. Age ≥ 18 years
  3. Admitted to the Intensive Care Unit
  4. Within 72 hours after admission to the initial hospital: ICP monitor in place (parenchymal probe, ventricular catheter, or both) and requiring sedation

Exclusion criteria 9

  1. Known pregnancy and/or lactation
  2. Imminent or actual brain death upon inclusion
  3. Allergy or intolerance to the study medication
  4. Pre-existing neurocognitive disorders, pre-existing congenital or non-congenital brain dysfunction.
  5. Inability to obtain informed consent
  6. Inclusion in an IMP-RCT of which the PI indicates that co-inclusion specifically in the BIKe study is prohibited
  7. Therapy restriction code upon inclusion
  8. Porphyria
  9. Glaucoma

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

  1. Reduction in cumulative daily TIL score.
  2. The number of high intracranial pressure episodes defined as an ICP >22 mmHg for >25 minutes

Secondary endpoints 13

  1. The average intracranial pressure (mmHg) per 24h
  2. Total duration of the first episode of sedative treatment (hours)
  3. Total duration of the first episode of mechanical ventilation
  4. Total dose of propofol in mg per 24 hours
  5. Total dose of midazolam in mg per 24 hours
  6. Length of stay in the Intensive Care Unit (ICU)
  7. Length of stay in the hospital (days)
  8. Average daily Richmond agitation and sedation score (RASS) (addendum 2) per hour
  9. Delirium-free days, defined with the Intensive Care Delirium Screening Checklist (ICDSC) or Confusion Assessment Method-ICU (CAM-ICU) every 8 hours (ICDSC)
  10. Extended Glasgow Outcome Score (GOSE) at 6 months after the onset of brain injury
  11. The incidence of barbiturate coma
  12. Incidence of decompressive craniectomy
  13. Incidence of Propofol-Related Infusion Syndrome (PRIS)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Ketalar 50 mg/ml solution injectable

PRD411196 · Product

Active substance
Ketamine
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
INTRAVENOUS INFUSION
Max daily dose
1 mg/kg/h milligram(s)/kilogram/hour
Max total dose
120 mg/h milligram(s)/hour
Max treatment duration
4 Week(s)
Authorisation status
Authorised
ATC code
N01AX03 — KETAMINE
Marketing authorisation
BE005293
MA holder
PFIZER S.A. (BELGIUM)
MA country
Belgium
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Placebo 1

0,9% NaCl

N/A · Product

Other product name
N/A
Pharmaceutical form
N/A
ATC code
N/A — N/A
Marketing authorisation
N/A
MA holder
N/A
MA country
Iceland
Paediatric formulation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

UZ Leuven

70 Total trials 41 Recruiting 22 Ended
Academic / Non-commercial
Sponsor organisation
UZ Leuven
Address
Herestraat 49
City
Leuven
Postcode
3000
Country
Belgium

Scientific contact point

Organisation
UZ Leuven
Contact name
Geert Meyfroidt

Public contact point

Organisation
UZ Leuven
Contact name
Geert Meyfroidt

Locations

1 EU/EEA country · 8 investigational sites

By country

CountryMS statusPlanned subjectsSites
Belgium Ongoing, recruiting 100 8
Rest of world — 0 —

Investigational sites

Belgium

8 sites · Ongoing, recruiting
CHU De Liege
Anesthésie-Réanimation, Avenue De L'hopital 1, 4000, Liege
Centre Hospitalier Regional De La Citadelle
Intensive Care Unit, Bld Du Douzieme-De-Ligne 1, 4000, Liege
AZ Turnhout
Intensive Care Medicine, Rubensstraat 166, 2300, Turnhout
Imelda
Intensive Care Medicine, Imeldalaan 9, 2820, Bonheiden
Az Delta
Intensive Care Medicine, Deltalaan 1, 8800, Roeselare
UZ Leuven
Intensive Care Medicine, Herestraat 49, 3000, Leuven
Az St-Jan Brugge-Oostende A.V.
Anesthesia and Critical Care, Ruddershove 10, 8000, Brugge
Jessa Ziekenhuis
Intensive care medicine, Stadsomvaart 11, 3500, Hasselt

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Belgium 2021-09-01 2021-09-08

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_Protocol 2023-505319-19-00 1.6
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC Ketalar 1
Synopsis of the protocol (for publication) D1_Protocol synopsis_BelgiumEn_2023-505319-19-00 1
Synopsis of the protocol (for publication) D1_Protocol synopsis_BelgiumFr_2023-505319-19-00 1
Synopsis of the protocol (for publication) D1_Protocol synopsis_BelgiumGe_2023-505319-19-00 1
Synopsis of the protocol (for publication) D1_Protocol synopsis_BelgiumNl_2023-505319-19-00 1

Application history

2 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-01-29 Belgium Acceptable
2024-02-08
 2024-02-21
2 NON SUBSTANTIAL MODIFICATION NSM-1 2026-02-09 Belgium Acceptable
2024-02-08
 2026-02-09

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