The Anaesthetic Ketamine as Treatment for Patients With Severe Acute Brain Injury (KETA-BID)

2024-515315-22-00 Protocol RHNIA-001-2021 Therapeutic use (Phase IV) Ongoing, recruiting

Start 15 Sep 2023 · Status Ongoing, recruiting · 1 EU/EEA countries · 1 sites · Protocol RHNIA-001-2021

Overview

Sponsor-declared trial summary

Phase Therapeutic use (Phase IV)
Status Ongoing, recruiting
Participants planned 400
Countries 1
Sites 1

subarachnoid hemorrhage, intracerebral hemorrhage, traumatic brain injury

This pilot and feasibility trial – the KETA-BID trial – aims to investigate the efficacy and safety of S-ketamine on the occurrence of SDs and the feasibility of the setup. More specifically, the KETABID trial investigates the efficacy of S-ketamine in patients in whom SDs persist despite physiological optimisation.

Key facts

Sponsor
Rigshospitalet
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Pathological Conditions, Signs and Symptoms [C23], Diseases [C] - Nervous System Diseases [C10]
Trial duration
15 Sep 2023 → ongoing
Decision date (initial)
2024-09-12
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
Yes
Funding sources
Sundhedsdonationer (2024-0378) · An open grant from the Research Board at Rigshospitalet · The A.P. Møller Foundation (Fonden til Lægevidenskabens Fremme, 20-L-0041) · The Danish Victims’ Foundation (20-610-00103) · The Novo Nordisk Foundation (NNF20OC0065750) · Snedkermester Sophus Jacobsen og hustru Astrid Jacobsens Fond · Research Fund at Department of Neurosurgery Rigshospitalet · Dagmar Marshall Foundation · Grosserer Jakob Ehrenreich og Hustru Grete Ehrenreichs Fond · A 3-year PhD grant from the Research Board at Rigshospitalet · Knud and Edith Eriksens Mindefond (62786-2021) · Læge Sofus Carl Emil Friis og hustru Olga Doris Friis legat · Danish Society for Anaesthesiology and Intensive Care Medicine (DASAIM) Research Initiative 2021

External identifiers

EU CT number
2024-515315-22-00
EudraCT number
2021-003716-12
ClinicalTrials.gov
NCT05095857

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Safety, Efficacy

This pilot and feasibility trial – the KETA-BID trial – aims to investigate the efficacy and safety of S-ketamine on the occurrence of SDs and the feasibility of the setup. More specifically, the KETABID
trial investigates the efficacy of S-ketamine in patients in whom SDs persist despite physiological optimisation.

Secondary objectives 1

  1. The secondary objectives of this trial is investigate the safety of using S-ketamine for patients with severe acute brain injury by investigating the rate of adverse events and adverse reactions after randomisation and throughout the intervention period, and to examine functional outcome at 6 months after ictus of brain injury

Conditions and MedDRA coding

subarachnoid hemorrhage, intracerebral hemorrhage, traumatic brain injury

VersionLevelCodeTermSystem organ class
21.0 LLT 10019529 Hemorrhage brain 10029205
21.1 LLT 10018061 General anesthesia 10042613
21.1 LLT 10070731 Electrocorticography 10042613
20.0 LLT 10056389 Brain damage 10029205

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

  1. Age ≥ 18 years
  2. Admitted to the Neurointensive Care Unit with a diagnosis of traumatic brain injury, aneurysmal subarachnoid hemorrhage or spontaneous intracerebral hemorrhage
  3. Planned for surgery with a supratentorial craniotomy or craniectomy
  4. Expected to continue sedation and mechanical ventilation after surgery

Exclusion criteria 8

  1. Neither patient or next of kin understand Danish or English
  2. Known allergy to S-ketamine (the active pharmaceutical ingredient or the excipients)
  3. Wake-up call to occur immediately after surgery
  4. Pregnancy (all female participants aged ≤ 50 years will have a urine or blood hCG to control for pregnancy)
  5. Active anti-psychotic treatment before admission
  6. Current abuse of ketamine
  7. Decision to withdraw active treatment
  8. Intracerebral hemorrhage secondary to a known brain tumour at the time of inclusion.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Occurrence of cortical spreading depolarisations per hour of monitoring after randomisation

Secondary endpoints 2

  1. Rate of adverse events and adverse reactions after randomisation and throughout the intervention period
  2. Functional outcome (using modified Rankin Scale and Glasgow Outcome Scale-Extended) at 6 months after randomisation

Investigational products

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

Test 1

Esketamine Hydrochloride

SUB25811 · Substance

Active substance
Esketamine Hydrochloride
Pharmaceutical form
SOLUTION FOR INJECTION/INFUSION
Route of administration
INFUSION
Max daily dose
3 mg/kg/h milligram(s)/kilogram/hour
Max total dose
984 mg/kg milligram(s)/kilogram
Max treatment duration
14 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Placebo 1

Sodium Chloride

SUB12581MIG · Substance

Active substance
Sodium Chloride
Pharmaceutical form
INFUSION
Route of administration
INFUSION
Max daily dose
2.88 millilitre(s)/kilogram
Max total dose
39.4 millilitre(s)/kilogram
Max treatment duration
14 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Rigshospitalet

Sponsor organisation
Rigshospitalet
Address
Blegdamsvej 9
City
Copenhagen Oe
Postcode
2100
Country
Denmark

Scientific contact point

Organisation
Rigshospitalet
Contact name
Kirsten Møller

Public contact point

Organisation
Rigshospitalet
Contact name
Trine Hjorslev Andreasen

Third parties 1

OrganisationCity, countryDuties
Frederiksberg Hospital
ORG-100028217
Frederiksberg, Denmark On site monitoring

Locations

1 EU/EEA country · 1 investigational sites

By country

CountryMS statusPlanned subjectsSites
Denmark Ongoing, recruiting 400 1
Rest of world 0

Investigational sites

Denmark

1 site · Ongoing, recruiting
Rigshospitalet
Department of Neurosurgery, Blegdamsvej 9, 2100, Copenhagen Oe

Country notifications

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

Country Trial startTrial end Recruitment startRecruitment end Early termination
Denmark 2023-09-15 2023-09-17

Results and documents

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

Documents 8 files

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

TypeTitleVersion
Protocol (for publication) D1_Protocol public version_2024-515315-22-00 1
Recruitment arrangements (for publication) K1_Recruitment procedure_2024-515315-22-00 2
Subject information and informed consent form (for publication) L1_ICF_nextofkin_KETA-BID_DA 2
Subject information and informed consent form (for publication) L1_ICF_participant_KETA-BID_DA 2
Subject information and informed consent form (for publication) L1_ICF_trialguardian_KETA-BID_DA 2
Subject information and informed consent form (for publication) L1_SIS_Nextofkin KETA-BID_DA 5
Subject information and informed consent form (for publication) L1_SIS_Participant KETA-BID_DA 5
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC S-ketamine_DA 1

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-08-23 Denmark Acceptable
2024-09-12
2024-09-12
2 NON SUBSTANTIAL MODIFICATION NSM-1 2025-03-25 Denmark Acceptable
2024-09-12
2025-03-25
3 NON SUBSTANTIAL MODIFICATION NSM-2 2025-03-25 Denmark Acceptable
2024-09-12
2025-03-25