The Anaesthetic Ketamine as Treatment for Patients With Severe Acute Brain Injury

NCT05095857 | Recruiting Phase 4 DMC

• 2 other identifiers: H-210569722021-003716-12
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

Cortical spreading depolarisations are pathological depolarisation waves that occur frequently after severe acute brain injury and has been associated with poor outcome. S-ketamine has been shown to inhibit cortical spreading depolarisations. The aim of the present study is to examine the efficacy and safety of using S-ketamine for treatment of patients with severe acute brain injury, as well as the feasibility of the trial design.

Conditions

Subarachnoid Hemorrhage, Aneurysmal; Intracerebral Hemorrhage; Traumatic Brain Injury

Keywords

Cortical Spreading Depolarisation; Ketamine

Outcome Measures

Primary Outcomes (1)

• Occurrence of SDs after randomisation

  Efficacy of S-ketamine on the occurrence of cortical spreading depolarisations

  From randomisation to end of ECoG monitoring, expected to be a maximum of 14 days

Secondary Outcomes (2)

• Rate of adverse events and adverse reactions

  During treatment with S-ketamine or placebo, a maximum of 14 days

• Functional outcome at 6 months after randomisation

  6 months after randomisation

Other Outcomes (10)

• All-cause mortality

  assessed at 6 months after randomisation

• Number of participants with signs of ischaemia or infarction on computed tomography (CT) or magnetic resonance imaging (MRI).

  Before discharge from NICU or the semi-intentisive care unit, expected up to be no later than day 21 postrandomisation

• Occurrence of metabolic crisis (defined as microdialysis (MD)-lactate/pyruvate ratio >40, MD-glucose < 0.8 μmol/L)

  Postrandomisation period, expected up to 21 days

Study Arms (2)

S-ketamine

ACTIVE COMPARATOR

S-ketamine is given as a continuous infusion started at a dose of 2.0 mg/kg/hour. The infusion rate will be re-evaluated after 24 hours, where (1) the infusion will be stopped if 24 hours ensue without SDs, (2) maintained at 2.0 mg/kg/hour if the 24-hour incidence of SDs decreases below the rate of the previous 24 hours but SD is not totally abolished, or (3) increased to 3.0 mg/kg/hour if the incidence of SD is at or above the rate of the previous 24 hours. If the infusion rate has been increased to 3.0 mg/kg/hour, the rate will be returned to 2.0 mg/kg/hour if 24 consecutive hours of ECoG show no SD.

Drug: S-ketamine

Isotonic saline

PLACEBO COMPARATOR

Isotonic saline is given as placebo. It will be given as a continuous infusion started at a dose corresponding to a dose of S-ketamine of 2.0 mg/kg/hour, and follow the criteria for increasing/decreasing infusion rates as S-ketamine. The infusion rate is read from a table listing different infusion rates (ml/hour) based on participant weight and if the treatment tier corresponds to a S-ketamine dose of 2 or 3 mg/kg/hour.

Other: Isotonic saline (placebo)

Interventions

S-ketamine DRUG

S-ketamines is an NMDA-receptor antagonist with sedative and analgesic properties. It will in the present trial be given in sedative doses (2-3 mg/kg/hour) in case of clustered SDs following a dosing algorithm according to SD occurrence.

Also known as: Esketamine

S-ketamine

Isotonic saline (placebo) OTHER

Isotonic saline has the same appearance as S-ketamine with both being clear liquids with no bubbles or other distinguishing features.

Isotonic saline

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Admitted to the NICU with a diagnosis of traumatic brain injury (TBI), aneurysmal subarachnoid haemorrhage (aSAH) or spontaneous intracerebral haemorrhage (ICH).
• Planned for surgery with a supratentorial craniotomy or craniectomy.
• Expected to continue sedation and mechanical ventilation after surgery.

You may not qualify if:

• Neither patient or next of kin understand Danish or English.
• Known allergy to S-ketamine (the active pharmaceutical ingredient or the excipients).
• Wake-up call to occur immediately after surgery.
• Pregnancy (all female participants aged ≤ 50 years will have a urine or blood hCG taken to control for pregnancy).
• Active anti-psychotic treatment before admission.
• Current abuse of ketamine.
• Decision to withdraw active treatment.

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead
• Copenhagen Trial Unit, Center for Clinical Intervention Research: collaborator

Study Sites (1)

Rigshospitalet

Copenhagen, Denmark

RECRUITING

Related Publications (27)

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  PMID: 40721263 DERIVED

MeSH Terms

Conditions

Subarachnoid Hemorrhage; Cerebral Hemorrhage; Brain Injuries, Traumatic

Interventions

Esketamine; Sodium Chloride

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Brain Injuries; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Trine H Andreasen, MD

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Trine H Andreasen, MD

CONTACT

+4535455982; trine.hjorslev.andreasen@regionh.dk

Kirsten Møller, Professor

CONTACT

Kirsten.Moeller.01@regionh.dk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Principal Investigator

Study Record Dates

• First Submitted: September 30, 2021
• First Posted: October 27, 2021
• Study Start: September 15, 2023
• Primary Completion (Estimated): September 15, 2028
• Study Completion (Estimated): September 15, 2028
• Last Updated: June 26, 2024

Record last verified: 2024-06

Locations

DK (1)