Clinical TrialNeurological InjuryEsketaminePlaceboRecruiting

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

This randomised, blinded, placebo-controlled, parallel-group pilot and feasibility trial (n=400) will investigate the efficacy and safety of using esketamine for the treatment of patients with severe acute brain injury. It will specifically focus on cortical spreading depolarisations (SDs) in TBI, aSAH, or ICH.

Target Enrollment
400 participants
Study Type
Phase IV interventional
Design
Randomized, quadruple Blind

Detailed Description

Cortical spreading depolarisations (SDs) are pathological depolarisation waves common after severe acute brain injury and linked to worse outcome; S-ketamine inhibits SDs in preclinical and case series.

Patients undergoing craniotomy/craniectomy for TBI, aSAH or ICH are monitored with electrocorticography (ECoG) and other neuromonitoring; those with clustered SDs despite optimisation are randomised 1:1 to S-ketamine infusion or matching saline placebo.

Primary aims are to assess the effect of S-ketamine on SD incidence, safety of sedative-dose infusion, and feasibility of the trial design; survivors will have functional follow-up to six months (mRS).

Study Arms & Interventions

S-ketamine

experimental

Continuous S-ketamine infusion titrated 2→3 mg/kg/hour per algorithm to suppress clustered cortical spreading depolarisations (SDs).

Interventions

  • Esketamine2 - 3 mg/kg/hour
    via IV• continuous infusion

    Start 2.0 mg/kg/hour; increase to 3.0 mg/kg/hour if SDs persist; reassess at 24 h; stop if 24 h without SDs.

Placebo (saline)

inactive

Isotonic saline infusion matching S-ketamine appearance and infusion-rate algorithm.

Interventions

  • Placebo
    via IV• continuous infusion

    Isotonic saline infused with ml/hour rates matched to S-ketamine dosing table by weight; follows same escalation/de-escalation algorithm.

Participants

Ages
17 – 99
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • 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.

Exclusion Criteria

  • Exclusion Criteria:
  • 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.
  • ICH secondary to a known brain tumour at the time of inclusion.
  • Since this is an emergency trial informed consent will be obtained from a trial guardian before inclusion of the participant, and informed consent will be sought from next of kin as soon as possible.

Study Details

  • Status
    Recruiting
  • Phase
    Phase IV
  • Type
    interventional
  • Design
    Randomizedquadruple Blind
  • Target Enrollment400 participants
  • Timeline
    Start: 2023-09-15
    End: 2026-12-01
  • Compounds
    EsketaminePlacebo
  • Topic
    Neurological Injury

Locations

Rigshospitalet — Copenhagen, Denmark

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