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Ketamine and Glutamate After Brain Injury : a Microdialysis Study (KETABRAIN)

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ClinicalTrials.gov Identifier: NCT02232347
Recruitment Status : Unknown
Verified September 2014 by Pierre-Julien CUNGI, Direction Centrale du Service de Santé des Armées.
Recruitment status was:  Not yet recruiting
First Posted : September 5, 2014
Last Update Posted : September 5, 2014
Sponsor:
Information provided by (Responsible Party):
Pierre-Julien CUNGI, Direction Centrale du Service de Santé des Armées

Brief Summary:

The objective of the study is to compare the effects of 48 hours ketamine infusion versus sufentanil infusion on brain glutamate concentrations measured with microdialysis after traumatic brain injury.

We hypothesize that ketamine infusion will decrease high glutamate values faster than sufentanil.


Condition or disease Intervention/treatment Phase
Head Trauma Drug: Ketamine Drug: Sufentanil Phase 2

Detailed Description:

Inclusion of 20 consecutive head trauma patients. Randomization and double-blind to compare the effects of ketamine versus sufentanil on brain glutamate concentrations measured with microdialysis.

Ketamine is an anti-N-methyl-D-aspartate (NMDA) medication. It is supposed to limit excitotoxicity of amino-acids, especially glutamate. Glutamate is known to be elevated in more than 60% of the severe head trauma patients. It induces cortical spreading depression which can aggravate prognosis. It's a daily used medication in anesthesia and intensive care units for sedation and induction of anesthesia. It's the recommended medication for induction of unstable wounded soldiers on the field because of its neutrality on haemodynamic state.

Sufentanil is the reference opioid for sedation in ICU in Europe. It can induce hypotension which is deleterious for cerebral perfusion pressure after brain trauma.

In our unit, patients with severe head injury are monitored by a triple lumen access device including ICP (IntraCerebral Pressure), PtiO2 (oxygen pressure in the brain) and microdialysis. This last monitoring allows measurement of brain parenchymal concentrations of small molecules : glucose, lactate, pyruvate, glutamate, glycerol,.... It's a tool to evaluate the metabolic state of the brain divided into 4 categories : normal, hyperglycolysis, ischemia and metabolic crisis.

Then, we will detail the effects of ketamine on metabolic state of the brain, especially glutamate concentration. Normal values are below 10 micromol/ml. After head trauma it can dramatically increase to values up to 50 or even 100 micromol/ml, with normalization after 24 hours. Ketamine is expected to decrease these high values faster than described in observational studies.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Ketamine Versus Sufentanil on Cerebral Glutamate After Traumatic Brain Injury : a Randomized, Double-blinded, Microdialysis Study
Study Start Date : October 2014
Estimated Primary Completion Date : October 2016
Estimated Study Completion Date : May 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ketamine
ketamine 5 mg/kg/h, continuous infusion for 48 hours
Drug: Ketamine
Active Comparator: sufentanil
sufentanil 0,5 mcg/kg/h, continuous infusion for 48 hours
Drug: Sufentanil



Primary Outcome Measures :
  1. brain glutamate concentrations [ Time Frame: H0-H12, H12-H24, H24-H36 and H36-H48 ]
    To compare the kinetic of brain glutamate concentration decrease during 4 periods of 12 hours between ketamine infusion group (KET) and sufentanil standard infusion group (STD)


Secondary Outcome Measures :
  1. metabolic profile [ Time Frame: H0-H12, H12-H24, H24-H36 and H36-H48 ]
    To compare the brain metabolic profile (normal, ischemic, hyperglycolytic and metabolic crisis) of the patients related to their group of treatment : ketamine (KET) and sufentanil (STD) by measuring brain glucose, brain lactate, brain glycerol concentrations and brain lactate/pyruvate ratio.

  2. Episodes of intracranial hypertension (ICHT) and brain ischemia [ Time Frame: H0-H12, H12-H24, H24-H36 and H36-H48 ]
    To compare the number of ICHT episodes (ICP>20 mm Hg more than 15 minutes) and to compare the number of ischemic episodes (PtiO2<20 mm Hg more than 15 minutes) between the 2 groups

  3. Therapeutic Intensity Level (TIL) [ Time Frame: Days 1 and 2 ]
    To compare the TIL value between the 2 groups. TIL is a score developed to measure the intensity of cares for head trauma patients. Lower scores are meaning less intense cares. It is calculated for 24 hours periods.

  4. Glasgow Outcome Scale (GOS) et extended Glasgow Outcome Scale (eGOS) [ Time Frame: 6 months and 1 year ]
    To describe the prognosis of the patients of the KETAMINE group versus SUFENTANIL group. GOS is the international validated score for evaluation of the prognosis after head trauma.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • > 18 years old
  • Glasgow Coma Scale (GCS) < 9
  • > 3 days of sedation expected at the arrival

Exclusion Criteria:

  • pregnancy
  • < 18 years old
  • estimated survival < 48 hours post-trauma
  • expected sedation < 3 days
  • coagulation impairment (platelets<100.000/mm3 and prothrombin time (TP) <60%)
  • Cardiac arrest before ICU admission
  • Admission > 12 hours after trauma
  • Multimodal monitoring implanted > 24 hours post trauma
  • Participation to the study refused by the next of kind
  • No next of kind

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02232347


Contacts
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Contact: Ambroise MONTCRIOL, MD 0483162358 ext 0033 ambroise.montcriol@free.fr

Locations
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France
Sainte Anne Military Teaching Hospital Not yet recruiting
Toulon, France, 83130
Sub-Investigator: Pierre Julien CUNGI, MD         
Sub-Investigator: Eric MEAUDRE, MD         
Sub-Investigator: Henry BORET, MD         
Sponsors and Collaborators
Pierre-Julien CUNGI
Investigators
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Principal Investigator: Ambroise MONTCRIOL, MD Direction Centrale du Service de Santé des Armées

Publications:

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Responsible Party: Pierre-Julien CUNGI, MD, Direction Centrale du Service de Santé des Armées
ClinicalTrials.gov Identifier: NCT02232347     History of Changes
Other Study ID Numbers: DCSSA KETABRAIN
First Posted: September 5, 2014    Key Record Dates
Last Update Posted: September 5, 2014
Last Verified: September 2014

Keywords provided by Pierre-Julien CUNGI, Direction Centrale du Service de Santé des Armées:
traumatic brain injury
ketamine
microdialysis
PtiO2
glutamate

Additional relevant MeSH terms:
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Brain Injuries
Brain Injuries, Traumatic
Craniocerebral Trauma
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Trauma, Nervous System
Wounds and Injuries
Ketamine
Sufentanil
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Analgesics, Opioid
Narcotics
Adjuvants, Anesthesia