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Impact of Early Optimization of Brain Oxygenation on Neurological Outcome After Severe Traumatic Brain Injury (OXY-TC)

Primary Purpose

Brain Injuries, Traumatic

Status
Completed
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
PbtO2 probes
No PbtO2 probes
Sponsored by
University Hospital, Grenoble
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain Injuries, Traumatic

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age between 18 and 75
  • Severe non- penetrating TBI (GCS score 3-8) with motor Glasgow score between 1 and 5
  • Possible associated extracranial lesions, except tetraplegia
  • Initiation of cerebral monitoring within the first 16 hours since primary traumaticinjury
  • Indication of ICP monitoring on admission as part of the management
  • Indication of continuous sedation/analgesia for more than 48 hours
  • Under mechanical ventilation with stable conditions: PaO2//FiO2 over 150 and PaCO2 between 35 and 45 mmHg, mean arterial pressure over 70 mmHg
  • Written informed consent from legal surrogate, patient's relative or investigator decision
  • Affiliation to the French Social Security or affiliated to a social security system of EU member state, Norway, Lichtenstein, Iceland or Switzerland
  • French-speaking or English-speaking patient

Exclusion Criteria:

  • Penetrating TBI
  • GCS 3 with bilateral fixed dilated pupils
  • Decompressive craniectomy and no repositioning of the bone flap after subdural hematoma evacuation surgery prior to enrolment
  • Contraindication of ICP and/or PbtO2 monitoring, i.e., hemostasis disorders and brain tissue infection
  • Persistent hemodynamic or respiratory instability despite treatments, i.e., mean arterial pressure < 70 mmHg, PaO2/FiO2 <150, PaCO2 <30 mmHg or >45 mmHg or lactate >5 mmol/l if available.
  • Hypothermia <34°C at randomization
  • Life expectancy < 24 hours
  • Cardiac arrest at initial presentation
  • Tetraplegia
  • Neuropsychiatric co-morbidities that could interfere with 6 and 12-months assessment outcomes.
  • Consent refusal
  • Pregnancy
  • Participation in another therapeutic study with written consent
  • Inability to have a 6-months follow-up
  • Ischemic stroke after carotid arterial dissection
  • Incapacitated patients in accordance with article L 1121-5 to L1121-8 of the public health code.

Sites / Locations

  • CHU Angers
  • General Hospital of Annecy
  • University Hospital Besançon
  • University Hospital of Bordeaux
  • CHU CAEN
  • University Hospital of Clermont-Ferrand
  • University Hospital of Dijon
  • Grenoble University Hospital
  • University Hospital of Kremlin-Bicetre
  • University Hospital of Lille
  • University Hospital of Lyon
  • University Hospital of Marseille-Nord
  • University Hospital of Marseille-Timone
  • University Hospital of Montpellier
  • University Hospital of Nancy
  • University Hospital of Nice
  • University Hospital of Nimes
  • University Hospital of Paris-Salpetriere
  • University Hospital of Poitiers
  • University Hospital of Rennes
  • University Hospital of Rouen
  • University Hospital Sud Réunion
  • University Hospital of St-Etienne
  • University Hospital of Strasbourg
  • Hôpital d'Instruction des Armées
  • University Hospital of Toulouse

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

ICP Management

PbtO2 + ICP Management

Arm Description

Outcomes

Primary Outcome Measures

Neurological outcome according to the extended Glasgow Outcome Scale (GOSE) blind assessed

Secondary Outcome Measures

Neurological outcome according to the extended Glasgow Outcome Scale (GOSE) and Disability Rating Scale
Disability Rating Scale (DRS)
Quality of life assessment: Functional Independence Measure (FIM) and Medical Outcomes Study Short-Form 12 (SF-12)
Mortality rate
Therapeutic intensity as reflected by the number of level 2 and level 3 treatments to treat elevated ICP
Incidence of critical events as defined by: ICP >30 mmHg during 30 min at least ICP >40 mmHg during 5 min at least PbtO2 <10 mmHg during 30 min at least (PbtO2 group)

Full Information

First Posted
April 15, 2016
Last Updated
May 17, 2022
Sponsor
University Hospital, Grenoble
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1. Study Identification

Unique Protocol Identification Number
NCT02754063
Brief Title
Impact of Early Optimization of Brain Oxygenation on Neurological Outcome After Severe Traumatic Brain Injury
Acronym
OXY-TC
Official Title
Impact of Early Optimization of Brain Oxygenation on Neurological Outcome After Severe Traumatic Brain Injury
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
June 2016 (Actual)
Primary Completion Date
October 17, 2021 (Actual)
Study Completion Date
April 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Grenoble

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Post-traumatic brain hypoxia/ischemia develops hours after traumatic brain injury (TBI), and its intensity is directly related to the neurological outcome. The thresholds for irreversible tissue damage following TBI indicate a particular vulnerability of injured brain. Improving brain oxygenation after severe TBI is the focus of modern TBI management in the intensive care unit (ICU). The calculation of cerebral perfusion pressure (CPP), with CPP = mean arterial pressure (MAP) - intracranial pressure (ICP), has become the most used estimator of cerebral blow flow. To prevent ischemia due to elevated ICP, current international guidelines recommend maintaining CPP at 60-70 mmHg and ICP below 20 mmHg. However, episodes of brain hypoxia/ischemia, as assessed with brain tissue oxygen pressure (PbtO2) measurements, might occur despite optimization of CPP and ICP, and have been independently associated with poorer patient outcome. PbtO2 values lower than 15 mmHg for more than 30 minutes were shown to be an independent predictor of unfavorable outcome and death. The aggressive treatment of low PbtO2 was associated with improved outcome compared to standard ICP/CPP-directed therapy in cohort studies of severely head-injured patients. On the basis of these findings, it is hypothesized that an early optimization of brain oxygenation, together with keeping ICP and CPP within recommended values, could reduce the volume of vulnerable lesions following severe TBI and possibly improve neurological outcome.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain Injuries, Traumatic

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
320 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ICP Management
Arm Type
Active Comparator
Arm Title
PbtO2 + ICP Management
Arm Type
Experimental
Intervention Type
Device
Intervention Name(s)
PbtO2 probes
Intervention Description
PbtO2/ICP/CPP-directed therapy according to international recommendations
Intervention Type
Other
Intervention Name(s)
No PbtO2 probes
Intervention Description
ICP/CPP-directed therapy according to international recommendations
Primary Outcome Measure Information:
Title
Neurological outcome according to the extended Glasgow Outcome Scale (GOSE) blind assessed
Time Frame
at 6 months post-trauma
Secondary Outcome Measure Information:
Title
Neurological outcome according to the extended Glasgow Outcome Scale (GOSE) and Disability Rating Scale
Time Frame
at 12 months post-trauma (GOSE)
Title
Disability Rating Scale (DRS)
Time Frame
at 6 and 12 months post-trauma
Title
Quality of life assessment: Functional Independence Measure (FIM) and Medical Outcomes Study Short-Form 12 (SF-12)
Time Frame
at 6 and 12 months post-trauma
Title
Mortality rate
Time Frame
at day 28
Title
Therapeutic intensity as reflected by the number of level 2 and level 3 treatments to treat elevated ICP
Time Frame
during the first 5 days of the ICU stay
Title
Incidence of critical events as defined by: ICP >30 mmHg during 30 min at least ICP >40 mmHg during 5 min at least PbtO2 <10 mmHg during 30 min at least (PbtO2 group)
Time Frame
during the first 5 days of the ICU stay
Other Pre-specified Outcome Measures:
Title
Ancillary outcome : Volume of cerebral lesions with abnormal MD values, i.e., decreased or increased MD values, using diffusion tensor MR imaging
Time Frame
at day 6-10 following initiation of cerebral monitoring after severe TBI

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age between 18 and 75 Severe non- penetrating TBI (GCS score 3-8) with motor Glasgow score between 1 and 5 Possible associated extracranial lesions, except tetraplegia Initiation of cerebral monitoring within the first 16 hours since primary traumaticinjury Indication of ICP monitoring on admission as part of the management Indication of continuous sedation/analgesia for more than 48 hours Under mechanical ventilation with stable conditions: PaO2//FiO2 over 150 and PaCO2 between 35 and 45 mmHg, mean arterial pressure over 70 mmHg Written informed consent from legal surrogate, patient's relative or investigator decision Affiliation to the French Social Security or affiliated to a social security system of EU member state, Norway, Lichtenstein, Iceland or Switzerland French-speaking or English-speaking patient Exclusion Criteria: Penetrating TBI GCS 3 with bilateral fixed dilated pupils Decompressive craniectomy and no repositioning of the bone flap after subdural hematoma evacuation surgery prior to enrolment Contraindication of ICP and/or PbtO2 monitoring, i.e., hemostasis disorders and brain tissue infection Persistent hemodynamic or respiratory instability despite treatments, i.e., mean arterial pressure < 70 mmHg, PaO2/FiO2 <150, PaCO2 <30 mmHg or >45 mmHg or lactate >5 mmol/l if available. Hypothermia <34°C at randomization Life expectancy < 24 hours Cardiac arrest at initial presentation Tetraplegia Neuropsychiatric co-morbidities that could interfere with 6 and 12-months assessment outcomes. Consent refusal Pregnancy Participation in another therapeutic study with written consent Inability to have a 6-months follow-up Ischemic stroke after carotid arterial dissection Incapacitated patients in accordance with article L 1121-5 to L1121-8 of the public health code.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean-François PAYEN, MD, PhD
Organizational Affiliation
University Hospital, Grenoble
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU Angers
City
Angers
Country
France
Facility Name
General Hospital of Annecy
City
Annecy
Country
France
Facility Name
University Hospital Besançon
City
Besançon
Country
France
Facility Name
University Hospital of Bordeaux
City
Bordeaux
Country
France
Facility Name
CHU CAEN
City
Caen
Country
France
Facility Name
University Hospital of Clermont-Ferrand
City
Clermont-Ferrand
Country
France
Facility Name
University Hospital of Dijon
City
Dijon
Country
France
Facility Name
Grenoble University Hospital
City
Grenoble
Country
France
Facility Name
University Hospital of Kremlin-Bicetre
City
Le Kremlin Bicetre
Country
France
Facility Name
University Hospital of Lille
City
Lille
Country
France
Facility Name
University Hospital of Lyon
City
Lyon
Country
France
Facility Name
University Hospital of Marseille-Nord
City
Marseille
Country
France
Facility Name
University Hospital of Marseille-Timone
City
Marseille
Country
France
Facility Name
University Hospital of Montpellier
City
Montpellier
Country
France
Facility Name
University Hospital of Nancy
City
Nancy
Country
France
Facility Name
University Hospital of Nice
City
Nice
Country
France
Facility Name
University Hospital of Nimes
City
Nimes
Country
France
Facility Name
University Hospital of Paris-Salpetriere
City
Paris
Country
France
Facility Name
University Hospital of Poitiers
City
Poitiers
Country
France
Facility Name
University Hospital of Rennes
City
Rennes
Country
France
Facility Name
University Hospital of Rouen
City
Rouen
Country
France
Facility Name
University Hospital Sud Réunion
City
Saint Pierre
Country
France
Facility Name
University Hospital of St-Etienne
City
Saint-Etienne
Country
France
Facility Name
University Hospital of Strasbourg
City
Strasbourg
Country
France
Facility Name
Hôpital d'Instruction des Armées
City
Toulon
Country
France
Facility Name
University Hospital of Toulouse
City
Toulouse
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
15888537
Citation
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Results Reference
background
PubMed Identifier
17511547
Citation
Brain Trauma Foundation; American Association of Neurological Surgeons; Congress of Neurological Surgeons; Joint Section on Neurotrauma and Critical Care, AANS/CNS; Bratton SL, Chestnut RM, Ghajar J, McConnell Hammond FF, Harris OA, Hartl R, Manley GT, Nemecek A, Newell DW, Rosenthal G, Schouten J, Shutter L, Timmons SD, Ullman JS, Videtta W, Wilberger JE, Wright DW. Guidelines for the management of severe traumatic brain injury. IX. Cerebral perfusion thresholds. J Neurotrauma. 2007;24 Suppl 1:S59-64. doi: 10.1089/neu.2007.9987. No abstract available. Erratum In: J Neurotrauma. 2008 Mar;25(3):276-8. multiple author names added.
Results Reference
background
PubMed Identifier
21673608
Citation
Oddo M, Levine JM, Mackenzie L, Frangos S, Feihl F, Kasner SE, Katsnelson M, Pukenas B, Macmurtrie E, Maloney-Wilensky E, Kofke WA, LeRoux PD. Brain hypoxia is associated with short-term outcome after severe traumatic brain injury independently of intracranial hypertension and low cerebral perfusion pressure. Neurosurgery. 2011 Nov;69(5):1037-45; discussion 1045. doi: 10.1227/NEU.0b013e3182287ca7.
Results Reference
background
PubMed Identifier
10764260
Citation
van den Brink WA, van Santbrink H, Steyerberg EW, Avezaat CJ, Suazo JA, Hogesteeger C, Jansen WJ, Kloos LM, Vermeulen J, Maas AI. Brain oxygen tension in severe head injury. Neurosurgery. 2000 Apr;46(4):868-76; discussion 876-8. doi: 10.1097/00006123-200004000-00018.
Results Reference
background
PubMed Identifier
16304983
Citation
Stiefel MF, Spiotta A, Gracias VH, Garuffe AM, Guillamondegui O, Maloney-Wilensky E, Bloom S, Grady MS, LeRoux PD. Reduced mortality rate in patients with severe traumatic brain injury treated with brain tissue oxygen monitoring. J Neurosurg. 2005 Nov;103(5):805-11. doi: 10.3171/jns.2005.103.5.0805.
Results Reference
background
PubMed Identifier
19463048
Citation
Narotam PK, Morrison JF, Nathoo N. Brain tissue oxygen monitoring in traumatic brain injury and major trauma: outcome analysis of a brain tissue oxygen-directed therapy. J Neurosurg. 2009 Oct;111(4):672-82. doi: 10.3171/2009.4.JNS081150.
Results Reference
background
PubMed Identifier
35281992
Citation
Mistral T, Roca P, Maggia C, Tucholka A, Forbes F, Doyle S, Krainik A, Galanaud D, Schmitt E, Kremer S, Kastler A, Tropres I, Barbier EL, Payen JF, Dojat M. Automated Quantification of Brain Lesion Volume From Post-trauma MR Diffusion-Weighted Images. Front Neurol. 2022 Feb 23;12:740603. doi: 10.3389/fneur.2021.740603. eCollection 2021.
Results Reference
derived
PubMed Identifier
32820002
Citation
Payen JF, Richard M, Francony G, Audibert G, Barbier EL, Bruder N, Dahyot-Fizelier C, Geeraerts T, Gergele L, Puybasset L, Vigue B, Skaare K, Bosson JL, Bouzat P. Comparison of strategies for monitoring and treating patients at the early phase of severe traumatic brain injury: the multicentre randomised controlled OXY-TC trial study protocol. BMJ Open. 2020 Aug 20;10(8):e040550. doi: 10.1136/bmjopen-2020-040550.
Results Reference
derived

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Impact of Early Optimization of Brain Oxygenation on Neurological Outcome After Severe Traumatic Brain Injury

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