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

Brain Injuries, Traumatic Clinical Trial

— OXY-TC  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02754063
• Other study ID #: 38RC14.039
• Status: Completed
• Phase: N/A
• Start date: June 2016
• Est. completion date: April 2022

Study information

• Verified date: May 2022
• Source: University Hospital, Grenoble
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 320
• Est. completion date: April 2022
• Est. primary completion date: October 17, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• Wounds and Injuries

Intervention

Device:
• PbtO2 probes
PbtO2/ICP/CPP-directed therapy according to international recommendations

Other:
• No PbtO2 probes
ICP/CPP-directed therapy according to international recommendations

Locations

Country	Name	City	State
France	CHU Angers	Angers
France	General Hospital of Annecy	Annecy
France	University Hospital Besançon	Besançon
France	University Hospital of Bordeaux	Bordeaux
France	CHU CAEN	Caen
France	University Hospital of Clermont-Ferrand	Clermont-Ferrand
France	University Hospital of Dijon	Dijon
France	Grenoble University Hospital	Grenoble
France	University Hospital of Kremlin-Bicetre	Le Kremlin Bicetre
France	University Hospital of Lille	Lille
France	University Hospital of Lyon	Lyon
France	University Hospital of Marseille-Nord	Marseille
France	University Hospital of Marseille-Timone	Marseille
France	University Hospital of Montpellier	Montpellier
France	University Hospital of Nancy	Nancy
France	University Hospital of Nice	Nice
France	University Hospital of Nimes	Nimes
France	University Hospital of Paris-Salpetriere	Paris
France	University Hospital of Poitiers	Poitiers
France	University Hospital of Rennes	Rennes
France	University Hospital of Rouen	Rouen
France	University Hospital Sud Réunion	Saint Pierre
France	University Hospital of St-Etienne	Saint-Etienne
France	University Hospital of Strasbourg	Strasbourg
France	Hôpital d'Instruction des Armées	Toulon
France	University Hospital of Toulouse	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Grenoble

Country where clinical trial is conducted

France, 

References & Publications (6)

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. Erratum in: J Neurotrauma. 2008 Mar;25(3):276-8. multiple author names added. — View Citation

Cunningham AS, Salvador R, Coles JP, Chatfield DA, Bradley PG, Johnston AJ, Steiner LA, Fryer TD, Aigbirhio FI, Smielewski P, Williams GB, Carpenter TA, Gillard JH, Pickard JD, Menon DK. Physiological thresholds for irreversible tissue damage in contusional regions following traumatic brain injury. Brain. 2005 Aug;128(Pt 8):1931-42. Epub 2005 May 11. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Ancillary outcome : Volume of cerebral lesions with abnormal MD values, i.e., decreased or increased MD values, using diffusion tensor MR imaging		at day 6-10 following initiation of cerebral monitoring after severe TBI
Primary	Neurological outcome according to the extended Glasgow Outcome Scale (GOSE) blind assessed		at 6 months post-trauma
Secondary	Neurological outcome according to the extended Glasgow Outcome Scale (GOSE) and Disability Rating Scale		at 12 months post-trauma (GOSE)
Secondary	Disability Rating Scale (DRS)		at 6 and 12 months post-trauma
Secondary	Quality of life assessment: Functional Independence Measure (FIM) and Medical Outcomes Study Short-Form 12 (SF-12)		at 6 and 12 months post-trauma
Secondary	Mortality rate		at day 28
Secondary	Therapeutic intensity as reflected by the number of level 2 and level 3 treatments to treat elevated ICP		during the first 5 days of the ICU stay
Secondary	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)		during the first 5 days of the ICU stay