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

NCT ID: NCT02754063

Last Updated: 2022-05-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

320 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-06-30

Study Completion Date

2022-04-30

Brief Summary

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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.

Detailed Description

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Conditions

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Brain Injuries, Traumatic

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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ICP Management

Group Type ACTIVE_COMPARATOR

No PbtO2 probes

Intervention Type OTHER

ICP/CPP-directed therapy according to international recommendations

PbtO2 + ICP Management

Group Type EXPERIMENTAL

PbtO2 probes

Intervention Type DEVICE

PbtO2/ICP/CPP-directed therapy according to international recommendations

Interventions

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PbtO2 probes

PbtO2/ICP/CPP-directed therapy according to international recommendations

Intervention Type DEVICE

No PbtO2 probes

ICP/CPP-directed therapy according to international recommendations

Intervention Type OTHER

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Grenoble

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jean-François PAYEN, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Grenoble

Locations

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CHU Angers

Angers, , France

Site Status

General Hospital of Annecy

Annecy, , France

Site Status

University Hospital Besançon

Besançon, , France

Site Status

University Hospital of Bordeaux

Bordeaux, , France

Site Status

CHU CAEN

Caen, , France

Site Status

University Hospital of Clermont-Ferrand

Clermont-Ferrand, , France

Site Status

University Hospital of Dijon

Dijon, , France

Site Status

Grenoble University Hospital

Grenoble, , France

Site Status

University Hospital of Kremlin-Bicetre

Le Kremlin-Bicêtre, , France

Site Status

University Hospital of Lille

Lille, , France

Site Status

University Hospital of Lyon

Lyon, , France

Site Status

University Hospital of Marseille-Nord

Marseille, , France

Site Status

University Hospital of Marseille-Timone

Marseille, , France

Site Status

University Hospital of Montpellier

Montpellier, , France

Site Status

University Hospital of Nancy

Nancy, , France

Site Status

University Hospital of Nice

Nice, , France

Site Status

University Hospital of Nimes

Nîmes, , France

Site Status

University Hospital of Paris-Salpetriere

Paris, , France

Site Status

University Hospital of Poitiers

Poitiers, , France

Site Status

University Hospital of Rennes

Rennes, , France

Site Status

University Hospital of Rouen

Rouen, , France

Site Status

University Hospital of St-Etienne

Saint-Etienne, , France

Site Status

University Hospital Sud Réunion

Saint-Pierre, , France

Site Status

University Hospital of Strasbourg

Strasbourg, , France

Site Status

Hôpital d'Instruction des Armées

Toulon, , France

Site Status

University Hospital of Toulouse

Toulouse, , France

Site Status

Countries

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France

References

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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. doi: 10.1093/brain/awh536. Epub 2005 May 11.

Reference Type BACKGROUND
PMID: 15888537 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17511547 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21673608 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10764260 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16304983 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19463048 (View on PubMed)

Payen JF, Vilotitch A, Gauss T, Adolle A, Bosson JL, Bouzat P; OXY-TC trial collaborators. Sex Differences in Neurological Outcome at 6 and 12 Months Following Severe Traumatic Brain Injury. An Observational Analysis of the OXY-TC Trial. J Neurotrauma. 2025 Jun;42(11-12):974-984. doi: 10.1089/neu.2024.0390. Epub 2025 Jan 23.

Reference Type DERIVED
PMID: 39846855 (View on PubMed)

Payen JF, Launey Y, Chabanne R, Gay S, Francony G, Gergele L, Vega E, Montcriol A, Couret D, Cottenceau V, Pili-Floury S, Gakuba C, Hammad E, Audibert G, Pottecher J, Dahyot-Fizelier C, Abdennour L, Gauss T, Richard M, Vilotitch A, Bosson JL, Bouzat P; OXY-TC trial collaborators. Intracranial pressure monitoring with and without brain tissue oxygen pressure monitoring for severe traumatic brain injury in France (OXY-TC): an open-label, randomised controlled superiority trial. Lancet Neurol. 2023 Nov;22(11):1005-1014. doi: 10.1016/S1474-4422(23)00290-9.

Reference Type DERIVED
PMID: 37863590 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35281992 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32820002 (View on PubMed)

Other Identifiers

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38RC14.039

Identifier Type: -

Identifier Source: org_study_id

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