Intermediate Normal Versus High Normal Oxygen Levels in the Emergency Department for Severe Traumatic Brain Injury

Traumatic Brain Injury Clinical Trial

— INACHOS  

Official title:

Impact of Intermediate Normal Compared to High Normal Oxygen Levels on Outcomes of Patients Presenting in the Emergency Department With Severe Traumatic Brain Injury (INACHOS): a Pilot Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05464277
• Other study ID #: 286/18-6-2020
• Status: Recruiting
• Phase: N/A
• Start date: December 2, 2022
• Est. completion date: January 2027

Study information

• Verified date: February 2024
• Source: Evangelismos Hospital
• Contact: Vassilis G Giannakoulis, MD
• Phone: +30 6955571300
• Email: vassilisg[@]med.uoa.gr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Despite almost universal usage of supplemental oxygen therapy in patients presenting in the emergency department with traumatic brain injury (TBI), optimal oxygen levels are unclear.

The investigators propose a pilot multi-center randomized controlled trial to test the hypothesis that maintaining intermediate normal as opposed to high normal oxygen levels in patients presenting in the emergency department with TBI is feasible, and to obtain preliminary data on the efficacy of the two approaches to oxygen therapy. The aim is that the investigators produce pilot data, which could inform the design of potential subsequent larger clinical trials.

Description:

Despite the worldwide burden of traumatic brain injury (TBI), medical research on the field as opposed to other health problems is underrepresented. Consequently, there are few data to support commonly used interventions for the management of TBI, especially in the setting of the emergency department. For example, despite almost universal usage of supplemental oxygen therapy, the effects of different oxygenation levels under normobaric conditions on outcomes of patients presenting in the emergency department with TBI are unknown.

On the one hand, liberal oxygenation may provide a margin of safety against hypoxemia and may be needed to meet the high oxygen demands of an acutely altered brain physiology. On the other hand, there are increasing concerns that excessive oxygen supplementation may have harmful effects, such as central nervous system toxicity, cerebral vasoconstriction, impaired immunity leading to predisposition to infections (including pneumonia) and acute lung injury/acute respiratory distress syndrome. Such effects could be avoided by intermediate normal oxygen levels.

Taken together, the relative merits and risks of the abovementioned two approaches to oxygen therapy (namely, intermediate normal versus high normal oxygen levels) of patients with TBI in terms of important clinical outcomes (namely, development of nosocomial pneumonia, acute respiratory distress syndrome, disability and mortality) remain undefined. This suggests the need for randomized controlled trials. However, randomized controlled trials focusing on patient-centered outcomes should be preceded by pilot randomized controlled trials, which demonstrate a separation in treatment and protocol compliance (feasibility) associated with the studied interventions.

Therefore, the investigators propose a pilot multi-center randomized controlled trial to test the hypothesis that maintaining intermediate normal as opposed to high normal oxygen levels in patients presenting in the emergency department with TBI is feasible, and to obtain preliminary data on the efficacy of the two approaches to oxygen therapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: January 2027
• Est. primary completion date: July 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult patient =18 years

• Glasgow Coma Scale = 8

• Non-penetrating traumatic brain injury

• Intubated patient

Exclusion Criteria:

• Age <18 years

• Lack of intention to admit to the intensive care unit

• Moribund patient expected to die within 24 hours

• Expected need for mechanical ventilation < 24 hours

• Time interval from intubation to group allocation more than 60 minutes

• Penetrating traumatic brain injury

• Pregnancy

• Lack of equipoise of the treating clinician

• Lack of informed consent

Related Conditions & MeSH terms

• Acute Brain Injury
• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Acute Respiratory Failure
• Brain Injuries
• Brain Injuries, Traumatic
• Emergencies
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn
• Respiratory Insufficiency
• Traumatic Brain Injury
• Wounds and Injuries

Intervention

Other:
• Oxygen
Oxygen to achieve assigned SpO2 (or FiO2) targets will be administered to study subjects. The treating clinician can alter oxygenation targets at any time if deemed necessary. The oxygenation goal will be based on SpO2 rather than arterial oxygen saturation (SaO2) or arterial pressure oxygen (PaO2) from arterial blood gases. However, PaO2 can be used instead in situations where the treating clinician considers that peripheral perfusion is poor or SpO2 readings are unreliable. Assigned SpO2 targets will apply to the study subjects for a total duration of 6 hours from intubation or until death or until transfer to the operating theater (whatever comes first).

Locations

Country	Name	City	State
Greece	Evangelismos Hospital	Athens
Greece	KAT General Hospital	Athens

Sponsors (1)

Lead Sponsor	Collaborator
Evangelismos Hospital

Country where clinical trial is conducted

Greece, 

References & Publications (19)

Andrews PJ, Sinclair HL, Rodriguez A, Harris BA, Battison CG, Rhodes JK, Murray GD; Eurotherm3235 Trial Collaborators. Hypothermia for Intracranial Hypertension after Traumatic Brain Injury. N Engl J Med. 2015 Dec 17;373(25):2403-12. doi: 10.1056/NEJMoa1507581. Epub 2015 Oct 7. — View Citation

Asehnoune K, Balogh Z, Citerio G, Cap A, Billiar T, Stocchetti N, Cohen MJ, Pelosi P, Curry N, Gaarder C, Gruen R, Holcomb J, Hunt BJ, Juffermans NP, Maegele M, Midwinter M, Moore FA, O'Dwyer M, Pittet JF, Schochl H, Schreiber M, Spinella PC, Stanworth S, Winfield R, Brohi K. The research agenda for trauma critical care. Intensive Care Med. 2017 Sep;43(9):1340-1351. doi: 10.1007/s00134-017-4895-9. Epub 2017 Jul 29. — View Citation

Asehnoune K, Seguin P, Allary J, Feuillet F, Lasocki S, Cook F, Floch H, Chabanne R, Geeraerts T, Roger C, Perrigault PF, Hanouz JL, Lukaszewicz AC, Biais M, Boucheix P, Dahyot-Fizelier C, Capdevila X, Mahe PJ, Le Maguet P, Paugam-Burtz C, Gergaud S, Plaud B, Constantin JM, Malledant Y, Flet L, Sebille V, Roquilly A; Corti-TC Study Group. Hydrocortisone and fludrocortisone for prevention of hospital-acquired pneumonia in patients with severe traumatic brain injury (Corti-TC): a double-blind, multicentre phase 3, randomised placebo-controlled trial. Lancet Respir Med. 2014 Sep;2(9):706-16. doi: 10.1016/S2213-2600(14)70144-4. Epub 2014 Jul 24. Erratum In: Lancet Respir Med. 2014 Sep;2(9):e15. — View Citation

Brenner M, Stein D, Hu P, Kufera J, Wooford M, Scalea T. Association between early hyperoxia and worse outcomes after traumatic brain injury. Arch Surg. 2012 Nov;147(11):1042-6. doi: 10.1001/archsurg.2012.1560. — View Citation

Busl KM. Nosocomial Infections in the Neurointensive Care Unit. Neurosurg Clin N Am. 2018 Apr;29(2):299-314. doi: 10.1016/j.nec.2017.11.008. — View Citation

Chu DK, Kim LH, Young PJ, Zamiri N, Almenawer SA, Jaeschke R, Szczeklik W, Schunemann HJ, Neary JD, Alhazzani W. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. Lancet. 2018 Apr 28;391(10131):1693-1705. doi: 10.1016/S0140-6736(18)30479-3. Epub 2018 Apr 26. — View Citation

Dewan MC, Rattani A, Gupta S, Baticulon RE, Hung YC, Punchak M, Agrawal A, Adeleye AO, Shrime MG, Rubiano AM, Rosenfeld JV, Park KB. Estimating the global incidence of traumatic brain injury. J Neurosurg. 2018 Apr 27;130(4):1080-1097. doi: 10.3171/2017.10.JNS17352. — View Citation

Girardis M, Busani S, Damiani E, Donati A, Rinaldi L, Marudi A, Morelli A, Antonelli M, Singer M. Effect of Conservative vs Conventional Oxygen Therapy on Mortality Among Patients in an Intensive Care Unit: The Oxygen-ICU Randomized Clinical Trial. JAMA. 2016 Oct 18;316(15):1583-1589. doi: 10.1001/jama.2016.11993. — View Citation

Hafner S, Beloncle F, Koch A, Radermacher P, Asfar P. Hyperoxia in intensive care, emergency, and peri-operative medicine: Dr. Jekyll or Mr. Hyde? A 2015 update. Ann Intensive Care. 2015 Dec;5(1):42. doi: 10.1186/s13613-015-0084-6. Epub 2015 Nov 19. — View Citation

Mackle DM, Bailey MJ, Beasley RW, Bellomo R, Bennett VL, Deane AM, Eastwood GM, Finfer S, Freebairn RC, Litton E, Linke NJ, McArthur CJ, McGuinness SP, Panwar R, Young PJ; Australian and New Zealand Intensive Care Society Clinical Trials Group. Protocol summary and statistical analysis plan for the intensive care unit randomised trial comparing two approaches to oxygen therapy (ICU-ROX). Crit Care Resusc. 2018 Mar;20(1):22-32. — View Citation

Panwar R, Hardie M, Bellomo R, Barrot L, Eastwood GM, Young PJ, Capellier G, Harrigan PW, Bailey M; CLOSE Study Investigators; ANZICS Clinical Trials Group. Conservative versus Liberal Oxygenation Targets for Mechanically Ventilated Patients. A Pilot Multicenter Randomized Controlled Trial. Am J Respir Crit Care Med. 2016 Jan 1;193(1):43-51. doi: 10.1164/rccm.201505-1019OC. — View Citation

Raj R, Bendel S, Reinikainen M, Kivisaari R, Siironen J, Lang M, Skrifvars M. Hyperoxemia and long-term outcome after traumatic brain injury. Crit Care. 2013 Aug 19;17(4):R177. doi: 10.1186/cc12856. — View Citation

Robba C, Poole D, McNett M, Asehnoune K, Bosel J, Bruder N, Chieregato A, Cinotti R, Duranteau J, Einav S, Ercole A, Ferguson N, Guerin C, Siempos II, Kurtz P, Juffermans NP, Mancebo J, Mascia L, McCredie V, Nin N, Oddo M, Pelosi P, Rabinstein AA, Neto AS, Seder DB, Skrifvars MB, Suarez JI, Taccone FS, van der Jagt M, Citerio G, Stevens RD. Mechanical ventilation in patients with acute brain injury: recommendations of the European Society of Intensive Care Medicine consensus. Intensive Care Med. 2020 Dec;46(12):2397-2410. doi: 10.1007/s00134-020-06283-0. Epub 2020 Nov 11. — View Citation

Siemieniuk RAC, Chu DK, Kim LH, Guell-Rous MR, Alhazzani W, Soccal PM, Karanicolas PJ, Farhoumand PD, Siemieniuk JLK, Satia I, Irusen EM, Refaat MM, Mikita JS, Smith M, Cohen DN, Vandvik PO, Agoritsas T, Lytvyn L, Guyatt GH. Oxygen therapy for acutely ill medical patients: a clinical practice guideline. BMJ. 2018 Oct 24;363:k4169. doi: 10.1136/bmj.k4169. No abstract available. — View Citation

The Lancet Neurology. A rally for traumatic brain injury research. Lancet Neurol. 2013 Dec;12(12):1127. doi: 10.1016/S1474-4422(13)70266-7. No abstract available. — View Citation

Tolias CM, Reinert M, Seiler R, Gilman C, Scharf A, Bullock MR. Normobaric hyperoxia--induced improvement in cerebral metabolism and reduction in intracranial pressure in patients with severe head injury: a prospective historical cohort-matched study. J Neurosurg. 2004 Sep;101(3):435-44. doi: 10.3171/jns.2004.101.3.0435. — View Citation

Vilalta A, Sahuquillo J, Merino MA, Poca MA, Garnacho A, Martinez-Valverde T, Dronavalli M. Normobaric hyperoxia in traumatic brain injury: does brain metabolic state influence the response to hyperoxic challenge? J Neurotrauma. 2011 Jul;28(7):1139-48. doi: 10.1089/neu.2010.1720. Epub 2011 Jun 30. — View Citation

Vincent JL, Taccone FS, He X. Harmful Effects of Hyperoxia in Postcardiac Arrest, Sepsis, Traumatic Brain Injury, or Stroke: The Importance of Individualized Oxygen Therapy in Critically Ill Patients. Can Respir J. 2017;2017:2834956. doi: 10.1155/2017/2834956. Epub 2017 Jan 26. — View Citation

Xu F, Liu P, Pascual JM, Xiao G, Lu H. Effect of hypoxia and hyperoxia on cerebral blood flow, blood oxygenation, and oxidative metabolism. J Cereb Blood Flow Metab. 2012 Oct;32(10):1909-18. doi: 10.1038/jcbfm.2012.93. Epub 2012 Jun 27. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean area-under-curve (AUC) for SpO2	SpO2 will be recorded each hour for a total duration of 6 hours from intubation. Subsequently, mean area-under-curve (AUC) will be calculated for each group. This will demonstrate the feasibility of the study.	Measurements will be obtained each hour for a total duration of 6 hours from intubation.
Primary	Mean area-under-curve (AUC) for FiO2	FiO2 will be recorded each hour for a total duration of 6 hours from intubation. Subsequently, mean area-under-curve (AUC) will be calculated for each group. This will demonstrate the feasibility of the study.	Measurements will be obtained each hour for a total duration of 6 hours from intubation.
Primary	PaO2	PaO2 will be recorded at least once during 6 hours from intubation. Subsequently, PaO2 values (mmHg) will be calculated for each group. This will demonstrate the feasibility of the study.	Measurements will be obtained at least once during 6 hours from intubation.
Secondary	Nosocomial pneumonia	Incidence of nosocomial pneumonia will be recorded for each arm	Within 7 days of subject enrollment
Secondary	Acute Respiratory Distress Syndrome (ARDS)	Incidence of ARDS will be recorded for each arm	Within 7 days of subject enrollment
Secondary	All-cause mortality	All-cause mortality will be recorded during ICU stay	Within 28 days of subject enrollment
Secondary	Extended Glasgow Outcome Score (GOS-E)	A combined outcome of disability and mortality at 6 months using the Extended Glasgow Outcome Score will be assessed	At 6 months following subject enrollment