Strategy to Avoid Excessive Oxygen for Critically Ill Trauma Patients

NCT04534959 | Active Not Recruiting Phase 3

• 1 other identifier: 19-2153
• Study Type: interventional
• Target: 6,000
• Locations: 1 country
• Sites: 8

Brief Summary

The objective is to determine the effectiveness of a multimodal educational intervention to reduce supplemental oxygen use in critically injured patients. Investigators will also evaluate the safety and clinical effectiveness of the more targeted use of oxygen therapy.

Conditions

Critical Illness; Wounds and Injury; Disease Attributes; Pathologic Processes

Keywords

hypoxia; hyperoxia; trauma; burn; critical illness; supplemental oxygen; oxygenation; SpO2; PaO2; FiO2; normoxia; hypoxemia; normoxemia; hyperoxemia

Outcome Measures

Primary Outcomes (1)

• Supplemental Oxygen Free Days (SOFD)

  Number of days alive and not on supplemental oxygen during the index hospitalization (0 days \[worst outcome\] to 28 days \[best outcome\])

  up to 28 days

Secondary Outcomes (16)

• Hospital-Free Days to day 90 (HFD90)

  up to 90 days

• In-hospital Mortality to day 90

  up to 90 days

• Time to Mortality to day 90

  up to 90 days

• Ventilator Free Day (VFD) to day 28

  up to 28 days

• Time to Room Air

  up to 90 days

Study Arms (2)

Pre-Implementation

NO INTERVENTION

The control (pre-implementation) group will be trauma patients admitted to the surgical/trauma ICU during the site's control period of the stepped-wedge implementation process (up to 22 months).

Post-Implementation Targeting Normoxemia in Trauma ICU

EXPERIMENTAL

The intervention (post-implementation) group will be patients admitted to the surgical/trauma ICU during the targeted normoxemia intervention period of the stepped-wedge implementation process (up to 25 months).

Other: Targeting Normoxemia (SpO2 90-96%; PaO2 60-100 mmHg)

Interventions

Targeting Normoxemia (SpO2 90-96%; PaO2 60-100 mmHg) OTHER

Post-implementation of targeted normoxemia through oxygen titration for individual patients. Interventions for treatment of hypoxemia will follow usual local practice. Interventions for treatment of hyperoxemia (SpO2 \>96% or PaO2 \>100 mmHg) will involve down titration of FiO2 (or supplemental oxygen for non-mechanically ventilated patients) within a time frame based on local site preferences-typically in increments of no greater than 0.10 until goal oxygenation in the normoxemia range is achieved (including room air \[no supplemental oxygen\] for non-mechanically ventilated patients).

Post-Implementation Targeting Normoxemia in Trauma ICU

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Acutely injured patients who meet the criteria for entry into the state or national trauma registry
• Admission to surgical/trauma ICU within 24 hours of hospital arrival

You may not qualify if:

• Age \<18 years
• Prisoners
• Known pregnancy
• Transferred patients not admitted through the emergency department

Sponsors & Collaborators

• University of Colorado, Denver: lead
• United States Department of Defense: collaborator

Study Sites (8)

University of Alabama-Birmingham Medical Center

Birmingham, Alabama, 35294, United States

Location

Denver Health

Denver, Colorado, 80204, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

Location

Oregon Health and Sciences University

Portland, Oregon, 97239, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15224, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Brooke Army Medical Center

Fort Sam Houston, Texas, 78234, United States

Location

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

Related Publications (40)

• Leverve XM. To cope with oxygen: a long and still tumultuous story for life. Crit Care Med. 2008 Feb;36(2):637-8. doi: 10.1097/CCM.0B013E31816296AD. No abstract available.

  PMID: 18216624 BACKGROUND

• Damiani E, Adrario E, Girardis M, Romano R, Pelaia P, Singer M, Donati A. Arterial hyperoxia and mortality in critically ill patients: a systematic review and meta-analysis. Crit Care. 2014 Dec 23;18(6):711. doi: 10.1186/s13054-014-0711-x.

  PMID: 25532567 BACKGROUND

• Panwar R, Capellier G, Schmutz N, Davies A, Cooper DJ, Bailey M, Baguley D, Pilcher V, Bellomo R. Current oxygenation practice in ventilated patients-an observational cohort study. Anaesth Intensive Care. 2013 Jul;41(4):505-14. doi: 10.1177/0310057X1304100412.

  PMID: 23808511 BACKGROUND

• Suzuki S, Eastwood GM, Peck L, Glassford NJ, Bellomo R. Current oxygen management in mechanically ventilated patients: a prospective observational cohort study. J Crit Care. 2013 Oct;28(5):647-54. doi: 10.1016/j.jcrc.2013.03.010. Epub 2013 May 15.

  PMID: 23683560 BACKGROUND

• Rachmale S, Li G, Wilson G, Malinchoc M, Gajic O. Practice of excessive F(IO(2)) and effect on pulmonary outcomes in mechanically ventilated patients with acute lung injury. Respir Care. 2012 Nov;57(11):1887-93. doi: 10.4187/respcare.01696. Epub 2012 May 15.

  PMID: 22613692 BACKGROUND

• Parke RL, Eastwood GM, McGuinness SP; George Institute for Global Health; Australian and New Zealand Intensive Care Society Clinical Trials Group. Oxygen therapy in non-intubated adult intensive care patients: a point prevalence study. Crit Care Resusc. 2013 Dec;15(4):287-93.

  PMID: 24289510 BACKGROUND

• Iscoe S, Beasley R, Fisher JA. Supplementary oxygen for nonhypoxemic patients: O2 much of a good thing? Crit Care. 2011;15(3):305. doi: 10.1186/cc10229. Epub 2011 Jun 30.

  PMID: 21722334 BACKGROUND

• Panwar R, Young P, Capellier G. Conservative oxygen therapy in mechanically ventilated patients. Crit Care Med. 2014 Sep;42(9):e630-1. doi: 10.1097/CCM.0000000000000439. No abstract available.

  PMID: 25126814 BACKGROUND

• de Graaff AE, Dongelmans DA, Binnekade JM, de Jonge E. Clinicians' response to hyperoxia in ventilated patients in a Dutch ICU depends on the level of FiO2. Intensive Care Med. 2011 Jan;37(1):46-51. doi: 10.1007/s00134-010-2025-z. Epub 2010 Sep 28.

  PMID: 20878146 BACKGROUND

• 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.

  PMID: 27706466 BACKGROUND

• de Jonge E, Peelen L, Keijzers PJ, Joore H, de Lange D, van der Voort PH, Bosman RJ, de Waal RA, Wesselink R, de Keizer NF. Association between administered oxygen, arterial partial oxygen pressure and mortality in mechanically ventilated intensive care unit patients. Crit Care. 2008;12(6):R156. doi: 10.1186/cc7150. Epub 2008 Dec 10.

  PMID: 19077208 BACKGROUND

• Pannu SR. Too Much Oxygen: Hyperoxia and Oxygen Management in Mechanically Ventilated Patients. Semin Respir Crit Care Med. 2016 Feb;37(1):16-22. doi: 10.1055/s-0035-1570359. Epub 2016 Jan 28.

  PMID: 26820270 BACKGROUND

• Kallet RH, Branson RD. Should Oxygen Therapy Be Tightly Regulated to Minimize Hyperoxia in Critically Ill Patients? Respir Care. 2016 Jun;61(6):801-17. doi: 10.4187/respcare.04933.

  PMID: 27235315 BACKGROUND

• 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.

  PMID: 26585328 BACKGROUND

• Helmerhorst HJ, Roos-Blom MJ, van Westerloo DJ, de Jonge E. Association Between Arterial Hyperoxia and Outcome in Subsets of Critical Illness: A Systematic Review, Meta-Analysis, and Meta-Regression of Cohort Studies. Crit Care Med. 2015 Jul;43(7):1508-19. doi: 10.1097/CCM.0000000000000998.

  PMID: 25855899 BACKGROUND

• Austin MA, Wills KE, Blizzard L, Walters EH, Wood-Baker R. Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial. BMJ. 2010 Oct 18;341:c5462. doi: 10.1136/bmj.c5462.

  PMID: 20959284 BACKGROUND

• Chi JH, Knudson MM, Vassar MJ, McCarthy MC, Shapiro MB, Mallet S, Holcroft JJ, Moncrief H, Noble J, Wisner D, Kaups KL, Bennick LD, Manley GT. Prehospital hypoxia affects outcome in patients with traumatic brain injury: a prospective multicenter study. J Trauma. 2006 Nov;61(5):1134-41. doi: 10.1097/01.ta.0000196644.64653.d8.

  PMID: 17099519 BACKGROUND

• 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.

  PMID: 26334785 BACKGROUND

• ICU-ROX Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group; Mackle D, Bellomo R, Bailey M, Beasley R, Deane A, Eastwood G, Finfer S, Freebairn R, King V, Linke N, Litton E, McArthur C, McGuinness S, Panwar R, Young P; ICU-ROX Investigators the Australian and New Zealand Intensive Care Society Clinical Trials Group. Conservative Oxygen Therapy during Mechanical Ventilation in the ICU. N Engl J Med. 2020 Mar 12;382(11):989-998. doi: 10.1056/NEJMoa1903297. Epub 2019 Oct 14.

  PMID: 31613432 BACKGROUND

• Schmidt B, Whyte RK, Asztalos EV, Moddemann D, Poets C, Rabi Y, Solimano A, Roberts RS; Canadian Oxygen Trial (COT) Group. Effects of targeting higher vs lower arterial oxygen saturations on death or disability in extremely preterm infants: a randomized clinical trial. JAMA. 2013 May 22;309(20):2111-20. doi: 10.1001/jama.2013.5555.

  PMID: 23644995 BACKGROUND

• BOOST II United Kingdom Collaborative Group; BOOST II Australia Collaborative Group; BOOST II New Zealand Collaborative Group; Stenson BJ, Tarnow-Mordi WO, Darlow BA, Simes J, Juszczak E, Askie L, Battin M, Bowler U, Broadbent R, Cairns P, Davis PG, Deshpande S, Donoghoe M, Doyle L, Fleck BW, Ghadge A, Hague W, Halliday HL, Hewson M, King A, Kirby A, Marlow N, Meyer M, Morley C, Simmer K, Tin W, Wardle SP, Brocklehurst P. Oxygen saturation and outcomes in preterm infants. N Engl J Med. 2013 May 30;368(22):2094-104. doi: 10.1056/NEJMoa1302298. Epub 2013 May 5.

  PMID: 23642047 BACKGROUND

• SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network; Carlo WA, Finer NN, Walsh MC, Rich W, Gantz MG, Laptook AR, Yoder BA, Faix RG, Das A, Poole WK, Schibler K, Newman NS, Ambalavanan N, Frantz ID 3rd, Piazza AJ, Sanchez PJ, Morris BH, Laroia N, Phelps DL, Poindexter BB, Cotten CM, Van Meurs KP, Duara S, Narendran V, Sood BG, O'Shea TM, Bell EF, Ehrenkranz RA, Watterberg KL, Higgins RD. Target ranges of oxygen saturation in extremely preterm infants. N Engl J Med. 2010 May 27;362(21):1959-69. doi: 10.1056/NEJMoa0911781. Epub 2010 May 16.

  PMID: 20472937 BACKGROUND

• Stockinger ZT, Mcswain NE Jr. Prehospital supplemental oxygen in trauma patients: its efficacy and implications for military medical care. Mil Med. 2004 Aug;169(8):609-12. doi: 10.7205/milmed.169.8.609.

  PMID: 15379072 BACKGROUND

• Meyhoff CS, Wetterslev J, Jorgensen LN, Henneberg SW, Hogdall C, Lundvall L, Svendsen PE, Mollerup H, Lunn TH, Simonsen I, Martinsen KR, Pulawska T, Bundgaard L, Bugge L, Hansen EG, Riber C, Gocht-Jensen P, Walker LR, Bendtsen A, Johansson G, Skovgaard N, Helto K, Poukinski A, Korshin A, Walli A, Bulut M, Carlsson PS, Rodt SA, Lundbech LB, Rask H, Buch N, Perdawid SK, Reza J, Jensen KV, Carlsen CG, Jensen FS, Rasmussen LS; PROXI Trial Group. Effect of high perioperative oxygen fraction on surgical site infection and pulmonary complications after abdominal surgery: the PROXI randomized clinical trial. JAMA. 2009 Oct 14;302(14):1543-50. doi: 10.1001/jama.2009.1452.

  PMID: 19826023 BACKGROUND

• Stub D, Smith K, Bernard S, Nehme Z, Stephenson M, Bray JE, Cameron P, Barger B, Ellims AH, Taylor AJ, Meredith IT, Kaye DM; AVOID Investigators. Air Versus Oxygen in ST-Segment-Elevation Myocardial Infarction. Circulation. 2015 Jun 16;131(24):2143-50. doi: 10.1161/CIRCULATIONAHA.114.014494. Epub 2015 May 22.

  PMID: 26002889 BACKGROUND

• Suzuki S, Eastwood GM, Glassford NJ, Peck L, Young H, Garcia-Alvarez M, Schneider AG, Bellomo R. Conservative oxygen therapy in mechanically ventilated patients: a pilot before-and-after trial. Crit Care Med. 2014 Jun;42(6):1414-22. doi: 10.1097/CCM.0000000000000219.

  PMID: 24561566 BACKGROUND

• Eastwood GM, Peck L, Young H, Suzuki S, Garcia M, Bellomo R. Intensive care clinicians' opinion of conservative oxygen therapy (SpO(2) 90-92%) for mechanically ventilated patients. Aust Crit Care. 2014 Aug;27(3):120-5. doi: 10.1016/j.aucc.2013.11.004. Epub 2013 Dec 24.

  PMID: 24369915 BACKGROUND

• Helmerhorst HJ, Schultz MJ, van der Voort PH, Bosman RJ, Juffermans NP, de Jonge E, van Westerloo DJ. Self-reported attitudes versus actual practice of oxygen therapy by ICU physicians and nurses. Ann Intensive Care. 2014 Jul 25;4:23. doi: 10.1186/s13613-014-0023-y. eCollection 2014.

  PMID: 25512878 BACKGROUND

• Helmerhorst HJ, Schultz MJ, van der Voort PH, Bosman RJ, Juffermans NP, de Wilde RB, van den Akker-van Marle ME, van Bodegom-Vos L, de Vries M, Eslami S, de Keizer NF, Abu-Hanna A, van Westerloo DJ, de Jonge E. Effectiveness and Clinical Outcomes of a Two-Step Implementation of Conservative Oxygenation Targets in Critically Ill Patients: A Before and After Trial. Crit Care Med. 2016 Mar;44(3):554-63. doi: 10.1097/CCM.0000000000001461.

  PMID: 26562347 BACKGROUND

• Acute Respiratory Distress Syndrome Network; Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000 May 4;342(18):1301-8. doi: 10.1056/NEJM200005043421801.

  PMID: 10793162 BACKGROUND

• Mohr CJ, Keenan S. Prolonged Field Care Working Group Position Paper: Operational Context for Prolonged Field Care. J Spec Oper Med. 2015 Fall;15(3):78-80. doi: 10.55460/1T85-6NB9. No abstract available.

  PMID: 26360359 BACKGROUND

• Ball JA, Keenan S. Prolonged Field Care Working Group Position Paper: Prolonged Field Care Capabilities. J Spec Oper Med. 2015 Fall;15(3):76-77. doi: 10.55460/B3NN-SY8Y. No abstract available.

  PMID: 26360358 BACKGROUND

• Gangidine MM, Blakeman TC, Branson RD, Johannigman JA. System Design Verification for Closed Loop Control of Oxygenation With Concentrator Integration. Mil Med. 2016 May;181(5 Suppl):177-83. doi: 10.7205/MILMED-D-15-00150.

  PMID: 27168570 BACKGROUND

• Baker DW, Persell SD. Criteria for waiver of informed consent for quality improvement research. JAMA Intern Med. 2015 Jan;175(1):142-3. doi: 10.1001/jamainternmed.2014.6977. No abstract available.

  PMID: 25560946 BACKGROUND

• McKinney RE Jr, Beskow LM, Ford DE, Lantos JD, McCall J, Patrick-Lake B, Pletcher MJ, Rath B, Schmidt H, Weinfurt K. Use of altered informed consent in pragmatic clinical research. Clin Trials. 2015 Oct;12(5):494-502. doi: 10.1177/1740774515597688. Epub 2015 Sep 15.

  PMID: 26374677 BACKGROUND

• Douin DJ, Schauer SG, Anderson EL, Jones J, DeSanto K, Cunningham CW, Bebarta VS, Ginde AA. Systematic review of oxygenation and clinical outcomes to inform oxygen targets in critically ill trauma patients. J Trauma Acute Care Surg. 2019 Oct;87(4):961-977. doi: 10.1097/TA.0000000000002392.

  PMID: 31162333 BACKGROUND

• Hussey MA, Hughes JP. Design and analysis of stepped wedge cluster randomized trials. Contemp Clin Trials. 2007 Feb;28(2):182-91. doi: 10.1016/j.cct.2006.05.007. Epub 2006 Jul 7.

  PMID: 16829207 BACKGROUND

• Campbell MK, Fayers PM, Grimshaw JM. Determinants of the intracluster correlation coefficient in cluster randomized trials: the case of implementation research. Clin Trials. 2005;2(2):99-107. doi: 10.1191/1740774505cn071oa.

  PMID: 16279131 BACKGROUND

• Douin DJ, Rice JD, Anderson EL, Jackson CL, Cheng AC, Xiao M, Cwik J, Beaty LE, Wild JL, Daya MR, Doshi PB, Eastham SC, Goodman MD, Gunn SR, Haukoos JS, Hudson JA, Jansen JO, McMullan JT, Rizzo JA, Schreiber MA, Self WH, Semler MW, Steinwand A, Werner N, Bebarta VS, Schauer SG, Ginde AA; Strategy to Avoid Excessive Oxygen (SAVE-O2) Investigators. Targeted Normoxemia and Supplemental Oxygen-Free Days in Critically Injured Adults: A Stepped-Wedge Cluster Randomized Clinical Trial. JAMA Netw Open. 2025 Mar 3;8(3):e252093. doi: 10.1001/jamanetworkopen.2025.2093.

  PMID: 40163121 DERIVED

• Dylla L, Douin DJ, Anderson EL, Rice JD, Jackson CL, Bebarta VS, Lindsell CJ, Cheng AC, Schauer SG, Ginde AA. A multicenter cluster randomized, stepped wedge implementation trial for targeted normoxia in critically ill trauma patients: study protocol and statistical analysis plan for the Strategy to Avoid Excessive Oxygen (SAVE-O2) trial. Trials. 2021 Nov 8;22(1):784. doi: 10.1186/s13063-021-05688-6.

  PMID: 34749762 DERIVED

MeSH Terms

Conditions

Critical Illness; Wounds and Injuries; Disease Attributes; Pathologic Processes; Hypoxia; Hyperoxia; Burns

Condition Hierarchy (Ancestors)

Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Respiratory; Signs and Symptoms

Study Officials

• Adit Ginde, MD, MPH

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2020
• First Posted: September 1, 2020
• Study Start: October 15, 2020
• Primary Completion: November 15, 2022
• Study Completion: June 30, 2025
• Last Updated: April 2, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)