Reduction of Oxygen After Cardiac Arrest

NCT03138005 | Terminated DMC

• 2 other identifiers: EXACT01APP1107509
• Study Type: interventional
• Target: 428
• Locations: 1 country
• Sites: 21

Brief Summary

The Reduction of oxygen after cardiac arrest (EXACT) is a multi-centre, randomised, controlled trial (RCT) to determine whether reducing oxygen administration to target an oxygen saturation of 90-94%, compared to 98-100%, as soon as possible following successful resuscitation from OHCA improves outcome at hospital discharge.

Conditions

Out-of-Hospital Cardiac Arrest

Keywords

Emergency Care, Prehospital; Resuscitation; Oxygen; Cardiac Arrest; Heart Arrest

Outcome Measures

Primary Outcomes (1)

• Survival to hospital discharge

  Survival to hospital discharge

  At hospital discharge, participants will be followed for the duration of hospital stay, an expected average of 2-4 weeks

Secondary Outcomes (13)

• Neurological outcome

  At hospital discharge, participants will be followed for the duration of hospital stay, an expected average of 2-4 weeks

• Incidence of hypoxia (SpO2<90%)

  Before ICU admission, an expected average of 4-6 hours

• Recurrent cardiac arrest

  Before ICU admission, an expected average of 4-6 hours

• Myocardial Injury

  First 24 hours of hospital admission

• Survival to intensive care unit discharge

  Intensive care discharge, an expected average of 7 days

Study Arms (2)

target SpO2 98-100%

ACTIVE COMPARATOR

Post ROSC oxygen titrated to maintain SpO2 between 98-100%

Other: target SpO2 98-100%

target SpO2 90-94%

EXPERIMENTAL

Post ROSC oxygen titrated to maintain SpO2 between 90-94%

Other: target SpO2 90-94%

Interventions

target SpO2 98-100% OTHER

Prehospital, post-ROSC oxygen maintained at ≥10L/minute of oxygen (equivalent to \~100% oxygen) into SGA/ETT if hand ventilated or 100% (i.e. FiO2 of 1.0) oxygen settings if mechanically ventilated. Patients will continue on treatment to handover in the ED. Between arrival at ED and first ABG in ICU, the oxygen setting may then be decreased provided SpO2 is maintained between 98-100%.

target SpO2 98-100%

target SpO2 90-94% OTHER

Prehospital, post-ROSC oxygen reduced initially to 4L/minute (i.e. approximately 70% oxygen) into SGA/ETT if hand ventilated or an air mix setting if mechanically ventilated. If oxygen saturation remains ≥94% for 5 minutes, the oxygen flow rate will be further reduced to 2L/minute (i.e. approximately 46% oxygen) and hand ventilated to target an oxygen saturation between 90-94%. This treatment will continue to patient handover in the emergency department. Between arrival at ED and first ABG in ICU, oxygen will be titrated to target a oxygen saturation of 90-94%.

target SpO2 90-94%

Eligibility Criteria

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

You may qualify if:

• Adults (age 18 years or older)
• Out-of-hospital cardiac arrest of presumed cardiac cause
• All cardiac arrest rhythms
• Unconscious (Glasgow Coma Scale \<9)
• Return of spontaneous circulation
• Pulse oximeter measures oxygen saturation at ≥95% with oxygen flow set at \>10L/min or FiO2 at 100%
• Patient has an endotracheal tube (ETT) or supraglottic airway (SGA) (e.g. laryngeal mask airway -LMA) and is spontaneously breathing or ventilated
• Transport is planned to a participating hospital

You may not qualify if:

• Female who is known or suspected to be pregnant
• Dependent on others for activities of daily living (i.e. facilitated care or nursing home residents)
• "Not for Resuscitation" order or Advanced Care Directives in place
• Pre-existing oxygen therapy (i.e. for COPD)
• Cardiac arrest due to drowning, trauma or hanging

Sponsors & Collaborators

• Monash University: lead
• Ambulance Victoria: collaborator
• SA Ambulance Service: collaborator
• St John Ambulance Australia (Western Australia): collaborator
• Flinders University: collaborator
• Curtin University: collaborator

Study Sites (21)

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

The Queen Elizabeth Hospital

Adelaide, South Australia, 5011, Australia

Location

SA Ambulance Service

Adelaide, South Australia, 5063, Australia

Location

Lyell McEwin Hospital

Adelaide, South Australia, 5112, Australia

Location

Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Western Health: Footscray Hospital

Melbourne, Victoria, 3011, Australia

Location

Western Health: Sunshine Hospital

Melbourne, Victoria, 3021, Australia

Location

The Royal Melbourne Hospital

Melbourne, Victoria, 3050, Australia

Location

St Vincents Hospital

Melbourne, Victoria, 3065, Australia

Location

Northern Health: The Northern Hospital

Melbourne, Victoria, 3076, Australia

Location

Austin Hospital

Melbourne, Victoria, 3084, Australia

Location

Box Hill Hospital

Melbourne, Victoria, 3128, Australia

Location

Ambulance Victoria

Melbourne, Victoria, 3130, Australia

Location

Eastern Health: Maroondah Hospital

Melbourne, Victoria, 3135, Australia

Location

Monash Medical Centre

Melbourne, Victoria, 3168, Australia

Location

Peninusla Health: Frankston Hospital

Melbourne, Victoria, 3199, Australia

Location

Barwon Health: Geelong

Melbourne, Victoria, 3220, Australia

Location

Royal Perth Hospital

Perth, Western Australia, 6000, Australia

Location

Sir Charles Gairdner Hospital

Perth, Western Australia, 6009, Australia

Location

Fiona Stanley Hospital

Perth, Western Australia, 6150, Australia

Location

St John Ambulance Western Australia

Perth, Western Australia, 6984, Australia

Location

Related Publications (25)

• http://www.ambulance.vic.gov.au/Media/docs/VACAR-Annual-Report-201112-39a60ff4-083f-4893-af52-efeef570f6d1-0.pdf

  BACKGROUND

• Kaneda T, Ku K, Inoue T, Onoe M, Oku H. Postischemic reperfusion injury can be attenuated by oxygen tension control. Jpn Circ J. 2001 Mar;65(3):213-8. doi: 10.1253/jcj.65.213.

  PMID: 11266197 BACKGROUND

• Richards EM, Fiskum G, Rosenthal RE, Hopkins I, McKenna MC. Hyperoxic reperfusion after global ischemia decreases hippocampal energy metabolism. Stroke. 2007 May;38(5):1578-84. doi: 10.1161/STROKEAHA.106.473967. Epub 2007 Apr 5.

  PMID: 17413048 BACKGROUND

• Pilcher J, Weatherall M, Shirtcliffe P, Bellomo R, Young P, Beasley R. The effect of hyperoxia following cardiac arrest - A systematic review and meta-analysis of animal trials. Resuscitation. 2012 Apr;83(4):417-22. doi: 10.1016/j.resuscitation.2011.12.021. Epub 2012 Jan 5.

  PMID: 22226734 BACKGROUND

• Balan IS, Fiskum G, Hazelton J, Cotto-Cumba C, Rosenthal RE. Oximetry-guided reoxygenation improves neurological outcome after experimental cardiac arrest. Stroke. 2006 Dec;37(12):3008-13. doi: 10.1161/01.STR.0000248455.73785.b1. Epub 2006 Oct 26.

  PMID: 17068310 BACKGROUND

• Saugstad OD. Resuscitation of newborn infants: from oxygen to room air. Lancet. 2010 Dec 11;376(9757):1970-1. doi: 10.1016/S0140-6736(10)60543-0. Epub 2010 Jul 19. No abstract available.

  PMID: 20663546 BACKGROUND

• Hellstrom-Westas L, Forsblad K, Sjors G, Saugstad OD, Bjorklund LJ, Marsal K, Kallen K. Earlier Apgar score increase in severely depressed term infants cared for in Swedish level III units with 40% oxygen versus 100% oxygen resuscitation strategies: a population-based register study. Pediatrics. 2006 Dec;118(6):e1798-804. doi: 10.1542/peds.2006-0102.

  PMID: 17142501 BACKGROUND

• Kilgannon JH, Jones AE, Shapiro NI, Angelos MG, Milcarek B, Hunter K, Parrillo JE, Trzeciak S; Emergency Medicine Shock Research Network (EMShockNet) Investigators. Association between arterial hyperoxia following resuscitation from cardiac arrest and in-hospital mortality. JAMA. 2010 Jun 2;303(21):2165-71. doi: 10.1001/jama.2010.707.

  PMID: 20516417 BACKGROUND

• Bellomo R, Bailey M, Eastwood GM, Nichol A, Pilcher D, Hart GK, Reade MC, Egi M, Cooper DJ; Study of Oxygen in Critical Care (SOCC) Group. Arterial hyperoxia and in-hospital mortality after resuscitation from cardiac arrest. Crit Care. 2011;15(2):R90. doi: 10.1186/cc10090. Epub 2011 Mar 8.

  PMID: 21385416 BACKGROUND

• Ihle JF, Bernard S, Bailey MJ, Pilcher DV, Smith K, Scheinkestel CD. Hyperoxia in the intensive care unit and outcome after out-of-hospital ventricular fibrillation cardiac arrest. Crit Care Resusc. 2013 Sep;15(3):186-90.

  PMID: 23944204 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

• Kuisma M, Boyd J, Voipio V, Alaspaa A, Roine RO, Rosenberg P. Comparison of 30 and the 100% inspired oxygen concentrations during early post-resuscitation period: a randomised controlled pilot study. Resuscitation. 2006 May;69(2):199-206. doi: 10.1016/j.resuscitation.2005.08.010. Epub 2006 Feb 24.

  PMID: 16500018 BACKGROUND

• Young P, Bailey M, Bellomo R, Bernard S, Dicker B, Freebairn R, Henderson S, Mackle D, McArthur C, McGuinness S, Smith T, Swain A, Weatherall M, Beasley R. HyperOxic Therapy OR NormOxic Therapy after out-of-hospital cardiac arrest (HOT OR NOT): a randomised controlled feasibility trial. Resuscitation. 2014 Dec;85(12):1686-91. doi: 10.1016/j.resuscitation.2014.09.011. Epub 2014 Sep 28.

  PMID: 25261605 BACKGROUND

• Young P, Pilcher J, Patel M, Cameron L, Braithwaite I, Weatherall M, Beasley R. Delivery of titrated oxygen via a self-inflating resuscitation bag. Resuscitation. 2013 Mar;84(3):391-4. doi: 10.1016/j.resuscitation.2012.08.330. Epub 2012 Sep 3.

  PMID: 22955052 BACKGROUND

• Bernard SA, Smith K, Cameron P, Masci K, Taylor DM, Cooper DJ, Kelly AM, Silvester W; Rapid Infusion of Cold Hartmanns Investigators. Induction of prehospital therapeutic hypothermia after resuscitation from nonventricular fibrillation cardiac arrest*. Crit Care Med. 2012 Mar;40(3):747-53. doi: 10.1097/CCM.0b013e3182377038.

  PMID: 22020244 BACKGROUND

• Smith K, Andrew E, Lijovic M, Nehme Z, Bernard S. Quality of life and functional outcomes 12 months after out-of-hospital cardiac arrest. Circulation. 2015 Jan 13;131(2):174-81. doi: 10.1161/CIRCULATIONAHA.114.011200. Epub 2014 Oct 29.

  PMID: 25355914 BACKGROUND

• Kenmure AC, Murdoch WR, Beattie AD, Marshall JC, Cameron AJ. Circulatory and metabolic effects of oxygen in myocardial infarction. Br Med J. 1968 Nov 9;4(5627):360-4. doi: 10.1136/bmj.4.5627.360.

  PMID: 5683582 BACKGROUND

• Mak S, Azevedo ER, Liu PP, Newton GE. Effect of hyperoxia on left ventricular function and filling pressures in patients with and without congestive heart failure. Chest. 2001 Aug;120(2):467-73. doi: 10.1378/chest.120.2.467.

  PMID: 11502645 BACKGROUND

• Nehme Z, Bernard S, Cameron P, Bray JE, Meredith IT, Lijovic M, Smith K. Using a cardiac arrest registry to measure the quality of emergency medical service care: decade of findings from the Victorian Ambulance Cardiac Arrest Registry. Circ Cardiovasc Qual Outcomes. 2015 Jan;8(1):56-66. doi: 10.1161/CIRCOUTCOMES.114.001185.

  PMID: 25604556 BACKGROUND

• O'Driscoll BR, Howard LS, Davison AG; British Thoracic Society. BTS guideline for emergency oxygen use in adult patients. Thorax. 2008 Oct;63 Suppl 6:vi1-68. doi: 10.1136/thx.2008.102947. No abstract available.

  PMID: 18838559 BACKGROUND

• Stub D, Bernard S, Duffy SJ, Kaye DM. Post cardiac arrest syndrome: a review of therapeutic strategies. Circulation. 2011 Apr 5;123(13):1428-35. doi: 10.1161/CIRCULATIONAHA.110.988725. No abstract available.

  PMID: 21464058 BACKGROUND

• Neumar RW, Otto CW, Link MS, Kronick SL, Shuster M, Callaway CW, Kudenchuk PJ, Ornato JP, McNally B, Silvers SM, Passman RS, White RD, Hess EP, Tang W, Davis D, Sinz E, Morrison LJ. Part 8: adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010 Nov 2;122(18 Suppl 3):S729-67. doi: 10.1161/CIRCULATIONAHA.110.970988.

  PMID: 20956224 BACKGROUND

• Soar J, Callaway CW, Aibiki M, Bottiger BW, Brooks SC, Deakin CD, Donnino MW, Drajer S, Kloeck W, Morley PT, Morrison LJ, Neumar RW, Nicholson TC, Nolan JP, Okada K, O'Neil BJ, Paiva EF, Parr MJ, Wang TL, Witt J; Advanced Life Support Chapter Collaborators. Part 4: Advanced life support: 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Resuscitation. 2015 Oct;95:e71-120. doi: 10.1016/j.resuscitation.2015.07.042. Epub 2015 Oct 15. No abstract available.

  PMID: 26477429 BACKGROUND

• Bernard SA, Bray JE, Smith K, Stephenson M, Finn J, Grantham H, Hein C, Masters S, Stub D, Perkins GD, Dodge N, Martin C, Hopkins S, Cameron P; EXACT Investigators. Effect of Lower vs Higher Oxygen Saturation Targets on Survival to Hospital Discharge Among Patients Resuscitated After Out-of-Hospital Cardiac Arrest: The EXACT Randomized Clinical Trial. JAMA. 2022 Nov 8;328(18):1818-1826. doi: 10.1001/jama.2022.17701.

  PMID: 36286192 DERIVED

• Bray JE, Smith K, Hein C, Finn J, Stephenson M, Cameron P, Stub D, Perkins GD, Grantham H, Bailey P, Brink D, Dodge N, Bernard S; EXACT investigators. The EXACT protocol: A multi-centre, single-blind, randomised, parallel-group, controlled trial to determine whether early oxygen titration improves survival to hospital discharge in adult OHCA patients. Resuscitation. 2019 Jun;139:208-213. doi: 10.1016/j.resuscitation.2019.04.023. Epub 2019 Apr 19.

  PMID: 31009695 DERIVED

MeSH Terms

Conditions

Out-of-Hospital Cardiac Arrest; Heart Arrest

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Stephen Bernard

  Ambulance Victoria

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 21, 2017
• First Posted: May 3, 2017
• Study Start: December 11, 2017
• Primary Completion: August 5, 2020
• Study Completion: August 5, 2020
• Last Updated: October 2, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

AU (21)