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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03138005




Registration number
NCT03138005
Ethics application status
Date submitted
21/04/2017
Date registered
3/05/2017
Date last updated
27/08/2020

Titles & IDs
Public title
Reduction of Oxygen After Cardiac Arrest
Scientific title
Reduction of Oxygen After Cardiac Arrest (EXACT): The EXACT Study
Secondary ID [1] 0 0
APP1107509
Secondary ID [2] 0 0
EXACT01
Universal Trial Number (UTN)
Trial acronym
EXACT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Out-of-Hospital Cardiac Arrest 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Coronary heart disease
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - target SpO2 98-100%
Other interventions - target SpO2 90-94%

Active comparator: target SpO2 98-100% - Post ROSC oxygen titrated to maintain SpO2 between 98-100%

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


Other interventions: target SpO2 98-100%
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%.

Other interventions: target SpO2 90-94%
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%.
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Survival to hospital discharge
Timepoint [1] 0 0
At hospital discharge, participants will be followed for the duration of hospital stay, an expected average of 2-4 weeks
Secondary outcome [1] 0 0
Neurological outcome
Timepoint [1] 0 0
At hospital discharge, participants will be followed for the duration of hospital stay, an expected average of 2-4 weeks
Secondary outcome [2] 0 0
Incidence of hypoxia (SpO2<90%)
Timepoint [2] 0 0
Before ICU admission, an expected average of 4-6 hours
Secondary outcome [3] 0 0
Recurrent cardiac arrest
Timepoint [3] 0 0
Before ICU admission, an expected average of 4-6 hours
Secondary outcome [4] 0 0
Myocardial Injury
Timepoint [4] 0 0
First 24 hours of hospital admission
Secondary outcome [5] 0 0
Survival to intensive care unit discharge
Timepoint [5] 0 0
Intensive care discharge, an expected average of 7 days
Secondary outcome [6] 0 0
Length of ICU stay
Timepoint [6] 0 0
Intensive care discharge, an expected average of 7 days
Secondary outcome [7] 0 0
Length of hospital stay
Timepoint [7] 0 0
At hospital discharge, participants will be followed for the duration of hospital stay, an expected average of 2-4 weeks
Secondary outcome [8] 0 0
Cause of death during hospital stay
Timepoint [8] 0 0
At hospital discharge, participants will be followed for the duration of hospital stay, an expected average of 2-4 weeks
Secondary outcome [9] 0 0
Quality of Life SF-12
Timepoint [9] 0 0
12 months
Secondary outcome [10] 0 0
Quality of Life EQ-5D-3L
Timepoint [10] 0 0
12 months
Secondary outcome [11] 0 0
Neurological Function
Timepoint [11] 0 0
12 months
Secondary outcome [12] 0 0
Degree of recovery (GOS-E)
Timepoint [12] 0 0
12 months
Secondary outcome [13] 0 0
Survival at 12 months
Timepoint [13] 0 0
12 months

Eligibility
Key inclusion criteria
* 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
UNKNOWN
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/12/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2020
Actual
Sample size
Target
1416
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC,WA
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
The Queen Elizabeth Hospital - Adelaide
Recruitment hospital [3] 0 0
SA Ambulance Service - Adelaide
Recruitment hospital [4] 0 0
Lyell McEwin Hospital - Adelaide
Recruitment hospital [5] 0 0
Alfred Hospital - Melbourne
Recruitment hospital [6] 0 0
Western Health: Footscray Hospital - Melbourne
Recruitment hospital [7] 0 0
Western Health: Sunshine Hospital - Melbourne
Recruitment hospital [8] 0 0
The Royal Melbourne Hospital - Melbourne
Recruitment hospital [9] 0 0
St Vincents Hospital - Melbourne
Recruitment hospital [10] 0 0
Northern Health: The Northern Hospital - Melbourne
Recruitment hospital [11] 0 0
Austin Hospital - Melbourne
Recruitment hospital [12] 0 0
Box Hill Hospital - Melbourne
Recruitment hospital [13] 0 0
Ambulance Victoria - Melbourne
Recruitment hospital [14] 0 0
Eastern Health: Maroondah Hospital - Melbourne
Recruitment hospital [15] 0 0
Monash Medical Centre - Melbourne
Recruitment hospital [16] 0 0
Peninusla Health: Frankston Hospital - Melbourne
Recruitment hospital [17] 0 0
Barwon Health: Geelong - Melbourne
Recruitment hospital [18] 0 0
Royal Perth Hospital - Perth
Recruitment hospital [19] 0 0
Sir Charles Gairdner Hospital - Perth
Recruitment hospital [20] 0 0
Fiona Stanley Hospital - Perth
Recruitment hospital [21] 0 0
St John Ambulance Western Australia - Perth
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
5011 - Adelaide
Recruitment postcode(s) [3] 0 0
5063 - Adelaide
Recruitment postcode(s) [4] 0 0
5112 - Adelaide
Recruitment postcode(s) [5] 0 0
3004 - Melbourne
Recruitment postcode(s) [6] 0 0
3011 - Melbourne
Recruitment postcode(s) [7] 0 0
3021 - Melbourne
Recruitment postcode(s) [8] 0 0
3050 - Melbourne
Recruitment postcode(s) [9] 0 0
3065 - Melbourne
Recruitment postcode(s) [10] 0 0
3076 - Melbourne
Recruitment postcode(s) [11] 0 0
3084 - Melbourne
Recruitment postcode(s) [12] 0 0
3128 - Melbourne
Recruitment postcode(s) [13] 0 0
3130 - Melbourne
Recruitment postcode(s) [14] 0 0
3135 - Melbourne
Recruitment postcode(s) [15] 0 0
3168 - Melbourne
Recruitment postcode(s) [16] 0 0
3199 - Melbourne
Recruitment postcode(s) [17] 0 0
3220 - Melbourne
Recruitment postcode(s) [18] 0 0
6000 - Perth
Recruitment postcode(s) [19] 0 0
6009 - Perth
Recruitment postcode(s) [20] 0 0
6150 - Perth
Recruitment postcode(s) [21] 0 0
6984 - Perth

Funding & Sponsors
Primary sponsor type
Other
Name
Monash University
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
Ambulance Victoria
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
SA Ambulance Service
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
St John Ambulance Australia (Western Australia)
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Flinders University
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
Curtin University
Address [5] 0 0
Country [5] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT03138005
Trial related presentations / publications
http://www.ambulance.vic.gov.au/Media/docs/VACAR-Annual-Report-201112-39a60ff4-083f-4893-af52-efeef570f6d1-0.pdf
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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. Erratum In: Thorax. 2009 Jan;64(1):91.
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.
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. Erratum In: Circulation. 2011 Feb 15;123(6):e236. Circulation. 2013 Dec 24;128(25):e480.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Stephen Bernard
Address 0 0
Ambulance Victoria
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Natasha Dodge
Address 0 0
Country 0 0
Phone 0 0
+6139930039
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03138005