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Reduction of Oxygen After Cardiac Arrest (EXACT)

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ClinicalTrials.gov Identifier: NCT03138005
Recruitment Status : Recruiting
First Posted : May 3, 2017
Last Update Posted : February 7, 2018
Sponsor:
Collaborators:
Ambulance Victoria
SA Ambulance Service
St John Ambulance Australia (Western Australia)
Flinders University
Curtin University
Information provided by (Responsible Party):
Professor Stephen Bernard, Monash University

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.

Condition or disease Intervention/treatment Phase
Out-of-Hospital Cardiac Arrest Other: target SpO2 98-100% Other: target SpO2 90-94% Not Applicable

Detailed Description:

Currently out-of-hospital cardiac arrest (OHCA) patients who achieve ROSC are routinely ventilated with the highest fraction of inspired oxygen (FiO2) possible (i.e. FiO2 1.0 or 100% oxygen) until admission to an intensive care unit (ICU) - usually a period of 2 to 6 hours post-ROSC.

Post-ROSC oxygen therapy begins in the field by emergency medical services (EMS). EMS typically deliver a high flow of oxygen at rate of >10L/min (~100% oxygen), and use a pulse oximeter to monitor oxygen levels (SpO2). Normal SpO2 levels are considered to be 94% to 100%. The delivery of 100% oxygen is then usually continued throughout a patient's stay in the emergency department (ED) and during any diagnostic testing (e.g. computed tomography scans and cardiac angiography). During this time, oxygen is delivered to patients who remain unconscious via a mechanical ventilator, with levels continuously monitored by pulse oximetry and periodically by a blood test called an arterial blood gas (ABG). The ABG measurements include the oxygen pressure in the blood (PaO2) in mmHg. Once a patient is admitted to the ICU, the PaO2 is assessed and the oxygen fraction is typically reduced and then titrated (reduced or increased) on the ventilator to achieve a normal level of PaO2 ("normoxia") of between 80-100mmHg.

The administration of 100% oxygen for the first hours after resuscitation is based largely on convention and not on any supportive clinical data. It has been thought that maximizing oxygen delivery for several hours might be beneficial in a patient who has suffered profound deprivation of oxygen supply ("hypoxia") during a cardiac arrest. In addition, if a lower fraction of inspired oxygen is delivered, there is a perceived risk that the patient might become hypoxic (i.e. SpO2 <90% or PaO2 <80mmHg). Until recently, there has been no particular reason to recommend a decrease in oxygen delivery to the post-arrest patient prior to admission to ICU.

However, recent systematic reviews of compelling experimental data and supportive human observational studies indicate that the administration of 100% oxygen can create "hyperoxic" levels in the early post arrest period which may lead to additional neurological injury, and thus result in worse clinical outcome. No randomised control trials have yet tested titrating oxygen administration to lower but normal levels (i.e. "normoxia").

EXACT is a Phase 3 multi-centre, randomised, controlled trial (RCT) aiming 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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1416 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Reduction of Oxygen After Cardiac Arrest (EXACT): The EXACT Study
Actual Study Start Date : December 11, 2017
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: target SpO2 98-100%
Post ROSC oxygen titrated to maintain SpO2 between 98-100%
Other: 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%.

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




Primary Outcome Measures :
  1. Survival to hospital discharge [ Time Frame: At hospital discharge, participants will be followed for the duration of hospital stay, an expected average of 2-4 weeks ]
    Survival to hospital discharge


Secondary Outcome Measures :
  1. Neurological outcome [ Time Frame: At hospital discharge, participants will be followed for the duration of hospital stay, an expected average of 2-4 weeks ]
    Cerebral Performance Category score

  2. Incidence of hypoxia (SpO2<90%) [ Time Frame: Before ICU admission, an expected average of 4-6 hours ]
    Incidence of hypoxia (SpO2<90%)

  3. Recurrent cardiac arrest [ Time Frame: Before ICU admission, an expected average of 4-6 hours ]
    Recurrent cardiac arrest requiring chest compressions before admission to ICU and not related to withdrawal of life sustaining-treatment

  4. Survival to intensive care unit discharge [ Time Frame: Intensive care discharge, an expected average of 7 days ]
    Survival to intensive care unit discharge

  5. Length of ICU stay [ Time Frame: Intensive care discharge, an expected average of 7 days ]
    Length of ICU stay

  6. Length of hospital stay [ Time Frame: At hospital discharge, participants will be followed for the duration of hospital stay, an expected average of 2-4 weeks ]
    Length of hospital stay

  7. Cause of death during hospital stay [ Time Frame: At hospital discharge, participants will be followed for the duration of hospital stay, an expected average of 2-4 weeks ]
    e.g. cardiogenic shock, re-arrest with no ROSC, treatment withdrawn -hypoxic brain injury, brain death

  8. Quality of Life [ Time Frame: 12 months ]
    SF-12

  9. Quality of Life [ Time Frame: 12 months ]
    EQ-5d

  10. Neurological Function [ Time Frame: 12 months ]
    Modified Rankin Score

  11. Degree of recovery (GOS-E) [ Time Frame: 12 months ]
    Extended Glasgow Outcome Scale

  12. Survival at 12 months [ Time Frame: 12 months ]
    Survival at 12 months



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03138005


Contacts
Contact: Natasha Dodge +6139930039 SPHPM.EXACT.Study@monash.edu
Contact: Janet Bray, PhD +6139930177 janet.bray@monash.edu

Locations
Australia, South Australia
Royal Adelaide Hospital Not yet recruiting
Adelaide, South Australia, Australia, 5000
Contact: Stefan Mazur    +618 8222 4000    Stefan.Mazur@sa.gov.au   
Principal Investigator: Stefan Mazur         
The Queen Elizabeth Hospital Not yet recruiting
Adelaide, South Australia, Australia, 5011
Contact: James Smyth    +618 8222 6000    James.Smyth@sa.gov.au   
Principal Investigator: James Smyth         
SA Ambulance Service Not yet recruiting
Adelaide, South Australia, Australia, 5063
Contact: Cathrin Parsch       Cathrin.Parsch2@sa.gov.au   
Principal Investigator: Cathrin Parsch         
Lyell McEwin Hospital Not yet recruiting
Adelaide, South Australia, Australia, 5112
Contact: Cathrin Parsch       Cathrin.Parsch2@sa.gov.au   
Principal Investigator: Cathrin Parsch         
Australia, Victoria
Alfred Hospital Recruiting
Melbourne, Victoria, Australia, 3004
Contact: Peter Cameron    +61 3 990 30581    peter.cameron@monash.edu   
Principal Investigator: Peter Cameron         
Principal Investigator: Dion Stub         
Western Health: Footscray Hospital Recruiting
Melbourne, Victoria, Australia, 3011
Contact: Anne-Maree Kelly       anne-maree.kelly@wh.org.au   
Principal Investigator: Anne-Maree Kelly         
Western Health: Sunshine Hospital Recruiting
Melbourne, Victoria, Australia, 3021
Contact: Anne-Marie Kelly       anne-maree.kelly@wh.org.au   
Sub-Investigator: Peter Ritchie         
Principal Investigator: Anne-Marie Kelly         
The Royal Melbourne Hospital Recruiting
Melbourne, Victoria, Australia, 3050
Contact: Jonathan Knott       jonathan.knott@mh.org.au   
Principal Investigator: Jonathan Knott         
St Vincents Hospital Recruiting
Melbourne, Victoria, Australia, 3065
Contact: Stuart Dilley       Stuart.Dilley@svha.org.au   
Principal Investigator: Stuart Dilley         
Northern Health: The Northern Hospital Not yet recruiting
Melbourne, Victoria, Australia, 3076
Contact: Peter Jordan       Peter.Jordan@nh.org.au   
Principal Investigator: Peter Jordan         
Austin Hospital Recruiting
Melbourne, Victoria, Australia, 3084
Contact: David Taylor    +61 39496 4711    David.TAYLOR@austin.org.au   
Principal Investigator: David Taylor         
Box Hill Hospital Recruiting
Melbourne, Victoria, Australia, 3128
Contact: Jane Lukins       Jane.Lukins@easternhealth.org.au   
Principal Investigator: Jane Lukins         
Ambulance Victoria Recruiting
Melbourne, Victoria, Australia, 3130
Contact: Karen Smith    +61 3 9840 3752    karen.smith@ambulance.vic.gov.au   
Principal Investigator: Karen Smith         
Maroondah Hospital Recruiting
Melbourne, Victoria, Australia, 3135
Contact: Jane Lukins       Jane.Lukins@easternhealth.org.au   
Principal Investigator: Jane Lukins         
Monash Medical Centre Recruiting
Melbourne, Victoria, Australia, 3168
Contact: Andis Graudins       Andis.Graudins@monashhealth.org   
Principal Investigator: Andis Graudins         
Peninusla Health: Frankston Hospital Recruiting
Melbourne, Victoria, Australia, 3199
Contact: Pamela Rosengarten       Prosengarten@phcn.vic.gov.au   
Principal Investigator: Pamela Rosengarten         
Barwon Health: Geelong Recruiting
Melbourne, Victoria, Australia, 3220
Contact: Jullian Stella    +61 3 4215 0108    julianst@barwonhealth.org.au   
Principal Investigator: Jullian Stella         
Australia, Western Australia
Royal Perth Hospital Not yet recruiting
Perth, Western Australia, Australia, 6000
Contact: Daniel Fatovich, MD    +61892242662    daniel.fatovich@health.wa.gov.au   
Sir Charles Gairdner Hospital Not yet recruiting
Perth, Western Australia, Australia, 6009
Contact: Antonio Celenza    +618 6457 3333    tony.celenza@uwa.edu.au   
Fiona Stanley Hospital Not yet recruiting
Perth, Western Australia, Australia, 6150
Contact: Judith Finn    +61 8 9266 1599    judith.finn@curtin.edu.au   
St John Ambulance Western Australia Not yet recruiting
Perth, Western Australia, Australia, 6984
Contact: Judith Finn, PhD    +618 9266 4447    judith.finn@curtin.edu.au   
Sponsors and Collaborators
Monash University
Ambulance Victoria
SA Ambulance Service
St John Ambulance Australia (Western Australia)
Flinders University
Curtin University
Investigators
Principal Investigator: Stephen Bernard Ambulance Victoria

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

Responsible Party: Professor Stephen Bernard, Professor, Monash University
ClinicalTrials.gov Identifier: NCT03138005     History of Changes
Other Study ID Numbers: EXACT01
APP1107509 ( Other Grant/Funding Number: NHMRC )
First Posted: May 3, 2017    Key Record Dates
Last Update Posted: February 7, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Professor Stephen Bernard, Monash University:
Emergency Care, Prehospital
Resuscitation
Oxygen
Cardiac Arrest
Heart Arrest

Additional relevant MeSH terms:
Heart Arrest
Out-of-Hospital Cardiac Arrest
Heart Diseases
Cardiovascular Diseases