Reduction of Oxygen After Cardiac Arrest (EXACT)

August 25, 2020 updated by: Professor Stephen Bernard, Monash University

Reduction of Oxygen After Cardiac Arrest (EXACT): The EXACT Study

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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

Enrollment (Anticipated)

1416

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Australia
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Not yet recruiting
        • Royal Adelaide Hospital
        • Contact:
        • Principal Investigator:
          • Stefan Mazur
      • Adelaide, South Australia, Australia, 5011
        • Not yet recruiting
        • The Queen Elizabeth Hospital
        • Contact:
        • Principal Investigator:
          • James Smyth
      • Adelaide, South Australia, Australia, 5063
        • Not yet recruiting
        • SA Ambulance Service
        • Contact:
        • Principal Investigator:
          • Cathrin Parsch
      • Adelaide, South Australia, Australia, 5112
        • Not yet recruiting
        • Lyell McEwin Hospital
        • Contact:
        • Principal Investigator:
          • Cathrin Parsch
    • Victoria
      • Melbourne, Victoria, Australia, 3004
        • Recruiting
        • Alfred Hospital
        • Contact:
        • Principal Investigator:
          • Peter Cameron
        • Principal Investigator:
          • Dion Stub
      • Melbourne, Victoria, Australia, 3128
      • Melbourne, Victoria, Australia, 3050
        • Recruiting
        • The Royal Melbourne Hospital
        • Contact:
        • Principal Investigator:
          • Jonathan Knott
      • Melbourne, Victoria, Australia, 3011
        • Recruiting
        • Western Health: Footscray Hospital
        • Contact:
        • Principal Investigator:
          • Anne-Maree Kelly
      • Melbourne, Victoria, Australia, 3021
        • Recruiting
        • Western Health: Sunshine Hospital
        • Contact:
        • Principal Investigator:
          • Peter Ritchie
        • Principal Investigator:
          • Anne-Marie Kelly
      • Melbourne, Victoria, Australia, 3065
        • Recruiting
        • St Vincents Hospital
        • Contact:
        • Principal Investigator:
          • Stuart Dilley
      • Melbourne, Victoria, Australia, 3076
        • Not yet recruiting
        • Northern Health: The Northern Hospital
        • Contact:
        • Principal Investigator:
          • Peter Jordan
      • Melbourne, Victoria, Australia, 3084
        • Recruiting
        • Austin Hospital
        • Contact:
        • Principal Investigator:
          • David Taylor
      • Melbourne, Victoria, Australia, 3130
      • Melbourne, Victoria, Australia, 3135
      • Melbourne, Victoria, Australia, 3168
      • Melbourne, Victoria, Australia, 3199
        • Recruiting
        • Peninusla Health: Frankston Hospital
        • Contact:
        • Principal Investigator:
          • Darsim Haji
      • Melbourne, Victoria, Australia, 3220
        • Recruiting
        • Barwon Health: Geelong
        • Contact:
        • Principal Investigator:
          • Jullian Stella
    • Western Australia
      • Perth, Western Australia, Australia, 6000
      • Perth, Western Australia, Australia, 6009
        • Not yet recruiting
        • Sir Charles Gairdner Hospital
        • Contact:
      • Perth, Western Australia, Australia, 6150
        • Not yet recruiting
        • Fiona Stanley Hospital
        • Contact:
      • Perth, Western Australia, Australia, 6984
        • Not yet recruiting
        • St John Ambulance Western Australia
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / 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%.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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%)
Time Frame: Before ICU admission, an expected average of 4-6 hours
Incidence of hypoxia (SpO2<90%)
Before ICU admission, an expected average of 4-6 hours
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
Before ICU admission, an expected average of 4-6 hours
Myocardial Injury
Time Frame: First 24 hours of hospital admission
Median peak troponin
First 24 hours of hospital admission
Survival to intensive care unit discharge
Time Frame: Intensive care discharge, an expected average of 7 days
Survival to intensive care unit discharge
Intensive care discharge, an expected average of 7 days
Length of ICU stay
Time Frame: Intensive care discharge, an expected average of 7 days
Length of ICU stay
Intensive care discharge, an expected average of 7 days
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
At hospital discharge, participants will be followed for the duration of hospital stay, an expected average of 2-4 weeks
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
At hospital discharge, participants will be followed for the duration of hospital stay, an expected average of 2-4 weeks
Quality of Life SF-12
Time Frame: 12 months
The SF-12 Health Survey (SF-12) is a 12-item questionnaire used to assess health outcomes from the patient's perspective.
12 months
Quality of Life EQ-5D-3L
Time Frame: 12 months
Quality of life assessment using the EQ-5D-3L descriptive system that comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems.
12 months
Neurological Function
Time Frame: 12 months
Modified Rankin Score
12 months
Degree of recovery (GOS-E)
Time Frame: 12 months
Extended Glasgow Outcome Scale
12 months
Survival at 12 months
Time Frame: 12 months
Survival at 12 months
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Monash University

Collaborators

Curtin University
Flinders University
Ambulance Victoria
SA Ambulance Service
St John Ambulance Australia (Western Australia)

Investigators

  • Principal Investigator: Stephen Bernard, Ambulance Victoria

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 11, 2017

Primary Completion (Anticipated)

October 1, 2020

Study Completion (Anticipated)

December 1, 2020

Study Registration Dates

First Submitted

April 21, 2017

First Submitted That Met QC Criteria

April 30, 2017

First Posted (Actual)

May 3, 2017

Study Record Updates

Last Update Posted (Actual)

August 27, 2020

Last Update Submitted That Met QC Criteria

August 25, 2020

Last Verified

August 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EXACT01
  • APP1107509 (Other Grant/Funding Number: NHMRC)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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