Reduction of Oxygen After Cardiac Arrest
- Conditions
- Out-of-Hospital Cardiac Arrest
- Interventions
- Other: target SpO2 98-100%Other: target SpO2 90-94%
- Registration Number
- NCT03138005
- Lead Sponsor
- 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.
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 1416
- 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
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description target SpO2 98-100% target SpO2 98-100% Post ROSC oxygen titrated to maintain SpO2 between 98-100% target SpO2 90-94% target SpO2 90-94% Post ROSC oxygen titrated to maintain SpO2 between 90-94%
- Primary Outcome Measures
Name Time Method Survival to hospital discharge 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
Name Time Method Survival at 12 months 12 months Survival at 12 months
Quality of Life EQ-5D-3L 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.
Neurological outcome At hospital discharge, participants will be followed for the duration of hospital stay, an expected average of 2-4 weeks Cerebral Performance Category score
Incidence of hypoxia (SpO2<90%) Before ICU admission, an expected average of 4-6 hours Incidence of hypoxia (SpO2\<90%)
Survival to intensive care unit discharge Intensive care discharge, an expected average of 7 days Survival to intensive care unit discharge
Recurrent cardiac arrest 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
Length of ICU stay Intensive care discharge, an expected average of 7 days Length of ICU stay
Length of hospital stay At hospital discharge, participants will be followed for the duration of hospital stay, an expected average of 2-4 weeks Length of hospital stay
Quality of Life SF-12 12 months The SF-12 Health Survey (SF-12) is a 12-item questionnaire used to assess health outcomes from the patient's perspective.
Myocardial Injury First 24 hours of hospital admission Median peak troponin
Cause of death during hospital stay 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
Degree of recovery (GOS-E) 12 months Extended Glasgow Outcome Scale
Neurological Function 12 months Modified Rankin Score
Trial Locations
- Locations (21)
Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Northern Health: The Northern Hospital
🇦🇺Melbourne, Victoria, Australia
Austin Hospital
🇦🇺Melbourne, Victoria, Australia
Box Hill Hospital
🇦🇺Melbourne, Victoria, Australia
St John Ambulance Western Australia
🇦🇺Perth, Western Australia, Australia
Sir Charles Gairdner Hospital
🇦🇺Perth, Western Australia, Australia
Fiona Stanley Hospital
🇦🇺Perth, Western Australia, Australia
Royal Perth Hospital
🇦🇺Perth, Western Australia, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
The Queen Elizabeth Hospital
🇦🇺Adelaide, South Australia, Australia
SA Ambulance Service
🇦🇺Adelaide, South Australia, Australia
Lyell McEwin Hospital
🇦🇺Adelaide, South Australia, Australia
Barwon Health: Geelong
🇦🇺Melbourne, Victoria, Australia
The Royal Melbourne Hospital
🇦🇺Melbourne, Victoria, Australia
St Vincents Hospital
🇦🇺Melbourne, Victoria, Australia
Western Health: Footscray Hospital
🇦🇺Melbourne, Victoria, Australia
Western Health: Sunshine Hospital
🇦🇺Melbourne, Victoria, Australia
Eastern Health: Maroondah Hospital
🇦🇺Melbourne, Victoria, Australia
Ambulance Victoria
🇦🇺Melbourne, Victoria, Australia
Monash Medical Centre
🇦🇺Melbourne, Victoria, Australia
Peninusla Health: Frankston Hospital
🇦🇺Melbourne, Victoria, Australia