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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
428
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%.
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%.
Royal Adelaide Hospital
Adelaide, South Australia, Australia
The Queen Elizabeth Hospital
Survival to hospital discharge
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
Neurological outcome
Cerebral Performance Category score
Time frame: 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%)
Incidence of hypoxia (SpO2\<90%)
Time frame: Before ICU admission, an expected average of 4-6 hours
Recurrent cardiac arrest
Recurrent cardiac arrest requiring chest compressions before admission to ICU and not related to withdrawal of life sustaining-treatment
Time frame: Before ICU admission, an expected average of 4-6 hours
Myocardial Injury
Median peak troponin
Time frame: First 24 hours of hospital admission
Survival to intensive care unit discharge
Survival to intensive care unit discharge
Time frame: Intensive care discharge, an expected average of 7 days
Length of ICU stay
Length of ICU stay
Time frame: Intensive care discharge, an expected average of 7 days
Length of hospital stay
Length of hospital stay
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Adelaide, South Australia, Australia
SA Ambulance Service
Adelaide, South Australia, Australia
Lyell McEwin Hospital
Adelaide, South Australia, Australia
Alfred Hospital
Melbourne, Victoria, Australia
Western Health: Footscray Hospital
Melbourne, Victoria, Australia
Western Health: Sunshine Hospital
Melbourne, Victoria, Australia
The Royal Melbourne Hospital
Melbourne, Victoria, Australia
St Vincents Hospital
Melbourne, Victoria, Australia
Northern Health: The Northern Hospital
Melbourne, Victoria, Australia
...and 11 more locations
Time frame: 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
e.g. cardiogenic shock, re-arrest with no ROSC, treatment withdrawn -hypoxic brain injury, brain death
Time frame: 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
The SF-12 Health Survey (SF-12) is a 12-item questionnaire used to assess health outcomes from the patient's perspective.
Time frame: 12 months
Quality of Life EQ-5D-3L
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.
Time frame: 12 months
Neurological Function
Modified Rankin Score
Time frame: 12 months
Degree of recovery (GOS-E)
Extended Glasgow Outcome Scale
Time frame: 12 months
Survival at 12 months
Survival at 12 months
Time frame: 12 months