Reduction of Oxygen After Cardiac Arrest

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Out-of-Hospital Cardiac Arrest

Intervention / Treatment
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* Other: target SpO2 98-100%
* Other: target SpO2 90-94%


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: target SpO2 98-100%<br>Post ROSC oxygen titrated to maintain SpO2 between 98-100% | Other: target SpO2 98-100%<br>* 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%.<br>|
| Experimental: target SpO2 90-94%<br>Post ROSC oxygen titrated to maintain SpO2 between 90-94% | Other: target SpO2 90-94%<br>* 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%.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival to hospital discharge | 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 | 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%) | Incidence of hypoxia (SpO2<90%) | 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 | Before ICU admission, an expected average of 4-6 hours | 
| Myocardial Injury | Median peak troponin | First 24 hours of hospital admission | 
| Survival to intensive care unit discharge | Survival to intensive care unit discharge | Intensive care discharge, an expected average of 7 days | 
| Length of ICU stay | Length of ICU stay | Intensive care discharge, an expected average of 7 days | 
| Length of hospital 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 | 
| Cause of death during hospital stay | 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 | 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 | 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 | Modified Rankin Score | 12 months | 
| Degree of recovery (GOS-E) | Extended Glasgow Outcome Scale | 12 months | 
| Survival at 12 months | Survival at 12 months | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Emergency Care, Prehospital, Resuscitation, Oxygen, Cardiac Arrest, Heart Arrest