Reduction of Oxygen After Cardiac Arrest (EXACT)

Monash University

Status: Terminated

Conditions: Out-of-Hospital Cardiac Arrest

Treatments: Other: target SpO2 98-100%; Other: target SpO2 90-94%

Study type: Interventional

Funder types: Other

Identifiers

NCT03138005

APP1107509 (Other Grant/Funding Number)

EXACT01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 428 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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428 participants in 2 patient groups

target SpO2 98-100%

Active Comparator group

Description:

Post ROSC oxygen titrated to maintain SpO2 between 98-100%

Treatment:

Other: target SpO2 98-100%

target SpO2 90-94%

Experimental group

Description:

Post ROSC oxygen titrated to maintain SpO2 between 90-94%

Treatment:

Other: target SpO2 90-94%