Reoxygenation After Cardiac Arrest (REOX Study) (REOX)

The broad objective of this study is to test the association between hyperoxia exposure after resuscitation from cardiac arrest and outcome. Our overarching hypothesis is that hyperoxia after ROSC is associated with increased oxidative stress and worsened neurological and cognitive outcomes.

Study Overview

• Status: Completed
• Conditions: Cardiac Arrest

Detailed Description

Specific Aim 1: Test if the degree and duration of hyperoxia following ROSC from cardiac arrest is associated with the degree of in vivo oxidative stress during the post-resuscitation phase of therapy.

Approach: We will conduct a multicenter prospective observational study of adult patients resuscitated from cardiac arrest. We will record data pertaining to oxygenation parameters and other factors and measure biomarkers of oxidative stress (isoprostanes and isofurans) in the plasma at 0 and 6 hours after ROSC using gas chromatography negative ion chemical ionization mass spectrometry. We will determine the exposure to post-ROSC hyperoxia by calculating the time-weighted average PaO2 and SaO2 for the post-resuscitation phase of therapy, and will test the association with plasma isoprostane and isofuran levels.

Specific Aim 2: Test if the degree and duration of hyperoxia following ROSC from cardiac arrest is associated with the degree of neurological disability at hospital discharge.

Approach: In the study described above, we will determine the Modified Rankin Scale at hospital discharge. We will perform multivariable analyses adjusted for numerous covariates known to be associated with outcome in post-cardiac arrest patients to determine if post-ROSC hyperoxia exposure is independently associated with neurological disability.

Specific Aim 3: Test if the degree and duration of hyperoxia following ROSC from cardiac arrest is associated with neuropsychological outcomes among survivors at 180 days.

Approach: In the study described above, we will assess neuropsychological outcome among survivors at 180 days. Neuropsychological testing will use validated instruments across five cognitive domains (attention, Wechsler Adult Intelligence Scale-IV-digit span; (2) reasoning, Wechsler Adult Intelligence Scale-IV-similarities; (3) immediate and delayed memory, Wechsler Memory Scale-III-logical memory I and II; (4) verbal fluency, Controlled Oral Word Association Test; and (5) executive functioning, Hayling Sentence Completion Test). We will perform multivariable analyses to determine if post-ROSC hyperoxia exposure is independently associated with neuropsychological deficits.

• Study Type: Observational
• Enrollment (Actual): 280

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University/ Methodist Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper University Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Adult patients resuscitated from cardiac arrest

Description

Inclusion Criteria:

• Age >17 years
• Cardiac arrest
• Return of spontaneous circulation
• Not following commands immediately after ROSC
• Endotracheal intubation
• Clinician intent to treat with therapeutic hypothermia (or absence of clinician intent to withhold therapeutic hypothermia)

Exclusion Criteria:

• Presumed etiology of arrest is trauma
• Presumed etiology of arrest is hemorrhage
• Presumed etiology of arrest is sepsis
• Permanent resident of nursing home or other long-term care facility
• Any other condition, that in the opinion of the investigator, would preclude the subject from being a suitable candidate, e.g. end stage chronic illness with no reasonable expectation of survival to hospital discharge

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Adult patients resuscitated from cardiac arrest

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Plasma isoprostanes/isofurans (mechanistic outcome)	0 and 6 hours post-ROSC

Secondary Outcome Measures

Outcome Measure	Time Frame
Modified Rankin Scale (mRS) (primary neurological outcome)	hospital discharge

Other Outcome Measures

Outcome Measure	Time Frame
Cognitive testing (primary neuropsychological outcome)	180 days

Collaborators and Investigators

• Sponsor: The Cooper Health System
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Study Director: Stephen Trzeciak, MD, MPH, The Cooper Health System

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: June 17, 2013
• First Submitted That Met QC Criteria: June 17, 2013
• First Posted (Estimate): June 19, 2013

Study Record Updates

• Last Update Posted (Actual): November 25, 2019
• Last Update Submitted That Met QC Criteria: November 22, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Cardiac Arrest, Hyperoxia, Ischemia-reperfusion Injury, Reactive Oxygen Species, Oxidative Stress, Neuropsychological Tests
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Arrest
• Other Study ID Numbers: REOX; R01HL112815 (U.S. NIH Grant/Contract)