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Reoxygenation After Cardiac Arrest II (REOX II Study) (REOX II)

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ClinicalTrials.gov Identifier: NCT02698826
Recruitment Status : Recruiting
First Posted : March 4, 2016
Last Update Posted : June 16, 2017
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
The Cooper Health System

Brief Summary:
The broad objective of this study is to test the association between hyperoxia exposure after resuscitation from cardiac arrest and outcome. After obtaining written informed consent subjects enrolled in REOX II will undergo a rapid faction of inspired oxygen (FiO2) optimization protocol to prevent exposure to hyperoxia. We will compare outcomes between subjects enrolled in REOX I (observational study only) and REOX II (intervention: rapid FiO2 optimization protocol). Our overarching hypothesis is that exposure to hyperoxia after return of spontaneous circulation (ROSC) is associated with increased oxidative stress and worsened neurological and cognitive outcomes.

Condition or disease Intervention/treatment Phase
Cardiac Arrest Other: Protocol for rapid FiO2 optimization Phase 1

Detailed Description:

Specific Aim 1: Test if initiation of the rapid FiO2 optimization protocol 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 interventional study (FiO2 optimization protocol) 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 (IsoPs) and isofurans (IsoFs)] in the plasma at 0 and 6 hours after ROSC using gas chromatography negative ion chemical ionization mass spectrometry. We will compare plasma IsoPs/IsoFs at each time point between subjects enrolled in REOX II (i.e. receive the study intervention, rapid FiO2 optimization) and REOX I (i.e. do not receive the study intervention) using t-test or Mann-Whitney U as appropriate with corrections for multiple comparisons.

Specific Aim 2: Test if initiation of the rapid FiO2 optimization protocol following ROSC from cardiac arrest is associated with a decrease in neurological disability at hospital discharge.

Approach: In the study described above, we will determine the Modified Rankin Scale (mRS) at hospital discharge. We will compare proportions of good neurological outcome [defined as a mRS ≤ 3] between subjects enrolled in REOX II (i.e. receive the study intervention, rapid FiO2 optimization) vs. those enrolled in REOX I (i.e. do not receive the study intervention), using binomial test.

Specific Aim 3: Test if initiation of the rapid FiO2 optimization protocol 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). Among survivors, we will compare the 180-day neuropsychological measures (composite z-scores for each cognitive domain) between the same two groups using t-test or Mann-Whitney U as appropriate with corrections for multiple comparisons. We will also compare the proportions of patients able to return to work between the two groups using binomial test


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Reoxygenation After Cardiac Arrest II (REOX II Study)
Study Start Date : April 2016
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : June 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cardiac Arrest

Arm Intervention/treatment
Experimental: Adult patients resuscitated from cardiac arrest
Rapid FiO2 optimization protocol
Other: Protocol for rapid FiO2 optimization
We plan to test a protocol for FiO2 optimization for mechanically ventilated post-cardiac arrest subjects, with a therapeutic goal of partial pressure of arterial oxygen (PaO2) of 60-99 mmHg, based on the PaO2 range that was associated with the lowest risk of poor outcome in our previously published work. We also use PaO2 (measured by arterial blood gas [ABG] analysis) as the ultimate goal rather than arterial oxygen saturation (SaO2) measured by pulse oximetry because an SaO2 value <100% on pulse oximetry monitoring does not always exclude supranormal PaO2. The protocol in this application begins with very rapid reduction of FiO2 as much as possible according to SaO2 values, and when FiO2 is maximally reduced by SaO2 an ABG is measured, followed by finer adjustment of FiO2 to achieve a PaO2 60-99 mmHg. The protocol not only prescribes each downward titration of FiO2 but it also includes detailed limbs for upward titration of FiO2 to account for potential "overshoot" in FiO2 reduction.




Primary Outcome Measures :
  1. Plasma isofurans (pg/mL)/isoprostanes (pg/mL) ratio [ Time Frame: Change in the isofurans/isoprostanes ratio between 0 and 6 hours post-ROSC ]

Secondary Outcome Measures :
  1. Modified Rankin Scale (mRS) (primary neurological outcome) [ Time Frame: Upon hospital discharge, on average two weeks ]

Other Outcome Measures:
  1. Composite neuropsychological testing score [ Time Frame: 180 days ]
    The neuropsychological testing uses validated instruments across five cognitive domains: (1) 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02698826


Contacts
Contact: Stephen Trzeciak, MD, MPH 856-342-3342 trzeciak-stephen@cooperhealth.edu

Locations
United States, Indiana
Indiana University/ Methodist Hospital Not yet recruiting
Indianapolis, Indiana, United States, 46202
Contact: Jeffrey A Kline, MD         
Principal Investigator: Jeffrey A Kline, MD         
United States, Massachusetts
Beth Israel Deaconess Medical Center Not yet recruiting
Boston, Massachusetts, United States, 02215
Contact: Nathan I Shapiro, MD, MPH         
Principal Investigator: Nathan I Shapiro, MD, MPH         
United States, Mississippi
University of Mississippi Medical Center Not yet recruiting
Jackson, Mississippi, United States, 39216
Contact: Alan E Jones, MD         
Principal Investigator: Alan E Jones, MD         
United States, New Jersey
Cooper University Hospital Recruiting
Camden, New Jersey, United States, 08103
Contact: J. Hope Kilgannon, MD         
Principal Investigator: J. Hope Kilgannon, MD         
United States, Pennsylvania
Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Benjamin S Abella, MD, MPhil         
Principal Investigator: Benjamin S Abella, MD, MPhil         
Sponsors and Collaborators
The Cooper Health System
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Study Director: Stephen Trzeciak, MD, MPH The Cooper Health System

Responsible Party: The Cooper Health System
ClinicalTrials.gov Identifier: NCT02698826     History of Changes
Other Study ID Numbers: REOX II
R01HL112815 ( U.S. NIH Grant/Contract )
First Posted: March 4, 2016    Key Record Dates
Last Update Posted: June 16, 2017
Last Verified: June 2017

Keywords provided by The Cooper Health System:
Cardiac Arrest, Hyperoxia, Ischemia-reperfusion Injury, Reactive Oxygen Species, Oxidative Stress, Neuropsychological Tests

Additional relevant MeSH terms:
Heart Arrest
Heart Diseases
Cardiovascular Diseases