Reoxygenation After Cardiac Arrest II (REOX II Study)

Cardiac Arrest Clinical Trial

— REOX II  

Official title:

Reoxygenation After Cardiac Arrest II (REOX II Study)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02698826
• Other study ID #: REOX II
• Secondary ID: R01HL112815
• Status: Completed
• Phase: Phase 1
• Start date: April 2016
• Est. completion date: October 2018

Study information

• Verified date: January 2022
• Source: The Cooper Health System
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: October 2018
• Est. primary completion date: October 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiac Arrest
• Heart Arrest

Intervention

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.

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Cooper University Hospital	Camden	New Jersey
United States	Indiana University/ Methodist Hospital	Indianapolis	Indiana
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
The Cooper Health System	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Composite Neuropsychological Testing Score	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.	180 days
Primary	Plasma Isofurans (pg/mL)/Isoprostanes (pg/mL) Ratio		Change in the isofurans/isoprostanes ratio between 0 and 6 hours post-ROSC
Secondary	Modified Rankin Scale (mRS) (Primary Neurological Outcome)	0: No symptoms at all; No significant disability despite symptoms; able to carry out all usual duties and activities; Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance; Moderate disability; requiring some help, but able to walk without assistance; Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance; Severe disability; bedridden, incontinent and requiring constant nursing care and attention; Dead	Upon hospital discharge, on average two weeks