Reoxygenation After Cardiac Arrest II (REOX II Study)
Study Details
Study Description
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 |
|---|---|---|
|
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 Design
Arms and Interventions
| 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.
|
Outcome Measures
Primary Outcome Measures
- Plasma Isofurans (pg/mL)/Isoprostanes (pg/mL) Ratio [Change in the isofurans/isoprostanes ratio between 0 and 6 hours post-ROSC]
Secondary Outcome Measures
- Modified Rankin Scale (mRS) (Primary Neurological Outcome) [Upon hospital discharge, on average two weeks]
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
Other Outcome Measures
- Composite Neuropsychological Testing Score [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.
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Indiana University/ Methodist Hospital | Indianapolis | Indiana | United States | 46202 |
| 2 | Beth Israel Deaconess Medical Center | Boston | Massachusetts | United States | 02215 |
| 3 | University of Mississippi Medical Center | Jackson | Mississippi | United States | 39216 |
| 4 | Cooper University Hospital | Camden | New Jersey | United States | 08103 |
| 5 | Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center | Philadelphia | Pennsylvania | United States | 19104 |
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
Study Documents (Full-Text)
More Information
Publications
None provided.- REOX II
- R01HL112815
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Adult Patients Resuscitated From Cardiac Arrest |
|---|---|
| Arm/Group Description | Rapid FiO2 optimization protocol 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. |
| Period Title: Overall Study | |
| STARTED | 16 |
| COMPLETED | 2 |
| NOT COMPLETED | 14 |
Baseline Characteristics
| Arm/Group Title | FiO2 Titration Group |
|---|---|
| Arm/Group Description | Rapid FiO2 optimization protocol 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. |
| Overall Participants | 16 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
55
(18)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
7
43.8%
|
| Male |
9
56.3%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
3
18.8%
|
| White |
13
81.3%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
0
0%
|
| Region of Enrollment (participants) [Number] | |
| United States |
16
100%
|
Outcome Measures
| Title | Plasma Isofurans (pg/mL)/Isoprostanes (pg/mL) Ratio |
|---|---|
| Description | |
| Time Frame | Change in the isofurans/isoprostanes ratio between 0 and 6 hours post-ROSC |
Outcome Measure Data
| Analysis Population Description |
|---|
| Not analyzed secondary to no measurements obtained for intervention arm. |
| Arm/Group Title | FiO2 Titration |
|---|---|
| Arm/Group Description | Not analyzed secondary to insufficient samples |
| Measure Participants | 0 |
| Title | Modified Rankin Scale (mRS) (Primary Neurological Outcome) |
|---|---|
| Description | 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 |
| Time Frame | Upon hospital discharge, on average two weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | FiO2 Titration |
|---|---|
| Arm/Group Description | Single arm |
| Measure Participants | 16 |
| Median (Full Range) [score on a scale] |
6
|
| Title | Composite Neuropsychological Testing Score |
|---|---|
| Description | 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. |
| Time Frame | 180 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| No analysis performed secondary to no patients were able to undergo the neuropsychological testing. |
| Arm/Group Title | FiO2 Titration |
|---|---|
| Arm/Group Description | Insufficient survivors to analyze. |
| Measure Participants | 0 |
Adverse Events
| Time Frame | 1.5 years | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | FiO2 Titration | |
| Arm/Group Description | Single arm | |
All Cause Mortality |
||
| FiO2 Titration | ||
| Affected / at Risk (%) | # Events | |
| Total | 13/16 (81.3%) | |
Serious Adverse Events |
||
| FiO2 Titration | ||
| Affected / at Risk (%) | # Events | |
| Total | 14/16 (87.5%) | |
| Cardiac disorders | ||
| Death | 13/16 (81.3%) | 13 |
| Nervous system disorders | ||
| Poor neurological outcome | 1/16 (6.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| FiO2 Titration | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/16 (0%) | |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Brian Roberts, MD/ REOX Study Director |
|---|---|
| Organization | Cooper University Health Care |
| Phone | 856-342-2352 |
| roberts-brian-w@cooperhealth.edu |
- REOX II
- R01HL112815