Cardiac ArrestPhase 1REOX IINCT02698826
Reoxygenation After Cardiac Arrest II (REOX II Study)
A Phase 1 study testing Protocol for rapid FiO2 optimization in people with Cardiac Arrest, run by Cooper Norcross Health at 5 sites in United States.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiac Arrest
- What is being tested?
- Protocol for rapid FiO2 optimization
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 5 sitesUnited States
- Study dates
- Apr 2016to Oct 2018
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Cooper University Hospital
Camden, New Jersey, 08103
Indiana University/ Methodist Hospital
Indianapolis, Indiana, 46202
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center
Philadelphia, Pennsylvania, 19104
About this study
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.
Read the 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
- Conditions
- Cardiac Arrest
- Being tested
- Protocol for rapid FiO2 optimization
- Keywords
- Cardiac Arrest, Hyperoxia, Ischemia-reperfusion Injury, Reactive Oxygen Species, Oxidative Stress, Neuropsychological Tests
- Medical subject headings
- Heart Arrest, Hyperoxia, Reperfusion Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Protocol for rapid FiO2 optimizationOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Adult patients resuscitated from cardiac arrest | Experimental | Rapid FiO2 optimization protocol Receives: Other: Protocol for rapid FiO2 optimization |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma Isofurans (pg/mL)/Isoprostanes (pg/mL) Ratio
Measured: Change in the isofurans/isoprostanes ratio between 0 and 6 hours post-ROSC
Secondary outcomes (1)
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
Measured: Upon hospital discharge, on average two weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2016 (estimated)
- Study startApr 2016
- Primary completionOct 2018
- Study completionOct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cardiac ArrestStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cooper Norcross Health
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Stephen Trzeciak, MD, MPH, Study director, Cooper Norcross Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02698826
- Sponsor's protocol ID
- REOX II
- Other IDs
- R01HL112815
- Acronym
- REOX II
- Status last verified
- Jan 2022
- First submitted
- 25 Feb 2016
- Last updated
- 29 Mar 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reoxygenation After Cardiac Arrest II (REOX II Study)
- ClinicalTrials.gov ID
- NCT02698826
- Acronym / sponsor ID
- REOX II / REOX II
- Conditions
- Cardiac Arrest
- Keywords
- Cardiac Arrest, Hyperoxia, Ischemia-reperfusion Injury, Reactive Oxygen Species, Oxidative Stress, Neuropsychological Tests
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Cooper Norcross HealthUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Apr 2016
- Primary completion
- Oct 2018 (actual)
- Study completion
- Oct 2018 (actual)
- First posted
- 4 Mar 2016 (estimated)
- Results
- Posted 29 Mar 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Adult patients resuscitated from cardiac arrest | Experimental | Other: Protocol for rapid FiO2 optimizationRapid FiO2 optimization protocol |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age >17 years
- Cardiac arrest
- Return of spontaneous circulation
- Not following commands immediately after ROSC
- Endotracheal intubation
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Protocol for rapid FiO2 optimizationWe 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. | Other | Adult patients resuscitated from cardiac arrest |
Primary outcome
Plasma Isofurans (pg/mL)/Isoprostanes (pg/mL) Ratio
Time frame: Change in the isofurans/isoprostanes ratio between 0 and 6 hours post-ROSC
1 secondary outcome
Modified Rankin Scale (mRS) (Primary Neurological Outcome)
Time frame: Upon hospital discharge, on average two weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephen Trzeciak, MD, MPH study director
Cooper Norcross Health
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Protocol for rapid FiO2 optimization in people with Cardiac Arrest, run by Cooper Norcross Health at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma Isofurans (pg/mL)/Isoprostanes (pg/mL) Ratio (time frame: Change in the isofurans/isoprostanes ratio between 0 and 6 hours post-ROSC). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Mar 2022.