This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Reoxygenation After Cardiac Arrest II (REOX II Study) (NCT02698826), a na phase 1 study. The primary outcome is Plasma Isofurans (pg/mL)/Isoprostanes (pg/mL) Ratio.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02698826 |
| Phase | Phase 1 |
| Condition | Cardiac Arrest |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 16 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Cooper Norcross Health |
| Results posted | Yes |
2. Clinical Question
The study asked whether rapid optimization of inspired oxygen after resuscitation from cardiac arrest could be associated with differences in oxidative stress and later outcomes. Its planned primary endpoint was the change in the plasma isofurans/isoprostanes ratio between 0 and 6 hours after return of spontaneous circulation (ROSC). The record states that this endpoint was not analyzed because no measurements were obtained for the intervention arm.
The broader study objective concerned the association between hyperoxia exposure after resuscitation and outcomes. The study description proposed comparing REOX II, which used an intervention protocol, with REOX I, an observational study. The registry record does not provide an analyzed comparison between those studies or results for neurological or cognitive outcomes.
Population
Adult patients resuscitated from cardiac arrest. The registry lists an enrollment of 16.
Intervention
A rapid FiO2 optimization protocol intended to prevent exposure to hyperoxia after resuscitation.
Comparator
There was no like-for-like control group within REOX II. The study description proposed comparing outcomes with REOX I, an observational study, but an analyzed comparison is not reported in the registry record.
Primary question
What change occurred in the plasma isofurans/isoprostanes ratio from 0 to 6 hours post-ROSC? The registry says the endpoint was not analyzed because intervention-arm measurements were not obtained.
3. Trial Design
REOX II is registered as a completed Phase 1 study with a single-group model and no allocation. Masking is listed as none. The record lists 16 enrolled participants and describes the group as adult patients resuscitated from cardiac arrest who received a rapid FiO2 optimization protocol. The study began in 2016-04 and reached primary completion in 2018-10.
The intervention was a protocol rather than a drug or device: rapid optimization of inspired oxygen after resuscitation. The stated aim was to prevent exposure to hyperoxia. That aim describes the intervention’s intent; the registry record does not report whether the protocol achieved that aim or how oxygen exposure differed over time.
The study description places REOX II alongside REOX I, an observational study, and proposes comparing outcomes between them. However, REOX II itself is a single-group study, and the record cautions that the arms are not a like-for-like control comparison. No adjusted or unadjusted comparative results are reported. The registry’s classification and design details therefore do not support interpreting REOX II as a randomized trial.
The primary outcome is listed as the plasma isofurans/isoprostanes ratio, with change between 0 and 6 hours post-ROSC as its timeframe. The record explicitly states that it was not analyzed because no measurements were obtained for the intervention arm. Modified Rankin Scale is listed as a secondary outcome and identified in the registry as a primary neurological outcome, but results for it are not reported in the registry record. The registry lists 3 outcome measures and 0 analyses.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Adult Patients Resuscitated From Cardiac Arrest |
|---|---|
| STARTED | 16 |
| COMPLETED | 2 |
| NOT COMPLETED | 14 |
Reasons for not completing this period:
| Reason | Adult Patients Resuscitated From Cardiac Arrest |
|---|---|
| Death | 13 |
| Adverse Event | 1 |
Analysis population for the primary outcome, as defined in the registry: Not analyzed secondary to no measurements obtained for intervention arm.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | FiO2 Titration Group |
|---|---|---|
| Participants analysed | 16 | |
| Age, Continuous | years | 55 (SD 18) |
| Sex: Female, Male: Female | Participants | 7 |
| Sex: Female, Male: Male | Participants | 9 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 3 |
| Race (NIH/OMB): White | Participants | 13 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 16 |
6. Primary Endpoint
The registry lists the primary outcome as Plasma Isofurans (pg/mL)/Isoprostanes (pg/mL) Ratio, measured over Change in the isofurans/isoprostanes ratio between 0 and 6 hours post-ROSC.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The stated primary endpoint is the plasma isofurans/isoprostanes ratio, expressed in pg/mL for each named component. The outcome timeframe is the change in that ratio between 0 and 6 hours post-ROSC. In general, a ratio expresses the relative level of one measured quantity to another; a change over time describes how that relative measure differs across the specified measurement times. The endpoint is not itself a neurological or cognitive outcome.
The study’s stated objective concerned hyperoxia exposure and oxidative stress after cardiac arrest. The biomarker ratio is aligned with that biological question, while the registry does not provide a more detailed rationale for selecting this particular ratio. A biomarker endpoint can inform a biological question without establishing whether patients experience a corresponding change in clinical outcomes.
For this trial, the key limitation is decisive: the registry states that the primary endpoint was not analyzed because no measurements were obtained for the intervention arm. It therefore reports no observed change in the ratio, no estimate of its variability, and no statistical comparison for this endpoint. The intended measurement window should not be mistaken for evidence that measurements were collected at both times.
Modified Rankin Scale is listed among secondary outcomes, but a result for that outcome is not reported in the registry record. Thus, the record does not provide a primary biomarker result or a reported neurological outcome result with which to assess the study’s clinical question.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical finding in the registry record is the absence of an analyzed primary endpoint. The plasma isofurans/isoprostanes ratio was intended to measure change between 0 and 6 hours post-ROSC, but the record says there were no measurements for the intervention arm and that the endpoint was not analyzed. There is consequently no reported effect estimate, uncertainty interval, or p-value for the primary outcome. The record does not show whether the ratio changed under the protocol.
This is not equivalent to finding no change. A null or small estimated change would require observed endpoint data and an analysis; neither is reported. Nor can the missing endpoint be treated as evidence that the intervention had no effect. Without the intervention-arm measurements, the primary question remains unanswered by the posted endpoint results.
The study description also proposed comparing outcomes with REOX I, an observational study. That proposed comparison is distinct from the single-group intervention design listed for REOX II. The registry explicitly cautions that the arms are not a like-for-like control comparison. An observational comparison could be affected by differences between study populations, care, measurement, or other factors; the record does not report an analysis addressing such differences. No comparative effect should be inferred from the stated intent to compare.
The registry lists 3 outcome measures and 0 analyses. Modified Rankin Scale is named as a secondary outcome, but its result is not reported in the registry record. The intended outcome list is not a substitute for outcome data. Likewise, the study’s hypothesis that hyperoxia is associated with oxidative stress and worse neurological and cognitive outcomes is a rationale, not a result established by the record.
The safety record lists 14 participants affected by serious adverse events among 16 at risk in the FiO2 Titration group, with 13 deaths recorded. Those counts describe events recorded during the study; they do not establish that the protocol caused the events. The registry does not report a comparison group suitable for estimating excess risk or a causal effect.
Planning illustrations based on an observed effect should be read cautiously in this setting. They are planning calculations rather than observed power, and no analyzed primary endpoint estimate is reported from which to judge the biomarker result. Overall, the posted results establish that the intended primary analysis was unavailable, not whether the protocol changed the biomarker or clinical outcomes.
9. Statistical Methods Explained
The registry identifies a single-group study with no allocation and no masking. It lists no randomized comparison within REOX II. The proposed comparison with REOX I, described as observational, does not turn the registered REOX II design into a randomized trial. The registry warns that the arms are not a like-for-like control comparison, so a contrast between them would need careful consideration of how participants and measurements differed.
What would an endpoint estimate represent?
In general, an effect estimate summarizes the observed difference or change for a defined outcome. For this study, the primary endpoint was a within-person-timeframe change in a biomarker ratio from 0 to 6 hours post-ROSC. Estimating that change requires endpoint measurements. The registry states that intervention-arm measurements were not obtained and that the endpoint was not analyzed, so no estimate is available. A missing estimate is not a zero estimate.
In general, a confidence interval describes the range of effect values compatible with the data and the method used, subject to its assumptions. It conveys precision as well as direction and size. No confidence interval for the primary endpoint is reported in the registry record. A p-value, when calculated, addresses compatibility with a specified statistical null model; it does not measure clinical importance or establish causation. No primary endpoint p-value is reported either.
Why does the study design matter?
In general, random allocation is used to make treatment groups comparable in expectation, while masking can reduce certain measurement or conduct biases. Neither a randomized allocation nor masking is listed for REOX II. The study is recorded as single-group, with allocation listed as NA and masking as none. Its intervention can be described, but an effect relative to an untreated or alternative-treatment group cannot be estimated from the single group alone without additional comparison data and assumptions.
The REOX I observational study was identified as a possible comparator in the study description. In general, observational comparisons may reflect differences in who entered each study, how care was delivered, or how outcomes were measured, in addition to any intervention effect. The registry record does not report a comparative analysis, adjustment strategy, or evidence that these features were aligned. The caution that the arms are not like-for-like is therefore important when interpreting any proposed cross-study contrast.
How should planning calculations be read?
The planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They are calculated from an observed effect, with the target effect stated as a fraction of that observed effect. These are planning assumptions, not a record of the trial’s own design or an analysis of REOX II outcomes. The registry record does not report the trial’s sample-size justification. The illustrations should not be described as observed power: power is a design concept, while the illustrations estimate sample sizes under stated assumptions.
Because the primary endpoint was not analyzed, a reader cannot use a primary biomarker estimate from the registry record to judge how the planning effect relates to the intervention’s observed outcome. The illustrations do not repair missing measurements, supply a treatment comparison, or establish that the study was adequately powered for its original aims. Their assumptions also do not establish that the normal approximation or equal-allocation scenario matches the actual single-group study.
Why do distributional assumptions matter?
In general, a statistical model uses assumptions about the outcome’s distribution and the way observations vary. A normal approximation can be useful for planning or inference when its conditions are reasonable. If observations are more variable than the model allows, uncertainty can be understated and tests may be poorly calibrated. Over-dispersion is the general term for variability exceeding what a model expects. The registry record does not report a distributional assessment or a model for the biomarker ratio, so no claim can be made about whether these assumptions fit the endpoint.
Ratios can also be statistically challenging in general: a ratio may be affected by variation in either component, and its distribution may not be symmetric. Analysts can consider transformations or models suited to the observed data, but the registry record does not report a method of that kind. Since the intervention-arm measurements were absent, there is no basis in the record for assessing the biomarker’s distribution or variability.
What can the adverse-event counts establish?
In general, safety counts describe events recorded in a specified group and period. A count alone does not identify the cause of an event or quantify risk relative to a suitable comparator. The registry lists serious adverse events and deaths for the FiO2 Titration group, but no like-for-like control group is registered. The counts should therefore be read descriptively, not as a causal estimate of harm from the protocol.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 3 outcome measures and 0 analyses. The primary outcome is the plasma isofurans/isoprostanes ratio, but the record says it was not analyzed because no intervention-arm measurements were obtained. Modified Rankin Scale is listed as a secondary outcome; its results are not reported in the registry record. The record does not report results for the other listed outcome measures.
Multiplicity arises in general when a study tests or estimates several outcomes, time points, subgroups, or contrasts. Repeated opportunities to declare a result can increase the chance of a misleading finding unless the analysis plan addresses them. The registry record does not report a multiplicity adjustment, a hierarchy among all outcomes, or a prespecified strategy for interpreting multiple analyses. With 0 analyses listed, the record also provides no testing results on which to assess that issue.
Missing data are central to interpretation of the primary endpoint: no intervention-arm measurements were obtained, so the planned ratio change could not be analyzed. The registry does not report why the measurements were unavailable, whether any other endpoint data were missing, or how missing values were handled for other outcomes. There is no basis to assume that missingness was random or to reconstruct an analysis.
The analysis population is not described beyond the enrollment and group information in the registry record. It does not report whether an intention-to-treat, per-protocol, or other analysis population was defined, or how participants were included in each outcome analysis. These details matter because analysis populations and missing-data methods can affect the interpretation of estimates. In their absence, the posted record does not support a population-specific efficacy estimate.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| FiO2 Titration | 14 | 16 | 87.5% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| FiO2 Titration | 13 of 16 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| FiO2 Titration | 0 of 16 |
Most frequent serious adverse event terms
| Event term | Organ system | FiO2 Titration |
|---|---|---|
| Death | Cardiac disorders | 13 of 16 |
| Poor neurological outcome | Nervous system disorders | 1 of 16 |
Serious events with the highest arm-level rate: death (81.2%), poor neurological outcome (6.2%).
The adverse-event record lists the FiO2 Titration group with 16 participants at risk for serious adverse events and 14 affected. It also lists 16 at risk for other adverse events and 0 affected. The record reports 13 deaths. Among the top serious terms, it lists Death (81.2%) and Poor neurological outcome (6.2%). These entries describe the safety information recorded for this group.
These counts should not be read as proof that the protocol caused the events. The registry record does not provide a like-for-like control group or a comparative analysis that could distinguish events associated with the underlying condition and clinical course from events attributable to the intervention. The counts also do not establish the timing, severity beyond the reported classification, or individual-level relationships among the listed outcomes.
The percentages attached to serious-event terms are reproduced as listed; the registry record does not provide further detail about their denominator in this entry. Serious-event counts and death counts are safety observations, not an estimate of treatment effect. The absence of other adverse events recorded in this group does not establish that no unrecorded events occurred.
12. What the Result Does, and Does Not, Mean
The record supports a limited but important conclusion about the availability of evidence: the planned primary biomarker endpoint was not analyzed because no measurements were obtained for the intervention arm. It therefore does not establish whether the plasma isofurans/isoprostanes ratio changed between 0 and 6 hours post-ROSC under rapid FiO2 optimization. No endpoint estimate or precision measure is reported.
This absence of a result should not be translated into a finding of no effect. It is also not evidence that the protocol did or did not prevent hyperoxia. The study’s objective and hypothesis describe questions the investigators intended to address; they are not findings from the posted endpoint data.
The study description proposed comparing outcomes with REOX I, an observational study, but the registry identifies REOX II as a single-group study and warns that the arms are not like-for-like. The record does not report a comparative analysis. It therefore cannot establish that the intervention caused a difference in biomarkers, neurological outcomes, or cognitive outcomes. Modified Rankin Scale is listed as a secondary outcome, but a result is not reported in the registry record.
The safety information is descriptive. Serious adverse events, deaths, and serious-event terms are recorded for the intervention group, but there is no suitable comparison in the record for attributing those events to the protocol or estimating comparative risk. Neither an adverse-event count nor a hypothesis about harm substitutes for causal evidence.
In general, a clinical trial’s conclusions depend on the availability and quality of outcome measurements, the design’s ability to support comparisons, and the precision of its estimates. For REOX II, the missing primary measurements and lack of a like-for-like comparator leave the central questions unresolved in the registry record. The findings should be interpreted as an incomplete outcome record rather than as evidence for or against a treatment effect.
13. Why This Trial Matters Statistically
This trial illustrates why a registered intervention and a completed study do not necessarily yield an interpretable estimate for the primary question. REOX II is listed as completed, but its primary biomarker endpoint was not analyzed because no intervention-arm measurements were obtained. Without those measurements, the planned change cannot be estimated, and the registry offers no precision measure for that endpoint.
It also highlights the distinction between a study objective and an analysis. The record describes a hypothesis about hyperoxia, oxidative stress, and neurological and cognitive outcomes, and it proposes comparison with an observational study. Those aims do not constitute results. The registry’s single-group design and warning about non-comparable arms matter when deciding what conclusions a comparison could support.
From a statistical perspective, the record underscores the importance of outcome completion, analysis populations, and transparent reporting of analysis methods. The registry lists 3 outcome measures but 0 analyses. It does not report the missing-data approach, the analysis population, or a multiplicity strategy. Those omissions make it difficult to assess how the intended outcomes were to be interpreted, apart from the explicit statement that the primary endpoint could not be analyzed.
The adverse-event listing also demonstrates why descriptive safety counts should not be confused with causal estimates. Without a suitable comparator, observed events cannot by themselves quantify what would have occurred under another approach. Taken together, the record is instructive about the limits imposed by unavailable measurements and design: a completed study can still leave its primary statistical question unanswered.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The most direct limitation is that the primary endpoint was not analyzed. The registry states that no measurements were obtained for the intervention arm, preventing analysis of the planned change in the plasma isofurans/isoprostanes ratio between 0 and 6 hours post-ROSC. The record does not explain why those measurements were unavailable or report an alternative primary-endpoint analysis.
The study is registered as single-group, with allocation listed as NA and masking as none. It therefore does not provide an internal randomized comparator. Although the study description proposed a comparison with REOX I, an observational study, the registry warns that the arms are not like-for-like. No comparison results or methods for addressing between-study differences are reported.
Clinical outcome interpretation is also limited. Modified Rankin Scale is listed as a secondary outcome, but its result is not reported in the registry record. The record does not provide reported cognitive outcomes or analyses linking biomarker measures with neurological or cognitive outcomes. The stated hypothesis should not be treated as an observed result.
The registry lists 3 outcome measures and 0 analyses. It does not report an analysis population, missing-data methods for outcomes beyond the stated absence of primary intervention-arm measurements, a multiplicity strategy, or a statistical model for the biomarker ratio. The trial’s sample-size justification is not reported in the registry record. These gaps limit evaluation of the original analysis plan and the precision that the study might have achieved.
Finally, the adverse-event record is not comparative. The reported serious events and deaths cannot establish causation or estimate excess risk without an appropriate comparator and analysis. The registry does not report further detail that would resolve those limitations.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Reoxygenation After Cardiac Arrest II (REOX II Study) — NCT02698826.
- Registry record last updated 2022-03-29; status last verified 2022-01.
- Results first posted 2022-03-29.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
REOX II (NCT02698826) is registered as a completed Phase 1, single-group study with no allocation and no masking. It enrolled 16 adult patients resuscitated from cardiac arrest, who received a rapid FiO2 optimization protocol. The stated objective concerned hyperoxia exposure, oxidative stress, and outcomes after resuscitation.
The primary endpoint was change in the plasma isofurans/isoprostanes ratio between 0 and 6 hours post-ROSC. The registry says it was not analyzed because no intervention-arm measurements were obtained. The record lists 3 outcome measures and 0 analyses. It also lists Modified Rankin Scale as a secondary outcome, without a reported result.
The study description proposed comparison with REOX I, an observational study, but the registry cautions that the arms are not a like-for-like control comparison. Safety entries include serious adverse events and deaths in the FiO2 Titration group; they are descriptive and do not establish causation. Overall, the registry record does not provide an analyzed primary endpoint or a comparative estimate of the intervention’s effect.