Pragmatic Trial Examining Oxygenation Prior to Intubation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pragmatic Trial Examining Oxygenation Prior to Intubation (NCT05267652), a randomized na study. The primary outcome is Incidence of Hypoxemia.

2. Clinical Question

The registry presents a randomized, parallel-group comparison of these two commonly used approaches. The posted primary result indicates more participants with the endpoint in the facemask oxygen group than in the non-invasive positive pressure ventilation group. This is a comparison of observed group outcomes in the trial; it does not, by itself, describe every patient or setting in which either approach might be used. The registry record does not report detailed baseline characteristics, eligibility rules, or subgroup results that would clarify how closely the enrolled population matches other groups of patients.

3. Trial Design

This was a randomized, parallel-group trial comparing two preoxygenation strategies before tracheal intubation. The registry lists the study as completed and reports enrollment of 1301. It records a start date of 2022-03-10 and a primary completion date of 2023-10-14. The trial is listed as not applicable for phase, and the masking field states none. Thus, the registry describes an unmasked comparison; it does not report that participants or clinicians were blinded to the assigned approach.

One group received non-invasive positive pressure ventilation through a tight-fitting mask during preoxygenation, ending when laryngoscopy began. The other received oxygen through a non-rebreather mask or bag-mask device, without manual ventilation, during preoxygenation until induction. The record says that the protocol did not dictate the equipment brand or type. These descriptions establish the broad contrast while leaving local implementation details unspecified.

The primary outcome was the incidence of hypoxemia, recorded as a count of participants meeting the endpoint. The registry defines an event as peripheral oxygen saturation below 85% between induction and two minutes after tracheal intubation. The posted primary group counts are 57 of 624 in the non-invasive positive pressure ventilation group and 118 of 637 in the facemask oxygen group. The registry also lists lowest oxygen saturation as a secondary outcome, but detailed secondary outcome results are not reported in the registry record.

The registry record does not report the trial's original sample-size assumptions, its planned statistical analysis methods, any interim analyses, or detailed analysis-population rules. It does post a comparison estimate and associated statistical results. The distinction matters: a posted analysis result can be described, but unreported design choices should not be inferred from that result or from the planning illustration associated with the observed effect.

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

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.

6. Primary Endpoint

The registry lists the primary outcome as Incidence of Hypoxemia, measured over from induction to 2 minutes following tracheal intubation.

The primary endpoint counts participants whose peripheral oxygen saturation fell below 85% during the period from induction to two minutes after tracheal intubation. It is a binary outcome at the participant level: each participant either met the registry's event definition during that interval or did not. The outcome is summarized as counts of participants with an event in each group.

This measure focuses on a clinically important consequence that can occur during airway management. The registry's background describes life-threatening hypoxemia as a concern around emergency tracheal intubation and frames preoxygenation as an attempt to reduce that risk. A threshold-based endpoint makes it possible to compare how often the specified low-saturation event occurred in the two randomized groups. It does not capture every aspect of oxygenation: for example, the primary measure does not describe the duration of a low saturation or the full pattern of oxygen saturation over time.

The endpoint's timing is part of its definition. Events outside the interval from induction to two minutes after intubation are not included in the primary definition as stated in the registry. The record does not report details such as how missing saturation readings were handled or whether endpoint assessment was independently adjudicated. Those details should not be assumed when interpreting the posted counts.

7. Results Posted in the Registry

• Preoxygenation With Facemask Oxygen Group: 18.5% (118/637) versus 9.1% (57/624) on control; risk difference 9.4 percentage points (95% CI 5.6 to 13.2), risk ratio 2.03 (1.51–2.73); unadjusted two-proportion z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary: a participant either met the hypoxemia definition during the stated interval or did not. For a binary outcome, the basic group summaries are the number of participants with an event and the number assessed in that group. The registry posts those counts for each arm. A risk is the event count relative to the group denominator, while a risk difference compares the two risks by subtraction. A risk ratio compares one group's risk with the other group's risk. An odds ratio compares event odds, where odds relate the number with the event to the number without it. These are standard ways to describe a two-group binary comparison; they are general statistical explanations.

The reported risk difference is 0.094, with a confidence interval from 0.056 to 0.132. These estimates are quoted in the registry but are not repeated in the interpretation because they have more than three decimal places. The registry additionally reports a risk ratio of 2.028 and an odds ratio of 2.262 for facemask oxygen relative to non-invasive positive pressure ventilation. The associated confidence intervals are reported with each measure. Since the measures use different scales, they are not interchangeable. In particular, an odds ratio should not automatically be described as a risk ratio, especially when event risks are not very small.

A confidence interval is a range of values produced by a statistical procedure that, under its assumptions, reflects uncertainty in an estimated effect. In general, a narrower interval indicates greater precision than a wider interval, while the interval's location indicates which effect values are compatible with the data under that procedure. A confidence interval is not a range containing a fixed proportion of individual outcomes, and it does not mean that the true value has a probability of falling inside the particular interval after the data are observed. The registry's estimates are accompanied by intervals, but details of the estimation procedure are not reported in the registry record.

The posted unadjusted p-value is <0.001. In general, a p-value assesses how incompatible observed data are with a specified null model, assuming the model and test assumptions hold. A small p-value is not a measure of effect size, nor does it indicate the probability that the result occurred by chance in the everyday sense. The registry calls this result unadjusted, and it does not report a different adjusted primary analysis. The specific test and its assumptions are not reported in the registry record, so those details should not be guessed.

Random allocation and a parallel-group structure define the broad comparison: participants are assigned to one of the two approaches, and outcomes are compared across those groups. In general, randomization can reduce systematic differences in prognostic factors at assignment, but it does not guarantee identical groups, eliminate issues in follow-up, or correct problems in outcome measurement. This trial is listed as unmasked. In general, lack of masking can affect care or assessment in some settings, although the registry record does not establish whether or how that occurred in this trial.

The record presents event counts and a comparison for the primary outcome, as well as a planning illustration based on fractions of the observed effect. These should not be confused with a full statistical analysis plan. The trial's original sample-size justification, prespecified model, handling of missing outcome data, and analysis-population definition are not reported in the registry record. The record lists no analysis records, while also posting the primary comparison statistics; the presence of a posted comparison does not supply the missing details about the underlying analysis plan.

Over-dispersion is generally a concern when data vary more than a statistical model expects, particularly in some count-data settings. The primary outcome is recorded as a participant-level binary event count rather than a repeated count outcome. Whether any modeling assumptions were assessed or whether a particular model was used is not reported in the registry record. General statistical concerns should therefore not be mistaken for documented features of this trial's analysis.

The trial also lists one secondary outcome, lowest oxygen saturation, and the registry describes 21 outcome measures. Detailed secondary results and their analyses are not reported in the registry record. Without those results and an account of prespecified outcomes, it is not possible to assess selective reporting or to reconstruct how the primary endpoint fit into a broader analysis plan. Such uncertainty does not alter the posted primary counts, but it limits what can be said about the completeness of the statistical record.

10. Confidence Intervals and Precision

The registry reports a risk ratio of 2.028 for facemask oxygen relative to non-invasive positive pressure ventilation, with a confidence interval from 1.508 to 2.727. It also reports an odds ratio of 2.262, with a confidence interval from 1.613 to 3.171. The intervals describe uncertainty in the estimated relative comparisons under the methods used. Both ranges are on the higher-than-null side for their ratio measures, consistent with the reported direction of the group counts.

In general, an interval is useful because a single point estimate does not show how much statistical uncertainty surrounds it. The lower and upper bounds indicate a range of effect values compatible with the data under the interval procedure and its assumptions. A broader range allows more uncertainty than a narrower one; interpretation also depends on the measure's scale and the clinical context. The registry's record does not report enough detail to evaluate every assumption behind the interval calculations.

The posted risk-difference confidence interval is 0.056 to 0.132, but those endpoints exceed the limit of three decimal places and are therefore not reproduced as numbers in this explanation. The interval is reported in the registry as positive, corresponding to a higher observed risk in the facemask oxygen group. The event counts are 57 of 624 and 118 of 637, respectively. The unadjusted p-value is <0.001.

Confidence intervals quantify statistical precision, not the likelihood that an effect will be identical in another population or clinical setting. They also do not address unreported issues such as missing data, outcome ascertainment, or deviations from assigned treatment. The record does not report subgroup-specific intervals or detailed secondary outcome estimates.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm for 80% power and participants per arm for 90% power. They are not total event counts. For planning based on 100% of the observed effect, the figures are 211 participants per arm for 80% power and 282 participants per arm for 90% power. For planning for 75% of the observed effect, they are 349 and 467 participants per arm, respectively. For planning for 50% of the observed effect, they are 723 and 967 participants per arm, respectively.

The calculation assumptions listed in the registry are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect used for each planning scenario is the stated fraction of the observed effect. The curve visualizes how the planning requirement changes as the effect used for planning changes; it should be read together with the corresponding participant-per-arm figures.

In plain terms, 80% power is a planning target for the chance of detecting an effect of the specified size under the calculation assumptions if that effect is present. The 90% column uses a higher power target. For a given effect assumption, the higher target requires more participants per arm in these calculations. Smaller effects need more participants to detect under the same general planning framework, which is why planning for a smaller fraction of the observed effect gives larger figures.

These are planning illustrations based on the observed effect, not the trial's original design assumptions, which are not reported in the registry record. This is not observed power.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.091; treatment proportion p₁ = 0.185; average p̄ = 0.138.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.4882 = 0.9569.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.4837 = 0.4071.
4. n = (0.9569 + 0.4071)² / (0.0939)² = 211.0, rounded up to 211 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.0913461538461538                          # control proportion
p1 <- 0.185243328100471                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(5267652)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 211 (80% power), 282 (90% power)
 75% of observed effect: n per arm = 349 (80% power), 467 (90% power)
 50% of observed effect: n per arm = 723 (80% power), 967 (90% power)
power.prop.test: 211 
Simulated power at n = 211 per arm: 0.806 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes, comparisons, or statistical tests are considered. In general, conducting many tests can increase the chance that at least one result appears statistically notable even when no corresponding effect exists. Approaches to multiplicity can include prespecifying a primary outcome, adjusting significance thresholds, or presenting secondary analyses as exploratory. Which approach is appropriate depends on the design and analysis plan.

The registry identifies incidence of hypoxemia as the primary outcome and lists lowest oxygen saturation as a secondary outcome. It also records 21 outcome measures. Detailed results for the secondary outcome are not reported in the registry record. The registry does not report a multiplicity adjustment, a hierarchy among outcomes, or a complete prespecified analysis plan. It is therefore not possible to determine from this record whether or how multiplicity was addressed.

The posted primary comparison is described as unadjusted, with p < 0.001. That designation should not be taken to mean that all potential multiplicity concerns have been resolved, nor does it establish whether the result was prespecified. The registry does not report enough information to assess the planned order of analyses or whether additional comparisons were conducted.

Missing data can affect a trial comparison if outcomes are unavailable or if the reasons for missingness differ between groups. The registry record does not report how many primary outcome observations, if any, were missing, how missing saturation readings were treated, or whether a sensitivity analysis was used. The record also does not describe the analysis population, such as whether the primary analysis followed all randomized participants as assigned. These omissions limit assessment of how the posted counts relate to the full randomized population.

Detailed participant flow, protocol deviations, and analysis-population definitions are not reported in the registry record. Those details would help readers assess whether the comparison preserved the intended randomized contrast and whether outcome availability could have affected the result. Their absence should be described as a reporting limitation, not as evidence that a particular problem occurred.

14. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: aspiration (0.3%).

The registry's adverse-event record lists serious adverse events for the non-invasive positive pressure ventilation group as 2 affected among 645 at risk, and for the facemask oxygen group as 0 affected among 656 at risk. It lists other adverse events as 0 affected among 645 at risk in the non-invasive positive pressure ventilation group and 0 affected among 656 at risk in the facemask oxygen group. The registry also records deaths as 209 and 217 in the respective groups.

These are descriptive counts as recorded in the safety section. The record does not provide details about event definitions, ascertainment procedures, timing, attribution, or a statistical comparison of safety outcomes. A zero count in a group does not establish that an event is impossible, and counts alone do not establish that an intervention caused or prevented an event. The at-risk figures in this safety summary should be read as stated and not assumed to be identical to the denominators used for the primary endpoint.

The registry names aspiration at 0.3% among its top serious adverse-event terms. It does not provide enough detail in this summary to assign that term to a particular group or to interpret it as a comparative risk. The safety figures should therefore be treated as a concise registry report, not as a complete account of comparative safety.

15. What the Result Does, and Does Not, Mean

The posted primary data show 57 hypoxemia events among 624 participants in the non-invasive positive pressure ventilation group and 118 among 637 in the facemask oxygen group. The registry's unadjusted comparison reports p < 0.001. The reported risk ratio and odds ratio are both greater than their null value of one, and the risk-difference interval is reported in the direction of more events in the facemask oxygen group. Taken together, the posted results describe a difference in the specified event between these randomized groups.

This finding is limited to the registry's definition of hypoxemia: peripheral oxygen saturation below 85% from induction through two minutes after tracheal intubation. It does not summarize all oxygenation measures, events at other times, or every outcome relevant to patients. Lowest oxygen saturation is listed as a secondary outcome, but its detailed results are not reported in the registry record.

The result does not establish that either approach will produce the same outcome in every setting or patient population. Applicability depends on the participants enrolled, clinical practices, equipment, and implementation. Detailed eligibility criteria, baseline characteristics, and relevant subgroup results are not reported in the registry record, limiting assessment of how broadly the result applies.

The trial's randomized design supports a comparison of assigned groups, but important details about implementation, missing data, analysis populations, and the statistical plan are not reported in the registry record. The posted estimates should be interpreted with that reporting context in mind. Statistical evidence against a null comparison does not by itself determine clinical importance, and the registry result should not be turned into medical advice or an individual prediction.

Finally, the safety summary is descriptive and does not establish comparative causation. Serious adverse events and deaths are listed, but the registry does not provide a detailed safety analysis in this record. The primary conclusion is therefore narrow: the registry reports a difference in the frequency of its defined hypoxemia endpoint between the two groups, with uncertainty summarized by the posted estimates and confidence intervals.

16. Why This Trial Matters Statistically

This trial addresses a statistical question where the outcome is a threshold-defined event during a short, specified clinical interval. Such an endpoint is straightforward to count, but its interpretation depends on the threshold, observation window, and completeness of measurement. By stating the definition explicitly, the registry makes clear what the primary comparison represents and what it leaves outside the endpoint.

The comparison is also informative as an example of how different effect measures describe the same binary outcome. A risk difference gives an absolute contrast, whereas a risk ratio and odds ratio give relative contrasts on different scales. Reading the measures alongside the event counts and confidence intervals helps avoid treating a single statistic as the entire result. The registry reports all three forms of comparison, although the risk-difference values are not repeated in this explanation because they exceed the permitted decimal precision.

Precision is central to interpreting the result. Confidence intervals add information beyond a point estimate, and the reported ratio intervals lie on the higher-than-null side. The unadjusted p-value is small, but it does not replace consideration of the estimated effect, uncertainty, trial design, or limitations in the registry record.

The sample-size illustration is another useful statistical distinction. It explores planning under specified assumptions and different fractions of the observed effect. It is not a reconstruction of the trial's original design rationale, which is not reported, and it is not an estimate of observed power. Separating a retrospective planning illustration from the actual design prevents a common misreading of power calculations.

Finally, this record shows why a statistical result needs to be interpreted alongside reporting completeness. Randomization is documented, but details of the analysis plan, missing-data handling, masking implementation, and secondary outcomes are not reported in the registry record. These gaps do not erase the posted result; they define the limits on how fully its methods and wider implications can be evaluated.

17. 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 registry record does not report detailed eligibility criteria, baseline participant characteristics, or participant flow. Without these details, it is difficult to assess the enrolled population, the balance of prognostic factors, and how participants progressed from assignment through outcome assessment. The registry lists enrollment as 1301 and gives separate primary endpoint denominators by group, but it does not explain their relationship in the record.

The trial is listed as unmasked. The registry does not describe whether outcome measurement was automated, independently reviewed, or otherwise protected from knowledge of assignment. It also does not provide detailed procedures for oxygen-saturation measurement, handling of missing readings, or adjudication of endpoint events. These are reporting gaps, not evidence that measurement problems occurred.

Implementation details are broad rather than fully standardized in the descriptions. The non-invasive ventilation and facemask approaches are described by device type and timing, while the record says brands or types were not dictated. The registry does not report adherence, crossover, or deviations from assigned preoxygenation. As a result, the amount of separation between the assigned strategies in practice cannot be assessed from this record alone.

The primary comparison is posted with confidence intervals and an unadjusted p-value, but the trial's original statistical plan, sample-size justification, interim analysis policy, missing-data methods, and analysis population are not reported in the registry record. Detailed results for the listed secondary outcome are also not reported. The adverse-event summary does not provide enough context to assess event ascertainment or comparative safety in depth.

These limitations constrain evaluation of generalizability, analysis choices, and outcome completeness. They should not be used to infer that the trial was improperly conducted or that the observed result is invalid; they indicate what cannot be assessed from the registry record.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Pragmatic Trial Examining Oxygenation Prior to Intubation — NCT05267652.
• Registry record last updated 2024-12-09; status last verified 2024-12.
• Results first posted 2024-12-09.
• 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.

21. Record Summary

The registry describes a completed, randomized, parallel-group trial comparing preoxygenation with non-invasive positive pressure ventilation against facemask oxygen before tracheal intubation. It lists acute respiratory failure as the condition and reports enrollment of 1301. The study is marked as unmasked, with phase listed as not applicable.

The primary outcome is the count of participants with peripheral oxygen saturation below 85% from induction to two minutes after tracheal intubation. The posted counts are 57 of 624 in the non-invasive positive pressure ventilation group and 118 of 637 in the facemask oxygen group. The registry reports an unadjusted p-value of <0.001, along with risk-difference, risk-ratio, and odds-ratio estimates and confidence intervals.

Lowest oxygen saturation is listed as a secondary outcome, but detailed secondary results are not reported in the registry record. The record also includes brief adverse-event counts. Detailed eligibility, participant flow, analysis-plan methods, missing-data handling, and the trial's original sample-size assumptions are not reported in the registry record.