Armodafinil (Nuvigil), Postoperative Recovery of OSA (Obstructive Sleep Apnea) and Obese Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Armodafinil (Nuvigil), Postoperative Recovery of OSA (Obstructive Sleep Apnea) and Obese Patients (NCT02478580), a randomized phase 3 study. The primary outcome is Postoperative Care Unit (PACU) Recovery Time.

2. Clinical Question

The trial addresses whether assigning armodafinil before surgery is associated with a different duration of recovery-unit stay in the population described in the registry. The clinical rationale recorded by the investigators concerns postoperative recovery and wakefulness in people with obstructive sleep apnea and obesity. The summary notes concerns about perioperative desaturations and monitoring, but the posted primary endpoint is recovery time, not a measure of desaturation, respiratory events, or need for intensive care.

The comparison is between randomized groups, rather than a comparison of participants before and after treatment. The registry describes a parallel-group design and reports 34 participants in the Nuvigil arm and 33 in the control arm for the primary outcome. The primary result therefore concerns the mean PACU recovery time in those two groups. It does not directly answer every question raised in the background summary, such as monitoring needs or postoperative narcotic use; those outcomes are not reported in the registry record as primary results.

3. Trial Design

The registry identifies NCT02478580 as a completed phase 3 randomized trial with a parallel design and quadruple masking. The sponsor was the University of Texas Southwestern Medical Center. The record lists 67 enrolled participants and identifies obesity and premature recovery from anesthesia among the conditions. Its description of the target population focuses on patients with obstructive sleep apnea undergoing surgery, and the study title also refers to obese patients.

Participants were assigned to Nuvigil or control. The intervention is described as a single oral dose of Nuvigil at 150mg in the preoperative area; the control group received a single oral placebo there. The primary outcome records 34 participants for Nuvigil and 33 for control. The registry does not report the sequence-generation method, the mechanism used to conceal allocation, or the identities of the groups included in quadruple masking. Those details are not reported in the registry record, so the design label alone cannot establish precisely how masking was implemented.

The primary outcome was measured over the immediate postoperative period, up to 3 hours, with follow-up for the duration of PACU stay and an expected average stay of 3 hours. The Aldrete Score is the one posted secondary outcome and is listed at 2 hours after extubation. Although the record states that the trial is completed, it does not report a full statistical analysis plan or analysis populations. The trial's original sample-size justification, planned interim analyses, missing-data procedures, and detailed allocation procedures are not reported in the registry record.

The completed status and randomized design describe how the study was organized, but they do not by themselves establish how completely outcomes were collected or whether all randomized participants were included in each analysis. The registry record gives outcome-group counts, but does not explain whether those counts represent every randomized participant or how any exclusions were handled.

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

Analysis population for the primary outcome, as defined in the registry: Patient with obstructive sleep apnea undergoing surgery

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.

Population: Patient with obstructive sleep apnea undergoing surgery

6. Primary Endpoint

The registry lists the primary outcome as Postoperative Care Unit (PACU) Recovery Time, measured over Immediate postoperative period (up to 3 hours).

The primary endpoint is Postoperative Care Unit (PACU) Recovery Time, measured in minutes. It represents how long participants remain in the recovery unit during the immediate postoperative period, with the recorded timeframe extending up to 3 hours. The description says participants were followed for the duration of their PACU stay and gives an expected average stay of 3 hours.

As a continuous outcome, recovery time can be summarized by a mean and a measure of spread. The posted results report the mean and standard deviation for each group. This allows a direct comparison of average stay duration, while the standard deviations convey how much individual recovery times varied within each group. A mean difference summarizes the contrast in group averages; it does not show each participant's experience or the full shape of the outcome distribution.

In general, a recovery-duration measure can be useful because it captures one aspect of postoperative recovery and use of the recovery unit. It is not, on its own, a complete measure of safety, alertness, respiratory status, or readiness for discharge. The registry background discusses wakefulness and desaturation concerns, but the primary endpoint is time in PACU rather than a direct measure of those concerns. The record does not report a more detailed operational definition of when PACU recovery time begins or ends, beyond the duration of the PACU stay, or the criteria used to determine readiness to leave PACU.

7. Results Posted in the Registry

• Nuvigil: mean 98.20 versus 95.00 on control; difference 3.20 (95% CI -25.29 to 31.69), standardized effect d = 0.05; z-test p = 0.826.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

The Aldrete Score

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Nuvigil: mean 9.40 versus 9.30 on control; difference 0.10 (95% CI -0.63 to 0.83), standardized effect d = 0.07; z-test p = 0.790.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Nuvigil and the control. The interval gives the range of effects that remain compatible with the data.

The registry posts one secondary outcome, the Aldrete Score, measured 2 hours after extubation. The overall pattern across the primary and secondary outcomes is that the estimated group contrasts are close to zero relative to the uncertainty reported for each. The group-mean direction is similar across the outcomes, but neither comparison provides a precise estimate that separates the groups clearly.

The secondary result complements the primary endpoint by addressing a different aspect of postoperative recovery. PACU time measures duration of stay, while an Aldrete Score is a score-based measure. Agreement in broad direction across two measures can be useful context, but it does not make the endpoints interchangeable or turn the secondary result into a replication of the primary one. They were collected in the same trial and are subject to many of the same design and data limitations.

Unadjusted secondary results generally carry less confirmatory weight because multiple outcomes or comparisons create more opportunities for apparently notable findings by chance. A multiplicity plan can distinguish primary, secondary, and exploratory questions and can adjust interpretation or thresholds accordingly. The registry record does not report a multiplicity procedure, a hierarchy for testing the secondary outcome, or a prespecified confirmatory role for it. Consequently, the Aldrete result is best read as supporting descriptive context, not as an independent test that settles the primary question.

The record lists no reported analyses, and does not describe how secondary-outcome missingness or analysis populations were handled. These omissions do not prove that the posted estimate is biased, but they leave important details unavailable for judging how robustly the secondary outcome was analyzed. The available results therefore support a cautious summary of the overall pattern, rather than a strong conclusion drawn from counting the number of outcomes pointing in a particular direction.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• The Aldrete Score

9. Statistical Interpretation

10. Statistical Methods Explained

The main reported outcome is continuous: recovery time is measured in minutes and summarized as a group mean with a standard deviation. The comparison is a difference between the Nuvigil mean and the control mean. The posted estimate is 3.2 minutes, with a confidence interval from -25.29 to 31.69 minutes and an unadjusted p-value of 0.826. The record's comparison is an unadjusted contrast; no adjusted estimate or model specification is reported in the registry record.

What does a mean difference describe?

In general, a mean difference describes the distance between the average outcomes of two groups, using a stated direction for the subtraction. Here, the contrast is expressed for Nuvigil relative to control. A positive estimate indicates a larger group mean for Nuvigil, while a negative estimate would indicate a smaller group mean. This summary is easy to interpret in the endpoint's original units, but it does not describe how much the individual observations overlap or whether a small number of unusually long or short stays influenced the average.

The standard deviation describes variability among observations within a group. It is not the same as the standard error, which describes the uncertainty in an estimated mean. For the primary endpoint, the registry reports standard deviations of 58.2 minutes for Nuvigil and 60.7 minutes for control. These values indicate appreciable within-group spread relative to the estimated difference. The record gives no distributional plots or other diagnostics, so the shape of recovery times and the influence of extreme observations are not reported in the registry record.

How should the confidence interval and p-value be read?

In general, a confidence interval gives a range of values compatible with the data under the assumptions of the method used. A 95% interval is not a statement that there is a 95% probability that the fixed true effect lies inside this particular interval. It reflects a procedure that, under its assumptions, would cover the true effect in 95% of repeated applications. In this trial, the interval includes zero and reaches to values on both sides of zero, so the estimate is uncertain in direction and size.

In general, a p-value is calculated under a null hypothesis and summarizes how unusual results at least as incompatible with that hypothesis would be, if the model assumptions held. The posted unadjusted p-value for the primary contrast is 0.826. It is not the probability that there is no difference, and it is not a measure of the size or clinical importance of a difference. A high p-value cannot demonstrate equivalence; an equivalence conclusion generally requires a prespecified margin and an analysis designed around that margin. Such a margin and an equivalence analysis are not reported in the registry record.

Why does variability matter?

In general, greater variation among individuals makes a group mean harder to estimate precisely when other aspects of the design are unchanged. This is because observed values are more dispersed around the group average. The primary outcome has standard deviations of 58.2 and 60.7 minutes, while the estimated mean difference is 3.2 minutes. The interval's width reflects uncertainty in that difference. No new result is inferred from comparing these values; they are useful context for understanding why a point estimate near zero can still have a broad range of compatible values.

Over-dispersion is a general concern when the variation in data is greater than a statistical model assumes. If a model underestimates the variation, its standard errors and confidence intervals may be too small, making results appear more precise than they are. This trial reports a continuous outcome and no model diagnostics or alternate variance analyses. Therefore, over-dispersion is a general statistical concept rather than a documented problem in this record. Whether the outcome distribution or variance assumptions were checked is not reported in the registry record.

What is and is not documented about the analysis?

The record lists group summaries and an unadjusted comparison but lists no reported analyses. It does not identify a regression model, covariate adjustments, handling of repeated measurements, or a plan for outliers. It also does not report whether the analysis followed intention-to-treat, per-protocol, or another analysis-population definition. The figures can be interpreted as posted descriptive results and a simple group contrast, but the analysis details necessary to reproduce or audit a fuller sponsor analysis are not reported in the registry record.

The same caution applies to missing values and multiplicity. The registry does not describe how missing outcomes were handled, whether all participants contributed to each endpoint, or whether the secondary outcome was adjusted for testing multiple outcomes. In general, missing-data choices can affect an estimate if the availability of outcomes is related to participant characteristics or outcomes. In general, testing multiple outcomes increases the chance of at least one apparently unusual result unless the analysis plan accounts for the number and role of tests. Those are general methodological considerations; the record does not establish that either issue changed these results.

11. Confidence Intervals and Precision

The primary mean difference is 3.2 minutes, with a 95% confidence interval from -25.29 to 31.69 minutes. The interval extends across zero, so the observed data are compatible with a shorter mean PACU time for Nuvigil, no mean difference, or a longer mean PACU time. The interval's breadth indicates that the estimate is not precise enough to pin down the direction or size of the group difference.

Precision is different from whether a result crosses a conventional statistical threshold. The unadjusted p-value is 0.826, but the interval is more informative about the range of effects compatible with the analysis. A non-significant p-value does not imply that the true difference is exactly zero. Nor does a confidence interval that includes zero show that the interventions are equivalent. An equivalence conclusion would require a clinically justified boundary for differences that count as equivalent, and no such boundary is reported in the registry record.

The interval should also be considered alongside the within-group standard deviations, which are 58.2 minutes for Nuvigil and 60.7 minutes for control. The reported variation among participants is substantial compared with the estimated mean difference. In general, larger variation and limited information can produce wider uncertainty intervals. The record does not report a precision target for the primary estimate or a clinically important difference against which to judge the interval's endpoints.

The Aldrete Score estimate also has a confidence interval that includes zero, but it is a secondary endpoint and should not be used to resolve the uncertainty in the primary result. More generally, confidence intervals address uncertainty under the calculation's assumptions; they do not account automatically for all potential biases, missing data, or problems with measurement. The statistical analysis details needed to assess those issues are not reported in the registry record.

12. 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, not total events. They are illustrative calculations based on the observed effect, not a report of the trial's original design calculation. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set at the stated fraction of the observed effect. The trial's own original sample-size assumptions are not reported in the registry record.

The 80% power column describes the number of participants per arm in a hypothetical study that would have an 80% chance of detecting the specified effect under those planning assumptions, if the assumptions held. The 90% power column uses a higher chance of detecting that same specified effect and therefore calls for a larger planned group size. For planning at 100% of the observed primary effect, the figures are 5,417 participants per arm for 80% power and 7,252 participants per arm for 90% power. Planning for 75% of the observed effect gives 9,631 participants per arm for 80% power and 12,892 participants per arm for 90% power. Planning for 50% of the observed effect gives 21,668 participants per arm for 80% power and 29,007 participants per arm for 90% power.

Smaller effects are harder to distinguish from random variation, so the planning calculations require more participants per arm as the effect to detect becomes smaller. These figures are not observed power: they are prospective planning illustrations and do not describe the chance that this completed trial detected an effect. They should not be read as evidence that the trial was designed to use these group sizes. The registry reports 34 participants in the Nuvigil group and 33 in control for the primary outcome, while the planning illustration is based on the observed effect and assumptions stated above.

13. 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, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 3.200; pooled standard deviation σ = 59.444.
2. n = 2 × (1.96 + 0.842)² × 59.444² / 3.200² = 5,416.9, rounded up to 5,417 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
delta <- 3.2                      # observed difference in means
sigma <- 59.4439102140704                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^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 (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(2478580)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 5,417 (80% power), 7,252 (90% power)
 75% of observed effect: n per arm = 9,631 (80% power), 12,892 (90% power)
 50% of observed effect: n per arm = 21,668 (80% power), 29,007 (90% power)
power.t.test: 5417.9 
Simulated power at n = 5,417 per arm: 0.801 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-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.

14. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when researchers assess more than one outcome, time point, subgroup, or comparison. In general, the more statistical tests that are interpreted together, the greater the chance that at least one will appear unusual by chance alone. Prespecified priorities and multiplicity procedures help readers distinguish a primary confirmatory question from secondary or exploratory ones. This record identifies PACU Recovery Time as the primary outcome and the Aldrete Score as a secondary outcome, but a formal multiplicity strategy is not reported in the registry record.

The record does not state whether the secondary endpoint was intended to support a separate confirmatory claim, whether it followed a testing hierarchy, or whether any adjustment was planned. Its posted p-value is unadjusted. That does not invalidate the descriptive result, but it means the p-value should not be read as if it necessarily accounted for the full set of outcome questions. The number of planned analyses, including any subgroup or interim analyses, is not reported in the registry record.

Missing-data handling is also not reported. The registry gives outcome counts of 34 for Nuvigil and 33 for control, but does not say whether these are the numbers randomized, the numbers with observed endpoint data, or the numbers included after any exclusions. It does not describe reasons for missing outcomes, imputation, sensitivity analyses, or whether missingness differed between groups. In general, missingness can affect comparisons when the availability of an outcome is related to the outcome itself or to characteristics associated with it.

The analysis population is not defined in the registry record. It is therefore not possible to determine from the record whether the reported comparison used all randomized participants, participants who followed the assigned treatment, or another set. The registry does not report an intention-to-treat analysis, a per-protocol analysis, or how departures from assigned treatment were handled. These omissions limit assessment of the relationship between randomization and the posted estimates; they should be treated as unknowns, not evidence that any particular method was or was not used.

15. 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.

The adverse-event figures list 34 participants at risk in the Nuvigil group and 33 in the control group. The record reports zero serious adverse events in each group, zero other adverse events in each group, and zero deaths in each group. No serious adverse-event terms are listed.

These figures describe the events recorded in the registry entry. They do not establish that no unrecorded events occurred, and they do not by themselves show that the groups have the same safety profile. With a limited number of participants, the absence of recorded events is not a precise estimate of the frequency of uncommon outcomes. The record does not report event definitions, surveillance procedures, severity details beyond the serious and other categories, or the duration of safety follow-up. Those details are not reported in the registry record.

The outcome results concern PACU recovery time and the Aldrete Score; the adverse-event listing is a separate part of the record. It should not be used to infer an effect on outcomes that were not listed as adverse events or otherwise reported. The figures are best read as the registry's recorded event counts during the reported study, with the limitations of the available safety detail.

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

The posted results describe a randomized comparison of a single preoperative oral dose of Nuvigil with placebo among participants undergoing surgery in the population described by the registry. The primary endpoint is mean PACU recovery time. The observed group means were 98.2 minutes with Nuvigil and 95.0 minutes with control, and the estimated mean difference was 3.2 minutes. Its confidence interval extends from -25.29 to 31.69 minutes, and the unadjusted p-value is 0.826.

These results do not provide a precise estimate of the direction or size of a difference in average recovery time. They are compatible with a range of group differences, including no difference. That uncertainty is not the same as evidence that the treatments are equivalent. Equivalence or non-inferiority would require an appropriate prespecified margin and analysis; neither is reported in the registry record.

The trial's background discusses postoperative wakefulness and concerns related to obstructive sleep apnea and obesity, but the posted primary endpoint is time spent in PACU. The result does not directly establish an effect on desaturation, respiratory safety, intensive-care use, narcotic use, or other aspects of postoperative care. The secondary Aldrete Score is a different measure and does not remove the primary estimate's uncertainty.

The registry record also does not report the original sample-size justification, a complete analysis plan, missing-data procedures, or analysis-population definitions. As a result, the posted estimates can be described, but some elements needed to judge design assumptions and analysis robustness remain unavailable. The appropriate statistical reading is that this record reports imprecise comparisons in a small completed trial, not a definitive conclusion for all outcomes or all patients.

17. Why This Trial Matters Statistically

This trial illustrates a central issue in clinical biostatistics: a small observed difference does not necessarily mean that the underlying effect is known to be small. The primary estimate is close to zero, but its confidence interval extends to differences in both directions. Reading the point estimate alone would obscure the uncertainty that is apparent in the interval.

It also demonstrates why a non-significant p-value should not be treated as proof of no effect. The unadjusted p-value does not establish equivalence, and the registry record reports no equivalence margin. A careful interpretation therefore considers the estimate, its precision, the outcome's units, and the limits of the analysis information available.

The planning illustration makes another statistical distinction visible: sample-size calculations depend on the effect a future study is intended to detect. Smaller target effects require more participants under the stated assumptions. The calculation uses the observed effect as a planning reference; it is not a record of the trial's original design and is not observed power. Keeping those concepts separate prevents a retrospective planning illustration from being mistaken for evidence about why the trial enrolled its participants.

Finally, the record shows why endpoint hierarchy, missing data, and analysis populations matter. There is one posted secondary outcome, but the registry does not describe multiplicity handling or the details needed to assess the analysis set. Reporting those features makes results easier to interpret and reproduce. Their absence does not demonstrate that the analysis was flawed; it limits the conclusions that can be drawn from the registry entry.

18. 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.

Several limitations specific to this record affect interpretation. The primary outcome is PACU stay duration, but the registry does not give a more detailed operational definition of the start and end points or the criteria for leaving the unit. The endpoint therefore captures duration as recorded, without enough detail to assess whether discharge decisions were standardized across participants.

The trial description identifies the target population as patients with obstructive sleep apnea undergoing surgery and refers to obesity in the title and summary. The registry does not provide detailed eligibility criteria or participant characteristics, so it is not possible to describe the enrolled group more specifically or assess how representative it was. It also does not report the types of surgeries or details of perioperative care that might help contextualize recovery time.

The posted primary group counts are 34 and 33, but the registry does not clarify the relationship between those counts and the randomized population. Missing-data handling, protocol deviations, treatment adherence, and analysis-population definitions are not reported. These details matter when interpreting a randomized comparison because they help readers understand who contributed outcome data and how the assigned groups were maintained in analysis.

The registry lists a secondary endpoint but does not report multiplicity procedures, the original statistical plan, an interim-analysis plan, or the original sample-size justification. It also gives no outcome-distribution diagnostics or sensitivity analyses. These are limits on what can be evaluated from the record, rather than proof that any one issue occurred. Finally, the safety listing provides event counts but does not give detailed event definitions or duration of safety follow-up. Together, these omissions leave uncertainty about the trial's analysis procedures and the scope of what the posted outcomes can establish.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Armodafinil (Nuvigil), Postoperative Recovery of OSA (Obstructive Sleep Apnea) and Obese Patients — NCT02478580.
• Registry record last updated 2018-12-04; status last verified 2018-12.
• Results first posted 2016-03-23.
• 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.

22. Record Summary

NCT02478580 is a completed phase 3 randomized, quadruple-masked, parallel-group trial sponsored by the University of Texas Southwestern Medical Center. The registry lists 67 enrolled participants. The intervention was a single oral 150mg dose of Nuvigil in the preoperative area, compared with a single oral placebo.

The primary outcome was PACU Recovery Time in minutes during the immediate postoperative period, up to 3 hours. The posted group means were 98.2 minutes for Nuvigil and 95.0 minutes for control. The mean difference was 3.2 minutes, with a 95% confidence interval from -25.29 to 31.69 minutes and an unadjusted p-value of 0.826. The secondary outcome was the Aldrete Score at 2 hours after extubation.

The registry reports zero serious adverse events, zero other adverse events, and zero deaths in both groups. The original sample-size rationale, detailed statistical analysis plan, multiplicity procedure, missing-data methods, and analysis-population definitions are not reported in the registry record.