Nitrous Oxide for Identifying the Intersegmental Plane in Segmentectomy: A Randomized Controlled Trial: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Nitrous Oxide for Identifying the Intersegmental Plane in Segmentectomy: A Randomized Controlled Trial (NCT04302350), a randomized na study. The primary outcome is The Intersegmental Border Appearance Time During the Surgery.

2. Clinical Question

The registry record describes a trial of inspired gas mixtures during surgery to identify the intersegmental plane. Its stated question was whether the mixture used during two-lung anesthesia affected the time until a clear boundary appeared between the target lung segment and the neighboring preserved segment. The study also described feasibility and safety as interests, although no secondary outcomes are posted.

The registry title refers to segmentectomy, while its summary uses the term pneumonectomy when describing the operative context. That difference in wording is present in the record; further clarification is not reported in the registry record. The trial was randomized, but the posted results do not establish how closely the enrolled participants or operative procedures represent other settings.

3. Trial Design

The registry describes a randomized, parallel-group trial with triple masking. Its status is completed, and enrollment is recorded as 81. The registry lists a start date of 2020-01-15 and a primary completion date of 2020-07-15. The trial phase is listed as not applicable. The sponsor is The First Affiliated Hospital with Nanjing Medical University.

Participants were assigned among three inspired-gas groups: 75% nitrous oxide, 50% nitrous oxide, and 100% oxygen. The brief summary states that the study was designed to investigate whether these mixtures affected intersegmental-border appearance time and to explore feasibility and safety. The primary outcome is reported as a mean with standard deviation, in seconds. The registry identifies Group75 as the control for the posted pairwise comparisons.

The primary outcome results list 24 participants in Group75, 23 in Group50, and 18 in Group0. These arm counts do not account for the full enrollment figure, and the reasons for the difference are not reported in the registry record. The record does not report a participant flow account, the number randomized to each group, or the number analyzed for every outcome.

Masking is recorded as triple, but the identities of the masked parties and the procedures used to maintain masking are not reported in the registry record. The arm descriptions repeat a description of surgical preparation, but the text ends before it specifies the gas administration details. The registry record therefore does not provide a complete account of the treatment protocol, allocation concealment, or implementation of the assigned mixtures.

The trial record contains two outcome measures, but results are posted for only the primary outcome and adverse events. No secondary outcome results are posted. The protocol’s original sample-size assumptions, statistical analysis plan, and any interim-analysis plan are not reported in the registry record.

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.

Before assignment: Three patients were excluded (1 refused to participate in the trial and 2 did not meet the inclusion criteria).

Overall Study

Reasons for not completing this period:

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 The Intersegmental Border Appearance Time During the Surgery, measured over The time of appearance of the intersegmental plane that can be performed satisfactorily by surgeons.

The primary endpoint is the time, in seconds, from complete expansion of the lung tissue after the relevant target-segment structures have been blocked until a clear demarcation forms between the target segment and the immediately preserved lung segment. The description says the boundary should not undergo significant changes over time. The endpoint is summarized as a mean and standard deviation for each group.

The endpoint addresses the practical timing question motivating the trial: how long it takes for the intersegmental boundary to become clearly visible during surgery. The registry summary explains that identifying this boundary is important to the operative approach and proposes that nitrous oxide’s diffusion properties could speed lung collapse. The measured endpoint therefore focuses on the timing of a visible border, rather than on a patient-centered outcome or a measure of long-term health.

As a continuous measure, the endpoint can be summarized by a group mean, while its standard deviation describes variation among the recorded times. A comparison of group means conveys the average difference in time between groups; it does not show whether every participant experienced a similar time or whether the boundary was equally clear in every case. The registry record does not report a separate quantitative measure of border clarity, a threshold for clinical importance, or a secondary measure of surgical performance.

The title refers to segmentectomy, whereas the brief summary and endpoint description use “pneumonectomy” in places. The registry record does not resolve this terminology. That ambiguity limits how specifically the operative context can be characterized from the record alone.

7. Results Posted in the Registry

• Group50: mean 552.39 versus 320.20 on control; difference 232.19 (95% CI 187.28 to 277.10), standardized effect d = 2.98; z-test p = <0.001.
• Group0: mean 968.33 versus 320.20 on control; difference 648.13 (95% CI 600.63 to 695.63), standardized effect d = 8.66; z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: each participant’s border-appearance time is recorded in seconds, and the registry reports group means and standard deviations. A mean is the arithmetic average of the observed times. A standard deviation describes how dispersed individual times are around their group mean. General statistical explanation: a larger standard deviation indicates more spread in the measurements, but it does not describe the full shape of their distribution.

What does a mean difference represent?

The posted pairwise comparisons express each mean difference as the comparison group’s mean minus Group75’s mean. The Group50 comparison is 232.2 seconds, and the Group0 comparison is 648.1 seconds. A positive difference means the comparison group’s reported mean time is longer than the reference group’s reported mean. These are differences in group averages, not predictions for an individual participant, and they do not indicate that every participant’s time differed by the same amount.

The two comparisons use different group sizes: Group75 has 24 participants, Group50 has 23, and Group0 has 18 in the primary outcome results. Their reported standard deviations are 65.89, 88.96, and 85.53 seconds, respectively. The comparison summaries also report pooled standard deviations of 78.03 seconds for Group50 versus Group75 and 74.87 seconds for Group0 versus Group75. A pooled standard deviation combines information about spread from the two groups being compared under the comparison’s assumptions. The registry does not report diagnostic checks for those assumptions.

How should the confidence intervals be understood?

General explanation: a confidence interval describes the precision of an estimated quantity under a statistical procedure and its assumptions. It gives a range of values compatible with the observed data and that procedure. It is not a range containing a stated proportion of individual participants’ times, nor does it by itself describe clinical importance. The posted intervals are 187.3 to 277.1 seconds for Group50 versus Group75 and 600.6 to 695.6 seconds for Group0 versus Group75.

The p-values are marked unadjusted and are each reported as p < 0.001. General explanation: a p-value measures how unusual data at least as inconsistent with a specified null hypothesis would be if that hypothesis and the statistical model were true. It is not the probability that the null hypothesis is true, nor a measure of effect size. The registry record does not report whether or how the trial’s planned analysis addressed multiple comparisons; no adjustment should be inferred from these unadjusted values.

What can be inferred from randomization?

General explanation: random assignment is intended to make comparison groups similar on average with respect to both measured and unmeasured characteristics. It can support a causal interpretation when the assignment, follow-up, and analysis are conducted appropriately. The registry identifies the design as randomized, but does not report the sequence-generation method, allocation concealment, or a full account of participants included in the outcome analysis. The posted description alone therefore cannot establish that all those safeguards were implemented as intended.

The design is also recorded as parallel-group and triple-masked. General explanation: a parallel-group design assigns participants to a group and compares outcomes between groups. Masking can reduce the influence of expectations on care or outcome assessment, depending on who is masked and how. The registry record does not identify the masked parties or describe how masking was maintained.

What is not described in the analysis record?

The registry lists no posted analysis count and does not give a detailed statistical analysis plan. It does not report an adjusted model, baseline-adjustment variables, handling of missing outcomes, analysis population definitions, distributional checks, or interim analyses. These procedures must not be assumed. The numerical comparisons are reported as unadjusted, and the p-values are explicitly unadjusted.

General explanation: over-dispersion matters when a model assumes less variation than the data actually contain; underestimated variation can make uncertainty appear too small. The posted endpoint is a continuous time measure and the registry gives standard deviations, but it does not report a model requiring a particular dispersion assumption or any over-dispersion assessment. No conclusion about such a diagnostic can be drawn.

The record gives no clinically important threshold for a difference in seconds. Statistical evidence that a mean difference is distinguishable from zero does not alone establish that the difference is important to patients, surgeons, or clinical decisions. The registry also does not post secondary outcome results, so statistical interpretation is limited to the primary timing measure and the recorded adverse-event counts.

10. Confidence Intervals and Precision

The Group50-versus-Group75 mean difference is 232.2 seconds, with a 95% confidence interval from 187.3 to 277.1 seconds. The Group0-versus-Group75 mean difference is 648.1 seconds, with a 95% confidence interval from 600.6 to 695.6 seconds. Each interval is entirely above zero, consistent with the posted positive mean differences and the longer group means in the comparison arms.

General explanation: interval width reflects precision in relation to the estimated difference and the method used to construct the interval. A narrower interval indicates less uncertainty about the estimate under those assumptions; it does not guarantee that the estimate is unbiased or clinically important. The intervals do not describe the range of individual participants’ times. The arm-level standard deviations provide information about individual variation, while the confidence intervals concern uncertainty in the group mean differences.

The posted estimates are accompanied by p < 0.001 for both comparisons, with those p-values identified as unadjusted. The registry record does not report an adjustment for making more than one comparison. Consequently, the confidence intervals and p-values should be understood as pairwise results, not as documented family-wide inference accounting for all comparisons.

Interpretation of precision is also limited by information absent from the record. The outcome analysis counts are 24, 23, and 18, while enrollment is 81; the reason for the difference is not reported in the registry record. There is no detailed missing-data account, analysis-population definition, or sensitivity analysis. The registry does not report a clinical threshold against which the intervals could be judged. Thus, the intervals indicate statistical precision for the posted comparisons, but cannot settle the practical importance or robustness of the 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 sample-size figures are planning illustrations based on the observed effect, not the trial’s original design calculations. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. These are planning assumptions for the illustrations; the original sample-size assumptions are not reported in the registry record.

For these comparisons, the figures refer to participants per arm, not total events. The 80% power column gives the number of participants per arm that the planning calculation estimates would be needed to have an 80% chance of detecting the specified effect under the stated assumptions. The 90% power column gives the corresponding number per arm for a 90% chance. Power describes a design’s ability to detect an effect of a chosen size if that effect is real, under the calculation’s assumptions; it is not the probability that a reported result is true.

The rows use the full observed effect and reduced effects described as 75% and 50% of the observed effect. In general, planning for a smaller effect requires more participants because a smaller difference is harder to distinguish from random variation. The displayed estimates are unusually small in some comparisons, so they should be read as the direct output of the stated normal-approximation planning setup, not as evidence that such small groups would necessarily be adequate in a future study. The registry record does not report the original trial’s design justification or whether these planning assumptions match the study’s actual planning.

This is not observed power. It is a hypothetical planning calculation using the posted effect estimates, and it does not describe the probability that the completed trial detected its true effect. The sample-size figures should not be substituted for the observed group counts or taken as a retrospective measure of trial success.

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

Worked calculation for this trial

1. Observed difference Δ = 232.190; pooled standard deviation σ = 78.026.
2. n = 2 × (1.96 + 0.842)² × 78.026² / 232.190² = 1.8, rounded up to 2 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 <- 232.19                      # observed difference in means
sigma <- 78.0255960139577                     # 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(4302350)
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 = 2 (80% power), 3 (90% power)
 75% of observed effect: n per arm = 4 (80% power), 5 (90% power)
 50% of observed effect: n per arm = 8 (80% power), 10 (90% power)
power.t.test: 3.1 
Simulated power at n = 2 per arm: 0.380 (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.

13. Multiplicity, Missing Data and Analysis Populations

The registry posts two comparisons for the primary continuous outcome: Group50 versus Group75 and Group0 versus Group75. Both p-values are explicitly unadjusted and reported as p < 0.001. The registry record does not report a multiplicity strategy, such as a testing order or an adjustment across comparisons. The results therefore should not be described as adjusted for the number of comparisons.

The record lists two outcome measures but posts no secondary outcome results. It does not report whether additional outcomes were planned, whether any outcomes were changed, or how the primary outcome was prioritized within a complete analysis plan. Those details are not reported in the registry record. The feasibility and safety aims in the summary do not substitute for posted secondary outcome analyses.

The registry’s enrollment is 81, whereas primary outcome results are listed for 24 participants in Group75, 23 in Group50, and 18 in Group0. The record does not explain the difference or provide participant flow, reasons for exclusions, or a missing-outcome analysis. It does not report whether the outcome analysis followed an intention-to-treat population, a per-protocol population, or another defined population. No imputation method or sensitivity analysis for missing outcome data is reported.

The analysis count is listed as zero, and there is no detailed statistical analysis plan in the posted record. The comparison results identify unadjusted p-values and provide mean differences and confidence intervals, but the registry does not state whether baseline covariates were considered or how model assumptions were evaluated. Interim analyses and any stopping rules are not reported in the registry record.

These omissions do not show that a particular method was or was not used outside the registry entry. They mean the record does not permit a full assessment of multiplicity, missing-data handling, or analysis-population choices. Interpretation should remain tied to the pairwise summary results that are actually posted.

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 non-serious adverse event terms

The registry reports serious adverse events for 24 participants at risk in Group75, 23 in Group50, and 18 in Group0. The number affected by a serious adverse event is 0 in each group. Deaths are also recorded as 0 in each group. No serious adverse-event terms are listed.

These are counts, not estimates of comparative risk. The registry record does not report a statistical comparison for serious adverse events or a detailed description of how events were collected and classified. The recorded counts are limited to the participants identified as at risk in each group; the record does not explain how those counts relate to the total enrollment.

The registry separately records other adverse events affecting 0 participants in Group75, 1 in Group50, and 2 in Group0. These are not serious adverse-event counts. The record does not provide event terms or further detail in the information posted. The absence of reported serious events in these groups should be read as a description of the registry entries, not as proof that an intervention has no safety risks or that the groups can be compared reliably on safety.

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

The posted results concern the time until a clear intersegmental border appeared during surgery. The mean was 320.2 seconds in Group75, 552.4 seconds in Group50, and 968.3 seconds in Group0. The pairwise mean differences relative to Group75 were 232.2 seconds for Group50 and 648.1 seconds for Group0, and both comparisons had p < 0.001. The confidence intervals for these differences were entirely above zero.

Those results describe group-average times in the participants whose outcomes are represented in the registry record. They do not establish that every participant’s time followed the same pattern, because individual observations are not posted. Nor do they establish a threshold for a meaningful improvement: the registry record does not report a clinically important difference for this endpoint.

The study summary proposes that nitrous oxide could speed lung collapse and facilitate surgery, but the posted primary result is a timing measure. It does not directly quantify surgical difficulty, the quality of the final resection, complications beyond the adverse-event entries, preservation of lung function, or longer-term outcomes. No secondary outcome results are posted, so conclusions about feasibility beyond the stated timing endpoint are not supported by those results.

The registry identifies the trial as randomized, which is relevant to interpreting group comparisons, but it does not provide a complete account of allocation, participant flow, missing outcomes, or analysis populations. The primary outcome counts are smaller than the enrollment figure, and reasons for that difference are not reported in the registry record. These gaps limit assessment of how representative the analyzed participants were and how robust the comparisons may be.

The record also uses differing surgical terms: the title refers to segmentectomy, while the summary includes the term pneumonectomy. The registry does not clarify this terminology. Results should therefore be understood in the context described by the posted record, rather than assumed to apply to every operation or clinical setting.

16. Why This Trial Matters Statistically

This trial illustrates how a physiologic or procedural rationale can be translated into a continuous intraoperative endpoint. Rather than asking only whether a border appeared, the registry defines the outcome as the time from complete lung expansion after target-segment structures are blocked until a clear, stable boundary forms. That definition makes the outcome a measurable duration and permits comparison of group means.

The three reported group means and two pairwise comparisons show why the choice of reference group and direction of subtraction matter. The estimates are defined relative to Group75, so positive differences indicate longer average times in Group50 and Group0. The confidence intervals add information about the precision of those differences that the p-values alone cannot convey. Reading estimates, intervals, and group-level spread together gives a more complete statistical description than treating statistical significance as the only result.

The record also highlights the importance of complete trial reporting. It identifies randomization and triple masking, but does not describe the allocation process, masked parties, analysis populations, or missing-data handling. Enrollment is recorded as 81, while the primary outcome group counts are 24, 23, and 18. Without participant flow and reasons for exclusions or absent outcomes, the relationship between enrollment and the analyzed results remains unclear.

Finally, the trial’s stated interest in feasibility and safety is broader than the posted primary endpoint. The registry posts adverse-event counts but no secondary outcome results, and does not report a threshold for a clinically important timing difference. Statistical interpretation therefore depends on keeping the scope of the observed endpoint distinct from claims about overall operative benefit, broader safety, or generalizability.

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 gives limited detail about the trial procedures. Although it records randomization, parallel groups, and triple masking, it does not report the allocation method, allocation concealment, who was masked, or how masking was maintained. The arm descriptions are incomplete in the posted text, so the full administration protocol cannot be reconstructed from the record.

Enrollment is recorded as 81, while the primary outcome results list 24 participants in Group75, 23 in Group50, and 18 in Group0. The reasons for the difference are not reported in the registry record. There is no posted flow diagram or account of exclusions, withdrawals, missing measurements, or the analysis population. This limits assessment of possible selection or missing-data effects.

The registry reports two outcome measures, but no secondary outcome results. It does not post a detailed statistical analysis plan, the trial’s original sample-size justification, an interim-analysis plan, or a multiplicity strategy. The primary comparisons have unadjusted p-values. No clinically important threshold is reported for the time endpoint, so the practical importance of a difference cannot be assessed from a stated criterion.

There is also a terminology inconsistency: the title concerns segmentectomy, while the summary uses pneumonectomy in describing the operation. The record does not clarify the intended surgical context. Participant characteristics and detailed eligibility criteria are not reported in the posted results, limiting assessment of applicability to other populations or settings.

The adverse-event entries are counts without detailed event descriptions or a reported comparative safety analysis. These limitations concern the registry information available for interpretation; they do not establish what may have been documented elsewhere.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Nitrous Oxide for Identifying the Intersegmental Plane in Segmentectomy: A Randomized Controlled Trial — NCT04302350.
• Registry record last updated 2023-03-02; status last verified 2023-03.
• Results first posted 2023-03-02.
• 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, triple-masked trial with enrollment of 81. The primary outcome was mean time in seconds until a clear intersegmental border appeared during surgery. Results are posted for Group75, Group50, and Group0, with Group75 serving as the reference in two unadjusted comparisons.

Mean times were 320.2 seconds, 552.4 seconds, and 968.3 seconds, respectively. The mean differences were 232.2 seconds for Group50 versus Group75 and 648.1 seconds for Group0 versus Group75; both p-values were p < 0.001. The posted confidence intervals were 187.3 to 277.1 seconds and 600.6 to 695.6 seconds, respectively.

Serious adverse events and deaths were recorded as 0 in each group. Primary outcome group counts were 24, 23, and 18; reasons for the difference from enrollment are not reported in the registry record. No secondary outcome results are posted, and key analysis details are not reported.