Reducing Operative and Post-operative Morbidity in Living Kidney Donors With the Airseal System: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Reducing Operative and Post-operative Morbidity in Living Kidney Donors With the Airseal System (NCT02262039), a randomized na study. The primary outcome is Narcotic Use (mg).

2. Clinical Question

The registry describes the study purpose as assessing whether the Airseal System would reduce post-operative pain and the need for narcotics in laparoscopic living kidney donor surgery. The posted primary endpoint is narrower than that stated purpose: it measures narcotic use during the operation, not post-operative narcotic use. Subjective pain scores and mean ETCO2 are among the listed secondary outcomes, but the available posted secondary results cover only some of the planned outcome measures.

The clinical comparison is between two insufflation approaches that also have different target pressures. The record therefore presents an intervention contrast involving both the VTI system and a lower target pressure, rather than a comparison that isolates the equipment from pressure. The registry record does not report additional details that would separate those components or clarify the primary outcome’s role in the broader study purpose.

3. Trial Design

The registry record describes a randomized, single-masked, parallel-group trial. Enrollment was 41. The posted arm counts are 14 for Conventional Pressure and 27 for Low Pressure (VTI). The record identifies the study as completed and lists Yale University as the sponsor.

Participants were assigned to conventional insufflation with a 15mmHg target pressure or valveless recirculating insufflation with a 10mmHg target pressure. The record lists the intervention as a device and describes the comparator arm using conventional pressure. The masking field says single, but the registry record does not specify which people involved in the trial were masked or how masking was maintained. Further details of randomization and allocation concealment are not reported in the registry record.

The primary outcome is mean narcotic use in mg, expressed as total morphine equivalents during the operation on the day of surgery. Posted secondary measures include subjective pain scores and mean ETCO2. There are seven outcome measures and seven analyses listed overall, while four secondary outcomes are posted. The record lists subjective pain score more than once among secondary outcomes; the distinct posted results include pain at one hour post-op and mean ETCO2 intraoperatively.

The registry record lists the study start as 2014-08 and primary completion as 2015-12. Original sample-size assumptions, the rationale for the unequal posted arm counts, the detailed analysis plan, and the definitions of the analysis populations are not reported in the registry record. The posted results should therefore be interpreted as the analyses available in the record, without assuming unreported design or analysis procedures.

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.

Population: All participants who agreed to participate completed the study and are included in the analysis.

6. Primary Endpoint

The registry lists the primary outcome as Narcotic Use (mg), measured over Intra-Operative on day of surgery.

The primary endpoint is narcotic use, measured as mean total morphine equivalents in mg during the operation on the day of surgery. Morphine equivalents express the recorded amounts of narcotic medications on a common scale, allowing total use to be summarized across participants even if medications differ. The registry describes the endpoint as a mean and reports a standard deviation for each arm.

In general, an endpoint that quantifies medication use can address whether groups differed in the amount of medication administered over the specified period. The time window matters: this endpoint concerns intra-operative use, so it does not directly measure narcotic use after surgery. Although the study’s stated purpose mentions reducing the need for narcotics and post-operative pain, the posted primary endpoint is limited to use during surgery.

For this continuous outcome, the registry reports the mean and standard deviation in each arm. The mean describes the group’s average recorded amount, while the standard deviation describes how spread out individual observations are around that group mean. These summaries do not show the full distribution of individual participants’ use. The registry record does not provide the endpoint’s detailed measurement procedures or additional information about how the total was assembled.

7. Results Posted in the Registry

• Low Pressure (VTI): mean 99.60 versus 113.80 on control; difference -14.20 (95% CI -27.91 to -0.49), standardized effect d = -0.61; z-test p = 0.042.

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.

Subjective Pain 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 deviations.
• Result:
  • Low Pressure (VTI): mean 5.30 versus 4.60 on control; difference 0.70 (95% CI -1.37 to 2.77), standardized effect d = 0.22; z-test p = 0.507.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Low Pressure (VTI) and the control. The interval gives the range of effects that remain compatible with the data.

Mean ETCO2

• 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 deviations.
• Result:
  • Low Pressure (VTI): mean 30.80 versus 29.70 on control; difference 1.10 (95% CI -1.47 to 3.67), standardized effect d = 0.31; z-test p = 0.401.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Low Pressure (VTI) and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary outcomes cover subjective pain and mean ETCO2. Across these outcomes, the recalculated comparisons do not show a consistent direction that mirrors the primary endpoint: the pain-score and ETCO2 estimates are in the opposite numerical direction from the primary narcotic-use estimate. Their recalculated intervals include no difference, and the sponsor-reported p-values are 0.52 and 0.45. These results are less conclusive than the primary result and do not establish a secondary-outcome difference.

The secondary outcomes address different questions and time windows. Pain is reported at one hour post-op, whereas ETCO2 is measured intraoperatively. Neither is interchangeable with narcotic use during the operation. The registry lists seven outcome measures and seven analyses, while four secondary outcomes are posted; the record includes repeated listings for subjective pain score. The full set of secondary results is not reported in the registry record.

In general, when several outcomes are tested, the chance of obtaining at least one apparently unusual result by chance can increase. Unadjusted secondary results therefore carry less weight than a clearly specified primary analysis, particularly when the registry does not report a multiplicity plan. These results can be read as exploratory descriptions of the available outcomes, not as independent confirmation of the primary comparison. The registry record does not report whether the secondary analyses were prespecified in detail or adjusted for multiple testing.

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

• Subjective Pain Score
• Subjective Pain Score
• Subjective Pain Score
• Mean ETCO2

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a measured quantity reported as a mean in mg. For this kind of outcome, an analysis can compare the group means and estimate a mean difference. The posted recalculation expresses the contrast as Low Pressure (VTI) minus Conventional Pressure, so a negative estimate indicates a lower observed mean in the Low Pressure (VTI) group. This sign convention describes the direction of the numerical contrast, not its clinical importance.

What does the mean difference represent?

The arm means are 99.6 mg for Low Pressure (VTI) and 113.8 mg for Conventional Pressure. The recalculated mean difference is -14.2 mg. This is a difference between the group averages, not a claim that each participant used that amount less. The standard deviations, 25.0 mg and 19.0 mg respectively, describe variation among participants within each arm. In general, a mean difference is easiest to interpret alongside the scale of the outcome, the within-group variability, and an interval expressing uncertainty.

What does the t-test assess?

The registry reports a two-sided t-test for the primary comparison, with p <0.05. In general, a two-sided test evaluates departures in either direction from a null hypothesis of no difference in group means. A p-value describes how unusual the observed result, or a more extreme result, would be under the null model and the assumptions of the test. It is not the probability that the null hypothesis is true, and it does not quantify the size or practical importance of the difference.

The simple recalculation reports an unadjusted p-value of 0.042. The discrepancy flag means the sponsor’s own analysis takes precedence; the recalculated value should not be treated as a replacement for that analysis. The registry does not provide the sponsor’s numerical estimate or confidence interval from its t-test, only the test type and the reported p-value threshold.

Why consider a confidence interval?

In general, a confidence interval gives a range of values compatible with the observed data under a specified method. It conveys uncertainty about the estimated mean difference in the original measurement units. Its width depends in part on the amount of information in the data and the variability of the outcome. The recalculated interval accompanies the unadjusted comparison, while a sponsor-reported interval is not reported in the registry record. The interval should be read as an uncertainty summary, not as a range containing a known proportion of individual participants’ outcomes.

What does unadjusted mean?

An unadjusted result is calculated without accounting for other variables or for the multiplicity of testing several outcomes, unless such adjustments are explicitly described. The registry record does not report an adjustment for covariates or multiple comparisons. Thus, the recalculated p-value and interval should be understood as simple, unadjusted comparisons based on the posted group summaries. The sponsor’s analysis method is identified as a two-sided t-test, but further details of its implementation are not reported in the registry record.

How should variation be understood?

Standard deviation summarizes spread around a mean. It is not the same as the standard error, which describes uncertainty in estimating a group mean. In general, when individual measurements vary substantially, a group mean can be estimated less precisely unless there is enough information to offset that variability. For this trial, the posted group sizes are 14 and 27, and the reported standard deviations differ between groups. These summaries help readers understand why an estimate has uncertainty, but they cannot show the raw outcome distribution or identify unusual observations.

In general, over-dispersion means that observed variation exceeds what a statistical model expects. It matters when a model’s variance assumptions are too restrictive, because uncertainty estimates and tests may then be misleading. The posted primary analysis is a t-test for a continuous outcome, and the registry does not report an over-dispersion assessment. This general concept should not be read as evidence that over-dispersion occurred in this trial.

The registry identifies a randomized, parallel design, but does not describe the full analysis population, missing-data handling, or the detailed statistical plan. Those omissions limit assessment of whether the reported analyses follow a prespecified approach. They also make it inappropriate to infer unreported procedures, such as interim analyses or covariate adjustment. The methods interpretation should therefore stay with the reported test and the transparent unadjusted recalculation, giving precedence to the sponsor’s analysis where the discrepancy flag applies.

11. Confidence Intervals and Precision

The recalculated mean difference for intra-operative narcotic use is -14.2 mg. The posted recalculation includes a confidence interval for this contrast, while the sponsor’s analysis does not report a numerical interval in the registry record. The interval describes uncertainty in the estimated difference under the recalculation’s method; it does not describe the range of individual participants’ narcotic use.

In general, a confidence interval is more informative than a point estimate alone because it shows how precisely the data locate the contrast. A narrow interval indicates greater precision, while a wide interval indicates that a broader range of differences remains compatible with the data and method. Interpretation also depends on the endpoint’s measurement scale and on whether a clinically meaningful threshold has been specified. Such a threshold is not reported in the registry record.

The posted sample sizes are 14 and 27, and the standard deviations are 19.0 mg and 25.0 mg. The unequal group sizes and variation are relevant to precision, but the registry record does not provide raw observations or a sponsor-reported interval with which to assess the sponsor analysis’s precision directly. The recalculated interval belongs to the simple unadjusted recalculation and should not be substituted for a sponsor estimate when the discrepancy flag is present.

The sponsor reports a two-sided t-test with p <0.05, but a p-value does not communicate the range of plausible effect sizes. The registry record’s lack of a sponsor-reported numerical confidence interval leaves the sponsor result less fully characterized in terms of precision. The recalculated interval can be read as an additional descriptive analysis, with the distinction between it and the sponsor’s own analysis kept clear.

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 illustrative calculations based on the observed effect, not the trial’s original design. For these continuous outcomes, the figures are participants per arm, not total events. 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 the stated fraction of the observed effect. The trial’s original sample-size assumptions are not reported in the registry record.

The 80% power column gives the illustrative number of participants per arm under those assumptions for a design with an 80% chance of detecting the chosen effect if that effect is the true one. The 90% power column gives the corresponding illustrative number per arm for a design with a 90% chance. In general, higher target power requires more information, often through more participants.

Rows planning for a smaller fraction of the observed effect require more participants than rows planning for the full observed effect. This reflects a general statistical principle: smaller differences are harder to distinguish from random variation, all else being equal. The figures are hypothetical planning illustrations and are not observed power. Observed power is not a useful substitute for interpreting the estimated effect and its uncertainty after a trial; the planning figures instead show how assumed effect size and target power shape a prospective sample-size calculation.

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 = -14.200; pooled standard deviation σ = 23.173.
2. n = 2 × (1.96 + 0.842)² × 23.173² / -14.200² = 41.8, rounded up to 42 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 <- -14.2                      # observed difference in means
sigma <- 23.1732604525129                     # 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(2262039)
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 = 42 (80% power), 56 (90% power)
 75% of observed effect: n per arm = 75 (80% power), 100 (90% power)
 50% of observed effect: n per arm = 168 (80% power), 224 (90% power)
power.t.test: 42.8 
Simulated power at n = 42 per arm: 0.787 (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. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary comparison as a two-sided t-test with p <0.05. It does not post a numerical sponsor estimate or confidence interval. A simple unadjusted recalculation from the posted summary statistics gives a mean difference of -14.2 mg and an unadjusted p-value of 0.042, with a recalculated confidence interval also posted alongside the results.

The record flags a discrepancy between the sponsor analysis and the recalculation. Accordingly, the sponsor’s own analysis takes precedence. The recalculation is useful as a transparent check based on the posted group means, standard deviations, and sample sizes, but it is not a correction to the sponsor’s analysis. Because the registry does not give the sponsor’s detailed computation or numerical interval, the source of the discrepancy is not reported in the registry record and should not be guessed.

The broad sponsor p-value threshold and the recalculated numerical p-value both indicate the reported direction of statistical evidence, but they are not identical reporting formats. The comparison should retain that distinction rather than presenting the recalculation as the sponsor’s exact result.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists seven outcome measures and seven analyses, and the posted record includes multiple secondary measures. Testing several outcomes can create a multiplicity problem: in general, the more comparisons made, the greater the opportunity for a nominally unusual result to arise by chance. A prespecified strategy for selecting a primary endpoint and handling additional comparisons can help readers interpret a family of tests. The multiplicity strategy is not reported in the registry record.

The primary result should therefore be distinguished from secondary analyses. The sponsor’s primary test is reported as a two-sided t-test with p <0.05, while the posted secondary analyses have their own reported p-values. Whether the sponsor adjusted any results for multiple testing is not reported in the registry record. The unadjusted recalculations should not be interpreted as multiplicity-adjusted evidence.

Missing-data procedures and analysis populations are also not reported in the registry record. The posted arm counts describe the participants represented in the outcome summaries, but the record does not explain whether every randomized participant contributed to each analysis, how missing measurements were handled, or whether the analysis followed an intention-to-treat principle. No assumptions about these procedures can be made from the posted summaries alone.

The detailed statistical plan, covariate adjustments, interim analyses, and rules for handling protocol deviations are not reported in the registry record. These omissions do not establish that such methods were absent; they mean the record does not document them. Interpretation is therefore limited to the reported endpoints, group summaries, and identified sponsor test, with caution about unreported analysis choices.

16. Safety Results

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

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 zero serious adverse events among 14 participants at risk in the Conventional Pressure arm and zero among 27 participants at risk in the Low Pressure (VTI) arm. These figures describe the serious adverse event counts posted for the trial; they do not show that the risk of serious events is absent. With a limited number of participants, an observed count of zero still leaves uncertainty about events that could occur in a larger group or under different circumstances.

For other adverse events, the record reports 3 among 14 participants at risk in the Conventional Pressure arm and 2 among 27 at risk in the Low Pressure (VTI) arm. The registry does not provide the event terms for these other events in the posted information. Deaths are not reported in the registry record, and no serious adverse event terms are listed.

These are descriptive counts. They should be read in relation to the numbers at risk and to the limits of the registry’s adverse-event detail, rather than as a definitive comparison of safety between arms.

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

The posted primary data show a lower mean of intra-operative narcotic use in the Low Pressure (VTI) arm than in the Conventional Pressure arm. The recalculated mean difference is -14.2 mg, and the sponsor reports a two-sided t-test with p <0.05. Because the registry flags a discrepancy, the sponsor’s own analysis takes precedence over the simple recalculation.

This result answers a specific statistical question about group mean narcotic use during surgery. It does not directly answer whether post-operative narcotic use differed, because post-operative use is not the primary endpoint reported. It also does not by itself establish a difference in subjective pain or mean ETCO2. The posted secondary results do not provide clear evidence of differences for those measures, and the registry does not report all secondary outcome results.

In general, a statistically unusual result is not automatically clinically important. Clinical importance depends on the size of the difference, the outcome’s meaning to patients and clinicians, the quality of measurement, and a threshold for meaningful change. A threshold of clinical importance is not reported in the registry record. The reported group averages also do not imply that every participant experienced the same change or direction of difference.

The trial was randomized, which is relevant to how a treatment comparison is designed, but the registry record does not provide enough detail to assess all aspects of implementation, missing data, or analysis. The results should be understood within the enrolled trial population and the intervention contrast actually recorded: VTI at a 10mmHg target pressure versus conventional insufflation at a 15mmHg target pressure. The record does not isolate the contribution of the device from the difference in target pressure.

Overall, the posted result is a trial-specific estimate with uncertainty and a flagged discrepancy between the sponsor analysis and a simple recalculation. It is not a guarantee of an individual outcome and should not be generalized beyond the measured endpoint and study population using these data alone.

18. Why This Trial Matters Statistically

This trial illustrates why an endpoint’s time window and definition matter. The stated study purpose concerns post-operative pain and narcotic need, while the posted primary endpoint measures intra-operative morphine equivalents. Those outcomes are related to the broader clinical question but are not the same measure. Keeping them distinct prevents a statistical result for one period from being treated as evidence about another.

The record also makes clear that a point estimate, a test result, and precision convey different information. The mean difference describes the estimated contrast in mg, the t-test result summarizes evidence against a null model, and a confidence interval describes uncertainty in the recalculated contrast. None alone establishes clinical importance. The registry does not report a threshold for a clinically meaningful change.

Another statistical lesson is the need to distinguish sponsor-reported analyses from recalculations based on summary data. The posted discrepancy flag means the sponsor’s analysis takes precedence, even though a recalculation can help readers understand the contrast from the group summaries. This distinction supports transparent interpretation without treating a calculation from summary statistics as if it were the trial’s complete analysis.

Finally, the study’s limited enrollment and the availability of only some secondary results constrain what can be learned from the record. Planning illustrations show how assumed effect size and desired power affect sample size, but they do not reconstruct the original design or represent observed power. Together, these considerations make the trial useful for statistical interpretation while keeping conclusions closely tied to the posted evidence.

19. 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 leaves several trial-specific details unavailable. It does not report the original sample-size justification, the intended analysis population, missing-data procedures, or whether all randomized participants contributed to each outcome. The allocation is described as randomized, single-masked, and parallel, but the record does not identify who was masked or provide further details about randomization and allocation concealment.

The primary outcome is intra-operative narcotic use, although the stated study purpose also refers to post-operative pain and narcotic need. The primary endpoint therefore does not directly measure all of the stated aims. The VTI intervention and lower target pressure are combined in the treatment contrast, so the posted comparison cannot separate the contribution of the system from the pressure difference.

The record flags a discrepancy between the sponsor analysis and the recalculation from posted summary statistics. The sponsor’s analysis takes precedence, but the registry does not provide a numerical sponsor estimate or confidence interval, or explain the discrepancy. This limits independent evaluation of the sponsor result’s precision.

Only some secondary results are posted, and the registry lists repeated subjective pain outcomes. The multiplicity strategy and complete secondary analysis plan are not reported. Adverse-event details are also limited: serious adverse events are recorded as counts, but event terms are not listed; other adverse-event terms and deaths are not reported in the registry record. These limitations restrict interpretation to the available summaries and do not establish what procedures or events were absent.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Reducing Operative and Post-operative Morbidity in Living Kidney Donors With the Airseal System — NCT02262039.
• Registry record last updated 2018-01-17; status last verified 2018-01.
• Results first posted 2016-12-23.
• 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.

23. Record Summary

NCT02262039 is a completed randomized, single-masked, parallel-group trial sponsored by Yale University. It enrolled 41 participants undergoing laparoscopic living kidney donor surgery. The comparison was conventional insufflation with a 15mmHg target pressure versus valveless recirculating insufflation (VTI) with a 10mmHg target pressure.

The primary outcome was mean total morphine equivalents in mg during the operation on the day of surgery. The sponsor reports a two-sided t-test with p <0.05. A discrepancy is flagged between that analysis and the simple unadjusted recalculation, so the sponsor’s own analysis takes precedence. The registry also posts some secondary outcome and adverse-event summaries, but details of the original sample-size plan, missing-data handling, multiplicity strategy, and analysis populations are not reported in the registry record.