Investigation of Sugammadex in Outpatient Urological Procedures: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Investigation of Sugammadex in Outpatient Urological Procedures (NCT03138967), a randomized phase 4 study. The primary outcome is Muscle Recovery Time.

2. Clinical Question

The registry record describes a comparison of two approaches to reversing neuromuscular blockade during cystoscopy with bladder tumor resection. The main statistical question is whether average time from administration of the reversal agent to a train-of-four ratio of 0.9 differed between the sugammadex group and the neostigmine/glycopyrrolate group.

3. Trial Design

This was a randomized, double-masked, parallel-group Phase IV study sponsored by M.D. Anderson Cancer Center. The registry records enrollment of 54 and a completed study. The start date is 2017-09-18, and primary completion is recorded as 2018-09-01.

The two groups received sugammadex or neostigmine/glycopyrrolate to reverse muscle relaxation induced with rocuronium. The registry describes participants and the surgeon as unaware of assignment, while the anesthesiologist and study staff knew the assignment. It also labels the study double-masked. Further details on implementation of masking are not reported in the registry record.

The primary endpoint was measured intraoperatively, up to 3 hours. The registry lists postoperative complications through up to 7 days and overall recovery time up to 3 hours after the end of surgery as secondary outcomes. It describes participants as being followed for up to 1 week after cystoscopy. The record does not report the number screened, participant flow by group, reasons for withdrawal, or the analysis population.

The primary outcome summaries list 25 participants in each group. The record does not explain how those outcome records relate to the enrollment figure or provide a participant disposition account. No protocol, original statistical analysis plan, or sample-size justification is 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.

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 Muscle Recovery Time, measured over Intraoperatively, up to 3 hours.

The primary endpoint, muscle recovery time, is a continuous measure recorded in minutes. It is defined as the time from administration of the neuromuscular blockade reversal agent until the train-of-four ratio reaches 0.9. The registry describes measurement during the intraoperative period, up to 3 hours.

This endpoint quantifies the interval until a specified measure of neuromuscular recovery is reached. Using a defined threshold gives the outcome a common operational stopping point across participants, while measuring the interval in minutes preserves information about how long recovery took rather than reducing it to a yes-or-no result. The endpoint is directly related to the study's comparison of reversal approaches; it is not itself a measure of postoperative complications or overall recovery.

The posted summaries report group means and standard deviations. They therefore describe average recovery time and variation around that average, rather than the full distribution of individual times. The registry record does not report additional details about how measurements were obtained, whether assessors were masked, or how values were handled if the threshold was not reached within the observation period.

7. Results Posted in the Registry

• Suggamadex or Treatment Group: mean 2.00 versus 9.24 on control; difference -7.24 (95% CI -10.34 to -4.14), standardized effect d = -1.30; z-test p = <0.001.

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.

PostOperative Complications

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Suggamadex or Treatment Group: 20.0% (5/25) versus 28.0% (7/25) on control; risk difference -8.0 percentage points (95% CI -31.6 to 15.6), risk ratio 0.71 (0.26–1.95); unadjusted two-proportion z-test p = 0.508.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Suggamadex or Treatment Group and the control. The interval gives the range of effects that remain compatible with the data.

Overall Recovery Time

• 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:
  • Suggamadex or Treatment Group: mean 2.08 versus 2.47 on control; difference -0.39 (95% CI -1.26 to 0.48), standardized effect d = -0.25; z-test p = 0.383.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Suggamadex or Treatment Group and the control. The interval gives the range of effects that remain compatible with the data.

The two secondary endpoints address different aspects of recovery: postoperative complications capture whether participants experienced recorded events, while overall recovery time summarizes a duration after surgery. Their estimates point toward lower observed values in the sugammadex group, but both comparisons are imprecise and their confidence intervals include zero. In contrast, the primary endpoint's interval excludes zero. Taken together, the posted pattern is stronger for the specifically measured intraoperative muscle-recovery interval than for a broader change in postoperative course.

That pattern should not be read as proof that the primary finding necessarily translates into fewer complications or shorter overall recovery. The endpoints measure different outcomes over different observation periods, and the registry does not report a causal pathway analysis linking them. The secondary results also have less statistical weight because the record provides no reported secondary analyses beyond unadjusted comparisons and does not describe a strategy for accounting for multiple outcomes.

When several outcomes are examined, unadjusted p-values do not account for the increased chance of finding a nominally unusual result somewhere among the comparisons. The secondary estimates are useful descriptive evidence, but they are not a substitute for a prespecified, multiplicity-aware analysis. Their uncertainty and the absence of reported analysis details call for a cautious reading rather than a single overall conclusion about recovery.

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

• PostOperative Complications
• Overall Recovery Time

9. Statistical Interpretation

10. Statistical Methods Explained

The registry presents continuous outcomes as means with standard deviations, and the primary comparison as a mean difference. For the primary endpoint, the contrast is sugammadex minus neostigmine/glycopyrrolate. A negative mean difference therefore corresponds to a lower observed average in the sugammadex group. For a time outcome, a lower average means a shorter observed interval to the specified measurement threshold; it does not imply that all individual times were lower.

What does a confidence interval describe?

A confidence interval expresses the uncertainty around an estimated group difference under the method's assumptions. Its endpoints mark a range of values compatible with the observed data and that procedure. An interval that excludes zero is evidence of a difference under those assumptions; an interval that includes zero does not rule out either a difference in one direction or a difference in the other direction. The interval does not give the probability that the true effect lies within its endpoints, and it does not capture every source of uncertainty, such as bias from missing data or departures from the analysis plan.

Why does variation matter?

The standard deviation describes how dispersed individual measurements are around the group mean. The primary outcome's reported standard deviations differ substantially between groups. A pooled standard deviation, when used to express a standardized effect or to inform planning calculations, compresses group variation into a shared quantity. That summary can be less representative when the groups have quite different spreads. Over-dispersion is a general concern when outcome variation exceeds what a model assumes: standard errors and intervals can then be too optimistic if the model does not accommodate that extra variation. The registry record does not report a variance-adjusted or alternative model for this endpoint.

How should the p-value be read?

A p-value measures how unusual data at least as inconsistent with a specified no-difference hypothesis would be under the test's assumptions. It is not the probability that the null hypothesis is true, a measure of clinical importance, or a measure of the chance that the result will replicate. The primary comparison has an unadjusted p < 0.001. The secondary p-values are also unadjusted, and the registry record does not report whether or how multiple comparisons were handled.

What is the difference between risk and mean contrasts?

Postoperative complications are reported as counts of participants and compared with a risk difference. That contrast is a difference between the proportions in the two groups, while the primary and overall recovery-time comparisons use differences between means. These measures answer different questions and have different uncertainty structures. A risk difference near zero means the observed proportions are similar; a confidence interval spanning zero leaves uncertainty about the direction of the underlying difference.

The posted continuous comparisons include standard deviations and mean differences, while the complication comparison includes a risk difference and a p-value. No adjusted analysis or secondary-outcome analysis is reported in the registry record. The calculations and summaries should therefore be interpreted as unadjusted group comparisons, not as estimates adjusted for participant characteristics or other outcomes. The record does not specify a model, covariate set, or detailed test procedure for the primary comparison.

11. Confidence Intervals and Precision

The primary mean difference is -7.24 minutes, with a 95% confidence interval from -10.34 to -4.143 minutes. The interval lies below zero, and its width conveys the remaining uncertainty around the estimated difference. Although the estimate is relatively precise about direction under the stated comparison, the interval still allows a range of possible magnitudes. It is an uncertainty interval for the mean contrast, not a range expected to contain most individual participants' recovery times.

Precision differs across outcomes. For postoperative complications, the risk-difference interval extends across zero, as does the interval for overall recovery time. Those intervals are compatible with differences in either direction as well as little or no difference. Their p-values, 0.508 and 0.383, respectively, likewise do not provide strong evidence against a no-difference hypothesis under the unadjusted comparisons. The confidence interval for overall recovery time runs from -1.26 to 0.484 hours; the complication interval's exact endpoints are not repeated.

Precision depends on both the amount of information and outcome variability. The primary outcome's standard deviations differ considerably between groups, so a single pooled spread should be interpreted with that contrast in mind. Confidence intervals also do not account for all possible sources of uncertainty: the registry does not report missing-data methods, adjusted analyses, or the original analysis plan. The posted intervals describe uncertainty conditional on the calculations used, not certainty about bias or generalizability.

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 for each outcome; none of these outcomes is a time-to-event endpoint reported as a total number of events. Each row considers a stated fraction of the observed effect: 100%, 75%, or 50%. The figures are illustrations based on the observed group contrast, not the trial's original design calculation. The original design assumptions and sample-size justification are not reported in the registry record.

The listed planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Under these assumptions, the 80% power column gives the estimated number of participants per arm for a design with an 80% chance of detecting the specified effect if that effect were the true one. The 90% power column uses a higher target chance of detecting that effect, and therefore generally requires more participants per arm. These are planning probabilities, not observed power; the figures are not observed power.

Smaller effects are harder to distinguish from random variation, so planning for a smaller fraction of the observed effect requires more participants per arm. The figures should not be treated as evidence that the trial was or was not adequately designed: the planning method uses the observed effect, which is uncertain, and the registry does not report the assumptions used to design the original study.

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 = -7.240; pooled standard deviation σ = 5.587.
2. n = 2 × (1.96 + 0.842)² × 5.587² / -7.240² = 9.3, rounded up to 10 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 <- -7.24                      # observed difference in means
sigma <- 5.58749364652883                     # 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(3138967)
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 = 10 (80% power), 13 (90% power)
 75% of observed effect: n per arm = 17 (80% power), 23 (90% power)
 50% of observed effect: n per arm = 38 (80% power), 51 (90% power)
power.t.test: 10.4 
Simulated power at n = 10 per arm: 0.775 (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

The registry record does not report a statistical plan describing which outcomes were confirmatory, how many hypotheses were to be tested, or whether multiplicity would be controlled. The primary endpoint is identified, but no family-wise or false-discovery procedure is described. The posted secondary comparisons have unadjusted p-values; no adjustment is reported. Therefore, those p-values should be interpreted as individual comparisons and not as evidence that a prespecified set of outcomes met a joint statistical criterion.

The record also does not report how missing outcome data were handled, whether imputation was used, or whether results were based on an intention-to-treat, per-protocol, or other analysis population. Participant flow, exclusions from each outcome analysis, and reasons for missing measurements are not reported in the registry record. Enrollment is listed as 54, while the primary outcome summaries list 25 participants in each group; the record does not explain the relationship between enrollment and the outcome counts.

Other analysis details are not reported, including covariate adjustment, assumptions checks, handling of protocol deviations, and any interim analyses. These omissions do not establish that such methods were or were not used; they mean that the posted record does not permit a reader to evaluate them. The absence of a reported analysis plan also makes it difficult to distinguish planned analyses from analyses selected after outcomes were observed.

Because the primary comparison is unadjusted and the secondary findings are also unadjusted, the results are best read as posted group summaries with their stated uncertainty. They do not answer whether conclusions would change under other missing-data assumptions, alternative models, or multiplicity adjustment.

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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: stroke (4.0%).

The adverse-event summary lists 0 participants with serious adverse events in the sugammadex group and 1 in the neostigmine/glycopyrrolate group. Other adverse events were reported for 5 and 6 participants, respectively. Deaths are listed as 0 and 1. The registry lists Stroke at 4.0% as the top serious adverse-event term.

These are descriptive counts from a small study and should not be treated as a comparative safety test. The registry record does not report event-level narratives, timing, severity details beyond the serious-event classification, or whether events were judged related to treatment. It also does not explain the denominator or method underlying the percentage attached to the listed serious term. The counts alone cannot establish a cause or distinguish chance variation from a reliable group difference.

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

The primary result describes a shorter observed mean time to the specified train-of-four threshold in the sugammadex group than in the neostigmine/glycopyrrolate group. The reported mean difference and confidence interval quantify that comparison for the participants represented in the posted outcome summaries. They do not show the distribution of every participant's experience, and they do not establish that the same contrast would occur in other settings or populations.

The result does not by itself answer whether differences in muscle recovery time lead to differences in postoperative complications, overall recovery, or other outcomes. The secondary comparisons are uncertain, and the registry does not report adjusted analyses or a multiplicity strategy. Nor does a small p-value measure clinical importance or guarantee that a finding is free from bias.

Random assignment supports a comparative interpretation, but the registry record does not provide enough information to assess participant flow, missing measurements, adherence, or the full analysis plan. The results should therefore be understood as the posted summaries for this completed study, rather than as a complete account of every design and analysis decision. They are evidence about the recorded endpoints in this trial, not a recommendation about which reversal approach to use.

17. Why This Trial Matters Statistically

This trial illustrates why endpoint definition matters in biostatistics. The primary outcome is not a broad notion of recovery: it is a measured interval from administration of a reversal agent to a defined train-of-four threshold. That specificity makes the group contrast interpretable, while also limiting the conclusion to that particular physiological measure and measurement period.

It also illustrates the distinction between a statistically clear primary contrast and less precise secondary comparisons. A confidence interval that excludes zero for one endpoint does not imply that every related outcome will differ or that a broad clinical benefit has been demonstrated. Reporting estimates and intervals alongside p-values helps show both direction and uncertainty.

The substantial difference between the primary outcome's group standard deviations is a reminder that model assumptions and variance summaries deserve attention. The secondary outcomes and safety counts further show why small studies can leave wide uncertainty around less frequent or more variable outcomes. Finally, the registry's lack of reported multiplicity, missing-data, and analysis-population details limits a full statistical audit. These features make the trial useful for learning how to separate an endpoint-specific result from stronger claims than the record supports.

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 trial-specific limitations constrain interpretation. The outcome summaries list 25 participants per group, while enrollment is recorded as 54; the registry does not provide participant flow or explain this difference. Without that account, readers cannot determine from the record whether all enrolled participants contributed to each endpoint or how exclusions and missing observations were handled.

The primary outcome's standard deviations differ markedly between groups. A comparison based on means remains interpretable as a descriptive contrast, but a shared pooled-variation summary may not fully represent both groups. The registry does not report alternative variance methods or checks that would clarify sensitivity to this difference.

The secondary outcomes have confidence intervals that include zero, and the registry does not report multiplicity adjustment. These outcomes therefore provide limited precision for distinguishing a group difference from no difference. Safety information is also limited to summary counts and a listed serious-event term, without event narratives, attribution, or a reported comparative safety analysis.

The record does not report participant demographics, detailed eligibility criteria, the original statistical analysis plan, missing-data methods, or adjusted analyses. Those gaps limit assessment of representativeness, analysis decisions, and robustness. The follow-up periods and outcome definitions are recorded, but further measurement and adjudication details are not reported in the registry record.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Investigation of Sugammadex in Outpatient Urological Procedures — NCT03138967.
• Registry record last updated 2020-09-22; status last verified 2020-09.
• Results first posted 2019-07-26.
• 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

NCT03138967 is a completed randomized, double-masked, parallel-group Phase IV study sponsored by M.D. Anderson Cancer Center. It compared sugammadex with neostigmine/glycopyrrolate for reversal of rocuronium-associated muscle relaxation in outpatient cystoscopy with bladder tumor resection. Enrollment is listed as 54.

The primary endpoint was intraoperative time in minutes from reversal-agent administration to a train-of-four ratio of 0.9. The posted primary comparison favors a shorter observed mean interval in the sugammadex group, with a confidence interval excluding zero. Secondary comparisons are less precise, and the record does not report multiplicity adjustment, missing-data handling, or a full analysis plan.