Pharmacokinetic-pharmacodynamic Analysis of Sugammadex in Children: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacokinetic-pharmacodynamic Analysis of Sugammadex in Children (NCT03943888), a randomized phase 2 study. The primary outcome is Neuromuscular Recovery.

2. Clinical Question

The trial focused on pharmacokinetic and pharmacodynamic analysis in children receiving general anesthesia and rocuronium. The registry describes plasma concentration measurement for sugammadex and monitoring of neuromuscular blockade. The posted primary endpoint is time to recovery of the train-of-four ratio to 90%, reported in minutes.

The central comparison is the mean recovery time in each sugammadex group against the 2mg/kg group, which is the reference used in the posted recalculated contrasts. A separate posted comparison places conventional reversal against that same reference. These are summaries of recovery timing, not a complete account of the study’s pharmacokinetic objectives: plasma concentrations are listed as a secondary outcome, while detailed concentration results are not reported in the registry record.

The record identifies the participants as pediatric but does not describe their ages, clinical characteristics, or the settings in which the endpoint was monitored. It also does not report a clinically important difference in recovery time. The results therefore address the measured timing outcome as recorded, without establishing what size of difference would matter clinically.

3. Trial Design

This was a randomized, parallel-group phase 2 study. The registry record lists the study as completed, with enrollment of 40. It identifies Seoul National University Hospital as the sponsor. The study start date is 2019-08-12 and the primary completion date is 2020-02-20.

The record describes four groups: sugammadex 2mg/kg, sugammadex 4mg/kg, sugammadex 8mg/kg, and conventional reversal with atropine and neostigmine. Each posted results group has 10 participants. The three sugammadex regimens and the conventional reversal regimen were administered 15 minutes after rocuronium administration, according to the arm descriptions.

Masking is listed as none. Thus, the registry characterizes the study as unmasked; it does not report whether outcome assessment or data analysis used any separate masking procedures. Allocation is listed as randomized, but the randomization method, allocation concealment procedures, and stratification factors are not reported in the registry record.

The primary outcome is the time, in minutes, to recovery of the train-of-four T4/T1 ratio to 90%. Its timeframe is described as up to 30 minutes to 1 hour. The secondary outcome listed is plasma concentrations. The registry record does not provide detailed methods for sampling, assay procedures, or the analysis of concentration data.

The trial is described as a pharmacokinetic-pharmacodynamic analysis of reversal of rocuronium-induced neuromuscular blockade by sugammadex in children. The record does not report the original statistical analysis plan, the rationale for the enrollment target, the intended primary contrast, or the basis for selecting the stated follow-up window. These omissions limit reconstruction of the study’s original design decisions.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Neuromuscular Recovery, measured over up to 30 minutes to 1 hour.

The primary endpoint is time to recovery of the train-of-four T4/T1 ratio to 90%, measured in minutes after administration of sugammadex or a conventional neuromuscular reversal agent. The train-of-four ratio is a measure of neuromuscular response; reaching the specified threshold gives a defined point at which recovery time can be recorded. The registry describes monitoring of neuromuscular blockade and gives the endpoint timeframe as up to 30 minutes to 1 hour.

Time to a threshold is useful for describing how quickly a measured physiologic response reaches a prespecified level. It produces a time-based outcome that can be summarized by a mean and standard deviation, as in the posted results. Here, the group means describe average recovery times, while the standard deviations indicate how dispersed individual times were around each mean.

That summary does not show the full distribution of recovery times, nor does it indicate whether every participant reached the threshold within the stated timeframe. The registry record does not report censoring rules, handling of participants who did not reach the threshold, or details of endpoint measurement. Those details affect how a time-to-threshold outcome should be interpreted, particularly when a mean and standard deviation are reported rather than a full time-to-event analysis.

The endpoint is a measured pharmacodynamic outcome. It does not, by itself, describe other clinical outcomes or establish what difference in recovery time would be important to patients or clinicians. The registry record does not report a threshold for clinical importance.

7. Results Posted in the Registry

• Sugammadex 4mg: mean 3.10 versus 5.70 on control; difference -2.60 (95% CI -5.58 to 0.38), standardized effect d = -0.77; z-test p = 0.087.
• Sugammadex 8mg: mean 1.10 versus 5.70 on control; difference -4.60 (95% CI -7.58 to -1.62), standardized effect d = -1.35; z-test p = 0.002.
• Conventional Reversal: mean 43.70 versus 5.70 on control; difference 38.00 (95% CI 20.28 to 55.72), standardized effect d = 1.88; z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports continuous endpoint summaries as means with standard deviations. A mean is the arithmetic average of observed values. A standard deviation describes how spread out those values are around the mean. General statistical explanation: the standard deviation describes variation among individual observations, whereas the standard error describes uncertainty in an estimated mean. A group can have a wide spread of individual recovery times while the uncertainty in its mean depends on both that spread and the group size.

What does a mean difference represent?

The posted comparisons express the difference in average recovery time between a comparison group and the 2mg/kg sugammadex reference group. Negative estimates for the 4mg/kg and 8mg/kg comparisons indicate lower reported means in those groups; the positive estimate for conventional reversal indicates a higher reported mean. The unit is minutes. These values are labelled recalculated because they are unadjusted calculations from the posted summary statistics. The registry record does not report a sponsor-generated analysis for these contrasts.

A mean difference is expressed on the original measurement scale, which makes it directly interpretable as a difference in average minutes. It does not describe the difference for every participant. It also does not show whether the group distributions overlap or whether particular observations strongly influence the mean.

How should a confidence interval be read?

General statistical explanation: a confidence interval gives a range of estimates compatible with the data and the calculation procedure, expressing uncertainty about the population difference. A narrower interval indicates greater precision than a wider interval, but an interval does not assign a probability to a particular fixed value after the data have been observed. For a mean difference, an interval containing zero includes no difference among the values compatible with the calculation; an interval not containing zero indicates that zero is outside that range. The interval does not by itself measure clinical importance.

For 4mg/kg versus 2mg/kg, the posted interval includes zero. For 8mg/kg versus 2mg/kg and conventional reversal versus 2mg/kg, the posted intervals exclude zero. These intervals accompany unadjusted recalculations, and the registry record does not report multiplicity adjustment. They should not be interpreted as adjusted inferential results.

What do the p-values convey?

General statistical explanation: a p-value describes how incompatible the observed data are with a specified null model, assuming that model and the calculation assumptions hold. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The posted p-values are unadjusted: 0.087 for 4mg/kg versus 2mg/kg, 0.002 for 8mg/kg versus 2mg/kg, and < 0.001 for conventional reversal versus 2mg/kg.

A p-value should be considered together with the point estimate, confidence interval, study design, group size, and variability. A larger p-value does not prove equivalence, and a smaller p-value does not establish that a difference matters clinically. The registry record does not report the sponsor’s hypothesis-testing procedure, including whether it used covariate adjustment or a different variance assumption.

Why does variability matter?

The group standard deviations are 4.7 minutes for 2mg/kg, 1.0 minute for 4mg/kg, 1.0 minute for 8mg/kg, and 28.2 minutes for conventional reversal. The conventional reversal group has notably more spread in the posted summary than the sugammadex groups. General statistical explanation: greater dispersion usually makes a group mean less precise when the group size is unchanged, because the observed values provide a less stable estimate of the group average. Unequal variability can also make the behavior of a comparison depend on the assumptions of the method used.

The recalculated comparisons use pooled standard deviations as posted. General statistical explanation: a pooled standard deviation combines information about variation across the compared groups under a common-variance model. If the groups have different underlying variability, that common-variance assumption may not represent both groups well. The registry record does not report the sponsor’s method or whether it evaluated unequal-variance alternatives. The recalculated values are therefore best treated as a transparent summary-based comparison rather than a substitute for a documented trial analysis.

What can be concluded from these calculations?

The calculations describe differences in posted group means and their uncertainty under the stated recalculation approach. Because they are unadjusted, they do not account for the presence of several comparisons. They also cannot address missing outcome values, participant-level covariates, or features of the endpoint distribution that are not captured by group means and standard deviations. The analysis populations and missing-data procedures are not reported in the registry record. No claim about the sponsor’s original statistical plan can be made from these recalculations.

10. Confidence Intervals and Precision

The confidence intervals quantify uncertainty around the recalculated mean differences, not around each group’s individual recovery times. For sugammadex 4mg/kg versus 2mg/kg, the interval includes zero and the estimate is -2.6 minutes. This leaves substantial uncertainty about the direction and size of the mean difference. The unadjusted p-value is 0.087; that value does not establish equivalence or prove there is no difference.

For 8mg/kg versus 2mg/kg, the estimated difference is -4.6 minutes, with an interval from -7.578 to -1.622. For conventional reversal versus 2mg/kg, the estimate is 38.0 minutes, with an interval from 20.28 to 55.72. These intervals exclude zero under the posted unadjusted calculations. Their widths show that the estimates still have uncertainty, particularly for the conventional reversal comparison.

Each group contains 10 participants. The standard deviation in the conventional reversal group is 28.2 minutes, compared with 4.7 minutes in the 2mg/kg group and 1.0 minute in each of the other sugammadex groups. This spread helps explain why the conventional reversal contrast has a broad interval. General statistical explanation: estimates from small groups can be sensitive to individual observations, and variation in the observed values affects how precisely a mean difference can be estimated.

The intervals are not reported as sponsor-adjusted results; they are recalculated from the posted summaries. The registry record does not report multiplicity adjustment, missing-data handling, or a prespecified analysis population. Accordingly, these intervals describe precision under the recalculation, not all uncertainty arising from the study’s design or reporting.

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 table and curve are planning illustrations based on the observed effect, not the trial’s original design assumptions. The figures are participants per arm, not total events. The listed calculation 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 to 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 gives the number of participants per arm that the planning calculation estimates would be needed for an 80% chance of detecting the selected effect under those assumptions. The 90% power column gives the corresponding estimate for a 90% chance. These are prospective planning quantities, not a measure of what the completed study achieved.

For the 4mg/kg comparison, planning for 100% of the observed effect gives 27 participants per arm for 80% power and 36 for 90% power. Planning for 75% gives 48 and 64, while planning for 50% gives 108 and 144. For the 8mg/kg comparison, the corresponding entries are 9 and 12 for 100%, 16 and 21 for 75%, and 35 and 46 for 50%. For conventional reversal, the entries are 5 and 6 for 100%, 8 and 11 for 75%, and 18 and 24 for 50%.

Smaller effects require more participants under these assumptions, because a smaller difference is harder to distinguish from sampling variation. These planning values are not observed power: observed power is not an appropriate summary of the uncertainty in the completed trial results.

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 = -2.600; pooled standard deviation σ = 3.398.
2. n = 2 × (1.96 + 0.842)² × 3.398² / -2.600² = 26.8, rounded up to 27 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 <- -2.6                      # observed difference in means
sigma <- 3.3977934016064                     # 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(3943888)
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 = 27 (80% power), 36 (90% power)
 75% of observed effect: n per arm = 48 (80% power), 64 (90% power)
 50% of observed effect: n per arm = 108 (80% power), 144 (90% power)
power.t.test: 27.8 
Simulated power at n = 27 per arm: 0.784 (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 posted recalculated results include comparisons of each of the 4mg/kg, 8mg/kg, and conventional reversal groups against the 2mg/kg group. The reported p-values are unadjusted. The registry record does not report a multiplicity plan, such as how the family of comparisons was defined or whether any adjustment was intended. When several comparisons are examined, the chance of at least one apparently unusual result can be affected by the number of tests. General statistical explanation: multiplicity procedures are used in some analyses to account for that issue, but the appropriate approach depends on the study’s planned questions and analysis plan. No adjustment should be inferred.

The registry record does not report the original statistical analysis plan, prespecified analysis populations, or procedures for handling missing endpoint measurements. It is therefore unclear from the record whether the posted group summaries include all randomized participants, only participants with measured endpoint data, or another analysis set. The listed group sizes are 10 per arm, but those counts alone do not establish how missing values, protocol deviations, or participants who did not reach the recovery threshold were handled.

The record lists a primary endpoint and a secondary outcome of plasma concentrations, but detailed methods for the secondary outcome are not reported in the registry record. It also does not report interim analyses or stopping rules. These omissions prevent a full assessment of how outcomes were selected, whether analyses were prespecified, or how incomplete measurements were treated.

The posted contrasts are recalculations from summary statistics and are not a substitute for a trial analysis based on participant-level data. They do not adjust for baseline characteristics, account for missing observations, or apply a reported multiplicity procedure. The record does not report whether the sponsor conducted other analyses or how any such analyses were specified.

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.

The registry reports serious adverse events, other adverse events, and deaths by group. For each of the four groups, the serious adverse event count is 0 among 10 participants at risk. The other adverse event count is also 0 among 10 participants at risk in each group. The death count is 0 in every group.

These are the counts recorded in the registry. They describe what was reported for the listed groups and should not be read as proof that no adverse events of any kind occurred. The registry record does not provide event terms, a detailed observation period, the method used to collect events, or information about events not classified in the reported categories. The absence of listed serious-event terms is consistent with the reported zero counts, but does not add detail about ascertainment.

Small group sizes limit how much can be learned about uncommon events from these counts. General statistical explanation: when a study observes no events, the result still leaves uncertainty about the underlying event frequency, especially when the number observed is limited. These safety summaries are descriptive and do not support a broader safety comparison or conclusion about risk.

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

The posted results describe average time to reach the specified neuromuscular recovery threshold in four randomized groups. The mean times were 5.7 minutes for 2mg/kg sugammadex, 3.1 minutes for 4mg/kg, 1.1 minutes for 8mg/kg, and 43.7 minutes for conventional reversal. The recalculated comparisons indicate that the mean was lower for the 8mg/kg group and higher for conventional reversal than for the 2mg/kg reference; the 4mg/kg comparison has an interval that includes zero.

These findings do not establish what size of difference is clinically important. The registry record does not report such a threshold, and a difference in average recovery time does not by itself establish a difference in other outcomes. The record also does not report detailed participant characteristics, so it is not possible to judge how well these results apply to children with different characteristics or in other clinical settings.

The trial was randomized, but the record does not report the randomization procedure or allocation concealment. It is listed as unmasked. The summary-based contrasts are unadjusted recalculations, and the registry does not report a multiplicity strategy, missing-data methods, or the original statistical analysis plan. Those limits matter when interpreting the apparent strength and precision of the comparisons.

The adverse-event entries show zero reported serious and other adverse events, and zero deaths, in each group. These counts are limited by the group sizes and by the event information reported in the registry. They should not be interpreted as evidence that uncommon risks are absent.

Overall, the posted information supports a description of observed group means, their variability, and unadjusted summary-based contrasts. It does not establish the full pharmacokinetic results, a complete clinical benefit-risk assessment, or the sponsor’s original inferential conclusions.

16. Why This Trial Matters Statistically

This trial illustrates how a pharmacodynamic endpoint can be framed as a measurable time to a defined recovery threshold. That makes the outcome interpretable in minutes and allows group means to be compared on the original scale. It also highlights why the summary should include more than a mean: the standard deviations show that recovery times varied substantially, particularly in the conventional reversal group.

The results also show the distinction between an effect estimate and the uncertainty around it. The 4mg/kg comparison has a negative mean difference, but its interval includes zero. The 8mg/kg comparison has an interval that excludes zero, as does the conventional reversal comparison. The p-values alone do not express the size of the differences or their clinical importance; the estimates and intervals provide essential context.

With only 10 participants in each group, the results are sensitive to the precision available from small groups. Unequal variation across arms is another statistical consideration, especially for comparisons involving conventional reversal. A documented analysis plan and participant-level results would help readers evaluate model assumptions, missing outcomes, and any multiplicity adjustments.

The study also provides a useful example of why planning calculations must be kept separate from trial findings. The sample-size illustrations use fractions of the observed effect and stated calculation assumptions; they do not show the study’s original sample-size rationale or its achieved power. Together, these features make the registry a case study in interpreting descriptive summaries and recalculated contrasts without overstating what they establish.

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 enrolled pediatric population. An age range, baseline characteristics, eligibility criteria, and relevant clinical subgroups are not reported in the registry record. This restricts assessment of how broadly the posted results apply.

The outcome is described as time to a train-of-four ratio of 90%, with a timeframe of up to 30 minutes to 1 hour, but the record does not explain measurement frequency, monitoring procedures, or how participants who did not reach the threshold were handled. Without those details, the endpoint’s full distribution and the treatment of incomplete observations cannot be reconstructed.

The study is listed as unmasked, and the record does not describe masking of outcome assessment or analysis. Randomization is reported, but its method and allocation concealment are not. The original statistical analysis plan, sample-size rationale, analysis populations, missing-data methods, and multiplicity procedures are not reported in the registry record.

The posted comparisons are unadjusted recalculations from group summaries, with 10 participants in each group. They do not use participant-level information and cannot account for unreported covariates, missing outcomes, or sensitivity to individual values. The reported standard deviations also vary notably between groups, especially for conventional reversal.

The registry record lists plasma concentrations as a secondary outcome but does not provide detailed results or methods for that analysis. Adverse-event reporting is limited to group counts, without event terms or a detailed account of ascertainment. These limitations narrow interpretation to the posted recovery-time summaries and reported event counts.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Pharmacokinetic-pharmacodynamic Analysis of Sugammadex in Children — NCT03943888.
• Registry record last updated 2022-11-14; status last verified 2022-10.
• Results first posted 2022-11-14.
• 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 record describes a completed, randomized, parallel-group phase 2 study of sugammadex reversal of rocuronium-induced neuromuscular blockade in children under general anesthesia. Enrollment is listed as 40, and the four groups each have 10 participants in the posted results. The trial was unmasked and sponsored by Seoul National University Hospital.

The primary endpoint was time in minutes to recovery of the train-of-four T4/T1 ratio to 90%. Posted means ranged from 1.1 minutes in the sugammadex 8mg/kg group to 43.7 minutes in the conventional reversal group. Summary-based contrasts are unadjusted recalculations; the registry record does not report the original statistical analysis plan.

The record lists plasma concentrations as a secondary outcome and reports zero serious adverse events, zero other adverse events, and zero deaths in each group. It does not report detailed pharmacokinetic results, analysis populations, missing-data procedures, or multiplicity methods.