Sugammadex Versus Neostigmine for Reversal of Rocuronium Neuromuscular: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sugammadex Versus Neostigmine for Reversal of Rocuronium Neuromuscular (NCT03322657), a randomized phase 4 study. The primary outcome is Time in Minutes to Reach Train of Four (TOF) Ratio ≥ 0.9 After the Administration of Reversal Agent.

2. Clinical Question

The clinical question is about the speed of measured neuromuscular recovery following reversal, rather than a broad comparison of all aspects of anesthesia or procedural outcomes. The registry describes TOF measurements taken repeatedly after administration of the reversal drug, until the threshold was reached or the stated observation limit was reached. A faster time to the threshold would correspond to earlier measured recovery on this outcome; it should not be treated as a direct measure of every aspect of respiratory recovery or overall clinical status.

The record also lists time to extubation and changes in diaphragmatic contractility during sniffing and deep breathing as secondary outcomes. Those outcomes address related but distinct questions. Their presence does not change the primary endpoint, and they cannot by themselves establish the full clinical consequences of differences in TOF recovery.

3. Trial Design

The registry describes a completed, randomized, double-masked, parallel-group phase 4 study sponsored by The Cleveland Clinic. It lists 69 participants enrolled and two treatment groups: neostigmine with glycopyrrolate and sugammadex. The brief summary says half of participants would receive each regimen. The posted primary outcome results list 33 participants in the neostigmine-with-glycopyrrolate group and 35 in the sugammadex group. The reason the outcome group counts do not account for the full enrollment is not reported in the registry record.

Both regimens were administered at the end of surgery. The neostigmine regimen included glycopyrrolate, whereas sugammadex was administered as a single listed regimen. This is a comparison of the named reversal strategies as recorded, not a comparison of either drug in isolation from the rest of the perioperative care.

The registry lists the study start as 2017-11-14 and primary completion as 2020-12-31, with overall status recorded as completed. It identifies the condition areas as neuromuscular blockade and anesthesia. The posted study type is “other”; further detail about how that classification relates to the trial design is not reported in the registry record.

Randomization is intended to reduce systematic differences between treatment groups at the start of a trial. Double masking is intended to limit the influence of treatment knowledge on participant care or outcome assessment. The registry record does not describe the randomization procedure, allocation concealment, which individuals were masked, or whether masking was maintained. It also does not report the protocol’s sample-size justification or other design assumptions. These details cannot be inferred from the randomized and double-masked labels alone.

The outcome denominators vary across the posted results. The primary outcome groups list 33 and 35 participants, while the diaphragmatic outcomes list 28 and 29. Reasons for these different analysis counts, and the analysis population definitions, are not reported in the registry record. Those differences matter when considering how broadly each estimate applies to all enrolled participants.

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 Time in Minutes to Reach Train of Four (TOF) Ratio ≥ 0.9 After the Administration of Reversal Agent, measured over within 90 minutes after endotracheal extubation.

The primary endpoint measures the time from administration of the reversal agent until a train-of-four ratio of at least 0.9 is reached. TOF is a measure of neuromuscular response to repeated stimulation. In this trial, the ratio served as a measurable threshold for recovery after reversal of rocuronium-associated block. The record says TOF was measured continuously every 12 seconds from administration of the reversal drug until the threshold was reached or until 90 minutes after administration.

A time-to-event endpoint retains information about how quickly an event occurs, rather than reducing the outcome to whether the threshold was reached at one selected time. The reported median is the time by which half of the observed group’s times to threshold are at or below that value, subject to the endpoint’s analysis and censoring. The 95% confidence interval expresses uncertainty around the reported median; it is not a range containing 95% of individual participants’ recovery times.

The registry’s timeframe wording refers to reaching the threshold “within 90 minutes after endotracheal extubation,” while its endpoint description says measurements continued until 90 minutes after administration of the reversal agent. These are different reference points. Which wording governed the analysis is not reported in the registry record. The outcome description also does not give further detail about handling participants who did not reach the threshold during observation.

This endpoint is a physiological measure of recovery time. It does not directly measure every clinically important consequence of reversal, and it should not be read as a complete measure of respiratory function or procedural recovery.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a time-to-event outcome: time from reversal-agent administration to reaching a TOF ratio of at least 0.9. Time-to-event methods account for both the timing of the event and the fact that some participants may not have a recorded event before observation ends. The registry reports continuous TOF measurement every 12 seconds and a limit of 90 minutes after administration. It does not report how any observations without a recorded threshold event were handled in the analysis.

What does the median time describe?

A median is the central point of a distribution: half of the observed times are at or below it and half are at or above it, subject to the details of the time-to-event estimation. Unlike a mean, it is not strongly driven by unusually long times. The primary group medians are reported with 95% confidence intervals. A confidence interval represents the uncertainty in an estimated group quantity under the statistical method; it is not an interval expected to contain a stated proportion of individual participants’ times.

The registry reports 8 minutes with a 95% confidence interval of 6 to 10 minutes for neostigmine with glycopyrrolate, and 3 minutes with a 95% confidence interval of 2 to 3 minutes for sugammadex. The intervals describe each group median separately. They should not be treated as a formal confidence interval for the difference between medians.

How should the hazard ratio be read?

The Cox proportional hazard model compares event rates over time. A hazard is the rate of an event at a given time among participants who have not yet experienced it. The reported hazard ratio of 3.8, with a 95% confidence interval of 2.2 to 6.5 and p < 0.001, indicates a higher rate of reaching the threshold in the sugammadex group as interpreted by the registry’s superiority analysis. The hazard ratio is not an absolute time difference and does not mean each participant’s recovery time is multiplied or divided by that value.

The Cox model is commonly interpreted under a proportional-hazards assumption: the relative event rate between groups is assumed to remain reasonably stable over time. The registry names the model but does not report diagnostic checks or other information on whether this assumption was assessed. It also does not report additional details about censoring or the model’s covariate structure. Those aspects of the analysis cannot be evaluated from the registry record.

What do p-values and confidence intervals contribute?

A p-value assesses how compatible the observed data are with a specified null hypothesis under the analysis model. 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 primary p-value is reported as less than 0.001. The confidence interval complements it by indicating a range of effect estimates compatible with the data and method, while retaining uncertainty about the true effect.

For the primary hazard ratio, the reported interval is entirely above 1, the value corresponding to equal hazards. That supports the direction of the reported comparison under the model. The interval’s width also matters: it shows that the hazard ratio is estimated with uncertainty, rather than known exactly. Neither a small p-value nor an interval excluding the null addresses unreported issues such as missing data, outcome measurement, or model fit.

Why do the recalculations differ from the sponsor analyses?

The recalculated secondary comparisons are simple, unadjusted calculations from the posted group summaries. They do not substitute for the sponsor’s own analyses, which are reported as two-sided t-tests on final values. Summary-statistic calculations can differ from the sponsor’s result because the estimand, analysis population, or implementation may differ; the registry record does not establish which explanation applies. The registry marks no discrepancy, so the posted sponsor analyses remain the reported analyses, while the recalculations should be understood as a separate check based on the available summaries.

The reported secondary p-values are not adjusted for multiple comparisons in the information available. An unadjusted p-value treats that comparison as if it were considered on its own. When several endpoints or analyses are examined, the chance of seeing at least one apparently notable result by chance can increase. The registry does not report a multiplicity adjustment or a prespecified hierarchy for the secondary outcomes.

How should sample-size illustrations be understood?

Planning illustrations based on an observed effect describe hypothetical future study sizes under stated assumptions; they are not evidence about the power of the completed trial. The record describes the illustrations as using a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect set to a stated fraction of the observed effect. For time-to-event planning, the quantities refer to total events; for other outcomes, they refer to participants per arm.

Because the observed effect itself is uncertain, planning directly from it can give an overly optimistic impression of the size of a future effect. Smaller target effects require larger studies under the stated planning framework. The illustrations do not establish the trial’s original design rationale: its own sample-size justification is not reported in the registry record. They must not be interpreted as observed power or as evidence that the completed study was adequately powered for every endpoint.

10. Analyses Reported by the Sponsor

The sponsor’s primary result is a Cox proportional hazard analysis, reporting a hazard ratio of 3.8 with a 95% confidence interval of 2.2 to 6.5 and p < 0.001. This is the trial’s reported primary inferential analysis. The registry does not identify a recalculated primary comparison that would replace it.

For the secondary diaphragmatic outcomes, the sponsor reports two-sided t-tests of mean differences in final values. For sniffing, the reported mean difference is 0.33, with a 95% confidence interval from -0.35 to 1.00 and p = 0.21. The unadjusted recalculation from the posted summaries has the same point estimate, but its interval and p-value differ somewhat. Both analyses are compatible with uncertainty about whether the group difference is zero.

For deep breathing, the sponsor reports a mean difference of 0.82, with a 95% confidence interval from -0.18 to 1.81 and p = 0.04. The recalculation from the posted summary statistics gives a different interval and p-value, with its interval not crossing zero. The registry does not explain the difference. Since the registry does not flag a discrepancy, the recalculated result should be read as an unadjusted check rather than a correction to the sponsor’s analysis. The contrast between these results is another reason not to treat an isolated secondary p-value as conclusive.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcomes and analyses, including a primary time-to-TOF-threshold endpoint and secondary measures of extubation and diaphragmatic contractility. It does not report whether the secondary outcomes were tested under a prespecified hierarchy, whether any multiplicity adjustment was used, or how the overall family of statistical tests was defined. Consequently, the reported secondary p-values should be read as unadjusted unless the registry record states otherwise.

Multiplicity matters because each additional statistical test creates another opportunity for a result to appear unusual by chance under its null hypothesis. An unadjusted p-value does not account for that broader set of tests. This does not make a secondary finding meaningless, but it does mean that isolated nominal significance carries less confirmatory weight when the testing plan is unknown. The primary endpoint is identified as primary, but the statistical plan and details of any decision rules are not reported in the registry record.

Missing-data handling is also not described in sufficient detail. The primary outcome lists 33 participants in one group and 35 in the other; the diaphragmatic outcomes list 28 and 29. The registry does not explain why the analysis counts differ, how missing observations were handled, or whether the analysis followed an intention-to-treat, per-protocol, or other population definition. Reasons for the difference between enrollment and the primary outcome group counts are not reported in the registry record.

The record also does not report whether any interim analyses were planned or conducted, whether there were stopping rules, or how the final analysis was selected. The protocol’s sample-size justification is not reported in the registry record. These omissions do not establish that the analyses were inappropriate; they limit the ability to judge prespecification, potential selection, and the impact of missing outcomes. Conclusions about robustness should therefore remain bounded by the information available in the registry.

12. 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 5% reporting threshold.

The registry lists zero participants with serious adverse events in the neostigmine-with-glycopyrrolate group and zero in the sugammadex group. It also lists zero participants affected by other adverse events in each group, and zero deaths in each group. The serious adverse event terms list is empty.

These are counts recorded in the registry, not proof that no adverse events occurred outside the definitions, collection period, or reporting procedures used for the trial. The registry record does not report further detail about the safety observation period, event definitions, ascertainment methods, or whether all randomized participants contributed to safety follow-up. The listed group counts are 33 and 35 participants at risk for the adverse-event summaries.

With no reported events in these summaries, a comparative estimate of relative event frequency cannot be inferred from the counts alone. Zero recorded events also does not establish equal safety between groups or exclude uncommon harms. These figures describe what was posted for this trial and should be interpreted within the limits of the registry’s safety reporting.

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

The primary result indicates that, in the posted analysis of this randomized trial, the time to reach a TOF ratio of at least 0.9 was shorter in the sugammadex group than in the neostigmine-with-glycopyrrolate group. The group medians and Cox model provide complementary descriptions: the medians summarize central times, while the hazard ratio compares rates of reaching the threshold over follow-up.

The result does not mean that every participant in one group recovered faster than every participant in the other. Group summaries cannot describe each person’s experience, and the hazard ratio does not state a fixed reduction in time for an individual. The endpoint is a measured neuromuscular threshold, not a complete measure of respiratory function, extubation, complications, or the quality of procedural recovery.

The randomized design supports a between-group comparison, but interpretation remains limited by the details not reported in the registry record. These include the analysis population definitions, reasons for differing outcome counts, handling of missing data, model diagnostics, and the full statistical plan. The registry’s differing timeframe descriptions for the primary endpoint also leave uncertainty about the precise reference point used in the analysis.

The secondary findings do not remove those limits. They address different outcomes, are not reported with a stated multiplicity strategy, and include a recalculated result that differs from the sponsor’s reported secondary analysis. The registry does not report a numerical result for time to extubation. The safety summaries record no events in the listed categories, but those counts alone cannot establish that risks are absent or equivalent.

Accordingly, the evidence supports a difference in the posted primary measure for these trial participants under the reported analysis. It does not establish the magnitude of benefit across all clinical outcomes, nor does it determine how the result applies outside the studied setting. The registry record does not report enough detail to settle those broader questions.

14. Why This Trial Matters Statistically

This trial illustrates why endpoint type matters in clinical research. The primary outcome is not simply whether a TOF threshold was reached; it is how long reaching that threshold took. A time-to-event analysis uses the timing of the event and can account for observations that end before the event is recorded, although the registry does not describe how such observations were handled.

It also demonstrates why medians and hazard ratios should not be interchanged. The median describes a central time, while the hazard ratio summarizes a relative event rate over follow-up under the Cox model. Both can contribute to interpretation, but neither alone describes the distribution of every participant’s recovery time or the clinical consequences of the measured threshold.

The record offers a useful contrast between a clearly identified primary analysis and multiple secondary outcomes. Secondary results can help assess whether findings are consistent across related measures, but unadjusted tests require caution when the number and hierarchy of analyses are not reported. The difference between the sponsor’s deep-breathing result and an unadjusted recalculation also shows why an analysis based on summary statistics is not automatically a replacement for the trial’s own analysis.

Finally, registry transparency shapes what can be concluded. Enrollment, analysis denominators, and outcome-specific results are not identical in the posted record, while explanations of missing data and analysis populations are absent. Recognizing these limits is part of statistical interpretation: a result can be informative for its stated endpoint while still leaving important questions about robustness, precision, and generalizability unresolved.

15. 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 does not describe the randomization sequence, allocation concealment, or which participants, clinicians, and assessors were masked. The labels randomized and double-masked convey important design features, but do not provide enough detail to assess how they were implemented or maintained.

The primary endpoint timeframe is described with two different reference points: one wording refers to 90 minutes after extubation, while the measurement description refers to 90 minutes after administration of the reversal agent. The record does not clarify which definition governed the analysis. Handling of participants who did not reach the TOF threshold during observation is also not reported.

Outcome counts differ across the primary and secondary analyses, and the record does not explain the reasons. It does not identify the analysis populations, describe missing-data methods, or establish whether all enrolled participants were included in each analysis. This limits assessment of selection and the extent to which outcome-specific estimates represent the randomized groups.

For the primary Cox analysis, the record does not report model diagnostics or details about the proportional-hazards assumption, censoring, or covariate adjustment. It also does not provide the protocol’s sample-size justification, interim-analysis information, or a complete statistical plan. The absence of these details in the registry is not evidence that procedures were not undertaken, but it prevents independent evaluation from the record alone.

The secondary outcomes are numerous relative to the information about multiplicity, and the deep-breathing sponsor result differs from the simple unadjusted recalculation. The registry does not explain that difference. Numerical results for the listed extubation outcome are not reported in the registry record. Safety counts are likewise limited by the absence of further detail about follow-up duration and event ascertainment.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Sugammadex Versus Neostigmine for Reversal of Rocuronium Neuromuscular — NCT03322657.
• Registry record last updated 2021-11-16; status last verified 2021-10.
• Results first posted 2021-04-08.
• 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.

19. Record Summary

NCT03322657 is a completed, randomized, double-masked, parallel-group phase 4 study sponsored by The Cleveland Clinic. It enrolled 69 participants having catheter-based neurointerventional procedures. The comparison was sugammadex versus neostigmine with glycopyrrolate for reversal of rocuronium neuromuscular block.

The primary endpoint was time to a TOF ratio of at least 0.9 after reversal-agent administration. The registry reports shorter median time in the sugammadex group and a Cox hazard ratio of 3.8, with a 95% confidence interval of 2.2 to 6.5 and p < 0.001. Secondary outcomes include extubation timing and changes in diaphragmatic contractility. The registry record does not report the numerical extubation result, and it does not provide enough information to resolve missing-data, analysis-population, or multiplicity questions.