This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Comparing 4.0 mg.Kg-1 Sugammadex With Placebo in the Reversal of Profound Neuromuscular Blockade (P05767) (NCT00758485), a randomized phase 3 study. The primary outcome is Time From Start of Administration of Investigational Medicinal Product (IMP, Sugammadex or Placebo) to Recovery of the Fourth Twitch/First Twitch (T4/T1) Ratio to 0.9.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00758485 |
| Phase | Phase 3 |
| Condition | Anesthesia, Neuromuscular Blockade |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Single |
| Enrollment | 140 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Merck Sharp & Dohme LLC |
| Results posted | Yes |
2. Clinical Question
Population
Adults scheduled for elective surgery requiring profound neuromuscular blockade induced by rocuronium. The primary endpoint population was the Intent-to-Treat population: participants who received sugammadex or placebo and had at least one efficacy measurement. The registry reports an enrollment of 140.
Intervention
Sugammadex 4.0 mg.kg-1, administered after the last dose of rocuronium when blockade had reached the target depth of 1-2 Post Tetanic Count (PTC).
Comparator
Placebo, identified as 0.9% sodium chloride (NaCl), administered at the same target depth of blockade after the last dose of rocuronium.
Primary question
How much time elapsed from the start of the investigational medicinal product administration until the T4/T1 ratio recovered to 0.9, and how did the posted geometric-mean recovery times compare between the randomized groups?
The endpoint concerns a monitored physiological response after reversal, rather than a patient-reported outcome or a measure of operating-room duration. The registry describes the target ratio as the minimum acceptable level indicating complete recovery from neuromuscular blockade. It also identifies operating-room and post-anesthetic care unit length of stay as aims of the trial, but the posted result details do not include results for those aims.
3. Trial Design
The registry describes a Phase 3, randomized, single-masked, parallel-group trial. Its official title specifies that the safety assessor was blinded. The registry does not report further details about who was masked, how masking was maintained, or how the random allocation sequence was generated. Those aspects of the design are not reported in the registry record.
The trial enrolled adults scheduled for surgery requiring profound neuromuscular blockade. Blockade was induced with rocuronium, and the assigned study product was given after the last rocuronium dose when the target blockade depth was 1-2 PTC. The intervention was sugammadex 4.0 mg.kg-1; the comparator was placebo (0.9% NaCl). The trial’s stated aim was to assess recovery of the T4/T1 ratio, safety, and operating-room and post-anesthetic care unit length of stay.
The registry lists 140 enrolled participants. For the primary endpoint, the posted group summaries are based on an ITT population defined as participants who received either study product and had at least one efficacy measurement. The group summaries report 69 participants for sugammadex and 65 for placebo. These endpoint-population counts should be read in the context of that stated analysis definition, rather than as a description of every enrolled participant.
The primary endpoint was time from the start of investigational medicinal product administration to recovery of the T4/T1 ratio to 0.9. The registry also lists time to recovery to 0.7 and 0.8 as secondary outcomes. It does not report detailed eligibility criteria, the randomization procedure, the full masking procedures, or the protocol’s sample-size justification. The registry lists the trial as completed.
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
| Stage | Sugammadex | Placebo |
|---|---|---|
| STARTED | 70 | 70 |
| TREATED | 69 | 68 |
| COMPLETED | 69 | 67 |
| NOT COMPLETED | 1 | 3 |
Reasons for not completing this period:
| Reason | Sugammadex | Placebo |
|---|---|---|
| Lost to Follow-up | 0 | 1 |
| Not Treated | 1 | 2 |
Analysis population for the primary outcome, as defined in the registry: The Intent-to-Treat (ITT) Population consisted of all participants who received either Sugammadex or Placebo and had at least one efficacy measurement. Imputed recovery times were used in cases of missing times.
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.
| Characteristic | Unit | Sugammadex | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 69 | 68 | 137 | |
| Age, Continuous | years | 57 (SD 17) | 57 (SD 14) | 57 (SD 16) |
| Sex: Female, Male: Female | Participants | 21 | 25 | 46 |
| Sex: Female, Male: Male | Participants | 48 | 43 | 91 |
6. Primary Endpoint
The registry lists the primary outcome as Time From Start of Administration of Investigational Medicinal Product (IMP, Sugammadex or Placebo) to Recovery of the Fourth Twitch/First Twitch (T4/T1) Ratio to 0.9, measured over From Start of IMP Administration to Recovery of the T4/T1 Ratio to 0.9 (estimated from ~2 minutes up to ~90 minutes).
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | minutes |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint measures elapsed time from the start of study-product administration until the T4/T1 ratio reached the recovery threshold of 0.9. T4 and T1 are the heights of the fourth and first muscle twitches, respectively, after train-of-four electrical stimulation. In the trial, stimulation was applied to the ulnar nerve and twitch responses were assessed at the adductor pollicis muscle. A higher T4/T1 ratio indicates greater recovery from neuromuscular blockade.
The ratio provides a defined physiological marker for recovery, while the elapsed time captures how quickly that marker is reached. A shorter time corresponds to faster recovery on this specific endpoint; it does not, by itself, describe every aspect of a participant’s recovery or experience. The registry describes 0.9 as the minimum acceptable ratio indicating complete recovery from blockade. It also states that twitch responses were recorded until the ratio reached >=0.9.
The endpoint is summarized as a geometric mean in minutes with a 95% confidence interval. A geometric mean is a summary suited to measurements represented on a multiplicative scale, such as positive elapsed times that may be skewed. The registry’s timeframe describes recovery time as estimated from ~2 minutes up to ~90 minutes. Missing recovery times were imputed according to the endpoint population description. The exact imputation procedure is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted geometric mean time to recovery of the T4/T1 ratio to 0.9 was 2.2 minutes for sugammadex, with a 95% confidence interval from 1.9 to 2.5 minutes. For placebo, the posted geometric mean was 89.8 minutes, with a 95% confidence interval from 80.1 to 100.7 minutes. The endpoint summaries therefore describe substantially different observed recovery times in these randomized groups. These are descriptive results for the specified endpoint and analysis population; the registry entries do not include a reported between-group test or p-value.
The confidence intervals indicate the uncertainty around each group’s estimated geometric mean under the analysis used. They are not ranges containing every participant’s recovery time, nor do they describe the full spread of individual observations. The intervals also do not substitute for a direct treatment-effect estimate with its own confidence interval. No such contrast is reported in the registry record.
The geometric-mean summaries are based on the stated ITT population: participants who received study product and had at least one efficacy measurement. The registry says imputed recovery times were used when times were missing, but does not give the number of imputed values or the imputation method. Interpretation therefore depends on the analysis definition and its handling of missing times, details that are only partly described in the record.
The registry’s primary endpoint is a monitored physiological threshold, not a direct measure of operating-room or post-anesthetic care unit length of stay. Although those durations are named among the trial aims, their results are not reported in the registry record details. The listed secondary outcomes concern recovery to T4/T1 ratios of 0.7 and 0.8, but numerical results for those outcomes are not included in the registry record used for this interpretation.
The estimates describe this trial’s groups and endpoint. They should not be extended to outcomes, populations, dosing approaches, or settings that are not described in the record. The posted values show the estimated times and their precision as expressed by the confidence intervals; they do not establish the size or certainty of every possible clinical consequence. The registry record does not report a formal statistical comparison, a prespecified analysis plan, or a clinically meaningful difference threshold.
9. Statistical Methods Explained
The primary endpoint is a time measurement, but the registry summarizes it using a geometric mean rather than an arithmetic mean. General statistical explanation: an arithmetic mean adds observed values and divides by their count, whereas a geometric mean works through multiplicative relationships. It is often useful for positive measurements that are right-skewed or naturally interpreted proportionally. This choice affects how the center of the data is described; it does not imply that individual recovery times were identical or close to the group summary.
The sugammadex geometric mean is 2.2 minutes, and the placebo geometric mean is 89.8 minutes. Each estimate is accompanied by a 95% confidence interval: 1.9 to 2.5 minutes for sugammadex, and 80.1 to 100.7 minutes for placebo. General statistical explanation: a confidence interval represents uncertainty in an estimated quantity under the assumptions of the method. It is not a prediction interval for individual participants. Its width reflects precision, but interpretation also depends on the analysis, measurement process, and assumptions used to construct it. The registry does not state the method used to calculate these intervals.
Time to a threshold is interpretable as elapsed time until a defined event: reaching the T4/T1 ratio of 0.9. In general, time-to-event methods can account for participants whose event time is not observed during follow-up, often called censoring. However, the registry’s primary endpoint is reported as a geometric mean and says imputed recovery times were used for missing times. It does not report whether any times were censored, how censoring was handled, or the imputation method. Those procedures should not be inferred from the endpoint’s time-based nature.
The endpoint population is described as ITT, comprising participants who received either study product and had at least one efficacy measurement. This is the registry’s operational definition; the label alone does not provide every detail of the analysis set. The endpoint population description also notes imputation for missing recovery times. The numbers of missing measurements and imputed times, the assumptions behind imputation, and any sensitivity analyses are not reported in the registry record.
The posted summaries are group-specific. A direct comparison would ordinarily estimate a contrast between groups and quantify uncertainty around that contrast, or report a test of a prespecified hypothesis. The registry entries contain no such comparison estimate, confidence interval for the contrast, or p-value. Comparing the two group summaries is informative descriptively, but it is not a replacement for a formally reported between-group analysis. The sponsor’s own analysis does not take precedence over a recalculation in this case because no discrepancy is identified; however, a recalculated treatment contrast is not included in the registry entries.
General statistical explanation: multiplicity arises when several outcomes or comparisons are tested, because repeated testing can increase the chance of at least one apparently unusual result. This trial has a primary endpoint and lists secondary recovery thresholds of 0.7 and 0.8. The registry entries do not describe a multiplicity adjustment or testing hierarchy. Without that information, the status of any secondary findings within a family of tests cannot be determined. Numerical results for the secondary endpoints are not included in the registry record used.
General statistical explanation: over-dispersion occurs when observed variation is greater than a statistical model expects. It can make standard errors too small if a model assumes less variability than the data contain. The registry entries do not identify an over-dispersion model or provide individual-level data to assess it. No claim about the presence or absence of over-dispersion can therefore be made for this trial.
The sample-size planning assumptions describe illustrations based on the observed effect, with two-sided significance level 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. Such figures are planning illustrations, not observed power and not evidence that the original trial was designed using those assumptions. The registry does not report the original sample-size justification. General statistical explanation: power is a design property conditional on a specified effect, variability, analysis, and significance level; calculating power from an observed effect after a trial does not establish the probability that the trial’s finding is true.
The posted summaries do not include a model specification, covariate adjustment details, a protocol-defined estimand, or a complete statistical analysis plan. The absence of those details limits reconstruction of the analysis and prevents independent assessment of choices such as transformations, outlier handling, and sensitivity analyses. Such details are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry describes a primary recovery endpoint and lists secondary outcomes for time to T4/T1 ratios of 0.7 and 0.8. Results for those secondary outcomes are not reported in the registry record details. The record does not state whether the primary and secondary outcomes were tested within a prespecified hierarchy, whether an adjustment for multiple testing was used, or how the overall type I error was controlled. A multiplicity strategy should not be inferred from the order in which endpoints are listed.
The endpoint population includes participants who received study product and had at least one efficacy measurement. The registry says imputed recovery times were used in cases of missing times. It does not report how many times were missing, the imputation method, or the assumptions made about missingness. Nor does it report sensitivity analyses evaluating alternative missing-data assumptions. These omissions matter because an imputed value contributes to the endpoint summary even though the underlying recovery time was not observed.
The record does not provide a detailed account of exclusions from the endpoint population, protocol deviations, or whether other analysis populations were used. It also does not report the statistical analysis plan, interim analyses, or the sample-size justification. Any of these details that are not described should be treated as not reported in the registry record, rather than assumed to have been absent from the trial conduct.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Sugammadex | 4 | 69 | 5.8% |
| Placebo | 4 | 68 | 5.9% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Sugammadex | 44 of 69 |
| Placebo | 48 of 68 |
Most frequent serious adverse event terms
| Event term | Organ system | Sugammadex | Placebo |
|---|---|---|---|
| Post Procedural Complication | Injury, poisoning and procedural complications | 1 of 69 | 1 of 68 |
| Post Procedural Haemorrhage | Injury, poisoning and procedural complications | 1 of 69 | 1 of 68 |
| Alcohol Withdrawal Syndrome | Psychiatric disorders | 1 of 69 | 0 of 68 |
| Lymphocele | Vascular disorders | 1 of 69 | 0 of 68 |
| Diverticular Perforation | Gastrointestinal disorders | 0 of 69 | 1 of 68 |
| Skin Laceration | Injury, poisoning and procedural complications | 0 of 69 | 1 of 68 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Sugammadex | Placebo |
|---|---|---|---|
| Procedural Pain | Injury, poisoning and procedural complications | 29 of 69 | 32 of 68 |
| Wound Complication | Injury, poisoning and procedural complications | 11 of 69 | 10 of 68 |
| Nausea | Gastrointestinal disorders | 9 of 69 | 11 of 68 |
| Headache | Nervous system disorders | 7 of 69 | 5 of 68 |
| Flatulence | Gastrointestinal disorders | 4 of 69 | 7 of 68 |
| Constipation | Gastrointestinal disorders | 6 of 69 | 4 of 68 |
| Vomiting | Gastrointestinal disorders | 5 of 69 | 5 of 68 |
| Pyrexia | General disorders | 4 of 69 | 4 of 68 |
| Sleep Disorder | Psychiatric disorders | 4 of 69 | 4 of 68 |
| Procedural Nausea | Injury, poisoning and procedural complications | 3 of 69 | 4 of 68 |
Serious events with the highest arm-level rate: post procedural complication (1.5%), post procedural haemorrhage (1.5%), diverticular perforation (1.5%), skin laceration (1.5%), alcohol withdrawal syndrome (1.4%).
The posted serious adverse event figures are 4 for sugammadex and 4 for placebo. The corresponding at-risk counts are 69 and 68. These are the registry’s group figures; they do not by themselves describe event timing, severity beyond the serious classification, relatedness to study product, or the number of events per affected participant. Those details are not reported in the registry record.
The record also lists other adverse event figures of 44 for sugammadex and 48 for placebo, with at-risk counts of 69 and 68, respectively. These figures should be read separately from the serious adverse event figures. The registry lists serious-event terms with percentages: Post Procedural Complication, Post Procedural Haemorrhage, Diverticular Perforation, and Skin Laceration are each listed as 1.5%; Alcohol Withdrawal Syndrome and Lymphocele are each listed as 1.4%. These listed terms do not establish causation by study product.
Deaths are not reported in the registry record. Safety counts alone do not provide a complete comparison of harms, particularly without definitions, follow-up details, event-level context, and a prespecified comparative analysis.
12. What the Result Does, and Does Not, Mean
The primary endpoint results describe time from study-product administration to recovery of the T4/T1 ratio to 0.9. The geometric mean was 2.2 minutes for sugammadex and 89.8 minutes for placebo, with the respective 95% confidence intervals of 1.9 to 2.5 minutes and 80.1 to 100.7 minutes. These figures express the posted group summaries and their uncertainty for the specified endpoint. They do not provide an individual participant’s expected recovery time.
The result is specific to the trial’s population and procedure: adults scheduled for elective surgery requiring profound rocuronium-induced blockade, treated at a target depth of 1-2 PTC. It also depends on the endpoint definition, the stated ITT population, and the use of imputed times where recovery times were missing. The record does not provide enough detail to assess the imputation assumptions or reconstruct the full analysis.
The endpoint is a monitored physiological recovery threshold. It is not a complete measure of recovery, and it does not directly report operating-room or post-anesthetic care unit length of stay, despite those outcomes being named among the trial aims. Results for those durations, as well as numerical results for the listed secondary endpoints, are not reported in the registry record details.
The posted group summaries do not include a treatment-effect estimate, a confidence interval for a between-group contrast, or a p-value. The registry entries also do not report a clinically meaningful difference threshold or a formal interpretation of the statistical evidence. The numerical separation between the group summaries should therefore be described as an observed difference in the posted estimates, not as a substitute for a reported inferential comparison.
The safety figures are also limited: the record lists serious and other adverse event counts and at-risk denominators, but not the additional context needed to assess timing, attribution, or event-level patterns. In general, trial results should be interpreted alongside design, analysis, missing data, and safety reporting. The available record supports a focused description of this endpoint and these safety figures, not conclusions about outcomes that were not reported.
13. Why This Trial Matters Statistically
This trial illustrates how a clinical endpoint can be tied to a physiological threshold and a clearly defined time origin. Starting the clock at investigational product administration and stopping it when the T4/T1 ratio reaches 0.9 gives the outcome a concrete interpretation: elapsed time to a specified recovery marker. That clarity is useful, but it also means the result answers a narrower question than overall recovery or length of stay.
The choice to report geometric means emphasizes a multiplicative summary of positive time measurements. Understanding that scale helps readers avoid treating the mean as a typical individual value or as a full description of variability. The confidence intervals add information about precision in the group estimates, while the absence of a reported contrast limits what can be said about formal between-group inference from the registry entries.
The endpoint population definition and imputation note are statistically important. A result can depend on which participants contribute measurements and on how missing times are handled. Here, the record states that imputation was used but does not give its method or extent. That makes the result interpretable at a high level while leaving important reproducibility questions unanswered.
The case also shows why endpoint multiplicity and planning need transparent reporting. Secondary recovery thresholds are listed, but their numerical results and the approach to multiple testing are not reported in the registry record. Sample-size planning illustrations based on an observed effect can help explore hypothetical design requirements, but they do not explain the original trial’s design or establish observed power. The original sample-size justification is not reported in the registry record.
14. 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 group-level geometric means and confidence intervals for the primary endpoint, but does not include a direct treatment-effect estimate, its confidence interval, or a p-value. It therefore supports a descriptive comparison of the posted summaries, not a complete account of the trial’s inferential analysis. The method used to calculate the confidence intervals is also not reported.
Missing-data information is limited. The endpoint definition states that imputed recovery times were used when times were missing, but the record does not give the number of missing times, the imputation procedure, or sensitivity analyses. The definition of the ITT population requires receipt of study product and at least one efficacy measurement, and the record does not provide further detail about exclusions or other analysis populations.
Although secondary outcomes for recovery to T4/T1 ratios of 0.7 and 0.8 are listed, numerical results are not reported in the registry record details. The record also does not give results for operating-room or post-anesthetic care unit length of stay, though these are included in the stated trial aims. A multiplicity plan, interim-analysis information, detailed statistical analysis plan, and sample-size justification are not reported in the registry record.
The design description identifies randomization, single masking, and a safety-assessor-blinded title, but does not provide the allocation-generation method or full masking procedures. Safety reporting includes group figures and selected serious-event terms, but lacks the event-level context needed to interpret timing and attribution. These limitations concern what the registry record reports; they should not be taken as evidence that unreported procedures or information did not exist elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Comparing 4.0 mg.Kg-1 Sugammadex With Placebo in the Reversal of Profound Neuromuscular Blockade (P05767) — NCT00758485.
- Registry record last updated 2015-08-21; status last verified 2015-08.
- Results first posted 2013-04-22.
- 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.
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18. Record Summary
NCT00758485 is a completed Phase 3 randomized, single-masked, parallel-group trial comparing sugammadex 4.0 mg.kg-1 with placebo (0.9% NaCl) after profound rocuronium-induced neuromuscular blockade. The registry reports enrollment of 140 and identifies adults scheduled for elective surgery as the study population.
The primary endpoint was time from study-product administration to recovery of the T4/T1 ratio to 0.9, summarized as a geometric mean with a 95% confidence interval. The posted estimates were 2.2 minutes (1.9 to 2.5) for sugammadex and 89.8 minutes (80.1 to 100.7) for placebo. The stated endpoint population included participants who received study product and had at least one efficacy measurement; imputed recovery times were used for missing times.
The registry also lists secondary recovery thresholds and safety figures. Detailed results for the secondary endpoints, a formal between-group test, the missing-time method, and the original sample-size justification are not reported in the registry record.