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 Efficacy, Safety, and Pharmacokinetics of Sugammadex for Reversal of Neuromuscular Blockade (NMB) in Pediatric Participants (MK-8616-089) (NCT03351608), a randomized phase 4 study. The primary outcome is Area Under the Plasma Concentration-Time Curve (AUC) From Dosing to Infinity (AUC0-∞) of Sugammadex [Part A].
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03351608 |
| Phase | Phase 4 |
| Condition | Neuromuscular Blockade |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 288 |
| Arms in the primary outcome | 6 |
| Lead sponsor | Merck Sharp & Dohme LLC |
| Results posted | Yes |
2. Clinical Question
Population
Pediatric participants with neuromuscular blockade induced by rocuronium or vecuronium. Part A reports pharmacokinetic groups for ages 2 to <6 years, 6 to <12 years, and 12 to <17 years. The age range for Part B is not reported in the registry record.
Intervention
Sugammadex was given as a single intravenous bolus at 2 mg/kg or 4 mg/kg. Part A examined both doses across the reported age groups; Part B included both doses.
Comparator
In Part B, the active comparator was a single intravenous bolus of neostigmine, 50 μg/kg up to a 5 mg maximum dose, with either glycopyrrolate or atropine. Part A has no neostigmine arm in the posted primary outcome.
Primary question
The registry’s posted primary outcome asks how much sugammadex exposure occurs from dosing to infinity, measured by the plasma concentration-time area under the curve in Part A. The trial summary also states an efficacy hypothesis about whether sugammadex is superior to neostigmine for reversing moderate blockade, measured by time to a train-of-four ratio of ≥0.9. Results for that recovery-time comparison are not reported in the registry record.
These are related but distinct questions. The primary posted outcome is pharmacokinetic: it describes drug exposure, rather than the speed of neuromuscular recovery or a clinical benefit. The efficacy hypothesis described in the trial summary concerns time to a specified train-of-four recovery threshold. The distinction matters when interpreting the posted results: exposure values alone do not answer whether one reversal regimen leads to faster recovery.
The registry describes evaluation of reversal of both moderate and deep blockade, with blockade induced by either rocuronium or vecuronium. It lists two secondary outcomes in Part B: time to recovery to a train-of-four ratio of ≥0.7 and time to recovery to ≥0.8. Numerical findings for these secondary recovery outcomes are not reported in the registry record.
3. Trial Design
This is a Phase 4, randomized, triple-masked, parallel-group, active comparator-controlled clinical trial. The registry reports enrollment of 288 participants and a completed status. The start date is 2018-02-12, and the primary completion date is 2020-01-28. Merck Sharp & Dohme LLC is listed as the sponsor.
The trial is organized into Part A and Part B. Part A concerns sugammadex pharmacokinetics. Its posted primary outcome separates participants receiving sugammadex 2 mg/kg or 4 mg/kg into age groups of 2 to <6 years, 6 to <12 years, and 12 to <17 years. The outcome population is participants with ≥5 post-dosing samples available. The posted Part A pharmacokinetic group sizes are not all identical, and these outcome-specific counts need not represent the trial’s overall enrollment.
Part B includes sugammadex 2 mg/kg, sugammadex 4 mg/kg, and neostigmine with either glycopyrrolate or atropine. The neostigmine regimen is a single intravenous bolus containing 50 μg/kg, up to a 5 mg maximum dose, together with glycopyrrolate 10 μg/kg or atropine sulfate 20 μg/kg. The registry lists recovery time to train-of-four ratios of ≥0.7 and ≥0.8 as secondary Part B outcomes. The trial summary states a primary efficacy hypothesis for recovery to a ratio of ≥0.9, but results for that comparison are not reported in the registry record.
The allocation ratio, detailed randomization procedures, masking roles, and reasons for the Part A and Part B group sizes are not reported in the registry record. The record also does not report the protocol’s sample-size justification or whether any interim analyses were planned. These omissions limit assessment of how the reported group sizes relate to the original design.
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 | Part A: Sugammadex 2 mg/kg | Part A: Sugammadex 4 mg | Part B: Sugammadex 2 mg/kg | Part B: Sugammadex 4 mg/kg | Part B: Neostigmine + (Glycopyrrolate or Atropine) |
|---|---|---|---|---|---|
| STARTED | 19 | 23 | 35 | 176 | 35 |
| Treated | 18 | 22 | 33 | 169 | 34 |
| COMPLETED | 18 | 21 | 32 | 168 | 33 |
| NOT COMPLETED | 1 | 2 | 3 | 8 | 2 |
Reasons for not completing this period:
| Reason | Part A: Sugammadex 2 mg/kg | Part A: Sugammadex 4 mg | Part B: Sugammadex 2 mg/kg | Part B: Sugammadex 4 mg/kg | Part B: Neostigmine + (Glycopyrrolate or Atropine) |
|---|---|---|---|---|---|
| Lost to Follow-up | 0 | 1 | 1 | 1 | 1 |
| Physician Decision | 1 | 0 | 0 | 2 | 1 |
| Randomized by mistake, no treatment given | 0 | 0 | 0 | 1 | 0 |
| Withdrawal by parent/guardian | 0 | 0 | 1 | 1 | 0 |
| Other | 0 | 1 | 1 | 3 | 0 |
Analysis population for the primary outcome, as defined in the registry: All participants with ≥5 post-dosing samples available are included.
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 | Part A: Sugammadex 2 mg/kg | Part A: Sugammadex 4 mg | Part B: Sugammadex 2 mg/kg | Part B: Sugammadex 4 mg/kg | Part B: Neostigmine + (Glycopyrrolate or Atropine) | Total |
|---|---|---|---|---|---|---|---|
| Participants analysed | 19 | 23 | 35 | 176 | 35 | 288 | |
| Age, Continuous | years | 7.1 (SD 4.7) | 7.2 (SD 5.0) | 7.9 (SD 4.4) | 7.9 (SD 4.4) | 8.7 (SD 4.4) | 7.9 (SD 4.4) |
| Age, Customized: Children (2-11 years) | Participants | 15 | 17 | 25 | 132 | 25 | 214 |
| Age, Customized: Adolescents (12-17 years) | Participants | 4 | 6 | 10 | 44 | 10 | 74 |
| Sex: Female, Male: Female | Participants | 11 | 12 | 20 | 95 | 18 | 156 |
| Sex: Female, Male: Male | Participants | 8 | 11 | 15 | 81 | 17 | 132 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 1 | 0 | 0 | 0 | 1 |
| Race (NIH/OMB): Asian | Participants | 0 | 2 | 3 | 5 | 2 | 12 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 2 | 1 | 2 | 0 | 6 |
| Race (NIH/OMB): White | Participants | 16 | 17 | 30 | 161 | 33 | 257 |
| Race (NIH/OMB): More than one race | Participants | 2 | 1 | 0 | 4 | 0 | 7 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 1 | 4 | 0 | 5 |
6. Primary Endpoint
The registry lists the primary outcome as Area Under the Plasma Concentration-Time Curve (AUC) From Dosing to Infinity (AUC0-∞) of Sugammadex [Part A], measured over 2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Geometric Coefficient of Variation |
| Unit | hr*μg/mL |
| Endpoint classification | not reduced to a single comparison |
The posted primary endpoint is the area under the plasma concentration-time curve for sugammadex from dosing to infinity, abbreviated AUC0-∞, expressed in hr*μg/mL. It represents the area beneath the measured plasma concentration-versus-time profile and is a measure of drug exposure. The record says that this outcome was determined in each Part A arm and reports geometric means with geometric coefficients of variation.
Concentrations were scheduled at 2 minutes, 15 min, 30 min, 60 min, 4-6 hours, and 10 hrs post-dose. The outcome population includes participants with ≥5 post-dosing samples available. The registry does not report how missing concentration measurements were handled or how the profile was extended from observed measurements to infinity.
In general, pharmacokinetic exposure measures help describe how much drug is present in the body over time. They are not themselves measures of recovery speed. AUC0-∞ therefore addresses the trial’s pharmacokinetic objective, while the stated efficacy hypothesis concerns the time to achieve a train-of-four recovery ratio of ≥0.9. The two endpoints answer different questions, and an AUC value should not be interpreted as a recovery-time result or as evidence of comparative efficacy.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary outcome is descriptive pharmacokinetic information, not a reported two-arm efficacy comparison. Across Part A, the geometric mean AUC values range from 14.1 to 49.2 hr*μg/mL. Within each reported age group, the posted geometric mean is higher for the 4 mg dose than for the 2 mg dose. The values also increase across the listed age groups within each dose. These are descriptive patterns in the posted group summaries; the registry does not report a formal dose comparison or age-group comparison for this endpoint.
The group counts for the primary outcome are 9.0, 5.0, and 4.0 for the 2 mg dose across the three age groups, and 8.0, 6.0, and 6.0 for the 4 mg dose. They describe participants represented in this endpoint’s posted summaries, whose analysis population requires ≥5 post-dosing samples. They should not be treated as the total randomized enrollment. In particular, the adverse-event denominators and the primary-outcome counts differ for some groups, reflecting that the registry reports different outcome-specific populations.
The geometric coefficients of variation range from 18.5 to 73.0 across the six Part A summaries. In general, a geometric coefficient of variation describes relative spread on a multiplicative scale. It is not a confidence interval and does not directly show the precision of a difference between treatment groups. The registry does not report confidence intervals for the posted AUC summaries, so the precision of each geometric mean and the uncertainty around between-group contrasts cannot be assessed from these results alone.
The registry lists one analysis and nine outcome measures, but a numerical analysis of the stated recovery-time efficacy hypothesis is not reported in the registry record. It also does not report p-values, a model for comparing groups, or an adjusted treatment effect for AUC or recovery time. Without those results, the posted AUC values cannot establish whether sugammadex is superior to neostigmine for recovery from moderate blockade. Nor do they answer whether the difference between doses is statistically distinguishable from random variation.
Safety counts are reported separately. Serious adverse events affected 3 participants in the Part B sugammadex 2 mg group, 3 in the Part B sugammadex 4 mg group, and 2 in the Part B neostigmine group. No deaths are reported in any listed group. These counts describe events recorded in the registry; they are not a comparative safety analysis and do not establish whether an event was caused by a study drug.
Overall, the most defensible reading is that the registry posts small age- and dose-specific pharmacokinetic summaries in Part A and adverse-event counts across Parts A and B. Recovery-time estimates for the stated efficacy question are not reported in the registry record. Any conclusion about that question would require results beyond the posted primary outcome.
9. Statistical Methods Explained
What does the geometric mean describe?
The primary outcome is summarized using a geometric mean rather than an arithmetic mean. In general, a geometric mean is suited to positive measurements that vary multiplicatively: it is based on averaging the logarithms of the measurements and then returning to the original scale. This type of summary can be useful for pharmacokinetic quantities, which may be skewed and whose variation is often naturally expressed as relative rather than additive change. The registry does not report the underlying participant-level measurements, so the geometric means cannot be independently reconstructed from the posted summaries.
A geometric mean is not the same as a median, and it does not describe every participant’s exposure. It gives a central summary on a multiplicative scale. A difference between two geometric means would describe a contrast between group summaries, but no such contrast is posted for the primary outcome. No new comparison should be inferred from the group means alone.
How should the geometric coefficient of variation be read?
The registry reports geometric coefficients of variation as the dispersion measure. In general, a coefficient of variation expresses spread relative to a central value, rather than in the original outcome units. The geometric version is calculated on a logarithmic scale and is often used with positive, right-skewed measurements. A larger value signals greater relative variability among the observations represented by that summary. It does not indicate whether the group mean is accurate, and it is not an interval estimate of the treatment effect.
Dispersion and precision are related but different. Precision of a group estimate depends on the observed variability and the number of observations, among other features of the analysis. Precision of a treatment contrast also depends on the comparison method and the data in both groups. The posted record gives group sizes and dispersion summaries but does not report confidence intervals or a comparative model for AUC. The uncertainty around the group means and any dose contrast is therefore not reported in the registry record.
Why does the AUC extend to infinity?
AUC0-∞ is intended to represent exposure over the interval from dosing through the remaining concentration-time profile. In general, a pharmacokinetic curve is constructed from concentration measurements over time, and an estimate extending to infinity includes an estimate of the remaining profile after the last measured time. That makes the outcome a summary of total exposure rather than a concentration at one sampling time. The registry lists the collection schedule and defines the AUC, but the method for estimating the terminal part of the curve is not reported in the registry record.
The scheduled sampling times were 2 minutes, 15 min, 30 min, 60 min, 4-6 hours, and 10 hrs post-dose. The analysis population requires ≥5 post-dosing samples. This rule identifies which participants are included according to the posted outcome description; it does not explain how measurements that are absent, below a quantification limit, or otherwise unusable were treated. Those handling details are not reported in the registry record.
What is the distinction between a pharmacokinetic result and an efficacy result?
The AUC endpoint describes drug exposure. The trial’s stated efficacy hypothesis instead concerns time to recovery to a train-of-four ratio of ≥0.9 after moderate blockade. A time-to-recovery endpoint concerns how long it takes to reach a defined state. In general, such outcomes can be summarized or compared using methods appropriate to event times, including methods that account for participants who do not reach the threshold during observation. The registry does not report the analysis method used for the stated recovery-time question, nor does it post its numerical result.
The two listed secondary outcomes concern time to recovery to ratios of ≥0.7 and ≥0.8. These are distinct thresholds, not repeated measurements of the primary AUC endpoint. Their numerical results and analytic details are not reported in the registry record. It is therefore not possible to assess how findings across recovery thresholds relate to one another or to the AUC summaries.
How do the planning illustrations differ from observed power?
In general, a sample-size calculation is a planning exercise that asks how many participants would be needed under stated assumptions to detect a specified effect with a chosen statistical procedure. The registry record does not report the trial’s own sample-size justification, so any planning illustration based on the posted effect and specified assumptions is not evidence of the original design rationale. The stated illustration assumptions include a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects defined as fractions of the observed effect. For time-to-event outcomes, the illustration uses a total number of events; for other outcomes, it uses participants per arm.
In general, power is a property of a planned design under assumptions, not a measure of whether a completed trial has produced a convincing result. A retrospective calculation based on an observed effect must not be interpreted as observed power or as a substitute for a confidence interval. The registry does not report the numeric planning outputs in the record summarized by these registry entries, so no required participant count can be stated from them. For this trial, the design assumptions and the relationship between any planning illustration and the enrolled population should remain separate from the observed outcome summaries.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists nine outcome measures, including the primary AUC outcome and two secondary Part B recovery-time outcomes. It lists one analysis. The record does not describe a multiplicity strategy, such as an adjustment to account for testing several outcomes or several comparisons. Whether such a strategy was specified in the protocol is not reported in the registry record. Without that information and without the relevant analysis results, the effect of multiple testing on interpretation cannot be assessed.
The primary outcome population includes participants with ≥5 post-dosing samples available. That is the only explicit analysis-population rule described for the posted primary endpoint. The registry does not report whether the primary analysis otherwise followed intention-to-treat principles, how participants were handled after randomization if they lacked enough samples, or whether any additional pharmacokinetic populations were defined. Those details are not reported in the registry record.
Missing-data handling for the recovery-time outcomes is not reported in the registry record. The record does not specify whether participants who did not reach a recovery threshold were censored, excluded, or handled by another method. The handling of missing adverse-event information and missing covariates is also not reported in the registry record.
The record does not report interim analyses, stopping rules, or a statistical analysis plan. It also does not report the trial’s sample-size justification. These gaps are important because they prevent a full assessment of prespecified analyses, decision rules, and the relationship between planned enrollment and the reported outcome populations. The posted enrollment of 288 is a trial-level figure, not a substitute for endpoint-specific analysis details.
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 |
|---|---|---|---|
| Part A: Sugammadex 2 mg (2 to <6 Years) | 0 | 9 | 0.0% |
| Part A: Sugammadex 2 mg (6 to <12 Years) | 0 | 5 | 0.0% |
| Part A: Sugammadex 2 mg (12 to <17 Years) | 0 | 4 | 0.0% |
| Part A: Sugammadex 4 mg (2 to <6 Years) | 0 | 10 | 0.0% |
| Part A: Sugammadex 4 mg (6 to <12 Years) | 0 | 6 | 0.0% |
| Part A: Sugammadex 4 mg (12 to <17 Years) | 0 | 6 | 0.0% |
| Part B: Sugammadex 2 mg | 3 | 33 | 9.1% |
| Part B: Sugammadex 4 mg | 3 | 169 | 1.8% |
| Part B: Neostigmine + (Glycopyrrolate or Atropine) | 2 | 34 | 5.9% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Part A: Sugammadex 2 mg (2 to <6 Years) | 0 of 9 |
| Part A: Sugammadex 2 mg (6 to <12 Years) | 0 of 5 |
| Part A: Sugammadex 2 mg (12 to <17 Years) | 0 of 4 |
| Part A: Sugammadex 4 mg (2 to <6 Years) | 0 of 10 |
| Part A: Sugammadex 4 mg (6 to <12 Years) | 0 of 6 |
| Part A: Sugammadex 4 mg (12 to <17 Years) | 0 of 6 |
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 |
|---|---|
| Part A: Sugammadex 2 mg (2 to <6 Years) | 8 of 9 |
| Part A: Sugammadex 2 mg (6 to <12 Years) | 3 of 5 |
| Part A: Sugammadex 2 mg (12 to <17 Years) | 2 of 4 |
| Part A: Sugammadex 4 mg (2 to <6 Years) | 8 of 10 |
| Part A: Sugammadex 4 mg (6 to <12 Years) | 5 of 6 |
| Part A: Sugammadex 4 mg (12 to <17 Years) | 6 of 6 |
Most frequent serious adverse event terms
| Event term | Organ system | Part A: Sugammadex 2 mg (2 to <6 Years) | Part A: Sugammadex 2 mg (6 to <12 Years) | Part A: Sugammadex 2 mg (12 to <17 Years) | Part A: Sugammadex 4 mg (2 to <6 Years) | Part A: Sugammadex 4 mg (6 to <12 Years) | Part A: Sugammadex 4 mg (12 to <17 Years) |
|---|---|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | 0 of 9 | 0 of 5 | 0 of 4 | 0 of 10 | 0 of 6 | 0 of 6 |
| Pyrexia | General disorders | 0 of 9 | 0 of 5 | 0 of 4 | 0 of 10 | 0 of 6 | 0 of 6 |
| Urinary tract infection | Infections and infestations | 0 of 9 | 0 of 5 | 0 of 4 | 0 of 10 | 0 of 6 | 0 of 6 |
| Femoral neck fracture | Injury, poisoning and procedural complications | 0 of 9 | 0 of 5 | 0 of 4 | 0 of 10 | 0 of 6 | 0 of 6 |
| Post procedural bile leak | Injury, poisoning and procedural complications | 0 of 9 | 0 of 5 | 0 of 4 | 0 of 10 | 0 of 6 | 0 of 6 |
| Post procedural haemorrhage | Injury, poisoning and procedural complications | 0 of 9 | 0 of 5 | 0 of 4 | 0 of 10 | 0 of 6 | 0 of 6 |
| Dehydration | Metabolism and nutrition disorders | 0 of 9 | 0 of 5 | 0 of 4 | 0 of 10 | 0 of 6 | 0 of 6 |
| Laryngospasm | Respiratory, thoracic and mediastinal disorders | 0 of 9 | 0 of 5 | 0 of 4 | 0 of 10 | 0 of 6 | 0 of 6 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Part A: Sugammadex 2 mg (2 to <6 Years) | Part A: Sugammadex 2 mg (6 to <12 Years) | Part A: Sugammadex 2 mg (12 to <17 Years) | Part A: Sugammadex 4 mg (2 to <6 Years) | Part A: Sugammadex 4 mg (6 to <12 Years) | Part A: Sugammadex 4 mg (12 to <17 Years) |
|---|---|---|---|---|---|---|---|
| Procedural pain | Injury, poisoning and procedural complications | 4 of 9 | 3 of 5 | 1 of 4 | 7 of 10 | 3 of 6 | 3 of 6 |
| Bradycardia | Cardiac disorders | 1 of 9 | 1 of 5 | 0 of 4 | 1 of 10 | 1 of 6 | 1 of 6 |
| Mouth swelling | Gastrointestinal disorders | 0 of 9 | 2 of 5 | 0 of 4 | 0 of 10 | 0 of 6 | 0 of 6 |
| Nausea | Gastrointestinal disorders | 0 of 9 | 0 of 5 | 0 of 4 | 1 of 10 | 0 of 6 | 1 of 6 |
| Incision site pain | Injury, poisoning and procedural complications | 0 of 9 | 0 of 5 | 1 of 4 | 0 of 10 | 1 of 6 | 0 of 6 |
| Procedural vomiting | Injury, poisoning and procedural complications | 0 of 9 | 0 of 5 | 1 of 4 | 1 of 10 | 0 of 6 | 0 of 6 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 0 of 9 | 0 of 5 | 0 of 4 | 0 of 10 | 1 of 6 | 1 of 6 |
| Headache | Nervous system disorders | 2 of 9 | 0 of 5 | 0 of 4 | 0 of 10 | 0 of 6 | 0 of 6 |
| Haematuria | Renal and urinary disorders | 2 of 9 | 0 of 5 | 0 of 4 | 0 of 10 | 0 of 6 | 0 of 6 |
| Pericardial effusion | Cardiac disorders | 0 of 9 | 0 of 5 | 0 of 4 | 1 of 10 | 0 of 6 | 0 of 6 |
Serious events with the highest arm-level rate: urinary tract infection (3.0%), post procedural bile leak (3.0%), post procedural haemorrhage (3.0%), dehydration (2.9%), laryngospasm (2.9%).
The registry reports serious adverse events by treatment group and gives the number at risk and the number affected. In Part A, no serious adverse events are reported in any of the six age-and-dose groups. In Part B, serious adverse events affected 3 participants among 33 at risk in the sugammadex 2 mg group, 3 among 169 at risk in the sugammadex 4 mg group, and 2 among 34 at risk in the neostigmine group. No deaths are reported in any listed group.
These are event counts, not estimates of comparative risk. The registry does not report a statistical comparison of serious adverse events between groups, and the counts alone do not establish that a treatment caused an event. The Part A and Part B group sizes also differ, so counts should be read with their stated denominators rather than compared in isolation.
The registry also reports participants affected by other adverse events: in Part A, the counts range from 2 to 8 across the listed groups; in Part B, they are 26, 117, and 29 for sugammadex 2 mg, sugammadex 4 mg, and neostigmine, respectively. These counts do not indicate severity or causality. The listed serious-event terms and percentages are urinary tract infection, 3.0%; post procedural bile leak, 3.0%; post procedural haemorrhage, 3.0%; dehydration, 2.9%; laryngospasm, 2.9%; and abdominal pain, 0.6%. The record does not clarify whether each term represents a unique participant or an event count.
12. What the Result Does, and Does Not, Mean
The posted AUC summaries describe sugammadex exposure in Part A across two doses and three age groups. They can be read as pharmacokinetic summaries for participants meeting the stated sample-availability rule. The group means and geometric coefficients of variation provide information about central exposure and relative spread, but they do not by themselves establish the precision of a comparison or the importance of any difference.
The record’s stated primary efficacy hypothesis is that sugammadex is superior to neostigmine for reversal of moderate neuromuscular blockade, as measured by time to recovery to a train-of-four ratio of ≥0.9. That is not the primary outcome for which numerical values are posted in the results: the posted primary outcome is AUC0-∞ in Part A. Recovery-time results for the stated efficacy hypothesis are not reported in the registry record. The posted pharmacokinetic values therefore cannot answer whether the efficacy hypothesis was supported.
Likewise, the record’s adverse-event counts are descriptive. They show how many participants were recorded as affected in each listed group, but do not establish causation or a statistically supported difference in safety. No formal safety comparison or treatment-effect estimate is reported in the registry record.
In general, a confidence interval communicates the range of values compatible with the data under a specified statistical method and helps convey uncertainty. No confidence intervals for the AUC summaries or recovery-time comparisons are reported in the registry record. No p-values or comparative effect estimates for these outcomes are reported either. Without those results, the strength and precision of evidence for treatment differences cannot be evaluated from the posted information.
The appropriate interpretation is limited to what is posted: Part A includes dose- and age-specific exposure summaries, and adverse events are reported by group. The efficacy comparison described in the trial summary remains unanswered by the numerical outcomes in the registry record.
13. Why This Trial Matters Statistically
This trial illustrates why the name of a primary endpoint matters. The trial summary describes a clinical efficacy hypothesis about time to neuromuscular recovery, while the posted primary outcome is a pharmacokinetic measure of sugammadex exposure in Part A. Exposure and recovery are scientifically related topics, but they are not interchangeable outcomes. Keeping them separate prevents a pharmacokinetic result from being mistaken for a comparative efficacy finding.
The age-stratified Part A summaries also demonstrate the importance of examining the analysis population and group sizes alongside the outcome. The primary endpoint includes participants with ≥5 post-dosing samples, and the posted counts vary across age and dose groups. These endpoint-specific counts are distinct from the trial’s enrollment of 288. A reader should not assume that every enrolled participant contributes to every outcome or that the overall enrollment explains the precision of a particular estimate.
Finally, the record makes clear that descriptive summaries, safety counts, and comparative inference answer different statistical questions. Geometric means and geometric coefficients of variation describe exposure and its relative variability. Adverse-event counts describe recorded events by group. Neither replaces a comparative estimate with its uncertainty for the recovery-time hypothesis. The absence of reported recovery-time results, confidence intervals, and analytic details limits how far conclusions can go. This is a useful example of how a completed trial record can contain a rich design description while still leaving a central efficacy question unresolved in the posted results.
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 main limitation is that the numerical primary results concern AUC0-∞ in Part A, whereas the registry summary emphasizes an efficacy hypothesis about recovery time to a train-of-four ratio of ≥0.9. Recovery-time results for that hypothesis are not reported in the registry record. The two secondary recovery outcomes are listed, but their numerical results are also not reported in the registry record.
Part A group sizes are small: the posted outcome counts range from 4.0 to 9.0 participants. The record’s inclusion rule requires ≥5 post-dosing samples, and the reported group counts do not match all corresponding adverse-event denominators. The registry does not explain the reasons for these differences or describe the missing-sample process in detail. Precision is difficult to assess because confidence intervals are not reported.
The registry reports geometric means and geometric coefficients of variation but does not report a comparative statistical model, dose contrasts, age contrasts, or associated uncertainty estimates for AUC. The method for estimating AUC through infinity and the handling of missing or unusable concentrations are not reported in the registry record. Details of allocation, masking roles, and the trial’s sample-size justification are also not reported.
Safety interpretation is limited to group-level counts and listed event terms. The registry does not provide a comparative safety analysis or establish event relatedness. Multiplicity procedures, interim analyses, stopping rules, and detailed analysis-population definitions are not reported in the registry record. These omissions restrict assessment of the prespecified analysis strategy and the certainty of conclusions that can be drawn from the posted outcomes.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Efficacy, Safety, and Pharmacokinetics of Sugammadex for Reversal of Neuromuscular Blockade (NMB) in Pediatric Participants (MK-8616-089) — NCT03351608.
- Registry record last updated 2021-02-05; status last verified 2021-01.
- Results first posted 2021-02-05.
- 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
NCT03351608 is a completed Phase 4 randomized, triple-masked, parallel-group, active comparator-controlled trial sponsored by Merck Sharp & Dohme LLC. The registry reports enrollment of 288, a start date of 2018-02-12, and a primary completion date of 2020-01-28. The trial evaluated sugammadex for reversal of neuromuscular blockade induced by rocuronium or vecuronium in pediatric participants.
The posted primary outcome is Part A sugammadex AUC0-∞, reported as geometric means and geometric coefficients of variation across age and dose groups. Part B includes sugammadex and neostigmine with glycopyrrolate or atropine; recovery-time outcomes are listed, but their numerical results are not reported in the registry record. Serious adverse-event counts and other adverse-event counts are reported by group, with no deaths listed.
The registry summary states an efficacy hypothesis concerning recovery to a train-of-four ratio of ≥0.9. The posted AUC results do not resolve that hypothesis, and comparative efficacy estimates and their uncertainty are not reported in the registry record.