Sublingual Sufentanil vs Intravenous Fentanyl for Acute Pain in the Ambulatory Surgery Center: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sublingual Sufentanil vs Intravenous Fentanyl for Acute Pain in the Ambulatory Surgery Center (NCT04177862), a randomized phase 4 study. The primary outcome is Recovery Room Time.

2. Clinical Question

The study summary frames the comparison as whether sublingual sufentanil is as or more efficacious than intravenous fentanyl in a post-anesthesia care setting. The registry’s primary outcome, however, is recovery-room time, reported as a median in minutes with an interquartile range. That outcome captures the interval until discharge criteria are met; it is not itself a direct measurement of pain relief. The registry also lists outcomes involving opioid use after intervention, adverse events, postoperative nausea and vomiting, supplemental oxygen, and an overall benefit of analgesic score.

The record identifies the study as randomized and describes two parallel treatment groups. It does not report eligibility details, the method used to assign treatments, or the criteria used to assess pain or discharge. Therefore, the clinical question can be described in terms of the interventions and the recorded endpoint, but the registry does not provide enough detail to characterize precisely which patients were eligible or how the discharge criteria were applied.

3. Trial Design

The registry describes a randomized, triple-masked, parallel-group phase 4 trial comparing sublingual sufentanil with intravenous fentanyl. Both interventions are described as single doses for acute pain. The sponsor is the University of Minnesota, and the record lists enrollment as 75. It gives a study start date of 2019-12-11, a primary completion date of 2020-01-31, and a status of completed.

The primary endpoint is recovery-room time, measured in minutes over a timeframe of 1 day. It is defined as the interval from arrival in the PACU immediately after surgery until all discharge criteria are met. The registry reports the endpoint separately for each arm as a median and interquartile range. The reported arm denominators are 35 for sublingual sufentanil and 40 for intravenous fentanyl. The record does not explain how those denominators relate to the listed enrollment or whether every randomized participant contributed to each outcome.

Randomization and parallel groups describe how the comparison is organized, while triple masking indicates that masking was recorded at that level. The identities of the masked parties and the details of allocation concealment are not reported in the registry record. Nor are the eligibility criteria, the dose amounts, the timing of administration, or the detailed conduct of follow-up. These missing details limit assessment of how the recorded comparison was implemented.

The registry lists five secondary outcomes in addition to the primary outcome. They cover opioid use after intervention until discharge, adverse events, postoperative nausea and vomiting, supplemental oxygen, and the Overall Benefit of Analgesic Score. Numerical arm-level results are posted for postoperative nausea and vomiting and supplemental oxygen; the adverse-event record is also summarized separately. Numerical results for opioid use after intervention and the analgesic score are not reported in the registry record. No statistical analyses are listed for the primary endpoint.

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.

Before assignment: Participants were assigned to groups after undergoing their surgical procedures if they had a self-reported pain score of 4 and above on the 11-point numeric rating scale during phase 1 of PACU.

Overall Study

Reasons for not completing this period:

5. Baseline Characteristics

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

6. Primary Endpoint

The registry lists the primary outcome as Recovery Room Time, measured over 1 day.

Recovery-room time measures the elapsed time from a patient’s arrival in the PACU after surgery until all discharge criteria are met. The registry specifies minutes as the unit and a timeframe of 1 day. It reports the outcome as a median with an interquartile range for each treatment group. The median describes the midpoint of the recorded recovery times; the interquartile range describes the middle portion of their distribution. Together, these summaries convey a typical value and some information about variability without assuming that recovery times follow a particular distribution.

This endpoint is relevant to an ambulatory surgery setting because it records time spent in the recovery area before discharge criteria are satisfied. It reflects the overall interval to that point rather than isolating a single mechanism. In particular, it is not a direct measure of pain intensity or opioid consumption, even though the study compares analgesic interventions. Other listed outcomes address related aspects of care, including rescue opioid use and postoperative symptoms.

The endpoint definition leaves some operational details unspecified. The individual discharge criteria, how they were assessed, and whether their application was standardized are not reported in the registry record. Those details matter to interpretation because the endpoint stops when all criteria are met. The registry also does not provide a primary-endpoint confidence interval or a statistical comparison between groups, so the arm-level medians and interquartile ranges describe the posted results but do not quantify the precision of a treatment contrast.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends on both the summary measure and the comparison being made. For recovery-room time, the registry reports a median and interquartile range. In general, the median is a robust way to describe a central value when observations may be skewed, as time measurements can be. The interquartile range describes the central spread of the observed values. These summaries do not, by themselves, estimate the uncertainty in a difference between treatment groups.

What does the median tell us?

The median is the point that divides an ordered set of observations into two halves. It is less influenced by unusually long or short observations than the arithmetic mean. This can be useful for recovery times, where a small number of lengthy stays could pull a mean away from the experience of a typical participant. The interquartile range gives context about the distribution around the median, but it is not a confidence interval for the group’s median and is not a confidence interval for a difference between groups.

The registry’s primary summaries are 73.0 minutes for sublingual sufentanil and 65.0 minutes for intravenous fentanyl, with an interquartile range of 56.0 to 89.0 minutes in each group. No primary-endpoint test or confidence interval is reported. A formal comparison would need to specify the estimand and analysis method, including how any skewness, ties, or other distributional features were handled. Those choices are not reported in the registry record, so the medians should be read as descriptive rather than as a complete comparative analysis.

How should a confidence interval be read?

In general, a confidence interval expresses the uncertainty around an estimated quantity under the assumptions of the analysis. A wide interval indicates that the data are compatible with a broader range of values than a narrow interval. For a risk difference, an interval that includes zero is compatible with no difference as well as with differences in either direction, subject to the analysis assumptions. It does not prove equality, and it does not show that any values inside the interval are equally plausible.

The registry’s secondary comparisons give risk differences and confidence intervals for postoperative nausea and vomiting and supplemental oxygen. Both intervals include zero, and the corresponding unadjusted p-values are 0.458 and 0.842. These are recalculated, unadjusted comparisons from the posted summary statistics. The record lists no reported analyses for these outcomes. They should not be mistaken for sponsor analyses or for results adjusted for multiple testing.

Why can sparse outcomes produce imprecise estimates?

In general, binary outcomes are recorded as whether an event occurred for each participant. When event counts are limited, the estimate of an event-rate contrast can be sensitive to a small number of observations. The confidence interval may consequently cover a range of potentially meaningful effects in either direction. A non-small p-value does not establish that two treatments are equivalent; it indicates that the observed data do not provide strong evidence against the tested null hypothesis under that particular analysis.

For the posted secondary outcomes, the arm-level event counts and denominators are available, but the registry does not state a formal analysis plan. The recalculated comparisons are therefore descriptive inferential aids, not a substitute for a prespecified analysis. They are unadjusted, and interpretation should account for the fact that several outcomes are listed. The record does not report whether an approach to multiplicity was planned or used.

What do the planning illustrations represent?

In general, a sample-size calculation describes how many participants might be needed under specified assumptions to detect a chosen effect with a chosen power and significance level. Such a calculation is a planning exercise, not a result about the power achieved by an already completed trial. The posted planning illustrations use the observed effect, and smaller stated fractions of that effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The registry explicitly characterizes these as illustrations rather than the trial’s own design.

Those assumptions should not be read as the study’s documented sample-size justification. The protocol’s original target, its assumptions, and whether the completed enrollment followed that target are not reported in the registry record. The illustrations also do not establish observed power. Using an observed effect to plan a hypothetical future study can yield unstable estimates, particularly when the original estimates are imprecise. The posted sample-size values are therefore best understood as conditional planning examples, not as evidence that the trial was adequately or inadequately powered.

Why does the analysis plan matter?

A prespecified statistical plan identifies the primary contrast, model, handling of missing outcomes, analysis population, and approach to secondary outcomes before results are examined. In general, advance specification reduces the risk that analytic choices are selected because they produce a preferred result. The registry identifies the primary endpoint and outcome timeframe, but the statistical analysis plan, randomization details, handling of protocol deviations, and missing-data methods are not reported in the registry record. The record lists no reported analyses. As a result, readers can describe the posted summaries and recalculated comparisons, but cannot verify how they relate to a prespecified sponsor analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary endpoint and five secondary outcomes, but it does not report a plan for controlling multiplicity. When several outcomes are examined, the chance of obtaining at least one apparently unusual result can increase. In general, a multiplicity strategy may define which outcomes are confirmatory, adjust significance thresholds, or specify an order for testing. Without a reported strategy, the secondary p-values should be regarded as unadjusted and exploratory. The registry also lists no reported analyses, so it is not possible to determine whether any analysis plan was used outside the registry record.

Missing-data handling is not reported in the registry record. The record does not state whether all randomized participants were included in each analysis, how incomplete outcome measurements were handled, or whether any imputation or sensitivity analysis was performed. The arm-level denominators differ across the primary results, and the registry does not explain the reasons for the denominators or describe losses, exclusions, or missing measurements. No conclusion about the completeness of outcome data can be drawn from the listed summaries alone.

The analysis population is also not reported. The record does not specify whether analyses followed an intention-to-treat, per-protocol, or other approach, or how crossovers and protocol deviations were handled. Those choices can affect the meaning of a randomized comparison. Likewise, the registry does not report the detailed statistical model or the prespecified contrast for recovery-room time. Consequently, the posted primary summaries cannot be matched to a documented analysis population or protocol-defined estimand.

These omissions do not prove that the trial team failed to plan or conduct such procedures. They mean only that the relevant details are not reported in the registry record. The distinction matters: the record supports description of the posted numbers, but it does not support claims about the analysis plan, missing-data strategy, or multiplicity control beyond what is explicitly recorded.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event record lists zero serious adverse events among 35 participants in the sublingual sufentanil group and zero among 40 participants in the intravenous fentanyl group. It also lists zero deaths in each group. These figures describe what was recorded in the registry for the groups and denominators shown. They do not demonstrate that serious events are impossible or that the treatments have identical safety profiles.

In general, a study with limited group sizes may have little ability to characterize uncommon events. A zero count in a trial therefore needs to be read alongside the amount of observation and the completeness of safety reporting. The registry’s serious-event terms list is empty, and the record does not provide further detail about event definitions, surveillance procedures, or the duration of safety follow-up beyond the listed outcome timeframe. Those details are not reported in the registry record.

The record separately lists other adverse events affecting 4 participants in the sublingual sufentanil group and 7 in the intravenous fentanyl group. Those counts are not serious-event counts and should not be combined with the serious adverse event figures. The posted data offer a limited account of recorded events; they are not a comprehensive basis for comparing safety or drawing conclusions about rare harms.

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

The registry results establish that recovery-room time was recorded for both treatment groups and reported as a median with an interquartile range. The posted medians are 73.0 minutes for sublingual sufentanil and 65.0 minutes for intravenous fentanyl, and both groups have an interquartile range of 56.0 to 89.0 minutes. These figures describe the observed summaries. Because the registry does not report a statistical comparison, confidence interval, or analysis plan for this endpoint, they do not establish the precision or statistical significance of a difference between groups.

The results also do not establish equivalence. A lack of a reported primary test cannot be interpreted as evidence that the interventions produce the same recovery time. Equivalence or non-inferiority would require a suitable prespecified framework and a defined margin; those details are not reported in the registry record. The trial summary’s wording about whether one intervention is as or more efficacious does not, by itself, establish that such a framework was used.

The findings are limited to the outcomes and populations represented in the registry record. Eligibility criteria and participant characteristics are not reported, and the analysis population is not specified. The primary endpoint concerns the time until discharge criteria are met, not pain intensity alone. Secondary outcomes may add context, but their limited reporting and unadjusted comparisons do not resolve the uncertainty about the primary endpoint.

In practical statistical terms, the posted information supports a transparent description of the trial and its available outcome summaries, while leaving key inferential questions unanswered. It does not justify a treatment recommendation or a claim that either intervention does or does not work. Any broader interpretation would require details that are not reported in the registry record, including the protocol, analysis plan, complete outcome results, and methods for handling missing data.

13. Why This Trial Matters Statistically

This trial illustrates why a clearly named outcome and arm-level summaries are not enough to support a complete comparative conclusion. The registry defines recovery-room time in a clinically interpretable way and reports medians and interquartile ranges for both groups. Those summaries are useful for describing recorded experience. But without an inferential analysis, they leave uncertainty about the size and precision of the treatment contrast unresolved.

The example also separates an endpoint’s clinical relevance from its statistical role. Recovery-room time may matter in ambulatory care, but it is a broad outcome that runs from PACU arrival until discharge criteria are met. It is not a direct measure of analgesia. A study framed around acute pain can therefore include outcomes that capture different dimensions of care, and each requires its own interpretation. Results for postoperative symptoms or supplemental oxygen cannot stand in for a primary comparison of recovery time.

Finally, the record shows why analysis-plan transparency matters. The study is identified as randomized, masked, and parallel, yet details such as the statistical method, analysis population, missing-data handling, and multiplicity strategy are not reported in the registry record. The posted secondary comparisons are unadjusted and limited, while the primary comparison has descriptive summaries only. Readers can distinguish what the numbers show from what the available record does not establish. That distinction is central to sound interpretation of clinical trial evidence.

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.

Several limitations specific to this record constrain interpretation. The primary endpoint is reported only through group medians and interquartile ranges. A treatment contrast, its uncertainty, and an inferential test are not reported. The interquartile ranges are identical as posted, but that descriptive similarity does not establish equivalence or show that the full distributions are alike.

The registry does not report eligibility criteria or participant characteristics, limiting assessment of which patients the results represent. Although the study is randomized and triple-masked, the details of allocation, concealment, and masking are not reported. The dose amounts and administration details are also absent. These omissions make it difficult to assess how the interventions were implemented and how broadly the findings might apply.

The listed enrollment is 75, while the primary outcome denominators are 35 and 40. The registry does not explain whether the denominators reflect all randomized participants or describe any missing measurements, exclusions, or analysis-population rules. Missing-data methods and protocol deviations are not reported. Without that information, completeness and potential selection effects cannot be evaluated.

Reporting of secondary outcomes is also limited. Numerical results for opioid use after intervention and the Overall Benefit of Analgesic Score are not reported in the registry record. The available recalculated comparisons for postoperative nausea and vomiting and supplemental oxygen are unadjusted, and no multiplicity approach is reported. The record lists no sponsor-reported analyses. Finally, the planning illustrations are based on the observed effect under stated assumptions; they do not document the trial’s original sample-size justification or establish observed power.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Sublingual Sufentanil vs Intravenous Fentanyl for Acute Pain in the Ambulatory Surgery Center — NCT04177862.
• Registry record last updated 2021-04-19; status last verified 2021-04.
• Results first posted 2021-02-02.
• 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.

18. Record Summary

NCT04177862 is a completed randomized, triple-masked, parallel-group phase 4 trial sponsored by the University of Minnesota. It compared a single dose of sublingual sufentanil with a single dose of intravenous fentanyl for acute pain in an ambulatory surgery center. The registry lists enrollment as 75, a start date of 2019-12-11, and a primary completion date of 2020-01-31.

The primary outcome was recovery-room time in minutes, from arrival in the PACU after surgery until all discharge criteria were met, with a timeframe of 1 day. The registry reports a median and interquartile range for each group but no primary statistical analysis. It names five secondary outcomes; numerical results are available for postoperative nausea and vomiting and supplemental oxygen, with adverse-event counts recorded separately. Further details about the analysis plan, missing data, and analysis populations are not reported in the registry record.