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 Sufentanil Infusion vs Sufentanil Bolus (NCT04226495), a randomized phase 4 study. The primary outcome is Time to Extubation.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04226495 |
| Phase | Phase 4 |
| Condition | Anesthesia |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Single |
| Enrollment | 65 |
| Arms in the primary outcome | 2 |
| Lead sponsor | University of Nebraska |
| Results posted | Yes |
2. Clinical Question
Population
Participants undergoing routine cardiac surgery in a trial concerning anesthesia. The primary-outcome description says its participant count includes people who made it to that portion of the study. Further eligibility details are not reported in the registry record.
Intervention
Sufentanil administered intra-operatively as a slow trickle, described as an infusion.
Comparator
Sufentanil administered in scheduled doses, described as bolus dosing.
Primary question
Does intra-operative sufentanil infusion reduce the time from procedure finish to extubation, compared with bolus dosing? The registry description states that the study would assess a decrease of 60 minutes. That stated target is not the same as a reported estimate of the treatment effect.
The practical contrast is between two ways of administering the same named medication during routine cardiac surgery. The main endpoint is elapsed time, in minutes, between the finish of the procedure and extubation. The registry also lists plasma concentration, post-operative oral morphine milligram equivalents, length of ICU stay and length of hospital stay as secondary outcomes.
The record describes a randomized, single-blind, parallel-group trial and lists 65 participants enrolled. For the primary endpoint, the posted group counts are 24 for bolus and 24 for infusion. The record does not explain why the endpoint counts are smaller than the enrollment total, or identify which participants contributed to other outcomes beyond their stated counts. The clinical question can therefore be described, but the available record does not establish a complete account of participant flow or the analysis population.
3. Trial Design
The registry classifies this study as a phase 4, randomized, single-blind, parallel-group trial. It lists sufentanil bolus as the control and sufentanil infusion as the other intervention. The arm descriptions distinguish scheduled medication doses from administration as a slow trickle. The record marks the study completed, lists enrollment of 65, and gives the start date as 2020-10-13 and primary completion date as 2021-10-28.
Random allocation supports a comparison between groups by design, but the registry record does not report how the random sequence was generated, whether allocation was concealed, or whether any stratification was used. It identifies the study as single blind but does not state who was blinded or how blinding was maintained. The parallel-group label indicates that participants were assigned to one of the two approaches rather than crossing between them; details of treatment delivery, co-interventions and adherence are not reported in the registry record.
The enrollment figure is 65, whereas each primary-outcome group has 24 participants. The primary-outcome note says the participant count represents those who made it to that portion of the study. Reasons for the difference, exclusions, withdrawals and missing outcome observations are not reported in the registry record. Counts also differ for one secondary outcome: plasma concentration has 22 bolus and 20 infusion participants. This means outcome-specific denominators should be kept in view rather than assumed to match enrollment or one another.
The record lists five outcome measures and four named secondary outcomes. Numerical results are posted for plasma concentration, oral morphine milligram equivalents and length of ICU stay. Results for length of hospital stay are not reported in the registry record. No sponsor-reported analyses are listed. The protocol, statistical analysis plan, sample-size justification, analysis populations and handling of missing data are not reported in the registry record, so the design features available for interpretation are limited to the registered classifications and posted outcome descriptions.
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 | Sufentanil Bolus | Sufentanil Infusion |
|---|---|---|
| STARTED | 32 | 33 |
| COMPLETED | 24 | 24 |
| NOT COMPLETED | 8 | 9 |
Reasons for not completing this period:
| Reason | Sufentanil Bolus | Sufentanil Infusion |
|---|---|---|
| Withdrawal by Subject | 3 | 3 |
| Physician Decision | 2 | 2 |
| Protocol Violation | 3 | 4 |
Analysis population for the primary outcome, as defined in the registry: The participant number represent the number of participant whom made it to this portion of the 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.
| Characteristic | Unit | Sufentanil Bolus | Sufentanil Infusion | Total |
|---|---|---|---|---|
| Participants analysed | 32 | 33 | 65 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 17 | 18 | 35 |
| Age, Categorical: >=65 years | Participants | 15 | 15 | 30 |
| Age, Continuous | years | 64.9 (SD 8.4) | 63.3 (SD 8.9) | 64.1 (SD 8.7) |
| Sex: Female, Male: Female | Participants | 6 | 5 | 11 |
| Sex: Female, Male: Male | Participants | 26 | 28 | 54 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 1 | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 32 | 32 | 64 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 32 | 33 | 65 |
6. Primary Endpoint
The registry lists the primary outcome as Time to Extubation, measured over Amount of time in minutes from procedure finish to time of extubation, up to 800 minutes..
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Full Range |
| Unit | Minutes |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is time to extubation, measured in minutes from procedure finish to extubation. The registry states that measurement is up to 800 minutes. This endpoint represents elapsed time after the operation rather than a laboratory value or a count of events. Comparing the groups addresses whether the timing of sufentanil administration is associated with a different average duration from procedure completion to extubation.
The registry describes the intended question as whether infusion would decrease time to extubation by 60 minutes compared with bolus administration. That is a stated target in the outcome description, not evidence that the observed group difference was 60 minutes or that a statistical test supported that target. The posted result is the mean and full range for each group, with 24 participants in each. The bolus mean is 230.5 minutes, with a range from 52.0 to 794.0. The infusion mean is 242.4 minutes, with a range from 58.0 to 691.0.
Means offer a direct summary of average elapsed time, while the full range shows the span of observed values. A range does not show how observations are distributed within that span, and it does not quantify uncertainty around the mean. The registry does not post a standard deviation, confidence interval or sponsor-reported comparison for the primary endpoint. The endpoint is relevant to the stated question, but the available summary statistics alone do not provide a formal estimate of the precision or statistical uncertainty of the between-group contrast.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The primary results are descriptive. The mean time to extubation was 230.5 minutes in the bolus group and 242.4 minutes in the infusion group. The group ranges were 52.0 to 794.0 minutes and 58.0 to 691.0 minutes, respectively. Those summaries do not show a shorter observed mean in the infusion group. However, the registry does not post a primary-endpoint treatment-effect estimate, confidence interval or p-value, and no sponsor-reported analyses are listed. A formal inferential conclusion about the primary comparison cannot be recovered from the posted results.
The primary endpoint has substantial spread across its observed ranges. Ranges convey the lowest and highest values but not the shape of the data, the typical distance of observations from the mean, or the precision of the estimated mean. Because a standard deviation is not posted for this endpoint, the usual uncertainty calculation for comparing two means cannot be reconstructed from the listed summaries without additional assumptions. No such assumption-based primary calculation is posted in the registry record.
Some secondary continuous-outcome comparisons are labeled recalculated. These are unadjusted calculations based on the posted summary statistics, not sponsor-reported analyses. For plasma concentration, the reported means are 2.8 ng/mL in both groups; the recalculated mean difference is 0.0, with a 95% confidence interval from -0.303 to 0.303 and an unadjusted p-value of 1.0. For oral morphine milligram equivalents, the reported means are 56.2 in the bolus group and 48.9 in the infusion group. The recalculated mean difference is -7.3, with a 95% confidence interval from -33.87 to 19.27 and an unadjusted p-value of 0.59. This interval includes zero, so the posted summary statistics are compatible with differences in either direction.
For length of ICU stay, the group means are 46.7 hours for bolus and 32.7 hours for infusion. The recalculated mean difference is -14.0 hours, with a 95% confidence interval from -22.92 to -5.08 and an unadjusted p-value of 0.002. This is an unadjusted secondary comparison, not a sponsor-reported primary finding. Its interval does not include zero under the calculation used, but interpretation should account for the secondary status, the small group counts, the outcome variability and the lack of a reported multiplicity strategy. It does not resolve the absence of a primary-endpoint inferential result.
The confidence intervals quantify uncertainty under the assumptions of the recalculation; they do not account for unreported design or analysis choices. The registry record does not report adjusted comparisons, a prespecified hierarchy among secondary outcomes or a plan for multiple testing. The results therefore support a careful description of what was posted, rather than a broad claim about the overall effects of the two dosing approaches.
9. Statistical Methods Explained
Continuous outcomes are commonly summarized with a mean and a measure of spread. The mean is the arithmetic average, while a standard deviation describes how dispersed individual observations are around that average. General: neither statistic gives a complete picture of a distribution. A range identifies only the smallest and largest observed values, and can be strongly affected by extreme observations. For the primary endpoint, the registry posts the mean and full range but no standard deviation. The secondary continuous outcomes report means and standard deviations.
What does a mean difference represent?
General: a mean difference expresses the average in one group minus the average in the comparison group, using the outcome's own units. A value below zero in the recalculated comparisons means the infusion-group mean is lower than the bolus-group mean under that subtraction convention. The unit remains important: the contrast for ICU stay is in hours, whereas plasma concentration uses ng/mL and oral morphine milligram equivalents use OMME. A mean difference describes an average contrast; it does not mean that every participant experienced that difference.
The posted recalculated comparisons use the group means, standard deviations and sample sizes for each secondary outcome. For plasma concentration, the group counts are 22 and 20; for oral morphine milligram equivalents and ICU stay, each group count is 24. These are outcome-specific counts. General: when counts differ, the precision of a group mean depends partly on its sample size and variability, so the same observed mean contrast can have different uncertainty in different outcomes.
How should confidence intervals be read?
General: a confidence interval is a range of effect estimates compatible with the observed data under a specified statistical procedure and its assumptions. It communicates precision as well as direction. A relatively narrow interval indicates less uncertainty under that procedure than a wider one; an interval that includes zero does not establish that there is no difference. It indicates that zero remains among the values compatible with the interval at that confidence level. The recalculated secondary comparisons post 95% confidence intervals. These intervals are not sponsor-reported results, and the registry does not provide a primary-endpoint interval.
The confidence intervals for the secondary comparisons are based on simple, unadjusted calculations from posted summary statistics. They do not include adjustment for other outcomes, covariates, clustering or additional features of the trial design. The registry record does not report whether the sponsor used another model or whether model assumptions were checked. The recalculations should therefore be read as transparent summaries of the posted means, spreads and counts, not as a reconstruction of an unreported analysis plan.
Why does variability matter?
General: greater variability makes group means less precise when sample sizes are otherwise similar. Variability also affects how much information a given difference between means carries. ICU stay has a standard deviation of 21.1 hours in the infusion group and 7.2 hours in the bolus group, compared with group means of 32.7 and 46.7 hours. This difference in reported spreads is a reason to avoid reading the mean contrast alone as a complete description of the outcome. For outcomes with skewed or unusually dispersed observations, methods designed for the distribution may be useful, but the registry record does not report distribution checks or alternative analyses.
General: over-dispersion means that observations vary more than a statistical model expects. If a model assumes less variability than is present, its uncertainty estimates may be too small and its intervals may be too narrow. The posted continuous summaries do not establish whether over-dispersion is present; this is a general reason to consider whether a model fits the data, not a claim about this trial. The primary endpoint's full ranges make clear that observed times span broad intervals, but ranges alone cannot diagnose a distribution or determine which statistical model is appropriate.
What do the p-values say?
General: a p-value measures how incompatible the observed data, or data more extreme, are with a specified null model, assuming that model and the analysis assumptions hold. It is not the probability that the null hypothesis is true, and it does not measure clinical importance. The p-values posted for the recalculated secondary comparisons are unadjusted. They do not take account of testing several outcomes. No sponsor-reported p-values or analyses are listed for the primary endpoint.
Because the secondary p-values are unadjusted, their interpretation is narrower than a prespecified, multiplicity-controlled analysis. When many outcomes are examined, the chance of at least one apparently notable result can increase. Whether that issue was handled in the trial's own analysis is not reported in the registry record. The recalculated results should not be treated as confirmatory sponsor findings.
How should the planning illustrations be understood?
The posted planning illustrations translate observed secondary-outcome effects into hypothetical participant counts for two-sided testing under stated assumptions: significance level 0.05, equal allocation and a normal approximation. They show planning for 100%, 75% and 50% of the observed effect, with separate targets for 80% and 90% power. These are prospective planning illustrations calculated from the observed effect, not the trial's design justification and not a measure of the trial's observed power. The registry record does not report its own sample-size justification or the assumptions used to choose the enrollment target.
General: a sample-size calculation asks how many participants a future study might need to have a stated probability of detecting a chosen effect under specified assumptions. It depends on the effect size, variability, significance threshold, allocation and analysis method. Planning around a fraction of an observed effect explores how the required sample might change if the true effect were smaller. Because an observed estimate from a small study can be unstable, such calculations are illustrative rather than guarantees of future study performance. The posted calculations apply only to the outcomes for which they are listed and should not be transferred to the primary endpoint.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary outcome and four secondary outcomes. Numerical results are posted for three secondary outcomes, while length of hospital stay has no reported result. No sponsor-reported analyses are listed. The record does not report a statistical analysis plan, a testing hierarchy, a family of hypotheses, or a procedure for adjusting significance thresholds or confidence intervals across outcomes. It is therefore not possible to determine from the registry whether multiplicity was addressed in the trial's own analyses.
General: multiplicity arises when several outcomes or comparisons are tested. Even if each individual test uses a conventional threshold, conducting many tests can increase the overall chance of at least one apparently unusual result when there are no true effects. Adjustment methods can limit that risk, but they can also change intervals and p-values. The recalculated secondary p-values are explicitly unadjusted, so they should not be interpreted as if they account for the full set of outcomes. The primary result has no posted p-value to weigh against secondary findings.
Missing-data handling is also not reported in the registry record. The primary endpoint has 24 participants per group, while enrollment is 65. The primary outcome note indicates that the count concerns participants who made it to that portion of the study, but gives no reasons for the difference. Plasma concentration has 22 bolus and 20 infusion participants, while the other posted secondary results have 24 per group. The record does not state whether these count differences reflect missing measurements, eligibility for a particular outcome, withdrawals, exclusions or another reason. It also does not report imputation, sensitivity analyses or assumptions about missingness.
The analysis population is not described in the registry record. It is not clear whether results follow an intention-to-treat principle, a per-protocol approach or another definition. These omissions constrain interpretation because the analyzed participants and missing-data assumptions can affect both estimated effects and their uncertainty. They should be treated as unknowns, not filled in by assuming a standard practice.
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 |
|---|---|---|---|
| Sufentanil Bolus | 1 | 24 | 4.2% |
| Sufentanil Infusion | 1 | 24 | 4.2% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Sufentanil Bolus | 0 of 24 |
| Sufentanil Infusion | 0 of 24 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Sufentanil Bolus | 4 of 24 |
| Sufentanil Infusion | 5 of 24 |
Most frequent serious adverse event terms
| Event term | Organ system | Sufentanil Bolus | Sufentanil Infusion |
|---|---|---|---|
| Acute left MCA stroke | Vascular disorders | 1 of 24 | 0 of 24 |
| Emergent OR procedure | Cardiac disorders | 0 of 24 | 1 of 24 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Sufentanil Bolus | Sufentanil Infusion |
|---|---|---|---|
| Hypotension | Cardiac disorders | 4 of 24 | 5 of 24 |
| Acute blood loss anemia | Blood and lymphatic system disorders | 0 of 24 | 3 of 24 |
| Gross Hematuria | Renal and urinary disorders | 0 of 24 | 2 of 24 |
Serious events with the highest arm-level rate: acute left mca stroke (4.2%), emergent or procedure (4.2%).
The registry reports serious adverse events in 1 of 24 participants in each group. It reports other adverse events affecting 4 of 24 participants in the bolus group and 5 of 24 in the infusion group. No deaths are listed in either group. These are counts of participants affected, not necessarily counts of every event, and the registry's categories should not be conflated.
The serious-event terms listed are acute left MCA stroke and emergent OR procedure, each reported as 4.2%. The record does not assign those terms to a treatment group in the posted term list, so they should not be attributed to one arm based on these figures. The registry does not provide further event narratives, timing, relatedness assessments or definitions in the available safety information. Such details are not reported in the registry record.
These safety counts are descriptive. With 24 participants at risk per group, the figures provide limited information about uncommon harms, and the registry does not report a comparative safety analysis. The counts alone cannot establish whether an event was caused by the intervention or whether the groups differ reliably in safety. They also should not be used to infer absence of risk from the absence of deaths listed.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a randomized, single-blind, parallel-group trial compared sufentanil infusion with scheduled bolus dosing in routine cardiac surgery. It reports group summaries for time to extubation and selected secondary outcomes. For the primary outcome, the posted mean was 230.5 minutes with bolus and 242.4 minutes with infusion. The registry does not provide a primary treatment-effect estimate, confidence interval or p-value. The posted descriptive means therefore do not, by themselves, quantify the precision of the comparison or support a formal inference about the primary question.
The registry's stated aim refers to a possible 60-minute decrease in time to extubation. That figure is part of the outcome description; it is not an observed effect estimate. The record does not show that the target was achieved, nor does it give a sponsor-reported test of that target. Secondary recalculations provide additional descriptive and inferential context for specific outcomes, but they are unadjusted and are not substitutes for the missing primary analysis. A secondary result should not be generalized to other endpoints or treated as proof of a broad effect.
General: statistical evidence and practical importance are distinct. An estimate can be statistically compatible with a range of effects, and deciding whether those effects matter requires context about the outcome and the research question. The registry does not report a clinical threshold for interpreting the secondary outcomes or a full analysis plan. The available data also do not establish why outcome counts differ from enrollment, how missing values were handled, or which analysis population was used.
Accordingly, the most defensible reading is limited to what the record posts: descriptive primary group summaries, selected secondary means and spreads, unadjusted recalculations for secondary outcomes and adverse-event counts. It does not establish causation beyond the trial's randomized design, a definitive primary comparison, the meaning of unreported outcomes, or a complete benefit-risk assessment. These limitations concern the available registry information and should not be resolved by assuming analyses or procedures that are not reported.
13. Why This Trial Matters Statistically
This trial illustrates why the presence of a randomized design does not by itself make every posted result conclusive. Randomization is an important design feature for comparing groups, but interpretation also depends on the endpoint definition, outcome counts, variability, analysis method and completeness of reporting. Here, the primary endpoint is clearly described in minutes from procedure finish to extubation, and group means and ranges are available. Yet the registry does not report a primary comparison estimate or its uncertainty. The gap between a stated research question and an inferential result is statistically important.
The record also shows why outcome-specific denominators matter. The primary endpoint and two secondary outcomes have 24 participants in each group, while plasma concentration has smaller group counts. Total enrollment is 65, but reasons for the endpoint counts are not reported. Without participant-flow details, readers cannot tell how the analyzed groups relate to the full enrolled population or assess the possible influence of missing observations.
Secondary outcomes can add useful context, but multiple unadjusted comparisons should be interpreted cautiously. The recalculated ICU comparison is not equivalent to a prespecified primary result, and the record does not report a multiplicity strategy. Similarly, planning illustrations based on observed effects are not evidence of observed power and do not reveal the study's original design assumptions. The registry does not report a sample-size justification.
These issues are common interpretive challenges in clinical trial reporting: distinguish descriptive summaries from inferential results, keep secondary findings in their proper role, and separate a planning scenario from what the trial actually observed. A complete protocol, analysis plan, participant flow and primary comparison would help readers understand the strength and limits of the evidence. Their absence from the registry record means conclusions should remain bounded by the statistics that are actually posted.
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 primary-endpoint reporting is limited to means and full ranges. The record does not report standard deviations, a confidence interval, a p-value or a sponsor-reported between-group estimate for time to extubation. The ranges show broad observed spans but do not describe the distribution of values or the precision of the means. This makes the primary comparison less informative than a complete estimate with uncertainty would be.
The primary-outcome sample includes 24 participants per group, while the registry lists enrollment of 65. Its note says the outcome count represents participants who made it to that portion of the study, but does not explain the participant flow or reasons for the count. Plasma concentration has still different counts. Missingness, eligibility rules, exclusions and withdrawal reasons are not reported in the registry record. The analysis population and missing-data methods are also not reported.
The trial is described as single blind, but the identity of the blinded parties and procedures are not reported. The randomization method, allocation concealment, protocol, statistical analysis plan and sample-size justification are not reported in the registry record. No sponsor-reported analyses are listed. As a result, the recalculated secondary comparisons cannot be checked against a prespecified model or analysis strategy.
Secondary comparisons are unadjusted, and no multiplicity plan is reported. Only three of the four named secondary outcomes have numerical results posted; length of hospital stay is not reported. The primary outcome's full range includes observations near the stated upper measurement limit of 800 minutes, but the registry does not describe any handling of that limit or the distribution of times. These reporting limitations do not show that a particular method was inappropriate; they identify uncertainties that cannot be resolved from the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Sufentanil Infusion vs Sufentanil Bolus — NCT04226495.
- Registry record last updated 2026-06-08; status last verified 2024-11.
- Results first posted 2023-02-28.
- 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
The registry record describes a completed phase 4, randomized, single-blind, parallel-group comparison of intra-operative sufentanil infusion and scheduled bolus dosing during routine cardiac surgery. It lists 65 participants enrolled. The primary outcome is time from procedure finish to extubation, measured in minutes up to 800 minutes.
For the primary outcome, 24 participants per group are reported. Mean time was 230.5 minutes with bolus and 242.4 minutes with infusion; full ranges were 52.0 to 794.0 and 58.0 to 691.0 minutes, respectively. No sponsor-reported primary comparison or inferential result is listed. Numerical secondary results are posted for plasma concentration, oral morphine milligram equivalents and length of ICU stay; length of hospital stay is named but its result is not reported in the registry record. Secondary comparisons are recalculated and unadjusted.
The registry reports 1 serious adverse event in each group and no deaths. It does not report the analysis plan, sample-size justification, missing-data handling or participant-flow details. The posted information supports descriptive interpretation, with important uncertainty about the primary comparison and the analysis context.