Opioid Reduction Initiative During Outpatient Pediatric Urologic Procedures Using Exparel: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Opioid Reduction Initiative During Outpatient Pediatric Urologic Procedures Using Exparel (NCT04826484), a randomized phase 3 study. The primary outcome is Percentage of Patients Who Are Opiate-free.

2. Clinical Question

The clinical question concerns opioid use after outpatient pediatric urologic procedures and whether the two local anesthetic regimens differ in the recorded postoperative opioid-free outcome. The outcome is a percentage at a specified postoperative time, rather than a continuous pain score or a time-to-event measure. The registry’s brief summary also describes an interest in pain scores and narcotic pain requirements, but the posted primary endpoint is the percentage opioid-free at 48 hours.

The trial’s stated intervention combines liposomal bupivacaine with 0.25% bupivacaine, while the comparison group receives 0.25% bupivacaine alone. Thus the randomized contrast concerns the addition of liposomal bupivacaine within the listed local infiltration regimens. It is not a comparison of local anesthetic use with no local anesthetic, and the record does not identify a no-treatment group.

The posted endpoint values are 60.0 for the combination group and 62.0 for the bupivacaine-alone group. The registry does not give a confidence interval, p-value, or other estimable comparative result for the primary endpoint. These values therefore describe the recorded group results, but do not by themselves establish the precision of a between-group effect. Additional eligibility criteria, participant characteristics, and the operational definition of opioid-free are not reported in the registry record.

3. Trial Design

This is a phase 3, randomized, single-masked, parallel-group trial sponsored by Johns Hopkins University. The registry lists enrollment as 104. The two arms are liposomal bupivacaine plus 0.25% bupivacaine and 0.25% bupivacaine alone; each arm has a posted group size of 52 for the primary outcome. The record does not describe the method used to generate or conceal the random allocation sequence.

The listed study start date is 2021-10-01, and the primary completion date is 2023-04-26. The current status in the registry record is terminated. The reason for termination is not reported in the registry record, so the status alone does not explain whether recruitment, follow-up, or another aspect of the study ended early. Nor does the record explain whether termination affected the planned analysis.

Single masking means the registry identifies the trial as masked to one party, but the identity of that party and the practical masking procedures are not reported in the registry record. The parallel design indicates that participants were assigned to one of the listed regimen groups rather than crossing between regimens in a sequence. Further details on treatment delivery, adherence, and whether outcome assessors were masked are not reported.

The primary endpoint is assessed at 48 hours postoperatively. A secondary opioid-leftover endpoint is assessed at 10-14 days postoperatively. Other listed secondary outcomes concern post-discharge opioid medication use and complications related to local anesthetic systemic toxicity. The record lists 7 outcome measures, but only some secondary results are posted. A full protocol, sample-size justification, analysis plan, and detailed schedule for all outcome measurements are not reported in the registry record.

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

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 Percentage of Patients Who Are Opiate-free, measured over 48 hours postoperatively.

The primary endpoint is the percentage of patients who are opioid-free at 48 hours postoperatively. It captures whether patients have used opioids by a defined postoperative time, as recorded by the study. It is a binary-status outcome summarized as a percentage, not a measure of the amount of medication used or of pain intensity itself. The registry record does not define the exact rules used to classify a patient as opioid-free.

This endpoint is relevant to the stated research question because the trial aims to evaluate postoperative opioid requirements following minor urologic procedures. A fixed-time opioid-free measure can describe the proportion of patients meeting that status at the selected follow-up point. However, it does not by itself describe when opioid use occurred, the amount used by those who were not opioid-free, or pain scores. Those are distinct questions and require their own outcome data.

The registry posts values of 60.0 for the combination group and 62.0 for the bupivacaine-alone group, with 52 participants listed in each group. Although the endpoint title and unit identify a percentage, the registry does not post an estimable two-arm comparison for this count-type outcome. A comparative confidence interval and p-value are not reported. Consequently, the group values should be read descriptively, without treating them as a precise estimate of a treatment contrast.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Randomized parallel comparison. The record describes randomized allocation to two local infiltration regimens in a parallel-group design. In general, random assignment is intended to make the groups comparable, on average, with respect to factors present before treatment assignment. It does not guarantee that the groups are identical, and interpretation still depends on complete follow-up, reliable outcome measurement, and an appropriate analysis. The allocation-generation method, concealment procedures, and detailed analysis populations are not reported in the registry record.

Single masking. The record labels the study single-masked. In general, masking can reduce the influence of expectations on treatment delivery, participant reporting, or outcome assessment, depending on who is masked and how the procedures are implemented. The record does not identify who was masked or describe the masking procedures. It is therefore not possible to assess from the registry description which potential sources of bias masking was intended to address.

Primary endpoint scale. Opioid-free status at 48 hours is summarized as a percentage. In general, a percentage expresses the share of the assessed group meeting a defined condition. Interpretation relies on a clear definition of that condition and on knowing which participants were assessed. Although the record gives arm sizes and endpoint values, it does not give the underlying event counts or an estimable primary comparison. It also does not report a confidence interval or p-value for the primary contrast. The group percentages alone do not quantify uncertainty around a between-group effect.

Risk difference for the posted secondary outcome. The leftover-opioid comparison is reported as a risk difference for 0.25% bupivacaine alone compared with liposomal bupivacaine plus 0.25% bupivacaine. In general, a risk difference is the difference between two outcome proportions, expressed on the probability scale; a value of zero corresponds to equal proportions. The posted estimate is 0.091, with a confidence interval from -0.059 to 0.240. The registry gives this estimate as an unadjusted comparison. It should not be confused with the primary endpoint, which concerns opioid-free status at an earlier time.

Confidence intervals and p-values. In general, a confidence interval describes statistical uncertainty around an estimate under the assumptions of the method used to construct it. It is not a guarantee that the true effect lies within the interval, nor does it describe every source of uncertainty, such as missing outcomes or measurement error. The interval for the secondary risk difference extends across zero, indicating that the posted data do not narrowly distinguish a positive difference from no difference or a difference in the opposite direction. The unadjusted p-value is 0.239. A p-value summarizes how compatible the data are with a specified null model under the analysis assumptions; it is not the probability that the null hypothesis is true, and it does not measure clinical importance.

Unadjusted analyses. The secondary comparison is unadjusted. In general, an unadjusted comparison uses the observed group results without accounting for additional covariates. That can be a straightforward summary, but it may not address imbalance in prognostic factors or other prespecified analytic considerations. No adjusted analysis is posted in the registry record. The record also does not report whether the sponsor conducted analyses beyond those posted.

Planning illustrations. The registry includes planning illustrations based on fractions of the observed secondary effect, with assumptions of a two-sided significance level of 0.05, equal allocation, and a normal approximation. For 100% of the observed effect, the illustration gives 287 participants per arm for 80% power and 384 participants per arm for 90% power. For 75% of the observed effect, the corresponding figures are 486 and 650 participants per arm. For 50% of the observed effect, they are 1,037 and 1,388 participants per arm. These are planning illustrations, not observed power and not evidence about what the original trial was designed to detect. The registry’s own design justification is not reported.

In general, smaller target effects require more participants to distinguish them from random variation under otherwise similar assumptions. These illustrations inherit uncertainty from the observed effect used as their starting point; they should not be treated as definitive requirements for a future study. The record does not report whether the illustration’s assumptions match any original protocol assumptions, and it does not report the trial’s sample-size justification.

Multiplicity and incomplete results. The record lists several outcomes, but only one secondary outcome includes a numerical comparison in the posted results. In general, testing multiple outcomes can increase the chance that at least one result appears notable by chance. An unadjusted p-value does not account for that issue unless a suitable multiplicity strategy is used. The registry’s statistical plan and any multiplicity adjustment are not reported. The absence of a posted analysis is not evidence that an outcome was not measured or analyzed; it means the corresponding result is not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 7 outcome measures and identifies a primary endpoint, but it does not report a detailed statistical analysis plan. It is not reported in the registry record whether the outcomes were arranged into a testing hierarchy, whether a multiplicity adjustment was planned, or whether any interim analyses occurred. Without that information, the interpretation of an unadjusted secondary p-value must remain cautious. When several outcomes are examined, the chance of obtaining at least one apparently notable result can rise; formal procedures can address that issue, but none is described in the record.

Missingness and analysis populations are also not adequately described for a full appraisal. The primary arm values are posted, yet the record says a two-arm comparison for this count-type endpoint was missing or not estimable. It does not explain the specific reason, identify the number of missing outcome assessments, state how missing observations were handled, or describe whether an intention-to-treat or other analysis population was used. Those details are not reported in the registry record. No assumptions about the missing data mechanism or imputation method can be made.

The registry reports 52 participants in each primary arm, while the secondary leftover-medication outcome has 50 participants listed for the combination group and 52 for the bupivacaine-alone group. The record does not explain the difference in listed group sizes across these outcomes. It does not report whether the secondary analysis excluded participants, reflected unavailable responses, or used another analysis population. The distinction matters because a result based on assessed participants can be affected if outcome availability is related to treatment or outcome status.

There are no posted analyses identified in the record’s analysis listing. That does not establish that no analyses were conducted; it establishes only that no such analyses are reported there. The registry does not report whether the posted result is the prespecified analysis, whether the analysis changed after trial termination, or whether the sponsor has additional results. The reason for termination is also not reported. These omissions limit assessment of selective reporting, multiplicity, and the robustness of the posted comparisons.

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 registry reports zero serious adverse events in the liposomal bupivacaine plus 0.25% bupivacaine group and zero in the 0.25% bupivacaine-alone group. It also reports zero deaths in each group. For other adverse events, the recorded counts are 7 in the combination group and 5 in the bupivacaine-alone group. These are descriptive counts in the registry record; event terms for those other adverse events are not reported.

Zero serious events in the posted groups means no serious events were recorded in these results, not that the treatments are free of serious risks. In general, absence of observed events does not rule out events that are uncommon, occur outside the observation period, or are not captured in the record. The registry does not report detailed follow-up duration for safety, event ascertainment procedures, severity categories for the other events, or a comparative safety analysis.

The listed secondary outcome concerning complications related to local anesthetic systemic toxicity does not have a numerical result posted. The zero serious-event counts should not be substituted for that specific outcome because the record does not state that the serious-event category is equivalent to toxicity complications. The available figures therefore offer a limited description of reported events, not a complete safety profile or a basis for concluding that the groups have equivalent safety.

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

The posted primary results describe opioid-free status at 48 hours postoperatively in the two randomized groups. The values are 60.0 for liposomal bupivacaine plus 0.25% bupivacaine and 62.0 for 0.25% bupivacaine alone. The registry does not report an estimable two-arm primary comparison, its uncertainty, or a p-value. The arm-level figures therefore do not establish the size or precision of a comparative effect.

The secondary leftover-opioid result provides a comparative estimate, but it addresses a different outcome at 10-14 days postoperatively. Its unadjusted risk difference is 0.091, with a confidence interval from -0.059 to 0.240 and an unadjusted p-value of 0.239. The estimate has substantial uncertainty as reflected by the interval. It should not be used to infer the primary endpoint’s comparative effect or to resolve the unanswered primary analysis.

These registry results do not establish that one regimen is superior, equivalent, or inferior. A failure to obtain a precise comparative estimate is not proof that the regimens have the same effect. Conversely, the observed group values and secondary estimate are not, by themselves, proof of a treatment effect. The record’s lack of a reported primary comparison, analysis plan, and complete secondary results makes strong comparative claims inappropriate.

The results also do not answer every clinical question named in the trial summary. The primary outcome is not a direct measure of pain intensity or the amount of opioid medication used, and posted numerical results for several listed secondary outcomes are absent. Safety figures are limited to the reported serious-event, death, and other-event counts, without detailed event descriptions or a comparative analysis.

The registry status is terminated, but the reason is not reported. It is therefore not possible to determine from this record why the study ended or how that status affected recruitment, outcome collection, or analyses. The record is best read as a limited account of posted outcomes, not as a complete report of all planned methods and findings.

13. Why This Trial Matters Statistically

This trial raises a statistical question common in clinical research: whether a clinically relevant randomized comparison can be interpreted when the primary group values are present but a comparative estimate is not. Percentages alone do not show the uncertainty around a treatment contrast. Without a confidence interval or other estimable comparison, readers cannot determine how precisely the primary effect is known from the registry results.

The distinction between an endpoint and the broader clinical concept also matters. Opioid-free status at 48 hours is one specific measure of postoperative opioid use. It does not describe pain scores or the amount of medication used by patients who were not opioid-free. Separate outcomes are needed for those questions, and their results are not all posted in the registry record.

The secondary leftover-medication comparison illustrates why estimates should be read with their uncertainty and context. Its confidence interval extends across zero, and the p-value is unadjusted. These features do not prove no difference; they show that the posted comparison does not tightly determine the direction or size of the association. The registry does not report whether multiplicity was addressed, which further limits the weight that can be assigned to an isolated secondary result.

Finally, the planning illustrations show how sample-size requirements depend on the effect a future study aims to detect and on the stated assumptions. They are not evidence of the trial’s original design rationale or of its achieved power. Distinguishing a planning scenario from an observed result is essential to avoid treating retrospective calculations as a substitute for a prespecified design and complete analysis report.

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 trial-specific limitations constrain interpretation of the registry results. The primary endpoint is reported as arm-level values, but a two-arm comparison is not estimable in the posted record. The reason is not explained, and the record does not give primary event counts, a confidence interval, or a p-value. This prevents a direct assessment of the precision of the main randomized contrast.

The study is listed as terminated, but the reason for termination and its consequences for enrollment or follow-up are not reported. The registry lists enrollment as 104 and 52 participants in each primary arm, but does not describe whether this reflects the planned or final analysis population. It also does not provide a sample-size justification, so adequacy relative to the trial’s intended effect cannot be assessed.

The record identifies the design as single-masked but does not say who was masked or how masking was maintained. It does not describe allocation concealment, eligibility criteria in detail, adherence, missing-data handling, or the analysis population. These omissions leave important aspects of risk of bias and analysis interpretation unresolved.

Only one secondary outcome has a posted numerical comparison. Other listed secondary outcomes do not have numerical results reported in the registry record. The available secondary comparison is unadjusted, while the analysis plan and any multiplicity strategy are not reported. The registry also does not explain why the listed participant counts differ between the primary and leftover-medication outcomes.

Safety reporting is similarly limited: no serious events or deaths are recorded, and other adverse-event counts are given without terms. The toxicity-related secondary outcome has no numerical result posted. These limits prevent a detailed evaluation of the trial’s safety findings from the registry record alone.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Opioid Reduction Initiative During Outpatient Pediatric Urologic Procedures Using Exparel — NCT04826484.
• Registry record last updated 2023-12-26; status last verified 2023-12.
• Results first posted 2023-12-26.
• 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

NCT04826484 is a phase 3 randomized, single-masked, parallel-group study sponsored by Johns Hopkins University. It compares local wound infiltration with liposomal bupivacaine plus 0.25% bupivacaine against 0.25% bupivacaine alone in pediatric patients undergoing minor urologic procedures. Listed enrollment is 104, and the registry status is terminated.

The primary outcome is the percentage of patients opioid-free at 48 hours postoperatively. The record posts values of 60.0 and 62.0, but no estimable two-arm comparison. A secondary leftover-opioid outcome at 10-14 days includes an unadjusted risk difference of 0.091, a confidence interval from -0.059 to 0.240, and a p-value of 0.239. Numerical results for other listed secondary outcomes are not reported in the registry record.

The record reports zero serious adverse events and zero deaths in both groups, with other adverse-event counts of 7 and 5. The reason for termination, detailed analysis methods, missing-data handling, and the primary comparison are not reported.