A Study of Loco-Regional Liposomal Bupivacaine Injection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Loco-Regional Liposomal Bupivacaine Injection (NCT05992896), a randomized phase 4 study. The primary outcome is Postoperative Use of Narcotics at 12 Hours.

2. Clinical Question

The trial addresses a specific perioperative question: whether using liposomal bupivacaine as a loco-regional anesthetic during lower extremity revascularization is associated with a change in narcotic use during the postoperative period. The registry describes the broader purpose as assessing narcotic use during and following the procedure, while the designated primary outcome focuses on postoperative use at 12 hours after injection.

The comparison is between an injection of liposomal bupivacaine and an injection of placebo, each given during clinically indicated surgery. Random assignment is intended to make the groups comparable on average, while blinding is intended to limit the influence of treatment knowledge on care, measurement, or interpretation. Those design features do not compensate for the very limited number of participants who completed the trial.

The clinical question cannot be answered from the posted primary outcome because no participant-level values or group summaries are reported. The registry explains that only 2 participants completed the study and that no data are reported to protect participant privacy and confidentiality. Consequently, the record does not establish the direction or size of any difference in postoperative narcotic use. It also does not support a statistical estimate of the uncertainty around a treatment contrast.

3. Trial Design

The registry describes a prospective, randomized, triple-blinded trial with a parallel-group design. It is listed as Phase 4 and concerns peripheral arterial disease in people undergoing lower extremity revascularization. Participants were assigned to receive either liposomal bupivacaine or placebo by injection during clinically indicated surgery. The named sponsor is Mayo Clinic.

The parallel design means that participants were assigned to one of the two groups rather than receiving both interventions in sequence. Randomization is a design method for allocating participants by chance; in a sufficiently large study, it can help balance measured and unmeasured characteristics between groups. With only 2 participants completing the study, 1 in each arm, chance imbalance remains a major concern, and the record does not permit assessment of baseline comparability.

Triple blinding is recorded, but the registry record does not report which people or roles were blinded, how blinding was maintained, or whether the success of blinding was assessed. The details of the randomization sequence and allocation concealment are not reported in the registry record. Further operational details, such as eligibility criteria, dosing, the exact surgical procedures included, or deviations from assigned treatment, are also not reported in the registry record.

The study status is terminated. The registry reports enrollment of 3 and says that only 2 participants completed the study. It does not report why the trial was terminated, so no explanation for the early termination can be inferred. The primary completion date is recorded as 2025-05-15; that administrative date does not establish that the planned evidence was obtained.

The registry lists 9 outcome measures and 0 analyses. The secondary outcomes include postoperative quality of recovery at 14 days and 28 days, intraoperative narcotic use, and hospital length of stay. Results for those outcomes are not reported in the registry record. The protocol, planned sample size, and rationale for the target enrollment are not reported in the registry record, so the planned scale of the trial cannot be reconstructed from the available 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:

Analysis population for the primary outcome, as defined in the registry: The study was terminated early. Only 2 participants completed the study (1 in each arm). Based on the low enrollment number, no data are reported here in order to protect and maintain participant privacy/confidentiality.

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.

Population: Due to concerns with confidentially and patient privacy, baseline characteristics will not be reported for the liposomal bupivacaine group or the placebo group as demographic information was collected on only 2 participants (1 participant in each arm).

6. Primary Endpoint

The registry lists the primary outcome as Postoperative Use of Narcotics at 12 Hours, measured over 12 hours after injection.

The primary endpoint is postoperative narcotic use at 12 hours after injection. It is described as the amount of narcotics used postoperatively, measured in morphine equivalent. This is a quantitative measure intended to express narcotic use on a common scale, allowing use of different narcotic medications to be represented in comparable units. The registry record does not report the conversion procedures or the detailed measurement protocol.

Narcotic use is used as an endpoint because the trial's stated purpose is to assess whether liposomal bupivacaine is associated with lower narcotic use during and following lower extremity revascularization. A postoperative measure at a specified time point narrows that broad question to a particular period after injection. It is distinct from the listed secondary outcome of intraoperative narcotic use, which concerns medication use during the procedure.

The endpoint is not reported as a numerical result. The registry states that only 2 participants completed the study, with 1 in each arm, and that the data are withheld to protect privacy and confidentiality. There is therefore no posted group mean, median, individual value, treatment contrast, or uncertainty estimate to interpret. The registry record also does not describe the planned summary measure, the handling of repeated doses, or how missing endpoint measurements would be treated.

Even when this kind of measure is reported, a comparison would need to be interpreted alongside the measurement methods, the clinical context, and the precision of the estimate. A numerical difference alone would not describe all aspects of recovery or establish the effect on other listed outcomes. In this trial, no primary endpoint comparison can be made from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does randomization contribute?

Randomization assigns participants to treatment groups by chance rather than by a clinician's or participant's preference. In general, this can reduce systematic differences between groups and gives a sound basis for comparing outcomes. It does not ensure that small groups will be similar in every relevant characteristic. With only 1 completer in each arm, the registry record offers no basis for checking whether the groups were comparable, and the randomization method itself is not reported in the registry record.

A randomized design supports causal interpretation only when the comparison is conducted and reported with adequate information. Important details include the assigned groups, outcome measurement, analysis population, missing measurements, and departures from the planned procedures. Some of those details are not reported in the registry record. The label randomized therefore describes the design, not a guarantee that the treatment effect can be estimated from the posted data.

What does blinding contribute?

Blinding is intended to limit the effects of knowing which intervention was assigned. In general, knowledge of assignment could influence treatment decisions, participant reports, outcome assessment, or analysis choices. The registry records triple masking but does not identify the masked roles or explain how masking was maintained. It is not possible to assess the effectiveness of blinding from the registry record.

What would an outcome comparison normally report?

For a quantitative endpoint such as narcotic use measured in morphine equivalent, an analysis would normally report a clearly defined group summary and a treatment contrast. The contrast could be accompanied by an interval estimate to show the range of values reasonably compatible with the data under the analysis assumptions. A confidence interval describes statistical uncertainty; it does not by itself establish clinical importance or remove potential bias.

A hypothesis test, if planned, would assess how compatible the observed data are with a specified null hypothesis under a statistical model. A p-value is not the probability that the treatment has no effect, nor is it a measure of the size or importance of an effect. In this record, no primary outcome values, test results, or interval estimates are reported, so none of these quantities can be interpreted.

Why do sample size and precision matter?

In general, larger samples tend to provide more precise estimates than smaller samples, assuming comparable measurement quality and study conduct. When data are sparse, estimates can be highly sensitive to individual observations, and uncertainty is typically substantial. The registry record reports only 2 study completers. Because the primary outcome results are withheld, the observed treatment contrast and its variability are unavailable. No estimate of precision can be reconstructed from the posted record.

A sample-size calculation is a planning exercise that depends on choices such as the target effect, variability, significance level, allocation, and analysis method. It is not a result from participants and is not observed power. The registry record does not report its original sample-size justification or target assumptions. It would be inappropriate to infer those from the final enrollment.

Planning illustrations based on a stated fraction of an observed effect are distinct from the trial's own design calculations. The general assumptions described for such illustrations are a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the stated effect to detect is a fraction of the observed effect. Such illustrations are meaningful only when an observed effect is available and should not be read as evidence that the trial had a particular probability of detecting an effect. Since the primary outcome estimate is not reported, an effect-based illustration cannot be anchored to a publicly reported primary outcome comparison in this record. The original design justification remains not reported in the registry record.

How should the outcome scale be understood?

Morphine equivalent is a common-unit approach for expressing narcotic use across medications. In general, converting medication use to a shared scale can make aggregate comparisons more interpretable than comparing drug names or doses directly. Interpretation still depends on the conversion rules, which medications were included, the time window, and how multiple administrations were summarized. Those measurement details are not reported in the registry record.

The primary outcome specifies 12 hours after injection. This defines the time point of interest but does not specify the exact observation schedule or whether the measure is cumulative use over that period. The registry description says use measured 12 hours after injection; additional operational detail is not reported in the registry record. A reader should not assume a particular calculation method beyond the stated description.

What is known about the analysis?

The registry lists 0 analyses. It does not identify a statistical model, adjustment variables, a primary contrast parameter, or a strategy for multiple outcome testing. It also does not report whether the primary comparison was intended to use a mean, median, or another summary, or how skewed or over-dispersed data would be handled. In general, over-dispersion means that observed variability exceeds what a chosen model expects; if present, it can make standard errors and inferential results from an unsuitable model unreliable. No distributional information is posted to assess whether that issue applies.

The record describes 9 outcome measures and several secondary outcomes, but the existence of multiple measures does not reveal how they were prioritized or analyzed. Statistical methods should ordinarily be tied to prespecified questions and outcome definitions. The protocol and a detailed statistical analysis plan are not reported in the registry record, so planned methods, multiplicity adjustments, and any interim analyses cannot be established. No interim analysis is reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates several outcomes, time points, treatment comparisons, or statistical tests. In general, examining more hypotheses can increase the chance of obtaining at least one apparently notable result by chance if the testing strategy is not addressed. Approaches to multiplicity may include prespecifying a primary outcome, controlling an error rate, or treating secondary results as exploratory. The registry lists 9 outcome measures, including several secondary outcomes and distinct follow-up times, but does not report a multiplicity strategy. Whether any adjustment was planned or used is not reported in the registry record.

The registry lists 0 analyses and provides no outcome estimates. Consequently, there are no posted hypothesis tests to evaluate for multiplicity, and no claim about statistical significance can be made. The absence of reported analyses does not establish that no analysis was conducted; the reason is not reported in the registry record.

Missing-data handling is also not described. The record says that 2 participants completed the study, 1 in each arm, while enrollment was 3. It does not state why the third participant did not complete the study, whether that participant had an outcome measurement, or how incomplete measurements were handled. It is therefore not possible to classify all participants' primary outcome availability or assess the consequences of missingness.

Analysis populations are not reported in the registry record. For example, the record does not say whether an intended analysis would include all randomized participants, only those who completed the study, or another defined group. Such choices matter because excluding participants after randomization can affect comparability, while including participants without outcomes requires explicit methods and assumptions. No analysis population or missing-data method can be inferred from the posted information.

The registry record also does not report an interim analysis plan or whether any interim review took place. No assumptions about stopping rules, monitoring, or the reasons for termination can be made from the status alone.

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.

The registry reports serious adverse events for the liposomal bupivacaine group as 0 among 1 participant at risk, and for the placebo group as 0 among 2 participants at risk. Other adverse events are also reported as 0 among 1 at risk in the liposomal bupivacaine group and 0 among 2 at risk in the placebo group. Deaths are reported as 0 in both groups.

These are event counts and denominators, not estimates from a large safety population. With so few participants at risk, zero reported events cannot demonstrate that an event is impossible or that the groups have the same safety profile. The counts also cannot support a reliable comparative rate or a precise estimate of the difference in event risk.

The registry record does not provide serious-event terms, and no top serious-event terms are listed. It does not report event timing, severity grading beyond the serious and other categories, relatedness assessments, or the duration of follow-up for safety. Those details should not be inferred. The adverse-event figures are best read as the counts posted for this small, terminated trial, not as conclusive evidence about safety.

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

The record documents a randomized, triple-blinded comparison of liposomal bupivacaine and placebo during lower extremity revascularization. It identifies postoperative narcotic use at 12 hours after injection as the primary outcome and describes the measurement in morphine equivalent. It also lists secondary outcomes concerning quality of recovery, intraoperative narcotic use, and hospital length of stay.

However, the registry reports that the study was terminated early and that only 2 participants completed it, 1 in each arm. It states that no primary outcome data are reported to protect privacy and confidentiality. Thus, the posted record does not provide a treatment-effect estimate, a confidence interval, or a test of the primary question. It cannot show whether the groups differed or how large any difference might have been.

This absence of a result should not be translated into a conclusion that the intervention has no effect, that it is equivalent to placebo, or that one group had better outcomes. Those conclusions require an interpretable comparison and adequate information about its uncertainty. The primary outcome data are unavailable, and the sample of completers is too limited to support a robust estimate even if values were accessible.

The posted safety counts report no serious or other adverse events in either group and no deaths. Because the denominators are only 1 and 2, respectively, these observations do not rule out adverse events or establish comparative safety. They describe the small set of participants represented in the registry safety entries.

The status, enrollment, completion count, outcome descriptions, and event counts are useful for understanding what the registry record documents. They do not replace a complete report of trial conduct and analysis. Reasons for termination, baseline characteristics, the statistical analysis plan, missing-data procedures, and results for secondary outcomes are not reported in the registry record. The defensible conclusion is that the available record does not permit an efficacy or comparative safety conclusion.

13. Why This Trial Matters Statistically

This trial illustrates an important distinction between a study question and an answer to that question. A randomized design can be appropriate for comparing interventions, and blinding can help reduce some sources of bias. But design labels alone do not produce an estimate. Participants must contribute usable outcome information, and the results must be reported in a form that allows the comparison and its uncertainty to be evaluated.

Here, the primary question concerns postoperative narcotic use at a defined time point, but the registry withholds the values because only 2 participants completed the study and privacy is to be maintained. That creates a limit that is statistical as well as clinical: there is no observed contrast to interpret, and no precision measure to communicate. The record therefore cannot distinguish a potentially important difference from no difference or from a wide range of plausible outcomes.

The trial also emphasizes why enrollment, completion, and analysis counts should be kept distinct. The registry records enrollment of 3 and completion by 2 participants, but does not explain the remaining participant's status or how missing outcomes were handled. Without those details, readers cannot assess the analysis population, evaluate potential attrition bias, or understand how the final data relate to randomization.

Safety interpretation faces a parallel challenge. Zero reported events in very small groups is a description of the observed record, not assurance that risk is absent. Precision and context matter when assessing uncommon events, and the posted counts cannot establish a comparative safety profile.

For researchers, the example underscores the value of clear outcome definitions, transparent methods, and complete reporting of both planned and conducted analyses. For readers, it shows why statistical interpretation must begin with what is actually estimable. A carefully stated question and a rigorous design are important, but neither can substitute for reportable outcome data. The limitations in the registry record should be kept separate from conclusions about the underlying intervention.

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 most consequential limitation is that the primary outcome data are not reported. The registry attributes this to privacy and confidentiality because only 2 participants completed the study, 1 in each arm. Without values or group summaries, the treatment contrast and its uncertainty cannot be assessed.

The registry reports enrollment of 3 and completion by 2 participants, but does not describe the status of the participant who did not complete the study. Reasons for noncompletion, outcome availability, and handling of missing information are not reported in the registry record. This prevents assessment of attrition and of how the randomized population relates to the participants included in any analysis.

The trial was terminated, but the reason for termination is not reported in the registry record. The original enrollment target, sample-size justification, and planned statistical methods are also not reported. The record lists 9 outcome measures but 0 analyses, leaving the planned hierarchy of outcomes, multiplicity approach, and analysis population unclear.

Further details that would help assess conduct are not reported in the registry record, including baseline characteristics, the randomization procedure, allocation concealment, which roles were masked, and how the morphine-equivalent measure was constructed. The listed secondary outcomes have no posted results. The safety denominators are small, and the registry does not provide serious-event terms or additional event details. These limitations mean that neither treatment effects nor a comprehensive benefit-risk comparison can be evaluated from the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Loco-Regional Liposomal Bupivacaine Injection — NCT05992896.
• Registry record last updated 2026-05-29; status last verified 2026-05.
• Results first posted 2026-05-29.
• 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

The registry record describes a Phase 4, randomized, parallel-group, triple-blinded trial sponsored by Mayo Clinic. It compares an injection of liposomal bupivacaine with placebo during clinically indicated lower extremity revascularization surgery for peripheral arterial disease. The primary outcome is postoperative narcotic use at 12 hours after injection, measured in morphine equivalent.

The study status is terminated. Enrollment is recorded as 3, and the registry states that only 2 participants completed the study, with 1 in each arm. No primary outcome data are reported because of privacy and confidentiality concerns. The record lists 9 outcome measures and 0 analyses. Reasons for termination and the original statistical plan are not reported in the registry record.

Safety entries report 0 serious adverse events, 0 other adverse events, and 0 deaths in both groups, with 1 participant at risk in the liposomal bupivacaine group and 2 in the placebo group. These small counts do not permit a reliable comparative safety conclusion. Overall, the posted information establishes the trial design and its limited completion, but not the direction, magnitude, or precision of a treatment effect.