Liposomal Bupivacaine vs Continuous Nerve Catheters for Below the Knee Amputations: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Liposomal Bupivacaine vs Continuous Nerve Catheters for Below the Knee Amputations (NCT05140499), a randomized phase 4 study. The primary outcome is Pain Assessed by Numerical Rating Scale (NRS).

2. Clinical Question

The clinical question concerns pain control after below-the-knee amputation, with the primary outcome defined as average pain on a numerical rating scale at 72 hours post-operatively. The record describes a prospective, randomized trial and identifies the single-shot block as the comparator group. It characterizes both approaches as currently accepted as standard care at Maine Medical Center, while framing the trial as a pilot intended to collect preliminary information for planning a larger study.

The registry lists opioid consumption, post-operative length of stay, post-operative pain assessed by the Short Form McGill Pain Questionnaire-2, and phantom limb pain assessed using questions from the Trinity Amputation and Prosthesis Experiences Scales-Revised as secondary outcomes. The posted results do not include analyses for those outcomes. The registry record does not report participant eligibility criteria, baseline characteristics, or details sufficient to characterize which patients might be represented beyond the surgical and nerve-block context.

3. Trial Design

This was a prospective, randomized, single-masked, parallel-group phase 4 trial. The registry reports enrollment of 11 and a status of terminated. Its listed start date is 2022-08-15, and its primary completion date is 2025-11-20. The reason for termination is not reported in the registry record. The record identifies Aurora Quaye as sponsor.

The comparison was between a single-shot perineural popliteal nerve block and a continuous perineural popliteal nerve block catheter. For the single-shot arm, the registry describes injection of 10cc 13.3% liposomal bupivacaine combined with 15cc 0.50% bupivacaine hydrochloride within one hour prior to surgery. For the catheter arm, it describes 30cc 0.5% bupivacaine within one hour prior to surgery, followed by continuous infusion of 10cc 0.3% ropivacaine for at least 72 hours following surgery. The catheter description also mentions a saphenous single shot of 20cc 0.2%, but does not provide further detail.

The primary outcome was pain assessed by numerical rating scale at 72 hours post-operatively. The outcome description calls the measure average NRS pain scores and defines the scale as 0-10, with 0=no pain and 10=worst possible pain. The registry reports results for 5 participants in the single-shot group and 6 in the catheter group. These outcome denominators should not be treated as proof that every enrolled participant completed follow-up or that the analysis included all randomized participants; the flow from enrollment and randomization to outcome analysis is not reported in the registry record.

The registry describes the study as a pilot intended to inform design of a larger, appropriately powered study. The planned sample-size justification, allocation procedure, masking details, and protocol for handling deviations 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 Pain Assessed by Numerical Rating Scale (NRS), measured over 72 hours post-operatively.

The primary endpoint is average pain measured with the numerical rating scale at 72 hours post-operatively. The registry defines the scale from 0-10, where 0=no pain and 10=worst possible pain. A numerical rating scale provides a structured way for participants to express pain intensity; using a common scale supports a direct description of responses between randomized groups at a specified assessment time.

The record labels the summary parameter as median and the dispersion as standard deviation. The posted single-shot group result is a median of 6.0 with standard deviation 3.07, based on 5 participants. The catheter group result is a median of 4.0 with standard deviation 3.32, based on 6 participants. These are descriptive summaries at the stated assessment time. The registry does not report confidence intervals, a comparative test, or an adjusted effect estimate for this endpoint.

As a general statistical point, a median describes the midpoint of the observed values after ordering them, whereas a standard deviation describes spread around a mean-based quantity. They convey different features of a distribution. Reporting them together does not by itself describe the uncertainty in the difference between groups. The registry record does not report how the endpoint was analyzed or how the reported standard deviations were calculated.

A fixed assessment time gives the comparison a defined clinical context, but the record does not report details of assessment completion, repeated pain measurements, or the approach to any unavailable scores. The posted summary therefore describes the recorded endpoint results without establishing the completeness of measurement or the precision of a between-group contrast.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does randomization contribute?

Random allocation is intended to make treatment groups comparable, on average, with respect to measured and unmeasured characteristics before the intervention. This helps support a causal comparison when allocation is implemented as planned and when outcomes are analyzed appropriately. Randomization does not guarantee balance in a small trial, and the record does not provide baseline characteristics or details of the allocation procedure. The trial is described as randomized, but further assessment of how allocation was generated or concealed is not possible from the registry record.

What does the parallel design mean?

In a parallel-group design, participants are assigned to a group and the groups are compared over the study period. Here, the record lists a single-shot block group and a continuous-catheter group, with pain assessed at 72 hours post-operatively. This design differs from a crossover comparison, in which a participant receives multiple interventions in sequence. The registry does not provide further details about follow-up timing beyond the primary outcome timeframe or report whether participants changed treatment after allocation.

How should the endpoint summaries be read?

The registry labels the primary result as a median and reports standard deviation as its dispersion measure. A median is the middle value in an ordered set of observations and is relatively resistant to extreme values. A standard deviation describes variability using deviations from the mean. As a general statistical explanation, these summaries answer different questions: the median locates the center by rank, while the standard deviation reflects spread around the mean. Their joint use does not provide a confidence interval or a direct estimate of uncertainty for the difference between groups.

The outcome description refers to average NRS pain scores, but the parameter field identifies the reported summary as median. That distinction matters when interpreting a result: an average often refers to a mean, while a median is a different measure of center. The registry record does not explain this wording or specify the calculation used to summarize scores. The safest interpretation is to retain the registry's stated parameter, median, and avoid recasting it as a mean.

What would a confidence interval add?

General explanation: a confidence interval gives a range of values compatible with the data and the assumptions of the statistical method, expressing uncertainty around an estimate. For a comparative result, it can show both the estimated direction and the precision of the contrast. The record does not report a confidence interval for the primary outcome, so the precision of a group comparison cannot be judged from a confidence interval. The reported group medians and standard deviations should not be substituted for one.

Why does the small outcome count matter?

The primary outcome summaries are based on 5 participants in the single-shot group and 6 in the catheter group. General statistical reasoning is that estimates from small samples can be unstable: individual observations can materially affect a summary, and the observed distribution may not represent the range of outcomes in a broader population. The reported standard deviations show that scores varied within each group, but they do not eliminate uncertainty about the comparison. No model-based estimate, uncertainty interval, or inferential test is reported in the registry record.

What is the role of an analysis plan?

A statistical analysis plan ordinarily clarifies the primary comparison, analysis population, handling of missing outcomes, covariate adjustment, and any planned subgroup or interim analyses. These choices affect interpretation and can help distinguish confirmatory analyses from exploratory ones. The registry record does not report the statistical analysis plan, the method used for the primary outcome, whether any adjustment was planned, or whether interim analyses were conducted. Those details cannot be inferred from the posted group summaries or from the randomized design alone.

What do the missing comparative results imply?

The registry lists zero analyses and does not post a formal comparative result for the primary endpoint. That means a reader cannot use the registry record to assess a p-value, confidence interval, model estimate, or prespecified hypothesis test. It does not establish that no analysis was conducted elsewhere; it means that such an analysis is not reported in the registry record. Likewise, the lack of posted secondary analyses means the listed secondary outcomes cannot be interpreted as trial findings.

General explanation: a p-value, when reported, assesses how compatible data are with a specified null model under the assumptions of a test. It is not a measure of clinical importance and does not describe the probability that a treatment works. A confidence interval and an estimate are generally more informative about magnitude and precision. None of these comparative inferential results is available in the registry record for the primary endpoint.

Why can over-dispersion matter?

General explanation: over-dispersion occurs when outcome variability is greater than a statistical model expects. If a model assumes less variability than is present, its uncertainty estimates may be too narrow and inference may be misleading. The posted endpoint is a bounded pain score, and the registry reports substantial within-group spread summaries, but it does not report a model or distributional assessment. It is therefore not possible to determine whether over-dispersion was assessed or whether a particular model was used.

Because the primary outcome is a score with an explicit lower and upper bound, the possible shape of its distribution may differ from that of an unbounded continuous measurement. General statistical practice is to consider the outcome scale and distribution when selecting a method. The registry does not state how those considerations informed analysis. These methodological points explain why the descriptive summaries alone should not be treated as a complete inferential analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies one primary outcome and four secondary outcomes. The primary outcome is pain assessed by numerical rating scale at 72 hours post-operatively. The secondary outcomes are opioid consumption, post-operative length of stay, post-operative pain assessed by the Short Form McGill Pain Questionnaire-2, and phantom limb pain assessed using questions from the Trinity Amputation and Prosthesis Experiences Scales-Revised. Results for the secondary outcomes are not posted.

When several outcomes or comparisons are tested, the chance of at least one apparently notable finding can increase. General statistical methods for addressing multiplicity include defining a primary endpoint in advance, adjusting inference across tests, or clearly identifying exploratory analyses. The registry record does not report a multiplicity strategy, the planned hierarchy of outcomes, or whether any adjustment was used. Since no secondary analyses are reported, their statistical significance and uncertainty cannot be evaluated.

The registry provides primary outcome results for 5 participants in the single-shot group and 6 in the catheter group. It does not report the number randomized to each group, reasons for missing endpoint data, completion rates, or whether the primary summaries include all randomized participants. Missing-data handling and the analysis population are not reported in the registry record. Consequently, the posted denominators should be understood as the counts attached to the reported outcome summaries, not as evidence of complete follow-up.

The record also does not describe imputation, sensitivity analyses, protocol deviations, or an intention-to-treat analysis. These omissions limit assessment of how missing outcomes or departures from assigned treatment may have affected the results. No assumptions about these procedures can be inferred from the published group summaries.

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 in 0 of 5 participants at risk in the single-shot group and 0 of 6 participants at risk in the continuous-catheter group. It reports 0 other adverse events in 5 participants at risk in the single-shot group and 0 in 6 participants at risk in the continuous-catheter group. Deaths are reported as 0 in each group. No serious adverse event terms are listed.

These figures describe the events recorded for the groups and the risk denominators stated in the registry. They should not be interpreted as proving that no adverse events occurred outside the registry's reporting scope, or that rare harms are excluded. With small reported groups, the absence of recorded events provides limited information about uncommon outcomes. The registry record does not provide event definitions, surveillance procedures, severity details beyond the serious/non-serious categories, or an explanation of the safety analysis population.

Safety counts are distinct from the primary pain outcome. They do not establish comparative safety, because the record does not report a formal analysis of adverse-event differences or uncertainty. The appropriate reading is that no serious or other adverse events and no deaths are listed for the reported groups in the registry record.

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

The registry results describe a pilot comparison of two popliteal nerve-block approaches in people undergoing below-the-knee amputation. At 72 hours post-operatively, the single-shot group had a reported median pain score of 6.0 with standard deviation 3.07, based on 5 participants. The continuous-catheter group had a reported median of 4.0 with standard deviation 3.32, based on 6 participants. These summaries show the recorded group-level results, but they do not constitute a formal estimate of the effect of one approach relative to the other.

The registry does not report a confidence interval, p-value, or comparative model for the primary outcome. Therefore, the precision and inferential uncertainty of a group contrast are unknown from this record. The small outcome counts and the reported within-group variability further limit how confidently the descriptive results can be generalized. This is not a basis for concluding that either approach is superior or inferior.

The results also do not answer whether the approaches differed in opioid consumption, post-operative length of stay, scores on the Short Form McGill Pain Questionnaire-2, or phantom limb pain measured using questions from the Trinity Amputation and Prosthesis Experiences Scales-Revised. Those outcomes are listed but have no posted analyses. The safety record lists no serious adverse events, other adverse events, or deaths for the reported groups, but this does not establish the absence of risks beyond those recorded.

The record identifies the study as a pilot and says its data were intended to inform the design of a larger, appropriately powered study. Such a role is different from providing a definitive efficacy estimate. The registry does not report a sample-size justification, a target enrollment, or a statistical plan that would clarify the intended precision or decision criteria. The terminated status is recorded, but the reason for termination and its implications for interpretation are not reported.

In short, the result is descriptive and preliminary. It reports observed pain summaries in the groups and limited safety counts. It does not establish a causal or statistically precise difference, resolve the secondary outcome questions, or support a broad conclusion about outcomes beyond this trial record.

13. Why This Trial Matters Statistically

This trial is statistically informative because its registry record illustrates the difference between reporting group summaries and reporting a comparative analysis. Randomized allocation can support a fair comparison in principle, but interpretation also depends on knowing how many participants contributed outcomes, how missing data were handled, and how the comparison was estimated. The record provides outcome denominators and descriptive summaries, but not the analysis details needed to assess a formal treatment contrast.

The pilot purpose is relevant to study design. Preliminary data can help investigators understand outcome variability, feasibility, and measurement procedures when planning a larger study. The registry explicitly says the data were intended to inform a larger, appropriately powered study. However, the planned sample-size justification and statistical analysis plan are not reported in the registry record. A reader should not treat the observed sample as an adequately powered confirmatory test or infer power from the posted results.

The endpoint summary also raises an interpretive issue: the outcome is described as average NRS pain scores, while the parameter is labeled median and dispersion is labeled standard deviation. Because these summaries represent different distributional features, clear reporting of the estimand and analysis method matters. A formal estimate with an uncertainty interval would make the comparative question more transparent than group summaries alone.

Finally, the trial status is terminated, the primary analysis is not posted, and the secondary analyses are absent. These features do not invalidate the descriptive findings, but they constrain what can be learned from the registry. The record supports a careful account of what was measured and reported, while emphasizing the need for transparent analysis and uncertainty reporting in future research.

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 registry record gives limited information for assessing representativeness. It identifies the surgical context and nerve-block groups, but participant eligibility criteria, demographic characteristics, baseline pain information, and other clinical features are not reported in the registry record. Generalizability beyond the recorded study population therefore cannot be evaluated.

The trial is listed as terminated, but the reason for termination, timing of the decision, and relationship to the planned recruitment are not reported. The record reports enrollment of 11, while the primary outcome summaries are based on 5 participants in the single-shot group and 6 in the catheter group. Randomized-group denominators, participant flow, withdrawals, and reasons for absent outcomes are not reported, so the completeness of follow-up cannot be assessed.

The registry reports medians and standard deviations but does not explain the mismatch between the outcome description's use of average and the parameter label median. It also does not report a formal between-group estimate, confidence interval, p-value, model, or statistical analysis plan. The analysis population, missing-data approach, protocol deviations, and any sensitivity analyses are not reported in the registry record.

Although four secondary outcomes are listed, their results are not posted. The record also does not provide detailed adverse-event definitions, ascertainment methods, or follow-up beyond the stated safety counts. The single-masked label is recorded, but who was masked and how masking was maintained are not reported. These gaps restrict assessment of bias, precision, and completeness, particularly in a pilot trial with small outcome counts.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Liposomal Bupivacaine vs Continuous Nerve Catheters for Below the Knee Amputations — NCT05140499.
• Registry record last updated 2026-01-27; status last verified 2026-01.
• Results first posted 2026-01-27.
• 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 describes a prospective, randomized, single-masked, parallel-group phase 4 pilot trial comparing a single-shot liposomal bupivacaine popliteal nerve block with a continuous perineural popliteal nerve block catheter for below-the-knee amputation. The record lists enrollment of 11, status terminated, start date 2022-08-15, and primary completion date 2025-11-20.

The primary outcome was pain on a 0-10 numerical rating scale at 72 hours post-operatively. The single-shot group had a reported median of 6.0 with standard deviation 3.07, based on 5 participants; the catheter group had a reported median of 4.0 with standard deviation 3.32, based on 6 participants. No formal comparative analysis is reported. Four secondary outcomes are listed without posted analyses. The registry lists no serious adverse events, other adverse events, or deaths in the reported groups. Reasons for termination and the statistical analysis plan are not reported in the registry record.