Evaluating Postoperative Non-Opioid Pain Management Utilizing Local Anesthetics Coupled With Modulated Coagulation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluating Postoperative Non-Opioid Pain Management Utilizing Local Anesthetics Coupled With Modulated Coagulation (NCT04814433), a randomized phase 4 study. The primary outcome is Change in Postoperative Pain Control.

2. Clinical Question

The clinical question concerns pain ratings after hand surgery and whether the posted summaries differ across treatment combinations. The interventions share topical lidocaine and bupivacaine, while the groups vary in the addition of thrombin and antifibrinolytic agents. This structure makes the local-anesthetic-only group the listed reference, but it does not mean the published group summaries isolate the effect of any one added ingredient. The record does not describe a statistical contrast designed to separate those components.

The diary scale runs from 1 to 10. Scores of 1-2 are categorized as no pain, 3-4 as mild pain, 5-6 as moderate pain, 7-8 as severe pain, and 9-10 as the worst pain imaginable. The record says that diary entries were made from the day of surgery through postoperative day 14. It does not clarify how daily observations were combined to produce the posted primary outcome summaries.

3. Trial Design

The registry describes a prospective, randomized, single-blinded, parallel-group study, listed as Phase 4. It evaluates topical local anesthetics combined with agents affecting coagulation in electively created hand-surgery wound beds. The study's official title calls it placebo-controlled. In the posted arm descriptions, however, the reference treatment is topical lidocaine and bupivacaine alone; no separate inert placebo arm is described.

Four treatment groups appear in the primary outcome results. The reference group received topical lidocaine and bupivacaine alone. The other groups received the same local anesthetics with thrombin; with thrombin and tranexamic acid; or with thrombin and aminocaproic acid. The intervention descriptions specify 5 ml of 1% lidocaine and 5 ml of 0.25% bupivacaine in each solution. The thrombin-containing combinations specify 10000 units of thrombin; the tranexamic acid combination specifies 500 mg, and the aminocaproic acid combination specifies 1000 mg.

Enrollment is listed as 46. The record gives a start date of 2021-03-24, a primary completion date of 2023-07-10, and a status of terminated. The reason for termination is not reported in the registry record. The posted primary endpoint groups have sample sizes of 8, 6, 5, and 6, respectively. These endpoint counts are not the same information as the overall enrollment figure, and the record does not explain the difference.

The record does not report the randomization procedure, allocation concealment, who was blinded, or how masking was maintained. It also does not report the planned sample-size justification, duration of follow-up beyond the endpoint timeframe, or any interim monitoring plan. Those details should not be inferred from the randomized or single-blinded labels alone.

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 Change in Postoperative Pain Control, measured over Day 1 preoperative , Day 14 postoperative.

The primary outcome is named “Change in Postoperative Pain Control.” It uses self-reported pain ratings recorded in a daily diary, with the registry describing entries from the day of surgery through postoperative day 14. The stated timeframe is Day 1 preoperative to Day 14 postoperative. The diary scale ranges from 1 to 10, with 1-2 representing no pain, 3-4 mild pain, 5-6 moderate pain, 7-8 severe pain, and 9-10 the worst pain imaginable.

Pain ratings are used because they capture the participant's own experience of pain over the postoperative period. Repeated diary recording can describe changes over time rather than relying solely on a single later recollection. That is a general reason to use a diary measure; it does not establish that this trial's diary data were complete or that the chosen measure was analyzed in a particular way.

The posted endpoint results are identified as means with full ranges for each group. The registry record does not describe precisely how the named “change” was calculated, such as which diary days were combined or how the preoperative and postoperative measurements were used. It does not report a standard deviation, confidence interval, adjusted estimate, or inferential test for this outcome. As a result, the displayed summaries describe the reported group values and ranges, but do not establish the precision of a between-group effect or whether group differences exceed random variation.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Randomization is intended, in general, to make treatment groups comparable on average with respect to measured and unmeasured characteristics. It does not guarantee that small groups will be balanced, nor does the label alone disclose how the assignment sequence was created or concealed. The registry identifies the study as randomized, but the randomization method and allocation concealment are not reported in the registry record.

What do the group means describe?

A mean is a measure of the center of a set of observations. Here, the registry reports a mean pain value for each treatment group and identifies the dispersion as the full range. A mean can be useful for comparing broad group summaries, but it can conceal variation among participants. The range gives the lowest and highest observed values, but does not show the shape of the distribution or how many participants had values near the middle. The registry does not report standard deviations or other distribution summaries for this endpoint.

Because the outcome is described as a change, readers would ordinarily want to know exactly which measurements were subtracted or summarized. For a diary collected over multiple days, the definition of the outcome can affect its interpretation: a single-day score and a summary across several days answer different questions. The registry's timeframe and diary description do not specify the calculation used for the posted mean. That calculation is not reported in the registry record.

What would a confidence interval add?

In general, a confidence interval expresses the uncertainty around an estimate under a statistical model and its assumptions. It helps readers distinguish an estimate's central value from the range of values that remain reasonably compatible with the data. A range of observed participant scores is not a confidence interval: it describes the sample's observed extremes, not uncertainty about a population estimate. No confidence intervals are reported for the primary outcome, so its estimation precision cannot be assessed from the registry results.

In general, an inferential comparison requires a defined contrast, such as a difference between two treatment groups or an overall comparison across groups, together with an estimate of uncertainty. The record lists four arms and their summaries, but reports no analyses. It therefore does not provide a test statistic, p-value, confidence interval, or adjusted treatment contrast. The fact that four descriptive means are available does not substitute for a prespecified inferential analysis.

Why does the analysis model matter?

General statistical practice calls for an analysis method suited to the outcome scale, trial design, and data structure. Pain diary values are bounded scale scores, and repeated measurements from the same participant are related rather than independent. An analysis could account for that repeated-measure structure, but the record does not say whether such an analysis was planned or conducted. It also does not report whether the primary outcome was treated as a continuous score, an ordinal measure, or another form.

In general, over-dispersion occurs when observed variability exceeds what a chosen model assumes. If a model is too restrictive about variability, standard errors can be too small and intervals or tests can appear more certain than warranted. This is a general modeling concern, not a finding about this trial: the registry does not report a fitted model or sufficient distributional detail to assess over-dispersion.

How should sample-size planning be read?

Sample-size calculations are planning exercises based on assumptions about the effect to detect, variability, significance threshold, allocation, and analysis method. They do not show that a study had a particular probability of obtaining a significant result after the data are observed. The registry record does not report the trial's own sample-size justification. Any separate planning illustration based on observed effects should be read only as a hypothetical design calculation, not as observed power or as evidence that the trial was adequately sized.

The posted assumptions for such illustrations describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of the observed effect. These are planning assumptions, not reported features of this trial's original design. The registry lists four treatment groups, and the primary results include no two-arm inferential analysis. Accordingly, a two-arm planning illustration cannot be treated as a trial result or as the protocol's documented sample-size plan.

More generally, clinical trial results are most interpretable when the outcome definition, analysis population, handling of missing data, model, contrast, and uncertainty estimates are reported together. The registry record does not provide those details for the primary endpoint. The descriptive results can be stated as posted, but they do not support a more elaborate statistical conclusion about comparative treatment effects.

10. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes, treatment contrasts, time points, or analysis choices are examined. In general, evaluating many comparisons can increase the chance of a false-positive finding unless the analysis plan addresses that issue. This record lists one primary outcome and two secondary outcomes, and the primary results cover four arms. It does not report a multiplicity strategy, a hierarchy of hypotheses, or which comparisons were planned. Since no inferential analyses are posted, there are no reported p-values whose multiplicity adjustment can be assessed.

The registry describes diary entries over the postoperative period, but it does not report how missing diary days were handled, whether participants with incomplete diaries were included, or how missing outcome values were treated. Those decisions can affect both the analysis population and the interpretation of a summary. The handling of missing data is not reported in the registry record.

The record does not state whether the primary analysis followed an intention-to-treat principle, used a per-protocol population, or applied another population definition. It also does not explain the gap between the overall enrollment of 46 and the smaller numbers listed for the primary endpoint groups. Those endpoint counts should therefore be read as the counts attached to the posted arm summaries, not as a complete account of participant flow.

The two listed secondary outcomes are amount of postoperative opioid pain medication required and total time in the post-anesthesia care unit. Their results are not reported in the registry record. There is consequently no basis in the posted results to assess whether missing secondary results reflect unavailable data, analysis decisions, or another reason.

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, other adverse events, and deaths by treatment group. For the topical lidocaine and bupivacaine alone group, 0 serious adverse events and 0 other adverse events were reported among 8 at risk, with 0 deaths. For the thrombin group, the corresponding figures are 0, 0, and 0 among 6 at risk. For the thrombin and tranexamic acid group, they are 0, 0, and 0 among 5 at risk. For the thrombin and aminocaproic acid group, they are 0, 0, and 0 among 6 at risk.

These entries describe events recorded in the registry for the listed groups and at-risk counts. Zero reported events is not proof that no events occurred outside the registry's reporting scope, nor does it establish the absence of risk. The groups are small, and the record does not provide uncertainty estimates for these safety summaries, a detailed event-collection description, or serious-event terms. No serious-event terms are listed.

Safety summaries should also be considered alongside the study's reporting status and endpoint counts. The record does not explain the difference between enrollment and the numbers at risk for these outcomes, or provide additional follow-up detail. The figures should be read as registry-reported counts, not as a comparative safety analysis or a conclusion about the relative safety of the treatment combinations.

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

The posted results establish that the registry contains descriptive primary-outcome summaries for four treatment groups, with means and full ranges for each. They also establish the group-specific sample sizes attached to those summaries and the registry-reported adverse-event counts. These are statements about the results as recorded, not estimates of causal treatment effects.

The results do not establish that any treatment combination reduces pain, changes pain compared with another group, or changes opioid use. The registry reports no inferential analyses for the primary outcome and no posted results for the two secondary outcomes. It provides no confidence intervals or adjusted estimates that would quantify the uncertainty around a between-group comparison. The numerical ordering of group means, on its own, is not evidence of a treatment difference.

The endpoint's name refers to change, but the registry does not define how the posted values were derived from the preoperative and postoperative diary measurements. This makes it difficult to interpret the means as a specific change over time. The ranges give observed endpoints within each group, but not the distribution of observations or the uncertainty of the group mean.

These findings also do not explain why the study was terminated. The registry lists the status as terminated, but the reason is not reported in the registry record. Likewise, the posted data do not explain the difference between overall enrollment and the smaller endpoint-specific counts, or indicate whether missing diary information or other exclusions account for it.

In general, a randomized design can support causal comparisons when allocation, outcome definitions, analysis populations, and inferential methods are clearly reported and the data are analyzed accordingly. Here, the record identifies randomization but does not provide the analysis needed to estimate comparative effects. The appropriate reading is therefore limited: the recorded group summaries and event counts can be described, while claims about efficacy, comparative safety, or clinical benefit are not supported by the posted results.

13. Why This Trial Matters Statistically

This study is statistically interesting because it places several treatment combinations in parallel groups while keeping topical lidocaine and bupivacaine common to all arms. That structure raises an important design and analysis question: which contrast is intended to answer the clinical question? Comparing the local-anesthetic-only group with a combination group would assess the added ingredients as a package. It would not, by itself, isolate the separate contribution of thrombin, tranexamic acid, or aminocaproic acid.

The primary measure is based on repeated self-reported pain ratings. Repeated measurements can contain more information about a postoperative course than a single observation, but they also require a clear outcome definition and a method that accounts for related measurements within participants. The registry describes the diary period but does not explain how its entries were condensed into the reported group means. This illustrates why a clinical endpoint's label and its operational definition both matter for statistical interpretation.

The small endpoint group counts and absence of reported uncertainty estimates also emphasize the difference between descriptive values and comparative evidence. Means and ranges can show what was recorded, but do not reveal how precisely a population contrast has been estimated. Without an analysis plan or inferential results, the group summaries cannot establish whether the observed ordering is more than sampling variation.

Finally, the registry's overall enrollment, endpoint-specific counts, secondary outcomes, and terminated status make completeness and transparent reporting central to interpretation. The record does not resolve these issues, so they remain relevant uncertainties rather than evidence for a particular explanation. The trial highlights how randomization alone does not make results self-interpreting: clear endpoint definitions, participant accounting, analysis methods, and uncertainty estimates are essential for understanding what a trial can support.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several limitations specific to this record constrain interpretation. The primary outcome is labeled as a change, while its description refers both to a preoperative-to-postoperative timeframe and to daily diary entries through postoperative day 14. The record does not specify how those repeated measurements produced the reported mean. It also does not report a standard deviation, confidence interval, or inferential analysis.

Although the study is identified as randomized and single-blinded, the registry does not describe the randomization procedure, allocation concealment, or who was blinded. The official title calls the study placebo-controlled, but the listed reference arm is topical lidocaine and bupivacaine alone, and no separate inert placebo arm is described. The record does not clarify this terminology.

Overall enrollment is 46, while the endpoint summaries list group counts of 8, 6, 5, and 6. The record does not provide participant flow or explain those counts. It does not report missing-data handling or the analysis population. The results for postoperative opioid medication amount and PACU time are not reported in the registry record.

The registry status is terminated, but its reason is not reported in the registry record. The record also does not report the trial's own sample-size justification, interim analyses, or a detailed statistical plan. These omissions prevent assessment of whether the reported endpoint summaries reflect the planned analysis and how completely the registered outcomes were observed.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Evaluating Postoperative Non-Opioid Pain Management Utilizing Local Anesthetics Coupled With Modulated Coagulation — NCT04814433.
• Registry record last updated 2024-06-26; status last verified 2024-05.
• Results first posted 2024-06-26.
• 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

NCT04814433 is a Phase 4 prospective randomized, single-blinded, parallel-group study of topical pain-management combinations in hand surgery. It enrolled 46 participants and is listed as terminated. The record gives a start date of 2021-03-24 and a primary completion date of 2023-07-10; the reason for termination is not reported in the registry record.

The primary outcome is named “Change in Postoperative Pain Control” and is based on self-reported diary ratings. Four treatment groups have posted means and full ranges, with endpoint counts of 8, 6, 5, and 6. No inferential analyses are reported. The two listed secondary outcomes concern postoperative opioid medication and PACU time, but their results are not reported in the registry record.

Registry safety entries report no serious adverse events, other adverse events, or deaths in the listed groups. These counts are descriptive and do not establish comparative safety. Missing-data methods, analysis populations, the primary outcome calculation, and the trial's own sample-size justification are not reported in the registry record.