Study of AxoGuard® Nerve Cap and Neurectomy for Treatment of Symptomatic Neuroma & Prevention of Recurrent Neuroma Pain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of AxoGuard® Nerve Cap and Neurectomy for Treatment of Symptomatic Neuroma & Prevention of Recurrent Neuroma Pain (NCT03940963), a randomized na study. The primary outcome is Change in Visual Analog Scale (VAS) For Pain Score at 12 Post-operative Months in Comparative Phase Subjects.

2. Clinical Question

3. Trial Design

This was a multicenter, prospective, randomized, subject-blinded, parallel-group comparative study. The registry lists the study as completed, with enrollment of 86. The start date is 2018-10-10 and the primary completion date is 2023-07-17. The study compared a device-assisted surgical approach with standard neurectomy for symptomatic neuromas of the foot or ankle. The registry does not report the number of centers or the details of how randomization was generated or concealed.

Participants assigned to AxoGuard® Nerve Cap underwent neuroma excision and placement of the cap over the proximal stump. Participants assigned to standard neurectomy underwent excision without the cap. The study description says participants were followed for 12 months. The listed primary measure was change in pain score at 12 post-operative months, while the secondary outcomes included patient-reported pain behavior, foot health, medication use, recurrence, total reported pain, and procedure- or device-related adverse events.

The primary outcome results are reported for 30 participants in the AxoGuard® group and 35 in the standard neurectomy group. These are the group sizes attached to the reported endpoint estimates, not the enrollment figure. The registry's stated intent-to-treat population also requires receipt of the assigned intervention and at least one post-baseline efficacy assessment, so the label does not mean that every randomized participant necessarily appears in these endpoint results.

The registry identifies the study phase as NA. It does not report the rationale for the planned enrollment, the allocation ratio, the duration of recruitment, or details of blinding beyond the description of subject blinding. Those design details 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

Analysis population for the primary outcome, as defined in the registry: Intent-to-treat (ITT) population, including all participants who were randomized, received the study device or underwent neurectomy, and completed at least one post-baseline assessment of efficacy. Analysis is based on treatment as randomized.

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: Modified intent-to-treat (mITT) population, participants that completed at least one post-baseline assessment of efficacy. Analysis was based on the treatment as received.

6. Primary Endpoint

The registry lists the primary outcome as Change in Visual Analog Scale (VAS) For Pain Score at 12 Post-operative Months in Comparative Phase Subjects, measured over 12 months.

The primary endpoint measures change from baseline in the Visual Analog Scale pain score at 12 post-operative months. Participants mark their current pain on a continuous line that is 10 centimeters long, recorded as a distance in millimeters from the line's left end. The scale ranges from 0-100 millimeters: 0 represents no pain and 100 millimeters represents the worst pain imaginable. A negative change indicates that the recorded score at follow-up is lower than at baseline.

The endpoint is patient reported, so it records the participant's own assessment rather than a clinician's rating of pain. A continuous score preserves gradations across the scale instead of reducing pain to a simple yes-or-no outcome. The reported summary is the mean change, accompanied by a 95% confidence interval for each group. That interval describes uncertainty around the group mean change; it is not an interval containing a specified proportion of individual participants.

Using a fixed follow-up point makes it possible to describe change at a common post-operative time, while the baseline comparison accounts for each participant's starting score in the change measure. The registry's primary endpoint is specifically the 12-month change in comparative-phase subjects. It does not report a minimum clinically important difference or another threshold for judging the importance of a score change.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical explanation: the endpoint is continuous because it is recorded on a millimeter scale, and the registry summarizes it with a mean. A mean represents the arithmetic center of measured changes in a group. It gives a useful group-level description but does not show the full distribution of participant scores or whether responses varied widely. No standard deviation or other measure of individual-level spread is reported alongside the group estimates.

The 95% confidence intervals quantify uncertainty in the estimated group means under the assumptions of the method used to construct them. In repeated samples under a suitable statistical model, intervals constructed in this way would capture the target mean at the stated long-run rate. For an individual trial, the interval is best read as a range of values compatible with the data and model, rather than as a guarantee about the true value. The intervals reported for the two groups concern separate means. A direct comparison requires an estimate of the difference and uncertainty calculated for that contrast.

The sponsor analysis is identified as a two-sided t-test and labeled non-inferiority. In general, a t-test evaluates a mean-based contrast using its estimated variability. A two-sided test considers departures in either direction; a non-inferiority question, however, requires a prespecified direction and margin that define how much worse the intervention could be while still meeting the criterion. The registry does not report that margin or the contrast estimate and its interval. As a result, the reported p-value cannot be fully interpreted as a non-inferiority decision from the registry record alone. The sponsor's own analysis takes precedence over any simple re-calculation when the registry reports a discrepancy; no discrepancy is flagged here, but the necessary summary statistics for a two-arm continuous re-calculation are missing or not estimable in the posted results.

The population definition matters. The registry calls the endpoint population intent-to-treat, but specifies that participants must have been randomized, received the device or undergone neurectomy, and completed at least one post-baseline efficacy assessment. Treatment is analyzed as randomized. This definition preserves randomized assignment for the analysis, while also requiring treatment receipt and post-baseline data. The registry does not report how participants without a qualifying efficacy assessment were handled, how missing follow-up values were addressed, or whether additional analysis populations were used.

What does a confidence interval add?

General statistical explanation: a point estimate alone does not indicate how precisely the underlying group mean has been estimated. A confidence interval displays a range of estimates consistent with the observed data under a specified procedure. Narrower intervals generally indicate greater precision for the target quantity, while broader intervals indicate more uncertainty. Precision is not the same as clinical importance: an interval can be precise without establishing whether the magnitude matters to patients.

Why is the non-inferiority margin important?

General statistical explanation: non-inferiority is not established simply because a conventional test fails to detect a difference. The analysis needs a clinically justified margin set before examining the results, and the treatment contrast must meet the prespecified rule relative to that margin. The margin helps define the largest acceptable loss on the chosen outcome. Without the margin, the reader cannot assess whether the reported analysis supports the intended claim. The registry's p-value is relevant information, but it does not replace the missing margin and comparative estimate.

What do planning illustrations mean?

General statistical explanation: sample-size planning illustrations based on an observed effect are hypothetical calculations about the size of a future study under stated assumptions. They are not estimates of power achieved by the completed trial. The registry describes such illustrations as using a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects set as stated fractions of the observed effect. These assumptions describe the illustration, not necessarily the trial's original design. The registry does not report the trial's own sample-size justification or planning assumptions.

The endpoint is a bounded scale, with possible recorded values from 0-100 millimeters before change is calculated. General statistical explanation: methods for comparing means often rely on assumptions about the sampling distribution and uncertainty. The registry does not provide enough detail to assess diagnostics, transformations, covariate adjustment, or robustness to departures from assumptions. Over-dispersion is mainly a concern for count outcomes when variability exceeds what a chosen count model expects; it is not the central issue for this mean-based continuous endpoint. The registry does not report a count-model analysis for the primary outcome.

10. Analyses Reported by the Sponsor

The registry's sponsor analysis is a two-sided t-test labeled non-inferiority, with p = 0.011. That result is distinct from the separate group mean changes and confidence intervals: it is the only posted inferential result explicitly attached to a comparison between AxoGuard® Nerve Cap and standard neurectomy.

The registry does not report the sponsor's treatment-contrast estimate, its confidence interval, the non-inferiority margin, or enough detail to reconstruct the test. It also flags that values for a two-arm comparison of this continuous endpoint are missing or not estimable, so no simple unadjusted re-calculation is available from the posted summary statistics. The sponsor's own analysis takes precedence if a recalculation differs; in this record, no discrepancy is flagged, but the missing comparison quantities still limit independent checking.

The p-value should not be treated as the size of the treatment effect, the probability that non-inferiority is true, or a stand-alone description of the clinical result. Interpretation requires the margin and the direction and scale of the contrast, as well as the sponsor's analysis details. Those elements are not reported in the registry record. The posted p-value can therefore be described accurately, but the full basis for the sponsor's non-inferiority conclusion cannot be evaluated from this record alone.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 15 outcome measures and reports 12 secondary outcomes as posted. It also lists 6 analyses. These figures indicate that the study considered multiple outcomes and analyses, but they do not reveal which results were prespecified, which were treated as confirmatory, or how the investigators handled the possibility of false-positive findings across multiple tests. The multiplicity adjustment strategy, if any, is not reported in the registry record.

This matters because each additional statistical test creates another opportunity for a chance finding. General statistical explanation: when several hypotheses are tested, a prespecified approach may control the overall error rate, prioritize a primary endpoint, or distinguish confirmatory analyses from exploratory ones. Without the analysis plan, it is not possible to determine whether the reported p-value was adjusted, whether it belongs to a hierarchy of tests, or how secondary outcomes should be weighed alongside the primary endpoint.

The registry defines the primary efficacy population as randomized participants who received the assigned intervention and completed at least one post-baseline efficacy assessment, with treatment analyzed as randomized. That definition is informative, but it does not describe missing-data methods. The number of participants lacking a qualifying assessment, reasons for missingness, assumptions used to handle missing values, and any sensitivity analyses are not reported in the registry record. The registry also does not report whether all randomized participants were included in other analyses or whether a per-protocol population was used.

Missing outcome data can affect both the estimated mean and its uncertainty, particularly if the chance of an assessment being missing is related to the outcome or treatment experience. General statistical explanation: different missing-data assumptions can produce different estimates, so transparent methods and sensitivity analyses help readers judge robustness. The registry record does not provide those details for this endpoint. It also does not report interim analyses, stopping rules, or the statistical analysis plan. These omissions limit assessment of how the endpoint, analysis population, and multiple outcomes were handled before results were known.

12. 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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: acute myocardial infarction (2.4%), impaired healing (2.4%), appendicitis (2.4%), covid-19 pneumonia (2.4%), postoperative wound infection (2.4%).

The registry reports serious adverse events among 6 of 41 participants at risk in the AxoGuard® Nerve Cap group and 5 of 43 participants at risk in the standard neurectomy group. For other adverse events, it reports 16 of 41 at risk in the AxoGuard® group and 16 of 43 at risk in the standard neurectomy group. No deaths are reported in either group. These are counts and denominators as recorded; the registry summary does not provide adjusted comparisons or confidence intervals for these safety results.

The serious-event terms listed include acute myocardial infarction, impaired healing, appendicitis, COVID-19 pneumonia, postoperative wound infection, and neuroma, each reported at 2.4%. The posted summary does not make clear which treatment group each term belongs to, whether a participant could contribute more than one term, or how the percentages were calculated. The terms should therefore be read as registry-listed event categories, not as a basis for a direct group comparison.

Serious adverse events and other adverse events are separate summaries, and the figures should not be added together. The registry describes procedure- or device-related adverse-event outcomes through 6 months among secondary outcomes, but the group counts above are not identified as a treatment-related subset. The record does not report event severity details, exposure-adjusted rates, or a statistical comparison. Counts alone do not establish whether an observed difference is meaningful, and absence of reported deaths does not describe every aspect of safety.

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

The registry documents a randomized comparison of AxoGuard® Nerve Cap and standard neurectomy, with mean VAS pain-score change reported at 12 post-operative months. Both group means are negative, and each group has a reported confidence interval. These estimates describe average within-group change among the participants included in the endpoint results. The sponsor also reports a two-sided p-value for an analysis labeled non-inferiority.

The posted results do not provide the treatment contrast, its confidence interval, or the non-inferiority margin. Consequently, the numerical group summaries and p-value do not allow readers to independently assess the distance between the treatments on the primary outcome or verify the non-inferiority criterion. The record also does not state a threshold for a clinically meaningful score change. These gaps limit conclusions about comparative magnitude and patient-relevant importance.

The findings do not establish that an individual participant will experience a particular change. Group means can conceal variation in responses, and the registry does not report individual-level distributions for the primary endpoint. The analysis population is defined by randomization, treatment receipt, and completion of at least one post-baseline assessment; missing-data handling is not reported. That uncertainty should be kept in mind when interpreting the endpoint estimates.

The registry's listed secondary outcomes cover several domains, but the posted record does not give numerical results for all of them. Safety summaries include serious and other adverse-event counts and no deaths, while details needed for a complete comparative safety assessment are not reported. Overall, the record supports a description of the reported endpoint estimates and sponsor test, but not an independent confirmation of the non-inferiority decision or a comprehensive judgment across all benefits and harms.

14. Why This Trial Matters Statistically

This study illustrates why a clinical trial result should be read at the level of the estimate, its uncertainty, and the actual hypothesis being tested. The group mean changes give useful descriptions of pain-score trajectories, while the sponsor's non-inferiority analysis addresses a comparative question. Those are related but different statistical summaries. A p-value without the contrast and its margin leaves a substantial part of the non-inferiority interpretation unauditable from the registry record.

The endpoint also highlights the distinction between statistical and clinical interpretation. A mean change and confidence interval quantify the average response and its precision, but a decision about whether that change matters requires a clinically meaningful threshold or other prespecified interpretation framework. Such a threshold is not reported. The result is therefore most informative when stated in its measured units and alongside the limits of the comparative analysis.

Another important feature is the analysis population. The registry's use of an intent-to-treat label is accompanied by eligibility conditions requiring treatment receipt and a post-baseline efficacy assessment. Reporting the definition, missingness, and sensitivity analyses is important because they influence how well the analysis preserves the benefits of randomization and how robust estimates are to incomplete follow-up. The record gives the population definition but not enough detail to assess missing-data consequences.

Finally, the trial considered a range of patient-reported, medication, recurrence, and safety outcomes. Multiple outcomes can broaden the clinical picture, but they also make prespecification and multiplicity methods important for interpreting isolated statistical findings. The registry record leaves those methods unreported. These features make the study a useful example of careful separation between observed group summaries, a sponsor's inferential claim, and what can be independently checked using the posted information.

15. 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 main limitation for interpreting the primary comparison is that the registry reports group means and confidence intervals but not a direct treatment contrast with its confidence interval. It labels the sponsor's test as non-inferiority yet does not report the margin. Without these elements, the comparative result cannot be independently assessed against the criterion that defines non-inferiority.

The registry does not report the detailed statistical analysis plan, the sample-size justification, or the method used to generate and conceal randomization. Blinding is described as subject blinded, but the record does not specify which other study personnel, if any, were blinded. The record also does not report whether the primary analysis was adjusted for baseline values or other covariates, or whether model assumptions were checked.

The stated analysis population requires participants to receive their assigned intervention and complete at least one post-baseline efficacy assessment. The registry does not give missingness counts or reasons, explain how incomplete follow-up was handled, or report sensitivity analyses. Since missing outcome data can affect estimates, the absence of these details leaves uncertainty about robustness.

The registry lists numerous outcomes and analyses, but multiplicity methods and the status of secondary analyses as confirmatory or exploratory are not reported. The summary also does not give numerical results for every listed secondary outcome. Safety summaries are limited to counts and selected event terms; attribution, detailed event timing, and comparative uncertainty are not reported. Finally, the endpoint results describe a particular study population with foot or ankle symptomatic neuromas and a 12-month follow-up. The registry record does not provide enough detail to assess how broadly the findings apply beyond that setting.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of AxoGuard® Nerve Cap and Neurectomy for Treatment of Symptomatic Neuroma & Prevention of Recurrent Neuroma Pain — NCT03940963.
• Registry record last updated 2025-01-09; status last verified 2024-12.
• Results first posted 2025-01-09.
• 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.

19. Record Summary

NCT03940963 is a completed, multicenter, prospective, randomized, subject-blinded, parallel-group comparison of AxoGuard® Nerve Cap with standard neurectomy for symptomatic neuromas of the foot or ankle. The registry lists enrollment of 86 and follow-up of 12 months. The primary endpoint is change in VAS pain score at 12 post-operative months.

The registry reports mean changes of -86.62 millimeters for AxoGuard® Nerve Cap and -72.67 millimeters for standard neurectomy, with a 95% confidence interval for each group. It also reports a two-sided t-test p-value of 0.011 labeled non-inferiority. The comparative estimate and non-inferiority margin are not reported, limiting independent interpretation of that analysis. Safety counts are reported for serious and other adverse events, with no deaths in either group. Missing-data methods, multiplicity handling, and the detailed analysis plan are not reported in the registry record.