Endovascular Denervation Improves Limb Ischemia in Patients With Peripheral Artery Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Endovascular Denervation Improves Limb Ischemia in Patients With Peripheral Artery Disease (NCT04060797), a randomized na study. The primary outcome is Change of Ankle Brachial Index (ABI) at 6-month Post-procedure..

2. Clinical Question

The clinical question is whether adding endovascular denervation to the revascularization procedure is associated with a different change in ankle-brachial index than revascularization alone. The proposed rationale in the registry is that sympathetic overactivity partly promotes peripheral artery disease and lower-limb ischemia, and that arterial denervation could alter sympathetic activity. That rationale explains the intervention being studied; it does not establish the mechanism or predict the trial result.

The primary measure is a change score, calculated as the ankle-brachial index at 6 months after the procedure minus the baseline value. The comparison therefore concerns change over time in the two randomized groups, rather than a single post-procedure measurement. The posted summaries give a median change for each group, with a standard deviation as the dispersion measure. They do not provide a confidence interval or p-value for the primary between-group contrast. The record also does not report the clinical question as a formal hypothesis test or describe a prespecified analysis method.

3. Trial Design

This was a randomized, parallel-group trial with no masking reported. The registry lists 38 participants as enrolled and identifies the study as completed. The study phase is listed as not applicable. Zhongda Hospital is named as sponsor. The recorded study start date is 2019-08-23, and the primary completion date is 2021-09-30.

The two groups differed by whether endovascular denervation was added to the procedure. The control group received balloon dilation or stent implantation only. The EDN group received endovascular denervation at the iliac artery site distal to the superficial femoral artery and proximal to balloon dilation or stent implantation. Thus the registry describes denervation as an addition to, rather than a replacement for, the procedural treatment used in the control group.

Random allocation can support a fair comparison by balancing participant characteristics across groups on average, but the record does not report how the random sequence was generated or concealed. It also does not state whether allocation was stratified, whether participants or outcome assessors were masked, or how adherence to assigned treatment was handled. Masking is listed as none. These omissions limit assessment of how the randomization was implemented and whether knowledge of treatment assignment could have influenced care, measurement, or reporting.

The primary endpoint was change in ankle-brachial index from baseline to 6 months after the procedure. The registry also lists secondary outcomes involving ankle-brachial index at 1 week and 3 months, transcutaneous oxygen pressure, and Rutherford category. It records 13 outcome measures and 12 posted secondary results. Details of the planned analysis populations and any formal sample-size justification 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

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 of Ankle Brachial Index (ABI) at 6-month Post-procedure., measured over From baseline to 6 months post procedure.

The primary endpoint is the change in ankle-brachial index from baseline to 6 months after the procedure. The ankle-brachial index is the ratio of blood pressure in the lower legs to blood pressure in the arms. It is used as a measure related to lower-limb arterial blood flow and disease severity. The registry gives a normal range of 0.90 to 1.30, describes 0.41 to 0.90 as indicating mild to moderate arterial disease, and describes 0.40 and lower as indicating severe disease.

A change score focuses on how the measure shifted from each participant’s baseline rather than comparing only the groups’ final measurements. The registry defines the change as the 6-month value minus the baseline value and states that a higher change value represents a better result. That direction is the record’s stated interpretation of the endpoint; the reported group summaries alone do not establish whether a between-group difference is statistically distinguishable from chance.

The registry reports the primary outcome using medians and standard deviations. For the control group, the posted median change is 0.24, with a standard deviation of 0.15; for the EDN group, the posted median change is 0.44, with a standard deviation of 0.3. Each group has 19 participants in the primary outcome record. No primary confidence interval, p-value, adjusted estimate, or analysis model is reported in the registry record. Therefore, the posted summaries describe the observed group values but do not quantify the uncertainty around a formal comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry gives descriptive primary outcome summaries but does not report a primary statistical comparison. Understanding what those summaries can and cannot show is important: a measure of central tendency describes the observed group data, while an inferential comparison estimates uncertainty about the difference between groups. The posted primary figures are medians with standard deviations, but no confidence interval, p-value, or model-based estimate for the between-group contrast appears in the registry record.

What does a median describe?

In general, a median is the middle value when observations are ordered. It can be useful when values are skewed or contain extreme observations because it is less influenced by unusually high or low values than the mean. A median does not by itself describe the full distribution, and two groups with different medians may still have substantial overlap. The registry reports median changes of 0.24 in the control group and 0.44 in the EDN group. Those are summaries of the observed change values, not adjusted effects.

The record pairs each median with a standard deviation. In general, standard deviation describes how dispersed individual observations are around a mean. It is not usually a direct measure of uncertainty around a median. Because no statistical method or explanation of this pairing is reported, readers cannot tell from the record whether the standard deviations were intended as descriptive spread, how they were calculated, or how they relate to a comparison of medians. It would be inappropriate to treat them as standard errors or to derive a confidence interval from them without an analysis plan and suitable assumptions.

Why is a confidence interval useful?

In general, a confidence interval presents a range of values compatible with an estimate under a stated statistical procedure. It communicates precision: a narrower interval indicates less sampling uncertainty under that method, while a wider interval indicates more. An interval for the primary between-group contrast would help show whether the data are compatible with a range of effects, including no difference. No such interval is reported for the primary endpoint, so its precision cannot be judged from the posted primary summaries alone.

What does the secondary comparison represent?

The secondary Rutherford category result is reported as counts of participants, with 17 of 19 in the control group and 19 of 19 in the EDN group. A recalculated, unadjusted risk-difference estimate is 0.105, with a 95% interval from -0.033 to 0.243; the unadjusted p-value is 0.146. The interval includes zero, the null value for a risk difference. In general, an interval that includes the null indicates that the data do not rule out no difference at the interval’s stated confidence level. It does not prove that the groups are identical, and it does not establish that any possible difference is clinically important. The recalculated result is a simple comparison from posted counts, not a sponsor-reported model or adjusted analysis.

For binary outcomes, a risk difference expresses the difference in proportions between groups. In general, an interval around a risk difference conveys uncertainty in that absolute contrast. The recalculated secondary comparison is unadjusted, so it does not account for other variables or any multiplicity from examining several outcomes. No adjustment strategy is reported. The confidence interval and p-value should therefore be interpreted as exploratory statistical summaries rather than as confirmation of a prespecified secondary hypothesis.

Why can over-dispersion matter?

In general, over-dispersion occurs when observed variability exceeds what a statistical model assumes. If a model underestimates variability, its confidence intervals may be too narrow and its p-values too small. Choosing an appropriate model requires knowing the outcome structure and analysis plan. The registry does not report a model for the primary outcome, so there is no basis to assess whether over-dispersion was considered or relevant to the sponsor’s analysis.

The record describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power and not evidence that the trial was designed around a prespecified effect. The protocol’s sample-size justification is not reported in the registry record, and no planning sample-size values are reported in the information available for interpretation.

10. Multiplicity, Missing Data and Analysis Populations

The registry record does not report how multiplicity was handled. Multiplicity arises when several outcomes, time points, or statistical comparisons are examined. In general, as the number of comparisons increases, the chance of at least one apparently unusual result can increase even when there is no true effect. A prespecified strategy can control or describe this issue, but no such strategy is reported for the secondary outcomes.

The record lists 13 outcome measures and 12 posted secondary results. Secondary measures include ankle-brachial index at 1 week and 3 months, transcutaneous oxygen pressure, and Rutherford category. Some outcome descriptions are repeated, and the registry does not explain whether the repetitions represent distinct measurements, time points, or reporting entries. It also does not report which secondary comparisons were planned as confirmatory, whether any were prioritized, or whether a correction or hierarchical testing procedure was used. The available unadjusted secondary comparison should therefore not be read as if it were the sole planned test.

Missing-data methods and analysis populations are not reported in the registry record. The record does not say how many participants contributed data at each assessment, whether any observations were missing, how missing outcomes were handled, or whether the primary analysis followed intention-to-treat principles. The 19 participants reported per group for the primary outcome describe the posted outcome summaries; they do not establish that all randomized participants were included at every time point or that missingness was absent.

The record also does not report the primary statistical model, covariate adjustment, sensitivity analyses, or a plan for handling protocol deviations. These details matter because different reasonable approaches can produce different estimates, particularly when outcome data are incomplete or follow-up differs between groups. Without a prespecified analysis description, the reader cannot assess whether the posted results follow the intended plan or whether selective reporting may have influenced which results appear.

These are reporting limitations, not evidence that data were necessarily missing or that analyses were necessarily changed. The registry simply does not document the information needed to evaluate those possibilities. This uncertainty reinforces the need to interpret the primary summaries descriptively and the secondary comparisons cautiously.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports zero serious adverse events in each group. It lists 19 participants at risk in the control group and 19 in the EDN group. No deaths are reported in either group. For other adverse events, the record lists 1 affected participant in the control group and 2 in the EDN group, with 19 at risk in each group.

These counts are small and describe only the events recorded in this registry entry. The record does not provide the event terms for the other adverse events, details about severity or timing, or information about how events were collected and assessed. It lists no serious adverse event terms. The absence of reported serious events in these groups is not proof that serious harms cannot occur, and the small group sizes limit what can be learned about uncommon events.

Counts should be read as descriptive safety reporting, not as a formal comparison of risk. The registry does not report a statistical safety analysis, a prespecified safety endpoint, or follow-up procedures for adverse events. Differences in counts alone cannot establish whether treatment assignment caused an event or whether the observed counts represent a meaningful difference between groups.

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

The result establishes what the registry reports: in a randomized comparison involving 38 participants, the EDN group had a posted median ankle-brachial index change of 0.44 at 6 months, compared with 0.24 in the control group. The registry states that a higher change value represents a better result. The standard deviations were 0.3 for the EDN group and 0.15 for the control group, with 19 participants in each group.

Those descriptive values do not establish the size or precision of a between-group effect. The primary outcome record contains no confidence interval, p-value, or sponsor-reported comparative estimate. It therefore cannot show how much uncertainty surrounds the apparent difference in medians or how compatible the observed data are with other possible group differences. A formal conclusion about the primary comparison cannot be drawn from the posted summaries alone.

The result also does not show that the procedure changes the underlying disease process, that the proposed sympathetic mechanism was demonstrated, or that any observed change persists beyond the reported assessment. The registry describes a 6-month primary time point and lists secondary measures, but the evidence available does not establish a complete pattern across outcomes or longer-term effects. The counts for adverse events likewise do not establish comparative safety.

More generally, a randomized design can support causal interpretation when allocation is implemented appropriately, follow-up is sufficiently complete, outcomes are measured consistently, and analyses respect the trial plan. Important details about those conditions are not reported in the registry record. Thus, the posted data can be described as a higher median change in the EDN group, but they do not by themselves demonstrate that adding denervation caused a reliable or clinically meaningful improvement.

This interpretation is about statistical evidence in the registry, not advice about treatment. Clinical meaning would also depend on context and evidence beyond the posted summaries, neither of which can be established by the primary descriptive statistics alone.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the difference between a randomized design and a fully reported comparative result. Randomization is intended to make treatment groups comparable in expectation, which supports estimation of an intervention effect. Yet a randomized label does not replace reporting the effect estimate, its uncertainty, the analysis population, and the procedures used to handle incomplete data. Those elements are essential for understanding what the results support.

The primary outcome is a change score assessed 6 months after the procedure, and the registry supplies group medians and standard deviations. Those summaries communicate the observed central values and some information about variability, but they do not quantify uncertainty in the between-group contrast. A reported confidence interval would help readers judge precision; a clearly described analysis would explain how the comparison was estimated. Neither is included for the primary endpoint.

The trial also illustrates why secondary outcomes require context. Multiple measures and time points can provide broader information, but their interpretation depends on prespecification, complete reporting, and a plan for multiplicity. Without those details, an isolated unadjusted comparison is exploratory and should not outweigh an incompletely reported primary result.

Finally, safety counts and efficacy summaries answer different questions and have different limitations. The adverse-event counts are useful as a record of what was reported, but a small trial cannot characterize uncommon events reliably. Transparent reporting of the protocol, analysis plan, participant flow, and outcome data would allow a more complete assessment of both benefits and harms. The registry entry highlights the importance of interpreting the numerical summary together with the completeness and clarity of the statistical record.

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 trial affect interpretation. The total enrollment was 38, with 19 participants in each group for the primary result. This provides a limited amount of information for estimating group differences and for describing variability. The registry does not report a formal sample-size justification, a target effect used in the trial’s design, or whether recruitment met the planned target. The planning illustrations described in the record are based on the observed effect and should not be mistaken for the trial’s original design rationale.

The primary result is reported as medians with standard deviations, but the registry does not provide a primary comparative estimate, confidence interval, p-value, or analysis method. The pairing of medians and standard deviations is not explained. Without the underlying participant-level distribution or a stated method, the summaries cannot be used to reconstruct a valid primary comparison.

The record states that allocation was randomized and masking was absent, but it does not report sequence generation, allocation concealment, outcome assessor masking, or details of the randomization process. It also does not describe participant flow at follow-up, missing-data handling, analysis populations, or sensitivity analyses. These are gaps in reporting; the registry does not establish whether any of these issues actually affected the results.

Secondary outcome reporting is incomplete for a broad interpretation. The record lists repeated outcome descriptions, reports 12 secondary results, and indicates that values are missing or not estimable for a two-arm comparison for another endpoint. No multiplicity strategy or sponsor-reported secondary analysis is described. The serious adverse event counts are zero in both groups, but the small groups and limited event detail do not permit strong conclusions about safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Endovascular Denervation Improves Limb Ischemia in Patients With Peripheral Artery Disease — NCT04060797.
• Registry record last updated 2024-05-20; status last verified 2024-05.
• Results first posted 2024-05-20.
• 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

NCT04060797 is a completed, randomized, parallel-group study sponsored by Zhongda Hospital. The registry lists enrollment of 38 participants, no masking, and a study phase of not applicable. The study start date is 2019-08-23, and primary completion is recorded as 2021-09-30.

The intervention group received endovascular denervation before balloon dilation or stent implantation; the control group received balloon dilation or stent implantation alone. The primary endpoint was change in ankle-brachial index from baseline to 6 months. The posted median changes were 0.44 in the EDN group and 0.24 in the control group, with 19 participants in each group. No primary comparative estimate or uncertainty interval is reported in the registry record.

The registry also lists secondary outcomes involving ankle-brachial index, transcutaneous oxygen pressure, and Rutherford category. It reports no serious adverse events or deaths in either group. Key information about the primary analysis, missing data, analysis populations, and multiplicity is not reported, so the posted results support descriptive interpretation rather than a complete assessment of comparative effects.