Adjuvant Benefit of NMES to Supervised Exercise in Patients With IC: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Adjuvant Benefit of NMES to Supervised Exercise in Patients With IC (NCT02429310), a randomized na study. The primary outcome is Initial Walking Distance Measured by Treadmill.

2. Clinical Question

The clinical question is whether the group receiving the additional device had a different change in treadmill walking distance from the group receiving supervised exercise alone. Descriptive results for each group are relevant to that question, but group medians by themselves do not establish the size or precision of a between-group difference. The registry record does not report an inferential comparison for this primary endpoint, so the reported values should be read as group summaries rather than as a test of whether the adjunctive intervention changed walking distance relative to the comparator.

3. Trial Design

The study is recorded as a randomized, open-label, parallel-group trial. Participants were assigned to supervised exercise only or to neuromuscular electrical stimulation plus supervised exercise. The device is identified as Revitive IX. Masking is listed as none, so the registry does not describe a masked trial. The sponsor is Imperial College London.

The registry lists enrollment as 42. The primary outcome summaries report 20 participants in the supervised-exercise-only group and 17 in the group receiving NMES plus supervised exercise. The record does not explain the relationship between the enrollment figure and the group counts in the primary outcome summary, or describe why the summary counts differ from the enrollment figure. The analysis population and the handling of participants without an outcome measurement are not reported in the registry record.

The study status is completed. Its recorded start is 2014-12 and its primary completion is 2016-10. The primary endpoint is change from baseline in treadmill initial walking distance at 6 weeks. Secondary outcome domains include femoral haemodynamics measured by femoral artery duplex ultrasonography, laser Doppler flow measured by optical laser, symptomatic questionnaire scores, quality-of-life questionnaire scores, and urine and serum metabolic profiles. Six secondary outcomes are listed as posted. The record identifies eight outcome measures overall, but it does not give analysis results for the listed secondary domains in the information.

The registry classifies the phase as NA and the study kind as other. It does not report details of the randomization sequence, allocation concealment, recruitment sites, participant flow, or the statistical analysis plan. Those design details should not be inferred from the randomized and parallel-group 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.

Population: This includes all patients that were recruited. As per the participant flow module, 2 patients were lost in Supervised Exercise Only group after baseline assessment and 3 were lost in the NMES + Supervised Exercise group after baseline assessment.

6. Primary Endpoint

The registry lists the primary outcome as Initial Walking Distance Measured by Treadmill, measured over Change in baseline treadmill walking distance at 6 weeks (positive numbers indicate increase from baseline, negative numbers indicate decrease from baseline) - 6 week - baseline values..

The primary endpoint is initial claudication distance measured on a treadmill. The registry describes a fixed-load test at 3.5 km/h with a 10% gradient. Initial claudication distance is the distance walked until the onset of pain. The endpoint is therefore a measure of walking performance under a specified treadmill condition, with the event of interest being the participant’s onset of claudication pain.

The reported quantity is change in distance at 6 weeks from baseline, expressed in metres. The registry defines positive values as an increase from baseline and negative values as a decrease. This makes the summary about change over the study period rather than the absolute distance walked at the final assessment. The endpoint is clinically relevant to the study question because it captures how far participants walk before pain begins, under the stated test conditions. It does not, by itself, describe walking in everyday settings or other aspects of symptoms and function.

The registry reports the median change as 65.6 metres for supervised exercise only, with interval bounds of 33.98 and 93.88, and 95.5 metres for NMES plus supervised exercise, with interval bounds of 81.4 and 155.3. The endpoint description specifies inter-quartile range as the dispersion measure. These are summaries within each group, not an estimated contrast between groups. The record does not report the baseline and 6-week distances separately or a confidence interval for the between-group difference.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, parallel-group design. In general, random assignment is intended to reduce systematic differences between groups at the point of allocation. It does not guarantee that every characteristic is balanced in a particular trial, especially when group sizes are limited, and it does not replace a clear account of the analysis. The registry record does not report the randomization procedure, allocation concealment, or the statistical plan used for the primary comparison.

What does the median describe?

The primary endpoint is summarized by the median change in treadmill walking distance. In general, the median is the central value after observations are ordered. It is less influenced by unusually large or small observations than the arithmetic mean, which can be useful when a distribution is skewed. The choice of a median can also make the endpoint summary easier to understand when individual changes vary considerably. The registry identifies the dispersion measure as the inter-quartile range, which describes the middle part of the observed distribution. It does not provide participant-level data or further distributional diagnostics.

The posted summaries give the median change and interval bounds separately for each group. These are descriptive statistics. They answer what the reported group-level distribution looked like, but do not alone answer whether the randomized groups differed under a specified inferential method. To estimate the comparative effect, an analysis would need to define a between-group contrast and an approach to uncertainty. No such contrast, confidence interval, or test result is reported in the registry record. It would be inappropriate to infer an unreported analysis from the fact that the trial was randomized.

How should uncertainty be understood?

In general, a confidence interval expresses uncertainty around an estimated quantity under the assumptions of the statistical method used. Its interpretation depends on what quantity it surrounds. An interval describing the middle portion of participant outcomes is not a confidence interval for a treatment effect. Here, the endpoint specifies inter-quartile range, while the registry record does not report a confidence interval for the between-group comparison. The interval bounds should therefore be read as descriptive dispersion bounds, not as limits on the comparative effect.

Over-dispersion is a general concern when outcome variability is greater than a statistical model assumes. If a method assumes less variability than is present, its standard errors and uncertainty estimates may be too small, leading to overly confident conclusions. A method suited to the outcome distribution should account for its scale, skewness, and variability. The registry record does not report which inferential method, distributional checks, or variance assumptions were used for the primary endpoint, so it is not possible to assess those choices for this trial.

What do the planning assumptions mean?

The registry describes sample-size planning illustrations based on the observed effect. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the groups, and a normal approximation; the effect to detect is defined as a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power. They do not show the probability that the completed trial detected an effect, and they are not a substitute for the trial’s actual analysis. The record does not report the original design justification or explain whether the planning illustration corresponds to the design decisions made before recruitment.

In general, planning calculations depend on the effect considered important, the variability assumed, the chosen significance threshold, and the method used. A calculation based on an effect observed in the completed trial is especially different from a prospective justification because the observed effect is itself uncertain. The registry record does not report enough detail to evaluate the assumptions behind any planning estimate beyond those explicitly stated. No additional sample-size result should be treated as a finding about participants in this trial.

Why does the outcome scale matter?

Change in walking distance is measured in metres and is defined as the 6-week value minus baseline. Positive values indicate an increase, and negative values indicate a decrease. In general, a change score can be useful for describing movement from baseline, but its interpretation depends on the baseline measurements and the way follow-up observations are collected. The registry does not report the baseline and follow-up distributions separately, the handling of repeated measurements, or whether any adjustment was made for baseline values. It also does not report an estimand defining how intercurrent events or missing outcomes were handled.

Because no inferential result is recorded for this endpoint, readers should distinguish the reported within-group summaries from a treatment-effect analysis. The descriptive medians and their inter-quartile ranges are informative about observed change, but they do not establish a comparative effect or its uncertainty. The methods used to reach a comparative conclusion are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists six secondary outcome domains, including femoral haemodynamics, laser Doppler flow, questionnaire-based symptom and quality-of-life scores, and urine and serum metabolic profiles. It also records eight outcome measures overall. Many outcomes can create a multiplicity issue: when several hypotheses are tested, the chance of obtaining at least one apparently noteworthy result by chance can increase. In general, a prespecified hierarchy, adjustment method, or clear distinction between confirmatory and exploratory outcomes can help readers interpret a collection of tests.

Multiplicity handling is not reported in the registry record. The listed secondary outcomes should not be treated as confirmatory evidence of benefit or harm without their results, analysis methods, and any multiplicity plan. The registry record reports no analyses in the available analysis count, and no secondary outcome results are included in the posted information.

Missing-data procedures are not reported in the registry record. The enrollment figure is 42, while the primary outcome group summaries list 20 and 17 participants. The record does not explain the difference between those descriptions, state how many participants had measurements at each assessment, or say whether missing values were excluded, imputed, or handled using another method. No analysis population is defined; for example, the registry does not state whether the primary analysis included all randomized participants or only those with available outcome data. These omissions matter because the assumptions used to handle missing observations can affect the interpretation of a change-from-baseline result.

The registry record also does not report whether there were interim analyses, how the primary endpoint was selected from the outcome measures, or which secondary analyses were planned in advance. These details are necessary to assess selective reporting and the scope of inference. Their absence should be understood as incomplete reporting, not as evidence that a particular procedure was or was not used.

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 zero serious adverse events among 20 participants at risk in the supervised-exercise-only group and zero among 17 participants at risk in the NMES-plus-supervised-exercise group. It also reports zero other adverse events in each group, with the same group-specific counts at risk. Deaths are recorded as zero in both groups. No serious adverse event terms are listed.

These figures describe what the registry records for the stated groups and reporting period. A zero count means that no event of that category was recorded in the registry results; it does not establish that the underlying risk is zero. In general, adverse-event counts are interpreted in relation to the period of observation, event definitions, completeness of reporting, and the number of participants monitored. The registry record does not provide further detail about adverse-event definitions, surveillance procedures, timing, severity classification beyond the serious/other categories, or duration of follow-up for safety.

The counts should not be used to compare safety with precision. The record reports no statistical comparison of adverse events, and the available group sizes and zero counts cannot establish that the groups have equivalent safety profiles. These are registry-reported observations, not a basis for medical advice or a conclusion about the safety of either approach.

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

The registry record documents a randomized comparison of supervised exercise alone with supervised exercise plus a Revitive IX neuromuscular electrical stimulation device. For the primary endpoint, it reports the median change in initial treadmill walking distance at 6 weeks in each group. Both group medians are positive, and the recorded median is numerically higher for the group receiving the device in addition to supervised exercise. The accompanying interval bounds describe the group-level spread as specified by the endpoint’s inter-quartile range measure.

Those descriptive findings do not establish the size of a comparative treatment effect. The registry does not report a between-group estimate, confidence interval, or p-value for the primary endpoint. Without those results, the precision of the comparison cannot be evaluated from the record. Nor can the group medians be treated as a direct estimate of how much additional change is attributable to the device. A causal interpretation would require an appropriate analysis and adequate information about participants, outcomes, and missing data.

The findings also do not show whether observed changes were meaningful to participants, whether they persisted beyond the 6-week assessment, or whether they corresponded to changes in daily activity. The endpoint reflects distance to pain onset during a fixed treadmill test at 3.5 km/h and a 10% gradient. It is one aspect of walking performance, not a complete measure of symptoms, quality of life, vascular physiology, or metabolic outcomes. Although several secondary outcome domains are listed, their results are not reported in the registry record.

The registry records no serious adverse events, other adverse events, or deaths in either group in the posted safety counts. These observations do not prove that an approach has no risk, and the record does not provide enough safety-reporting detail to assess event ascertainment or longer-term experience. Overall, the posted data support a description of the trial’s group summaries and recorded adverse events, but not a definitive comparative claim about efficacy or safety.

13. Why This Trial Matters Statistically

This trial raises a clear statistical question: how should a randomized comparison be interpreted when the primary endpoint is reported as group medians and inter-quartile ranges, but a between-group analysis is not reported? The distinction is important. Within-group change describes what was observed in each group; a treatment comparison estimates how outcomes differ between groups under a defined analysis. Those quantities are related but are not interchangeable.

The endpoint also illustrates why outcome definitions matter. Initial claudication distance is measured under a specified treadmill protocol, and the reported outcome is change from baseline at 6 weeks. A precisely stated measurement condition supports interpretation of what the endpoint captures, while also defining its limits: treadmill performance is not identical to ordinary walking or to the full experience of intermittent claudication. The presence of other outcome domains points to a broader set of questions, but those outcomes cannot inform conclusions when their analysis results are not reported.

Reporting the analysis population, missing-data approach, and uncertainty around a between-group estimate would help readers assess how robust the comparison is. The enrollment figure and the outcome-summary counts are not reconciled in the registry record, and the record does not describe the statistical plan or multiplicity handling. These are not minor technicalities: they shape what evidence the results can support and how confidently it can be interpreted.

The study is also a useful example of the limits of zero adverse-event counts. Such counts are meaningful registry observations, but they do not establish absence of risk or equivalence between groups. Statistical interpretation depends not only on the numerical summaries but on definitions, follow-up, analysis methods, and completeness of reporting. The record makes the intended randomized comparison and primary outcome understandable, while leaving key inferential details unreported.

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 trial-specific limitations of interpretation arise from the registry record. Although the study is described as randomized, the method used to generate and conceal allocation is not reported. Masking is listed as none, but the record does not explain whether outcome assessors were masked or how the treadmill endpoint was administered and recorded across groups. The registry also does not provide recruitment sites, detailed eligibility criteria, or baseline characteristics, so group comparability cannot be assessed from the posted information.

The primary outcome is summarized by group medians and inter-quartile range bounds, but no between-group estimate, confidence interval, or p-value is reported. The registry does not report baseline and follow-up distances separately, the distribution of individual changes, or the statistical method used for the primary comparison. It also does not explain the relationship between enrollment of 42 and the group counts attached to the primary outcome summaries. Participant flow, reasons for missing measurements, and the analysis population are not reported.

The record lists multiple secondary outcome domains but does not provide their results or explain how multiplicity was addressed. It does not report the original sample-size justification, a prespecified analysis plan, interim analyses, or whether outcome selection changed during the study. These omissions limit assessment of selective reporting and of whether the observed summaries were analyzed according to a prespecified plan.

The primary endpoint is measured at 6 weeks on a fixed treadmill protocol. The registry does not report longer-term outcomes or establish whether the treadmill measure reflects other dimensions of function. Adverse-event counts are recorded as zero, but event definitions, monitoring procedures, and safety follow-up are not described. These reporting gaps mean the posted record supports a limited descriptive reading, rather than a complete evaluation of comparative effectiveness or safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Adjuvant Benefit of NMES to Supervised Exercise in Patients With IC — NCT02429310.
• Registry record last updated 2020-10-08; status last verified 2020-10.
• Results first posted 2019-09-09.
• 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.

18. Record Summary

NCT02429310 is a completed, randomized, open-label, parallel-group study sponsored by Imperial College London. The registry lists enrollment as 42 and records study start in 2014-12 and primary completion in 2016-10. The comparison was supervised exercise alone versus supervised exercise with the Revitive IX neuromuscular electrical stimulation device in patients with intermittent claudication.

The primary outcome was change from baseline in treadmill initial claudication distance at 6 weeks, measured in metres. The reported median changes were 65.6 for supervised exercise only and 95.5 for NMES plus supervised exercise, with interval bounds identified for the endpoint’s inter-quartile range. The registry does not report an inferential between-group result, an analysis population, or missing-data methods. It lists six secondary outcomes and reports zero serious adverse events, other adverse events, and deaths in each group. Important statistical and reporting details, including the primary comparison method and multiplicity handling, are not reported in the registry record.