Vagus Nerve Stimulation for Management of Bronchoconstriction in Patients Hospitalized With COPD Exacerbations: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Vagus Nerve Stimulation for Management of Bronchoconstriction in Patients Hospitalized With COPD Exacerbations (NCT01612793), a registered phase not stated study. The primary outcome is Change in the Length of Stay in the Hospital.

2. Clinical Question

3. Trial Design

The registry record describes a study of non-invasive vagus nerve stimulation with the AlphaCore device in people hospitalized with COPD. Its stated aims include examining safety, symptom improvement, and hospital length of stay. The primary outcome measure is hospital length of stay, while the record lists one outcome measure in total. Enrollment was 4.

The record names an AlphaCore Active Device group and an AlphaCore Sham Device group in the adverse-event information. However, allocation is not stated, and the record explicitly says this was not a randomized comparison and that the arms are not a like-for-like control comparison. The design should therefore not be interpreted as establishing balanced comparison groups or supporting a causal contrast. The registry record does not report the allocation method, the rationale for it, or details of how the sham device was used.

The study is classified as “other” in the registry record. Its status is terminated. The start is recorded as 2012-10 and primary completion as 2013-04. The record does not explain why the study was terminated, and no reason should be inferred from the status alone.

Although the primary outcome is defined, no outcome analysis is listed and no length-of-stay values are reported. The registry record does not give group-specific outcome summaries, an estimated treatment contrast, uncertainty intervals, or a test result. The registered study description and the posted results therefore support discussion of the design and endpoint, but not a quantitative assessment of the primary outcome.

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: Safety population

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: Safety population

6. Primary Endpoint

The registry lists the primary outcome as Change in the Length of Stay in the Hospital, measured over Admission to hospital, 1 week in-person visit and a 30 day phone call follow-up visit from time of discharge from the hosptal.

The primary endpoint is hospital length of stay, expressed in days. It is defined as the time from admission until the participant met the medical elements of the GOLD Discharge Criteria. This definition makes the endpoint a measure of the interval to meeting specified medical discharge criteria, rather than simply a count of days until a discharge event without stated criteria. The registry record cites the GOLD report and its Revised 2011 version as the source for those criteria.

Length of stay can be used to describe the duration of hospitalization in a population and to compare durations between groups when the design and analysis support such a comparison. It is also an operational endpoint: its value depends on when admission occurs and when the stated discharge criteria are judged to have been met. Care practices and the timing of assessments can influence the recorded duration, so a clear definition is important.

The registry lists the outcome unit as days and the summary parameter as a mean with full range as the dispersion measure. These describe the planned form of reporting, not actual findings. No mean, range, participant-level duration, or group comparison is reported in the registry record. The listed timeframe includes admission, a one-week in-person visit, and a 30-day phone follow-up from discharge; those follow-ups do not change the stated definition of length of stay, which ends when the medical elements of the discharge criteria are met.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is described using a mean and full range. A mean is a measure of the arithmetic center of observed values. A full range gives the lowest and highest observed values, showing the span of the data but not how observations are distributed within that span. With a very small sample, both the mean and the endpoints of the range can be strongly affected by an individual participant. This is general statistical context; the registry record does not report the actual length-of-stay observations or summaries.

Length of stay is a duration measured in days, but the registered endpoint is not described as a time-to-event analysis. It is defined as the number of days from admission until the participant met the medical elements of the GOLD Discharge Criteria. A time-to-event method is often useful when the event of interest is the occurrence of a defined event and some participants have not experienced it by the end of observation. Whether such methods were planned or appropriate in this study is not reported in the registry record. No time-to-event analysis is listed.

To estimate a difference between groups, an analysis would need to define the contrast and account for the design. A confidence interval, as a general statistical concept, expresses a range of values compatible with the data and the assumptions of a specified method. It conveys precision as well as direction and magnitude. A p-value, also as a general concept, assesses how incompatible the observed data are with a stated null model under the chosen analysis assumptions; it is not a measure of the size or clinical importance of an effect. Neither a confidence interval nor a p-value for length of stay is reported in the registry record.

Comparative analyses also rely on assumptions about how participants entered each group and whether the groups can be compared. Random allocation, when used and properly implemented, can help balance measured and unmeasured characteristics on average. The registry record does not state an allocation method and explicitly cautions that this was not a randomized comparison and that the arms are not a like-for-like control comparison. Thus, a difference between the group summaries, if one were reported, could not automatically be attributed to device stimulation. The record does not provide a model or adjustment strategy that would address potential group differences.

Over-dispersion is a general issue for count outcomes when variability exceeds what a simple statistical model expects. It can lead to uncertainty estimates that are too narrow if the model fails to account for the extra variability. This concept is not directly a description of the primary outcome, which is a duration summarized by a mean and full range. The registry record does not report a count-outcome model, a dispersion assessment, or an adjustment for over-dispersion.

The record's sample-size description characterizes its planning illustrations as calculations based on an observed effect, rather than the trial's own design. It specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a stated fraction of the observed effect. It also says that time-to-event planning entries use total events and other entries use participants per arm. Such calculations are planning illustrations, not observed power and not evidence that a study has a particular probability of finding an effect. Their interpretation depends on an effect estimate and other assumptions. No observed length-of-stay effect estimate or calculated sample-size requirement is reported in the registry record, so a numerical planning conclusion cannot be drawn from the available outcome information.

The registered outcome population is called the safety population. That label does not by itself specify which enrolled participants contributed to the primary outcome analysis, and there is no primary outcome analysis listed. The record does not report an intention-to-treat population, a per-protocol population, exclusion rules, or the handling of participants with incomplete measurements. These distinctions matter because the analyzed population and missing-data method can affect both the estimate and its interpretation.

Finally, a methods description cannot replace results. The registry gives a named endpoint, unit, summary parameter, dispersion description, and timeframe, but no observed endpoint values. Without the data summaries and analysis details, it is not possible to reproduce or assess an effect estimate, its uncertainty, model assumptions, or robustness. The statistical interpretation must therefore remain descriptive of what is registered and what is absent from the posted outcome record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure and identifies hospital length of stay as primary. It does not report an analysis for that outcome. A multiplicity plan—how to control the chance of false-positive findings when multiple outcomes, time points, or comparisons are tested—is not reported in the registry record. The study summary mentions safety and symptom improvement as aims, but the record does not give a testing hierarchy or explain how those aims relate analytically to the primary outcome. No adjustment method or prespecified approach to multiple testing is reported.

Missing-data procedures are not reported in the registry record. There is no description of how incomplete length-of-stay records, withdrawals, or other unavailable measurements would be handled. The record also does not indicate whether all enrolled participants contributed to the primary outcome or whether any were excluded from an outcome analysis. As no primary outcome analysis is listed, the extent and consequences of missing outcome data cannot be assessed.

The primary outcome population is identified as the safety population, but the registry record does not further define it for efficacy analysis. It does not report an intention-to-treat or per-protocol analysis population, nor does it explain which participants were included in any primary outcome calculation. These omissions prevent assessment of whether the analyzed population matches the enrolled population or how any exclusions might affect a comparison.

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 adverse-event record lists the AlphaCore Active Device group and the AlphaCore Sham Device group separately. In each group, 2 participants are listed as at risk for serious adverse events, and 0 are listed as affected. For other adverse events, 2 are listed as at risk and 1 as affected in each group. Deaths are listed as 0 in both groups. No serious adverse-event terms are listed.

These are counts, not rates or comparative estimates. They should be read with the listed at-risk counts and the enrollment of 4 in mind; no percentages or further calculations are needed to describe them. The record does not give event narratives, timing, severity grading beyond the serious versus other categories, relationship to the device, or information about recurrence. It also does not report statistical comparisons of adverse events between groups.

Zero serious events recorded in these groups does not establish that serious events cannot occur, and the equal counts for other events do not establish equivalence of safety. The small number of participants means the entries provide only a limited description of events recorded during the study. The registry record does not report additional safety analyses or explain the study's termination in relation to these counts.

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

The record establishes that a study of AlphaCore vagus nerve stimulation in hospitalized patients with COPD was registered, that enrollment was 4, and that hospital length of stay was designated as the primary outcome. It also records adverse-event counts for active and sham device groups. Those details describe the study and its posted safety entries, but they do not supply an efficacy estimate.

No length-of-stay observations or comparative analysis are reported in the registry record. Accordingly, the posted information cannot show whether stimulation changed the duration of hospitalization, whether any apparent difference favored one group, or how precise such a difference might be. The endpoint definition alone is not a result. Nor does the device's intended purpose of helping open the airways demonstrate that it achieved that purpose.

The record's caution that this was not a randomized comparison and that allocation was not stated is important. The named active and sham groups should not be treated as if they were necessarily comparable at baseline or as if their contrast established a causal effect. Even if an outcome contrast were available, the design information would limit its interpretation; in the absence of a reported contrast, no treatment effect can be characterized.

The adverse-event entries describe counts in a very small study, not a definitive safety conclusion. They neither establish that the device is safe nor demonstrate that it causes harm. The study's terminated status also does not explain why the study ended. That reason is not reported in the registry record, so no conclusion about early stopping, recruitment, safety, or efficacy should be inferred from status alone.

Overall, the registry record is informative about the intended endpoint, study status, and limited adverse-event reporting. It does not report enough outcome data to determine the direction or magnitude of any change in hospital length of stay or to make a comparative efficacy claim.

13. Why This Trial Matters Statistically

This study illustrates the difference between a registered research question and an answer supported by posted outcome data. A clearly named primary endpoint can define what investigators intended to measure, but it cannot establish what happened to participants. Here, length of stay is defined in relation to admission and the medical elements of the GOLD Discharge Criteria, yet no numerical results for that endpoint are reported.

The record also demonstrates why design details matter when interpreting a comparison. Active and sham labels can suggest a controlled contrast, but the registry explicitly says allocation was not stated and the arms are not a like-for-like control comparison. Without knowing how groups were formed and whether they were comparable, the labels alone cannot justify a causal interpretation.

Enrollment of 4 highlights a further statistical issue: estimates based on very few observations are generally uncertain and can be sensitive to individual values. That consideration does not permit a conclusion about the outcome in this study, because the outcome values are absent. It does underscore why an analysis should report both the effect estimate and its uncertainty, rather than relying on a study description or on event counts alone.

Finally, registry transparency matters for outcomes, analysis populations, missing-data handling, multiplicity, and study termination. The record specifies some endpoint metadata and limited safety counts but does not report many details needed to evaluate the primary outcome. Recognizing what is documented—and what remains unreported—keeps interpretation aligned with the evidence actually available.

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 main trial-specific limitation is the absence of reported primary outcome results. Although hospital length of stay is defined and specified in days, the registry record gives no observed values, mean, full range, group-specific summary, effect estimate, or uncertainty interval. No analysis is listed. The primary question therefore cannot be answered quantitatively from the posted record.

Enrollment was 4, limiting the amount of information available even for descriptive summaries. The adverse-event groups each list 2 participants at risk, but those counts do not provide a basis for a precise comparative safety assessment. The record does not report participant characteristics that would help readers understand the enrolled population or assess whether the groups were similar.

The registry record states that allocation was not stated, that this was not a randomized comparison, and that the arms are not a like-for-like control comparison. It does not describe the allocation process or sham procedures. These gaps restrict interpretation of any potential group contrast and prevent assessment of whether differences could reflect factors other than the intervention.

Other trial-specific details are also not reported in the registry record: the reason for termination, a statistical analysis plan, missing-data procedures, outcome-analysis populations beyond the safety-population label, and the handling of multiple aims or comparisons. The absence of those details should not be filled by assumptions. Together with the missing endpoint results, these limitations leave the study record descriptive rather than conclusive about length of stay or comparative treatment effects.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Vagus Nerve Stimulation for Management of Bronchoconstriction in Patients Hospitalized With COPD Exacerbations — NCT01612793.
• Registry record last updated 2019-02-28; status last verified 2018-03.
• Results first posted 2019-02-28.
• 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

NCT01612793 concerns non-invasive vagus nerve stimulation with the AlphaCore device for people hospitalized with COPD exacerbations. The primary outcome is hospital length of stay, defined from admission until meeting the medical elements of the GOLD Discharge Criteria and summarized as a mean with full range. Enrollment was 4; the study status is terminated.

The record lists active and sham device groups for adverse-event reporting, but allocation is not stated and the comparison is explicitly described as non-randomized and not like-for-like. Each group has 2 participants listed at risk for serious adverse events, with 0 affected; each has 1 other adverse event among 2 at risk, and deaths are 0.

No primary outcome analysis or length-of-stay result is reported in the registry record. The reason for termination and additional analysis details are also not reported.