Effect of Upper Airway Stimulation on Vascular Function in Obstructive Sleep Apnea: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Upper Airway Stimulation on Vascular Function in Obstructive Sleep Apnea (NCT03051165), a na na study. The primary outcome is Change in Peripheral Arterial Tonometry (PAT).

2. Clinical Question

3. Trial Design

The registry describes a single-group study of hypoglossal nerve stimulation (HGNS) in people with obstructive sleep apnea who had received an implant at the study site. It lists the allocation as NA and masking as none. The listed intervention is Hypoglossal Nerve Stimulation Treatment Withdrawal. The study was not a randomized comparison, and its groups should not be read as like-for-like control and treatment arms.

The planned sequence involved cardiovascular measurements and blood draws before HGNS activation, during treatment, and after a temporary treatment withdrawal period. After the 30-day withdrawal period, HGNS therapy was to be reactivated. The registry says potential participants would be told about the study at their 2-week post-operative appointment. These descriptions establish the intended sequence, but the record does not report how many participants completed each stage or whether all planned procedures took place.

The primary outcome was change in PAT, with listed time points of Baseline, Day 105, and Day 137. The registry states that PAT assessment was not performed for any participants at any study visit. The posted record lists 9 outcome measures, including the primary PAT outcome and secondary cardiovascular, vascular, and biomarker measures. It reports 0 analyses. No participant-level or summary results for the secondary measures are stated in the registry record.

The study status is TERMINATED. The record lists a start date of 2016-11-21 and a primary completion date of 2017-12-14. It does not report the reason for termination, a statistical analysis plan, or a sample-size justification. The enrollment field lists 13, but that value alone does not establish how many participants contributed data to any 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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: PAT assessment was not performed for any participants at any study visit.

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 Peripheral Arterial Tonometry (PAT), measured over Baseline, Day 105, Day 137.

Peripheral arterial tonometry (PAT) is a non-invasive method used to assess endothelial dysfunction. As described in the registry, blood flow is measured in the fingertips after compression with an inflatable cuff on the upper arm. Participants were to lie on their backs with a probe on a finger of each hand; the probes connect to a computer that records finger blood flow continuously for 10 minutes.

The measure is intended to capture a vascular response using fingertip blood-flow signals rather than an invasive procedure. The study listed PAT change at Baseline, Day 105, and Day 137, in the context of planned measurements before stimulation activation, during treatment, and after temporary treatment withdrawal. The registry record does not specify how those named time points map to each treatment stage.

For this endpoint to answer the primary question, measurements would need to be available at the relevant visits and compared according to a defined analysis. The registry explicitly reports that PAT assessment was not performed for any participants at any study visit. Thus, there are no posted PAT values, changes, or uncertainty estimates to interpret. The record explains what PAT was intended to measure, but it does not provide evidence about the direction or size of a PAT response.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the registered design allow?

The study is listed as SINGLE GROUP, with allocation NA and masking NONE. These features describe a study without randomized allocation to separate treatment and control groups. The planned observations concerned HGNS treatment stages in people who had received an implant. The design therefore does not yield a randomized between-group contrast. General statistical explanation: random allocation can help balance both measured and unmeasured factors across comparison groups, while a single-group sequence does not provide that same protection. A change across time in one group may be informative descriptively, but it does not isolate a treatment effect from all other potential influences.

The registry describes measurements before activation, during treatment, and after temporary withdrawal. Following the 30-day withdrawal period, HGNS was to be reactivated. The primary outcome lists Baseline, Day 105, and Day 137. The record does not explain the mapping between these named time points and the described treatment stages, nor does it give a statistical model for repeated observations. Such details are not reported in the registry record.

What would an endpoint estimate mean?

In general, an endpoint estimate condenses observed data into a quantity relevant to the research question. For a change outcome, that could be a difference between measurements taken at specified times, or a model-based estimate using repeated measurements. The appropriate estimate depends on the analysis plan and the available data. The registry does not report a PAT estimate or an analysis method, and PAT was not performed for any participants at any visit. There is consequently no PAT estimate to interpret, regardless of which statistical method might otherwise have been chosen.

A confidence interval, in general, expresses uncertainty around an estimated quantity under the assumptions of the chosen analysis. It does not repair absent observations, and it cannot be interpreted when the registry reports no endpoint estimate. No PAT confidence interval or other uncertainty measure is reported in the registry record. No p-value for the primary endpoint is reported either.

Why does the absence of PAT data matter?

When an outcome has no measurements, the problem is not simply that an estimate is imprecise. The analysis has no observed endpoint values from which to calculate a change. The registry explicitly states that PAT assessment was not performed for any participants at any study visit. It does not say whether the measure was omitted by design, unavailable for logistical reasons, or affected by another circumstance; the reason is not reported in the registry record.

The registry also reports 0 analyses. This is consistent with the absence of posted analysis results, but it should not be expanded into claims about unreported work outside the registry. The record gives no statistical analysis plan, including no specified model, handling of repeated measurements, or criteria for analysis inclusion. General statistical explanation: a prespecified analysis plan helps readers understand which estimand, model, and uncertainty calculation were intended. Without a reported plan, readers cannot evaluate whether a particular model would have matched the study question.

What are the sample-size assumptions for?

The stated sample-size assumptions describe a planning illustration, not the trial's own design: two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. The record says time-to-event calculations use a total number of events, while other calculations use participants per arm. Those are planning conventions, not observed findings. The registered study is single-group, so the equal-allocation, two-arm framework does not describe its listed design.

General statistical explanation: planning calculations explore the amount of information a hypothetical study might need under specified assumptions. Their output depends on the selected effect size, variability, significance threshold, allocation, and analysis framework. Such calculations do not show that a completed study had a particular probability of detecting an effect. They are never observed power. The PAT endpoint has no observed measurements in this record, so an illustration based on an effect assumption cannot be treated as a trial estimate or as evidence that the study detected or missed a PAT effect.

What can be said about multiplicity and other outcomes?

The registry lists secondary outcomes involving flow mediated dilation, peripheral arterial stiffness, 24-hour ambulatory blood pressure, C-reactive protein, fibrin degradation products, HSP70, HS-troponin, and suPAR. The record does not report analyses for these outcomes or state how multiplicity was addressed. General statistical explanation: when several outcomes are tested, interpreting each test as if it were the only test can increase the chance of at least one chance finding. A planned hierarchy or adjustment can address that concern, but no such strategy is reported. Because no outcome analyses are posted, there are no secondary estimates or tests to weigh against the primary endpoint.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary PAT outcome and secondary measures covering vascular function, ambulatory blood pressure, and biomarkers. It does not report a multiplicity strategy, such as a prespecified hierarchy among outcomes or an adjustment for multiple testing. General statistical explanation: when investigators assess several outcomes, the overall chance of a chance-positive finding can differ from the interpretation of a single isolated test. A multiplicity plan helps define how that family of results should be read. In this record, no outcome analyses are reported, so there are no posted tests whose multiplicity-adjusted interpretation can be assessed.

The registry explicitly states that PAT assessment was not performed for any participants at any study visit. This is a lack of primary endpoint measurement, not a reported pattern of measured values that happen to be missing for some participants. The reason PAT was not performed is not reported in the registry record. The record also does not describe missing-data methods, imputation, sensitivity analyses, or rules for excluding participants from analysis.

Although the enrollment field lists 13, the record does not say how many participants completed each planned visit or contributed data to any secondary outcome. It reports 0 analyses and provides no analysis-population definition, such as which enrolled participants would have been eligible for a particular endpoint analysis. The number listed as enrolled therefore should not be assumed to be the number with outcome data or the analysis denominator.

General statistical explanation: missing-data handling matters because conclusions can depend on why measurements are absent and whether absence is related to participant characteristics or outcomes. Imputation and sensitivity analyses can be considered when there are data to analyze, but they require explicit assumptions. No such assumptions or methods are reported, and absent PAT measurements cannot be reconstructed from the registry record. The status TERMINATED does not explain the missing endpoint assessments or resolve these reporting gaps.

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 13 as at risk for serious adverse events and 0 affected by serious adverse events in the listed study group. It separately reports 13 at risk for other adverse events and 0 affected by other adverse events. The death count is 0. These figures are registry safety counts for the reported group, not estimates of comparative risk from a randomized treatment-versus-control analysis.

General statistical explanation: a count of zero reported events is a description of what the record reports, not proof that an event is impossible or that no safety concern could occur in another setting. The interpretation of a zero count depends on how events were defined, monitored, and collected, as well as the amount of observation. The registry record does not give further detail about event definitions, observation duration for safety, or the method used to collect events.

The group is associated with the intervention label Hypoglossal Nerve Stimulation Treatment Withdrawal. The record does not provide a separate control group for comparison. Thus, these counts should not be described as showing that withdrawal is safer or less safe than another condition. They also do not establish safety beyond the participants and reporting captured in this registry record. No serious adverse event terms are listed.

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

This record describes a planned study of cardiovascular measures in people with obstructive sleep apnea who had received hypoglossal nerve stimulation. Its primary question concerned change in PAT across listed assessment times, in the context of treatment activation and temporary withdrawal. The design is single-group, unmasked, and not a randomized comparison. Those features set limits on the kinds of causal comparisons the design could support even if measurements had been collected.

The central result for interpretation is not a measured increase or decrease. The registry states that PAT assessment was not performed for any participants at any study visit. There is no reported primary endpoint estimate, no confidence interval, and no test result. The record therefore does not show whether PAT changed, by how much it might have changed, or how precisely a change could be estimated.

The registry lists secondary outcome measures, but it reports 0 analyses and gives no numerical results for them. Their presence in the outcome list is not evidence that a particular biomarker or vascular measure changed. The record lists 13 enrolled and reports zero serious adverse events, zero other adverse events, and zero deaths in its safety summary. These are descriptive safety counts and do not constitute a randomized comparison or establish the absence of risk.

The study status is TERMINATED, and the reason for termination is not reported in the registry record. No statistical analysis plan, sample-size justification, or multiplicity approach is reported. General statistical interpretation: planned procedures, outcome definitions, and sample-size illustrations cannot substitute for observed data. Any planning calculations should be understood as hypothetical design exercises, not observed power or findings from this trial. Overall, the record describes the intended research question and its outcome definitions, but it does not provide primary PAT evidence or reported analyses that answer the question.

13. Why This Trial Matters Statistically

Statistically, this study is a useful example of the distinction between a registered research question and an answer supported by observed outcome data. The registry defines PAT as the primary measure and describes a sequence involving HGNS activation, treatment, and temporary withdrawal. Yet it also states that PAT assessment was not performed at any study visit. A well-described endpoint cannot yield an effect estimate in the absence of measurements.

The design information also matters. A single-group study can describe outcomes over time, but it does not create a randomized control comparison. If repeated measures had been collected, interpretation would still depend on the timing, analysis plan, and other influences on outcomes. Here, the primary measure was not collected, so the record does not reach the stage of estimating within-group change.

The registry lists 9 outcome measures, while reporting 0 analyses. This makes it important to distinguish an outcome's registration from its completion and analysis. The names of secondary outcomes indicate what the study planned to assess; they do not establish that measurements were obtained or that results support a particular conclusion. The record does not report a multiplicity plan, which would also be relevant to interpreting findings across several outcomes if analyses were available.

The safety figures offer a separate example of cautious interpretation. The registry reports zero serious adverse events, zero other adverse events, and zero deaths, with 13 listed at risk in each adverse-event category. These counts describe what is recorded, but they are not a comparison with a control group and do not establish that risk is absent.

Finally, the study's TERMINATED status and the absence of a reported reason highlight why registry status, completion, and results should not be conflated. The record supports clear statements about planned methods and missing primary assessments. It does not support an estimate of PAT response or a claim about treatment effect.

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.

A trial-specific limitation is the absence of the primary PAT assessment. The registry says it was not performed for any participants at any study visit, leaving no observed primary endpoint values. This is more consequential than a small or imprecise set of PAT measurements: no change estimate or uncertainty interval can be calculated from the reported record.

The study was single-group, unmasked, and not a randomized comparison. There is no separate control group reported. Consequently, the registered design does not provide a randomized contrast, and any hypothetical change across treatment stages would require cautious interpretation. In this case, there are no posted PAT observations to support even that descriptive comparison.

The registry lists 13 enrolled but does not report completion by visit, participant flow, endpoint-specific denominators, or analysis populations. It also reports 0 analyses and no numerical results for the listed secondary outcomes. The reason PAT was not performed and the reason for the TERMINATED status are not reported in the registry record. The record does not give a statistical analysis plan, missing-data approach, sample-size justification, or multiplicity procedure.

The safety summary reports zero serious adverse events, zero other adverse events, and zero deaths, but does not provide further information about event definitions or collection methods. These limitations prevent detailed assessment of the scope and precision of safety monitoring. The design assumptions stated for sample-size illustrations include equal allocation between two arms, whereas the registered study is single-group; such planning assumptions do not describe the study's actual allocation structure.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effect of Upper Airway Stimulation on Vascular Function in Obstructive Sleep Apnea — NCT03051165.
• Registry record last updated 2018-12-11; status last verified 2018-11.
• Results first posted 2018-12-11.
• 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

The registry record describes a single-group, unmasked study of hypoglossal nerve stimulation in people with obstructive sleep apnea. It lists 13 enrolled and a TERMINATED status, with a start date of 2016-11-21 and primary completion date of 2017-12-14. The planned primary outcome was change in peripheral arterial tonometry at Baseline, Day 105, and Day 137.

The registry states that PAT assessment was not performed for any participants at any study visit and reports 0 analyses. Although secondary outcome measures are listed, no numerical outcome analyses are reported. The reason for termination and the reason for the absence of PAT assessment are not reported in the registry record. Safety counts list 0 serious adverse events, 0 other adverse events, and 0 deaths. These details describe the registry entry but do not provide an estimate of change in the primary endpoint or a randomized comparison.